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DO NASCIMENTO, MARINA, BRUNA GALDORFINI CHIARI ANDRÉO, and THALITA PEDRONI FORMARIZ PILON. "Padronização de excipientes para cápsulas gelatinosas duras contendo o extrato seco de Valeriana officinalis." Revista Brasileira Multidisciplinar 18, no. 2 (July 10, 2015): 167. http://dx.doi.org/10.25061/2527-2675/rebram/2015.v18i2.334.
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Neste artigo foi realizada a avaliação de quatro diferentes excipientes para encapsulação do extrato seco de Valeriana officinalis¸ sendo para isto empregadas diferentes misturas de componentes convencionalmente empregados para esta finalidade. Os principais fatores que influenciam as propriedades dos pós e consequente enchimento de cápsulas gelatinosas duras são: o fluxo, a ausência de adesão e a coesividade. A determinação da densidade aparente tem como importância a escolha do tamanho adequado da cápsula. O controle de qualidade das cápsulas contendo quatro diferentes tipos de excipiente e o extrato seco de Valeriana officinalis foi realizado através do peso médio e do tempo de desintegração do fármaco em três tipos de meios de dissolução (água, suco de laranja e leite). Os resultados de peso médio das cápsulas contendo quatro diferentes tipos de excipiente e o extrato seco de Valeriana officinalis estão dentro dos limites de variação. Além disso, o tempo de desintegração das cápsulas contendo os quatro diferentes tipos de excipiente e o extrato seco de Valeriana officinalis também estão dentro dos limites aceitáveis de dissolução (30 minutos) nos três meios de issolução. Dessa forma, o extrato seco de Valeriana officinalis, pode ser ingerido com água, suco e leite e também manipulado com os quatro diferentes tipos de excipientes de diferentes polaridades.
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Ortega Inclán, M. N., P. Hernanz Hernanz, T. Sainza Rúa, and P. Seguido Aliaga. "Reacción alérgica al excipiente de un genérico." Atención Primaria 28, no. 3 (2001): 212–13. http://dx.doi.org/10.1016/s0212-6567(01)78935-4.
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Roth Damas, Patricia, Mara Sempere Manuel, Cristina Vivas Maiques, and Vicente Palop Larrea. "Hipersensibilidad al aroma de melocotón como excipiente." Atención Primaria 46, no. 1 (January 2014): 50–51. http://dx.doi.org/10.1016/j.aprim.2013.04.012.
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Amaral, Pedro Augusto, Maiara Rodrigues Federeci, and Jéssica Laira Ulian Candido Sant'ana. "ANÁLISE DE EXCIPIENTES UTILIZADOS EM CÁPSULAS PREPARADAS EM FARMÁCIAS MAGISTRAIS." Revista Brasileira Multidisciplinar 19, no. 1 (January 18, 2016): 24. http://dx.doi.org/10.25061/2527-2675/rebram/2016.v19i1.365.
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Atualmente os excipientes farmacotécnicos estão sendo vistos não só como componentes da forma farmacêutica, mas também como substâncias capazes de influenciar na biodisponibilidade e, consequentemente, no efeito terapêutico dos fármacos, considerando que a utilização adequada destes é um ponto crucial para o sucesso de uma formulação. Baseado neste fato, o objetivo do estudo foi avaliar o uso de excipientes em cápsulas de fármacos previamente elencados e, com isso, verificar a qualidade destas formulações, bem como a perícia dos profissionais responsáveis por estas manipulações. A coleta de dados se deu por meio de um formulário a ser preenchido pelo farmacêutico de cada estabelecimento pesquisado, selecionando os excipientes utilizados pela farmácia para o preparo de cada fármaco. Para avaliação e consolidação dos resultados foram definidas pontuações para cada formulação, considerando se o uso dos excipientes estava adequado, aceitável ou inadequado. Os dados foram expostos percentualmente em gráficos. A média geral de acerto das farmácias voluntárias foi de 40,1%. Dentre os medicamentos, a Bupropiona aparece em destaque por apresentar 100% de erro na utilização de excipientes. A Ranitidina apresentou menor índice de erro 31,3%. O excipiente mais utilizado com 72,2% foi o amido. Concluiu-se que se faz necessário um melhor preparo das farmácias magistrais bem como de seus profissionais, pois apresentaram de forma geral, e também, na avaliação individual de cada fármaco, um baixo índice de acerto na escolha dos excipientes, comprometendo a qualidade, eficácia e segurança do medicamento.
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Callero, Ariel, and Lidon Martin-Fernandez. "Sospecha de alergia a benzodiazepinas: ¿excipiente o principio activo?" Atención Primaria 48, no. 6 (June 2016): 423–24. http://dx.doi.org/10.1016/j.aprim.2015.10.002.
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Barrientos, Marcia Otto, Fernanda Cristina Figueira Teixeira, and Roberto Paulo Correia de Araújo. "Presença de lactose em medicamentos isentos de prescrição." Revista de Ciências Médicas e Biológicas 17, no. 3 (December 18, 2018): 337. http://dx.doi.org/10.9771/cmbio.v17i3.28671.
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<p><strong>Introdução: </strong>A polifarmácia e a automedicação estão presentes na população brasileira, sendo frequente sua ocorrência com medicamentos isentos de prescrição. Ademais, a lactose é utilizada como excipiente em formas farmacêuticas sólidas. <strong>Objetivo:</strong> O presente estudo constitui uma pesquisa sobre lactose, na condição de excipiente, em medicamentos isentos de prescrição (MIPs). <strong>Metodologia: </strong>Em 391 MIPs presentes em cinco formas farmacêuticas sólidas e analisadas por classes, categorias e marcas, foram coletadas, nos meses de abril e maio de 2018, informações quanto à presença de lactose em bulas disponíveis nos sites da Agência Nacional de Vigilância Sanitária e da indústria farmacêutica no Brasil. <strong>Resultados: </strong>Constatou-se que a lactose está presente em 43,48% dos MIPs, sendo mais frequente nos comprimidos e comprimidos revestidos, nas proporções de 42,94% e 36,47%, respectivamente. Ela foi encontrada, predominantemente, em medicamentos similares, principalmente antialérgicos, analgésicos não opioides e anti-inflamatórios não esteroides, bem como na totalidade dos antidiarreicos e laxantes. Das 88 marcas analisadas, 30 apresentaram mais de 50% dos produtos com lactose. Identificou-se um percentual expressivo de medicamentos utilizados no controle dos sintomas de intolerância à lactose que continham esse carboidrato como excipiente. <strong>Conclusão:</strong> Nas formas farmacêuticas analisadas, a presença de lactose nos MIPs é superior a 40%. A lactose presente pode ser agravante de sintomas gastrintestinais. Portanto, é essencial incluir, na embalagem dos medicamentos, a frase de alerta sobre a presença desse açúcar, visando à sua ampla divulgação, particularmente dirigida aos indivíduos com restrição de uso dessa substância.</p>
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Reyes Balaguer, Javier, Amparo Melchor Penella, and M. Ángeles Guzmán Roa. "Consideraciones a la hipersensibilidad al aroma de melocotón como excipiente." Atención Primaria 47, no. 7 (August 2015): 471–72. http://dx.doi.org/10.1016/j.aprim.2015.02.004.
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Pagnano, Leonardo de Oliveira, Silvana Martinez Baraldi-Artoni, Maria Rita Pacheco, Edanir dos Santos, Daniela Oliveira, and Jeffrey Frederico Lui. "Morfometria de fibroblastos e fibrócitos durante o processo cicatricial na pele de coelhos da raça Nova Zelândia Branco tratados com calêndula." Ciência Rural 38, no. 6 (September 2008): 1662–66. http://dx.doi.org/10.1590/s0103-84782008000600026.
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O objetivo deste estudo foi avaliar a capacidade cicatrizante da calêndula (Calendula officinalis L.) sobre feridas cutâneas experimentais, em 15 coelhos, distribuídos em três grupos denominados: excipiente, calêndula e controle. Cada animal foi submetido à uma incisão cirúrgica de 6cm de comprimento, lateral à coluna vertebral e suturada no padrão U. Os produtos avaliados foram colocados sobre as incisões durante sete dias na quantidade de 0,1ml (loção cremosa não-iônica - grupo excipiente; tintura de calêndula a 5% - grupo calêndula) e nos animais do grupo controle não se utilizou nenhum produto. A biópsia de pele foi realizada no 1°, 3°, 5° e 7° dia após a incisão cirúrgica para avaliação morfométrica do processo cicatricial, analisando-se o número de fibroblastos e fibrócitos. A morfometria foi realizada por meio de microscópio óptico adaptado a um sistema computadorizado de análise de imagens. De acordo com os resultados, a calêndula propiciou obtenção dos maiores valores médios das células envolvidas no processo cicatricial, os fibroblastos, deduzindo que a mesma, inferiu uma resposta mais satisfatória na cicatrização em relação aos demais tratamentos.
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Bin, Liew Kai, Anand Gaurav, and Uttam Kumar Mandal. "A REVIEW ON CO-PROCESSED EXCIPIENTS: CURRENT AND FUTURE TREND OF EXCIPIENT TECHNOLOGY." International Journal of Pharmacy and Pharmaceutical Sciences 11, no. 1 (January 1, 2019): 1. http://dx.doi.org/10.22159/ijpps.2019v11i1.29265.
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There is no single-component excipient fulfills all the requisite performance to allow an active pharmaceutical ingredient to be formulated into a specific dosage form. Co-processed excipient has received much more attention in the formulation development of various dosage forms, specially for tablet preparation by direct compression method. The objective of this review is to discuss the emergence of co-processed excipients as a current and future trend of excipient technology in pharmaceutical manufacturing. Co-processing is a novel concept of combining two or more excipients that possess specific advantages that cannot be achieved using a physical admixture of the same combination of excipients. This review article discusses the advantages of co-processing, the need of co-processed excipient, general steps in developing co-processed excipient, limitation of co-processed excipient, technologies used in developing co-processing excipients, co-processed excipients in the literature, marketed products and future trends. With advantages offered by the upcoming newer combination of excipients and newer methods of co-processing, co-processed excipients are for sure going to gain attraction both from academia and pharmaceutical industry. Furthermore, it opens the opportunity for development and use of single multifunctional excipient rather than multiple excipients in the formulation.
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Silveira, Alexsander Augusto da, Amanda Evely Teixeira Pereira, Ikaro Silva de Oliveira, Flávio Silva de Carvalho, Adibe Georges Khouri, and Álvaro Paulo Silva Souza. "Polimorfismo de fármacos no controle de qualidade de medicamentos: uma revisão bibliográfica." Revista Eletrônica Acervo Saúde, no. 29 (August 9, 2019): e791. http://dx.doi.org/10.25248/reas.e791.2019.
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Objetivo: Revisar na literatura sobre os testes de identificação do polimorfismo de fármacos, a importância desse fenômeno no desenvolvimento de fármacos para a indústria farmacêutica e demonstrar os estudos mais recentes e atuais de fármacos que possuem estruturas polimórficas. Método: O artigo foi realizado a partir da análise de artigos científicos, com a seleção de artigos diretamente ligado ao tema. Resultado: O polimorfismo, dependendo das aplicações e alterações físico –químicas impacta diretamente na produção de fármacos no estado sólido, com alterações na biodisponibilidade, pode apresentar efeito placebo e efeito tóxico. Dependendo do fármaco, das condições de produção, como pH e temperatura e do excipiente utilizado no desenvolvimento da forma farmacêutica, diferentes formas de polimorfos do mesmo fármaco podem ser observadas. Considerações Finais: O Brasil tem a sua produção farmacêutica baseada na produção de medicamentos genéricos e similares, desta forma, formulações, excipientes e o processamento são adaptados para uma nova demanda. Dependendo das condições de obtenção e produção novas estruturas no estado sólido podem ser observadas, o que exige um melhor monitoramento pelo controle de qualidade de medicamentos nas indústrias farmacêuticas. Novos princípios ativos e otimizações de fármacos podem ser explorados por este processo. Trabalhos nessa área são escassos, novos estudos e descrições são imprescindíveis.
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Araújo Vieira Manoel, Lucas, Patrícia Porto, Amanda Batalha Teixeira, Arthur Girardi Carpanez, Richard Michael Grazul, Ademar Alves da Silva Filho, and Priscila Faria Pinto. "Desenvolvimento e estabilidade de formulação cosmética obtida com corante natural azul." HU Revista 45, no. 3 (November 28, 2019): 254–60. http://dx.doi.org/10.34019/1982-8047.2019.v45.28748.
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Introdução: Dentre os corantes de fontes naturais disponíveis no mercado, os mais comuns são aquelas capazes de conferir as cores vermelha, roxa, laranja e amarela, sendo a coloração azul relativamente escassa. A espécie Ravenala madagascariensis, também conhecida como árvore dos viajantes, é uma planta oriunda da Ilha de Madagascar, África do Sul, característica por sementes recobertas por arilos fibrosos de coloração azul intensa. Objetivo: Descrever uma metodologia capaz de extrair e incorporar os corantes azuis presentes nos arilos em uma formulação dermocosmética estável. Material e métodos: Foi realizado screening com distintos líquidos extratores para a obtenção do extrato dos arilos. O extrato em ciclometicone foi incorporado em preparações cosméticas empregando-se as bases Polawax® e Cold cream. Após a avaliação dos aspectos sensoriais, a formulação preparada com Polawax foi direcionada para avaliação de estabilidade acelerada (15 dias) de acordo com o protocolo definido pela ANVISA. Resultados: O melhor processo extrativo foi obtido pela utilização do ciclometicone, que é um excipiente compatível com o preparo de formulações cosméticas. O produto contendo 1% do extrato dos arilos em ciclometicone, incorporado à base Polawax, foi avaliado em relação às variáveis aspecto, cor (azul), odor, sensação ao tato e pH (5,5) e não apresentou alterações no ensaio de estabilidade acelerado. Conclusão: Com a metodologia apresentada, foi possível extrair e preparar uma formulação dermocosmética estável com nova proposta de corante azul, aplicável como excipiente para formulações.
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Pradeep Krishna Baskaran and Arun Radhakrishnan. "A review on novel excipient for tableting." International Journal of Research in Pharmaceutical Sciences 11, no. 3 (July 27, 2020): 4261–69. http://dx.doi.org/10.26452/ijrps.v11i3.2637.
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Despite the fact that the standards administering direct compression method have been notable for a long time, the system has as of late become progressively settled because of the presentation of excipients explicitly intended for direct compression method. These excipients are straightforwardly compressed by their own, yet can likewise be blended in with an enormous extent of medication substance with no noteworthy decay in tablet quality. Excipients with better usefulness can be acquired by growing brand-new substance excipients, recent evaluations of already available products, and novel blends of already available products. Any novel substance excipient being created as an excipient should experience different phases of administrative endorsement planned for tending to issues of wellbeing and poisonous quality, which is an extensive and exorbitant procedure. Furthermore, the excipient should experience a period of conventional advancement, which abbreviates the market selectiveness period. Co-processing is the alternative way novel excipients are approaching to showcase without experiencing the thorough security trial of a totally new concoction. It tends to be characterized as joining at least two built up excipients by a fitting procedure. The primary point of co-preparing is to acquire an item with added esteem identified with the proportion of its usefulness/cost. Advancement of co-handled straightforwardly compressible excipient beginnings with the determination of excipients can joined, their focused on extent, choice of readiness technique to get improved item with wanted both physical and chemical substance parameters and then it closes with limiting shirking with cluster to group varieties.
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Sopyan, Iyan, and Rizka Guntina Khairunisa. "Mini Review : Sedem System as a Tool to Characterize Excipients in Solid Dosage Form." Indonesian Journal of Pharmaceutics 3, no. 1 (March 20, 2021): 20. http://dx.doi.org/10.24198/idjp.v3i1.34038.
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SeDem System is a new system that can be applied in solid dosage form preformulation studies of medicines. It have parameters to evaluates critical quality attributes of materials that have an impact on final drug product’s quality. SeDeM studies could be used as a method for identifying the best excipient and calculating the maximum amount of excipient required for formulation. SeDeM method can , providing formulation with the lowest amount of excipients as it combines the Active Pharmaceutical Ingredients (API) with only one excipient and the standard formula of lubricants, thus avoiding the used of unnecessary excipients, such as diluents, binders and agglutinants. The information given by the SeDeM system contributes to a quality by drug design development.Keywords: SeDeM System, Excipients
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Surini, Silvia, Lusiana Ariani, Kurnia Ss Putri, Hayun Hayun, and Effionora Anwar. "COPROCESSED EXCIPIENTS OF CROSSLINKED AMYLOSE AND XANTHAN GUM FOR USE IN CONTROLLED RELEASE DOSAGE FORMS." International Journal of Applied Pharmaceutics 10, no. 1 (December 20, 2018): 59. http://dx.doi.org/10.22159/ijap.2018.v10s1.13.
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Objective: This study was aimed to obtain a new excipient that can be used as a polymer matrix for the formulation of controlled release dosage forms.Methods: This study used coprocessing and crosslinking methods on amylose and xanthan gum (XG) to obtain a new excipient that can be usedfor controlled release matrix of pharmaceutical dosage forms. The coprocessing step was conducted by drum drying, and the crosslinking step wasprepared using 6 and 12% sodium trimetaphosphate (STMP). The produced novel excipients were characterized in terms of infrared (IR) spectrum,substitution degree, moisture content, swelling index, and gel strength.Results: Our results showed that amylose–XG excipients crosslinked using 6% STMP have greater gel strength and better swelling indexes thanexcipients crosslinked using 12% STMP. All coprocessed excipients exhibited no differences in their IR spectra, whereas the crosslinked excipientsdid, indicating a structural change due to the addition of phosphate groups. Crosslinking amylose–xanthan-coprocessed excipients using 6% STMPproduced degrees of substitution (DSs) of 7–8 phosphates per 100 monomeric subunits. The excipients had a moisture content of 8.21–12.85%, andthe pH of a 1% solution of excipients was 6.21–6.43. In addition, the swelling index and gel strength of the excipient where both amylose and XG werecrosslinked together Were more than 1 where only amylose was crosslinked.Conclusion: The crosslinking amylose–xanthan-coprocessed excipient using 6% STMP is more suitable for use in controlled release dosage forms,particularly when the polymer ratio is 1:1.
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Sulbarán, Alexander, Germán E. Matiz, and Yolima Baena. "Acetilación del almidón de millo (Pennisetum glaucum) y evaluación de su aplicación como posible excipiente." Revista Colombiana de Ciencias Químico-Farmacéuticas 47, no. 2 (May 1, 2018): 255–76. http://dx.doi.org/10.15446/rcciquifa.v47n2.73969.
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Los almidones nativos se utilizan en la fabricación de productos farmacéuticos, cosméticos y de alimentos. Tienen limitaciones que pueden mejorarse mediante modificaciones físicas, químicas o enzimáticas. Los almidones de millo y maíz (referencia) se modificaron por acetilación a tres niveles. Se evaluaron fisicoquímicamente y farmacotécnicamente, para comparar el comportamiento de los almidones modificados frente al nativo. El almidón de maíz alcanzó mayores índices de sustitución. A mayor acetilación, la capacidad del almidón de incorporar agua mejoró, reflejándose en índices de hinchamiento y de sorción más altos, así como un incremento en la viscosidad. Se evidenció una mayor estabilidad de los geles del almidón de millo con menor tendencia a la sinéresis. La temperatura de gelatinización disminuyó a medida que aumentaba la acetilación, lo que permitiría obtener geles más rápido y con menor consumo de energía. El perfil de cristalinidad no se vio modificado sustancialmente. No se evidenciaron cambios importantes en las propiedades farmacotécnicas de los almidones modificados frente a los nativos. La captación de agua en el estado sólido favoreció la rápida desintegración en tabletas. Estos aspectos muestran un potencial del uso del almidón de millo acetilado en la industria farmacéutica y de alimentos como agente gelificante y desintegrante.
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Pituanan, Baginda Sati, and Silvia Surini. "FAST-DISINTEGRATING TABLET FORMULATION OF GINGER (ZINGIBER OFFICINALE ROSC.) EXTRACT USING COPROCESSED EXCIPIENT OF PRE-GELATINIZED CASSAVA STARCH-ACACIA GUM." International Journal of Applied Pharmaceutics 9 (October 30, 2017): 154. http://dx.doi.org/10.22159/ijap.2017.v9s1.77_84.
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Objective: Fast-disintegrating tablets (FDTs) are tablets that disintegrate and/or dissolve rapidly in the mouth, thereby helping patients who havedifficulty in swallowing tablets. Ginger extract contains gingerol and is generally known for its antiemetic property. This study aimed to obtain anduse coprocessed excipients of pre-gelatinized cassava starch (PCS) with acacia gum (AG) in FDT formulations of ginger extract.Materials and Methods: In this research, five types of PCS-AG coprocessed excipients (Co-PCS-AG) were prepared by mixed PCS and AG with thefollowing ratios mass of PCS and AG were 5:5, 6:4, 7:3, 8:2, and 9:1. The prepared Co-PCS-AG excipients were characterized in terms of morphology,particle size distribution, moisture content, pH, flow-ability properties, and swelling index. Based on the results, three types of Co-PCS-AG excipients,which were 7:3, 8:2, and 9:1, were selected for use in FDT formulation of ginger extract. The FDTs were then examined for tablet hardness, tabletfriability, wetting time, and disintegration time.Results: The results indicated that Co-PCS-AG 9:1 was ideal excipient to be used in FDT formulation, as it revealed good flow properties and swellingindex compare to the other ratios. The Co-PCS-AG excipients were formulated into tablets and evaluated. Analysis of the ginger extract FDTs revealedthat the FDT prepared using Co-PCS-AG 9:1 excipient had the best performance with tablet hardness, friability, wetting time, and disintegration timeof 0.7 kp, 2.12%, 93 seconds, and 134 seconds, respectively.Conclusions: Co-PCS-AG 9:1 excipient is a potential excipient with ideal binder, disintegrant, and filler properties for use in FDT formulation.
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Steinberg, Marshall, and Irwin Silverstein. "The Use of Unallowed Excipients." International Journal of Toxicology 22, no. 5 (September 2003): 373–75. http://dx.doi.org/10.1177/109158180302200506.
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The laws governing the U.S. Food and Drug Administration (FDA) do not provide for the approval of stand-alone excipients. Current regulations do not permit the use of excipients, but allow their use. The acceptance process for excipients is slow and only recently did the FDA propose draft guidance for nonclinical studies for pharmaceutical excipients. The FDA has made four suggestions to the U.S. Pharmacopoeia concerning including excipient monographs in the National Formulary for excipients not yet allowed. This article reviews these four proposals to identify the proposal that is most appropriate.
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Patel, Rahul, James Barker, and Amr ElShaer. "Pharmaceutical Excipients and Drug Metabolism: A Mini-Review." International Journal of Molecular Sciences 21, no. 21 (November 3, 2020): 8224. http://dx.doi.org/10.3390/ijms21218224.
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Conclusions from previously reported articles have revealed that many commonly used pharmaceutical excipients, known to be pharmacologically inert, show effects on drug transporters and/or metabolic enzymes. Thus, the pharmacokinetics (absorption, distribution, metabolism and elimination) of active pharmaceutical ingredients are possibly altered because of their transport and metabolism modulation from the incorporated excipients. The aim of this review is to present studies on the interaction of various commonly-used excipients on pre-systemic metabolism by CYP450 enzymes. Excipients such as surfactants, polymers, fatty acids and solvents are discussed. Based on all the reported outcomes, the most potent inhibitors were found to be surfactants and the least effective were organic solvents. However, there are many factors that can influence the inhibition of CYP450, for instance type of excipient, concentration of excipient, type of CYP450 isoenzyme, incubation condition, etc. Such evidence will be very useful in dosage form design, so that the right formulation can be designed to maximize drug bioavailability, especially for poorly bioavailable drugs.
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Okunlola, A., and T. A. Gbadamosi. "Compaction and Tableting Behavior of a Novel Co-Processed Excipient in the Formulation of Metoprolol Succinate Tablets." Nigerian Journal of Pharmaceutical Research 16, no. 2 (January 19, 2021): 127–42. http://dx.doi.org/10.4314/njpr.v16i2.4.
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Background: Pregelatinized starches exhibit good swelling and flow properties, imparting fast disintegration time but low mechanical strength in tablets. On the other hand, acacia gum acts as a binder in tablets by imparting high mechanical strength but prolonged disintegration time. Development of a co-processed excipient involving combination of the two excipients at sub-particle level will improve the functionality of the final product.Objective: To develop a direct compressible co-processed excipient with pregelatinized cocoyam starch and acacia gum and to evaluate its compaction behavior and tableting properties in metoprolol succinate tablets.Material and Methods: Batches of the co-processed excipient were prepared by co-fusion using different ratios (97.5:2.5; 95:5; 92.5:7.5; 90:10; 85:15; 80:20) of pregelatinized cocoyam starch and acacia gum. Flow and compaction properties and Fourier transform Infrared (FT-IR) analysis were carried out on native and pregelatinized starches and on the co-processed excipients. Metoprolol succinate tablets were formulated by direct compression using selected batches of co-processed excipients, pregelatinized cocoyam starch and acacia gum and then evaluated for mechanical strength and drug release.Results: Pregelatinization produced starch with larger granules (138.75±59.21μm), improved swelling (2.03±0.00) and flow (flow rate 0.52±0.03g/s). The FTIR analysis of the co-processed excipients confirmed absence of chemical interaction. Flow properties, compressibility (Kawakita value, a = 0.190 – 0.223) and rate of packing (Consolidation rate, K = 0.1221 – 0.2551) of the co-processed excipients were enhanced. Metoprolol succinate tablets containing the co-processed excipients had higher mechanical strength (Crushing strength 106.03±15.80 MNm-2) than those containing starch alone but faster drug release (disintegration time 1.80 ±0.20 -5.75±0.25; dissolution time; t80 30-50 min) than those containing acacia gum. Cocoyam starch: acacia gum ratio 97.5:2.5 gave the optimum formulation with high crushing strength (106.03 ± 15.8MNm-2) and fast release (t80 = 30 min).Conclusion: Co-processed excipients of pregelatinized cocoyam starch and acacia gum could serve as suitable alternatives to other directly-compressible excipients for the formulation of tablets.
Keywords: Acacia gum, Cocoyam starch, Compaction properties, Co-processing, Metoprolol
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Iyan Sopyan, Ni Made Widya Sukma Santi, Alif Virisy Berlian, Noer Erin Meilina, Qisti Fauza, and Restu Amelia Apriyandi. "A review: Pharmaceutical excipients of solid dosage forms and characterizations." International Journal of Research in Pharmaceutical Sciences 11, no. 2 (April 3, 2020): 1472–80. http://dx.doi.org/10.26452/ijrps.v11i2.2020.
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Excipients play an important role in formulating dosage forms. Exertion is empowered to help manufacture, provide, or collect dosage forms. Although considered pharmacological, excipients may consider a drug, due to chemical or physical interactions with the composition of the drug. Excipients have many functions in pharmaceutical dosage forms, including enhancing active ingredients in dosage forms, assisting active ingredients, disintegration, lubricants, binders, and suppliers. Each excipient has different characteristics. In this review, a library of studios is provided relating to the function, function, and content of solid excipients in a solid sedan. Various choices can be used on different compositions; resulting, this difference is also different. In this example, describe the types of excipients that can be used for various components in solid preparations that can be used in the formulation of solid preparations and select the right type of excipient according to the character of the desired solid preparation. In this review also presented a method, combining in and characterizing solid excipients to see the quality. The most commonly used methods for analysis of solid excipients are flow properties, compressibility index, Hausner index ratios, and angle of repose, while the instrumentation commonly used is Fourier transform infrared spectroscopy (FTIR), H and C-Nucleo magnetic resonance (H-CNMR), Scanning electron microscopy (SEM), Particle size analysis (PSA), X-ray diffraction (XRDP) and Differential scanning calorimeter (DSC).
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Preuss, James F., Catherine E. Goddard, Russell C. Clarke, Peter R. Platt, and Paul HM Sadleir. "Anaphylaxis to intravenous paracetamol containing povidone. A case report and narrative review of excipient allergy related to anaesthesia." Anaesthesia and Intensive Care 48, no. 5 (September 2020): 404–8. http://dx.doi.org/10.1177/0310057x20940318.
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Investigation of intraoperative anaphylaxis includes the exclusion of potential trigger agents the individual was exposed to within a plausible interval preceding the reaction. Occasionally, none of these agents will test positive. In this situation it is important to consider that excipients may be responsible for anaphylaxis, that the dilutions prepared to test the medication may not contain an appropriate concentration of the excipient to induce a positive skin reaction, or if an alternative formulation of the medication is tested, it may not contain the culprit excipient. This case describes a patient, who previously experienced an anaphylactic reaction to Betadine® (Sanofi-Aventis Australia Pty Ltd, North Ryde BC, NSW) experiencing anaphylaxis in the recovery period after general anaesthesia where Betadine was avoided. The recently administered therapeutics were excluded by skin testing, however further investigation determined that a povidone-containing formulation of paracetamol had been administered. Skin testing with povidone-containing paracetamol resulted in a positive reaction in the patient, but not in a volunteer control. Pharmaceutical excipients are added to medications to increase absorption, shelf-life and efficacy. Different brands of the same drug may contain different excipients. When testing for anaphylaxis with such compounds one must be sure the dilution is appropriate for both the parent compound and the excipient to ensure the accuracy of skin-prick and intradermal testing. This case demonstrates the potential for excipients to cause severe allergy and the importance of detailed history pertaining to previous allergic episodes as even the most unlikely of medications can potentially result in anaphylaxis due to excipients.
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Patel, Jalpa, and Dhaval Mori. "Application of 32 Full Factorial Design and Desirability Function for Optimizing The Manufacturing Process for Directly Compressible Multi-Functional Co-Processed Excipient." Current Drug Delivery 17, no. 6 (August 6, 2020): 523–39. http://dx.doi.org/10.2174/1567201817666200508094743.
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Background: Developing a new excipient and obtaining its market approval is an expensive, time-consuming and complex process. Compared to that, the co-processing of already approved excipients has emerged as a more attractive option for bringing better characteristic excipients to the market. The application of the Design of Experiments (DoE) approach for developing co-processed excipient can make the entire process cost-effective and rapid. Objective: The aim of the present investigation was to demonstrate the applicability of the DoE approach, especially 32 full factorial design, to develop a multi-functional co-processed excipient for the direct compression of model drug - cefixime trihydrate using spray drying technique. Methods: The preliminary studies proved the significant effect of atomization pressure (X1) and polymer ratio (microcrystalline cellulose: mannitol - X2) on critical product characteristics, so they were selected as independent variables. The angle of repose, Carr’s index, Hausner’s ratio, tensile strength and Kuno’s constant were selected as response variables. Result: The statistical analysis proved a significant effect of both independent variables on all response variables with a significant p-value < 0.05. The desirability function available in Design Expert 11® software was used to prepare and select the optimized batch. The prepared co-processed excipient had better compressibility than individual excipients and their physical mixture and was able to accommodate more than 40 percent drug without compromising the flow property and compressibility. Conclusion: The present investigation successfully proved the applicability of 32 full factorial design as an effective tool for optimizing the spray drying process to prepare a multi-functional co-processed excipient.
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AbouDaya, Mohammed, Stephen Tomlin, and Asia N. Rashed. "P47 Extent of paediatric exposure to pharmaceutical excipients: an exploratory study." Archives of Disease in Childhood 105, no. 9 (August 19, 2020): e31.1-e31. http://dx.doi.org/10.1136/archdischild-2020-nppg.56.
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AimThe assumption that excipients are inactive therefore non-harmful to patients is a declining opinion due to raised safety concerns of excipient activity, particularly in children.1 There is limited data on the safety of excipients in children and a lack of standardisation of the risk-benefit use of excipients in the different paediatric populations.2 This study aimed to investigate the extent of excipient exposure in children taking long-term oral liquids, admitted to Hospital, and to identify whether patients could be switched to a solid alternative due to the harm posed from liquid formulations.MethodA prospective observational study conducted in a UK paediatric hospital. The electronic medication chart for hospitalised children aged 0–18 years on long-term (for ≥6 weeks) oral liquid medicines, were reviewed over a four-week period. A priority list of eight excipients (called harmful excipients) with known reported hazards was developed based on literature: propylene glycol, ethanol, parabens, benzyl alcohol, aspartame, sorbitol, polysorbate 80 and benzoic acid. The list was used to determine the extent of children exposure to the harmful excipients. Considering patient factors (age, swallowing ability, treated condition), prescribed dose and availability of solid dosage forms, the included long-term liquid medicines were assessed for a potential solid form alternative by a specialist paediatric clinical pharmacist.ResultsA total of 302 oral liquid medicine formulations prescribed for 60 patients (age range 10 days – 17 years) were included in the study, of which 68.9% (208/302) were long-term oral liquid formulations. The 208 oral liquid formulation contained a total of 1044 excipients resulted in 17.4 (± 9) excipients per patients. Majority of patients (98.3%, 59/60) were exposed to at least one harmful excipient in their medicines. Children aged 2–11 years and 6–11 years were exposed the most to harmful excipients (mean 8.2 ± 4.9 exposure per patient). Parabens (81.7%, 49/60) was the most common harmful excipient patients were exposed to, followed by sorbitol (76.7%, 46/60), ethanol (75.0%, 45/60) and propylene glycol (70.0%, 42/60). Considering patient factors, prescribed dose and availability of solid formulations, it was found that almost third of the prescribed long-term oral liquid medicines (33.0%, 68/208) could be switched to tablet or capsule forms by pharmacist without any change to the prescribed dose. While for another 3.4% (7/208) long-term liquid medicines could be switched to solid dosage forms with prescriber approval, as prescribed doses would need to be adjusted slightly.ConclusionThe study highlights the extent of excipients exposure in children on long-term oral liquid medicines, many of which could potentially be harmful. Healthcare professionals should aim to reduce the long-term risks of excipients by providing an oral solid substitute to replace oral liquid formulation, where possible, and ensuring excipients are within safe, acceptable limits.ReferencesFabiano V, Mameli C, Zuccotti GV. Paediatric pharmacology: remember the excipients. Pharmacol Res 2011;63:362–365.Buckley L, Salunke S, Thompson K, et al. Challenges and strategies to facilitate formulation development of pediatric drug products: Safety qualification of excipients. Int J Pharm 2018; 536:563–569.
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Kriegel, Christina, Matthias Festag, Ravuri S. K. Kishore, Dieter Roethlisberger, and Georg Schmitt. "Pediatric Safety of Polysorbates in Drug Formulations." Children 7, no. 1 (December 20, 2019): 1. http://dx.doi.org/10.3390/children7010001.
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Polysorbates 20 and 80 are the most frequently used excipients in biotherapeutics, the safety data for which have been well documented in adults. The polysorbate content in therapeutic formulations that are administered to children, however, has been less clearly regulated or defined with regard to safety. In pediatric patients, excessive amounts of polysorbate in biotherapeutics have been linked to hypersensitivity and other toxicity-related effects. To determine safe levels of polysorbates for young patients, we have developed the progressive pediatric safety factor (PPSF), an age- and weight-based tool that estimates the amount of parenterally administered polysorbates 20 and 80 in formulations that will avoid excipient-related adverse events. Compared with existing modalities for calculating maximum acceptable doses of excipients for initial clinical trials in pediatrics, the PPSF is far more conservative, thus constituting an added margin of safety for excipient exposure in the most sensitive subpopulations—i.e., neonates and infants. Further, the PPSF may be applied to any relevant excipient, aiding pharmaceutical developers and regulatory authorities in conservatively estimating the safety assessment of a biotherapeutic’s formulation, based on excipient levels.
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Caballero, ML, and S. Quirce. "Delayed Hypersensitivity Reactions Caused by Drug Excipients: A Literature Review." Journal of Investigational Allergology and Clinical Immunology 30, no. 6 (December 10, 2020): 400–408. http://dx.doi.org/10.18176/jiaci.0562.
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The European Medicines Agency (EMA) defines excipients as the constituents of a pharmaceutical form apart from the active substance. Delayed hypersensitivity reactions (DHRs) caused by excipients contained in the formulation of medications have been described. However, there are no data on the prevalence of DHRs due to drug excipients. Clinical manifestations of allergy to excipients can range from skin disorders to life-threatening systemic reactions. The aim of this study was to perform a literature review on allergy to pharmaceutical excipients and to record the DHRs described with various types of medications, specifically due to the excipients contained in their formulations. The cases reported were sorted alphabetically by type of medication and excipient, in order to obtain a list of the excipients most frequently involved for each type of medication.
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Tita, Ioana Cristina, Lavinia Lupa, Bogdan Tita, Roxana Liana Stan, and Laura Vicas. "Compatibility Studies of Valsartan with Different Pharmaceutical Excipients." Revista de Chimie 70, no. 7 (August 15, 2019): 2590–600. http://dx.doi.org/10.37358/rc.19.7.7386.
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Compatibility studies between active drugs and excipients are substantial in the pharmaceutical technology. Thermal analysis has been extensively used to obtain information about drug-excipient interactions and to perform pre-formulation studies of pharmaceutical dosage forms. The objective of the present study was to evaluate the compatibility of the valsartan (VALS) with pharmaceutical excipients of common use including diluents, binders, disintegrants, lubricants and solubilising agents. Thermogravimetry (TG), derivative thermogravimetry (DTG), but especially differential scanning calorimetry (DSC) were used for a first screening to find small variations in peak temperature and/or their associated enthalpy for six drug/excipient mixtures (starch, cross caramelose sodique, microcrystalline cellulose 102, povidone K30, lactose monohydrate and magnesium stearate), which indicate some degree of interaction. Additional methods using Fourier transformed infrared spectroscopy (FT-IR) and X-ray powder diffraction (XRPD) confirmed the incompatibility of VALS with starch, povidone K30, lactose monohydrate and magnesium stearate. Those excipients should be avoided in the development of solid dosage forms.
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Iancu, Valeriu, Florentina Roncea, Radu George Cazacincu, and Dumitru Lupuleasa. "Preparation and evaluation of diclofenac sodium orally disintegrating tablets." Ovidius University Annals of Chemistry 27, no. 1 (June 1, 2016): 58–61. http://dx.doi.org/10.1515/auoc-2016-0004.
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Abstract Orally disintegrating tablets (ODTs) are dosage forms which disintegrate in mouth within seconds without need of water. This type of quality in dosage form can be attained by addition of different varieties of excipients. Pharmaburst™ 500 is a co-processed excipient system which allows rapid disintegration and low adhesion to punches. The aim of the present study was to develop and evaluate 25 mg diclofenac sodium ODTs (orodispersible tablets) batches by direct compression method at different compression forces 10 kN (F1) and 20 kN (F2) and directly compressible excipients used in different ratio (Avicel PH 102, magnesium stearate and coprocessed excipient Pharmaburst™ 500, 70% and 80% w/w). The obtained batches were analyzed for appearance, tablet thickness, uniformity of weight, hardness, friability, disintegration time, and non-compendial methods (wetting time). Co-processed Pharmaburst™ 500 excipient 70% used for sodium diclofenac ODT obtaining determined good results for quality control tests evaluation.
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Martins, Manoela Domingues, Marcia Martins Marques, Sandra Kalil Bussadori, Raquel Agneli Mesquita-Ferrari, Vanessa Christina Santos Pavesi, Nilsa Sumie Wadt, and Kristianne Porta Fernandes. "Citotoxicidade in vitro de extratos de arnica brasileira (Solidago microglossa) e arnica paulista (Porophyllum ruderale)." ConScientiae Saúde 8, no. 1 (May 11, 2009): 99–104. http://dx.doi.org/10.5585/conssaude.v8i1.1457.
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Um fitoterápico muito utilizado na clínica médica é arnica, que tem ações analgésicas, anti-inflamatórias e cicatrizantes, na forma tópica ou de tintura no tratamento de golpes, contusões, hematomas, distensões, edemas e ferimentos em geral. Neste estudo, avalia-se a citotoxicidade do extrato de arnica brasileira (Solidago microglossa) e paulista (Porophyllum ruderale) em excipiente para utilização em úlceras bucais sob fibroblastos de mucosa bucal humana (FMM1) cultivados. Os FMM1 foram mantidos por 24 horas em contato com os meios condicionados com arnica paulista e brasileira. A análise da citotoxicidade foi realizada pelo método do MTT. Os resultados foram comparados pelo método ANOVA, complementado pelo teste de Tukey, considerando p≤0,05. As substâncias analisadas mostraram-se biocompatíveis, apresentando atividade mitocondrial similar à do controle. Concluímos que os extratos são biocompatíveis in vitro com fibroblastos da mucosa bucal humana e devem ser realizados testes in vivo para analisar sua ação anti-inflamatória e reparadora.
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Dzitko, Jakub, Przemyslaw Zalewski, Daria Szymanowska, Piotr Garbacki, Magdalena Paczkowska, and Judyta Cielecka Piontek. "The Influence of Excipients on the Physicochemical and Biological Properties of a Bactericidal, Labile Ester Prodrug in a Salt Form – A Case Study of Cefetamet Pivoxil Hydrochloride." JOURNAL OF ADVANCES IN CHEMISTRY 15, no. 2 (August 23, 2018): 6218–34. http://dx.doi.org/10.24297/jac.v15i2.7560.
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The article presents an innovative approach to a bactericidal drug design based on a cephem prodrug analogue – cefetamet pivoxil hydrochloride. The emergence of cefetamet pivoxil hydrochloride excipient systems (mannitol, hydroxypropyl methyl cellulose, pregelatinised starch, lactose monohydrate, magnesium stearate, polyvinylpyrrolidone) caused changes in the physicochemical properties of cefetamet pivoxil hydrochloride. They are significant for planning the development of an innovative pharmaceutical formulation. The biological activity profile of the prodrug was also modified. FTIR spectra were used to study interactions between cefetamet pivoxil hydrochloride and the excipients. The theoretical approach to the analysis of experimental spectra enabled precise indication of cefetamet pivoxil hydrochloride domains responsible for interaction with the excipients. The interactions between cefetamet pivoxil hydrochloride and the excipients resulted in some important physicochemical modifications: acceptor fluid-dependent changes in solubility and the dissolving rate as well as a decrease in the chemical stability of cefetamet pivoxil hydrochloride in the solid state, especially during thermolysis. The interactions between cefetamet pivoxil hydrochloride and the excipients also had biologically essential effects. There were changes in its permeability through artificial biological membranes simulating the gastrointestinal tract, which depended on the pH value of the acceptor solution. Cefetamet pivoxil hydrochloride combined with the excipient systems exhibited greater bactericidal potential against Staphylococcus aureus. Its bactericidal potential against Enterococcus faecalis, Pseudomonas aeruginosa and Proteus mirabilis doubled. The new approach provides an opportunity to develop treatment of resistant bacterial infections. It will enable synergy between the excipient and the pharmacological potential of an active pharmaceutical substance with modified physicochemical properties induced by the drug carrier.
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Villanova, Janaina Cecília Oliveira, Tadeu Henrique Lima, Patrícia Santiago Patrício, Fabiano Vargas Pereira, and Eliane Ayres. "Síntese e caracterização de beads acrílicos preparados por polimerização em suspensão visando aplicação como excipiente farmacêutico para compressão direta." Química Nova 35, no. 1 (2012): 124–31. http://dx.doi.org/10.1590/s0100-40422012000100023.
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Mai, Yang, Liu Dou, Christine M. Madla, Sudaxshina Murdan, and Abdul W. Basit. "Sex-Dependence in the Effect of Pharmaceutical Excipients: Polyoxyethylated Solubilising Excipients Increase Oral Drug Bioavailability in Male but Not Female Rats." Pharmaceutics 11, no. 5 (May 10, 2019): 228. http://dx.doi.org/10.3390/pharmaceutics11050228.
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It is known that males and females respond differently to medicines and that differences in drug behaviour are due to inter-individual variability and sex specificity. In this work, we have examined the influence of pharmaceutical excipients on drug bioavailability in males and females. Using a rat model, we report that a portfolio of polyoxyethylated solubilising excipients (polyethylene glycol 2000, Cremophor RH 40, Poloxamer 188 and Tween 80) increase ranitidine bioavailability in males but not in females. The in vivo sex and excipient effects were reflected in vitro in intestinal permeability experiments using an Ussing chamber system. The mechanism of such an effect on drug bioavailability is suggested to be due to the interaction between the excipients and the efflux membrane transporter P-glycoprotein (P-gp), whose expression in terms of gene and protein levels were inhibited by the solubilising agents in male but not in female rats. In contrast, the non-polyoxyethylated excipient, Span 20, significantly increased ranitidine bioavailability in both males and females in a non-sex-dependent manner. These findings have significant implications for the use of polyoxyethylated solubilising excipients in drug formulation in light of their sex-specific modulation on the bioavailability of drugs that are P-gp substrates. As such, pharmaceutical research is required to retract from a ‘one size fits all’ approach and to, instead, evaluate the potential impact of the interplay between excipients and sex on drug effect to ensure effective pharmacotherapy.
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Osterberg, Robert E., Christopher C. DeMerlis, David W. Hobson, and Timothy J. McGovern. "Trends in Excipient Safety Evaluation." International Journal of Toxicology 30, no. 6 (December 2011): 600–610. http://dx.doi.org/10.1177/1091581811423582.
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Excipients are used in all drug products and in most food products. New technologies are being tested to increase the amount or rate of absorption of drugs and new and novel excipients may be included among them. New physical approaches such as nanoparticles of drug and excipients or lysosomes may offer better drug delivery especially of hard to absorb or difficult to formulate oral drugs. New excipients may improve or mask the flavor of foods, drugs, and dietary supplements. Recently, impurities in drug products have become subject to greater scrutiny and various international and national guidelines, guidances, and regulations have been proposed and accepted for use; excipient evaluation is included in these efforts. This symposium discussed new developmental concepts, guidelines/guidances and regulations involving impurities in excipients, new drug delivery systems involving excipients, and thoughts for possible improvement to these guidelines to promote faster regulatory acceptance of these substances.
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Pottel, Joshua, Duncan Armstrong, Ling Zou, Alexander Fekete, Xi-Ping Huang, Hayarpi Torosyan, Dallas Bednarczyk, et al. "The activities of drug inactive ingredients on biological targets." Science 369, no. 6502 (July 23, 2020): 403–13. http://dx.doi.org/10.1126/science.aaz9906.
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Excipients, considered “inactive ingredients,” are a major component of formulated drugs and play key roles in their pharmacokinetics. Despite their pervasiveness, whether they are active on any targets has not been systematically explored. We computed the likelihood that approved excipients would bind to molecular targets. Testing in vitro revealed 25 excipient activities, ranging from low-nanomolar to high-micromolar concentration. Another 109 activities were identified by testing against clinical safety targets. In cellular models, five excipients had fingerprints predictive of system-level toxicity. Exposures of seven excipients were investigated, and in certain populations, two of these may reach levels of in vitro target potency, including brain and gut exposure of thimerosal and its major metabolite, which had dopamine D3 receptor dissociation constant Kd values of 320 and 210 nM, respectively. Although most excipients deserve their status as inert, many approved excipients may directly modulate physiologically relevant targets.
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Amaral Silva, Daniela, Raimar Löbenberg, and Neal Davies. "Are Excipients Inert? Phenytoin Pharmaceutical Investigations with New Incompatibility Insights." Journal of Pharmacy & Pharmaceutical Sciences 21, no. 1s (April 20, 2018): 19s—31s. http://dx.doi.org/10.18433/jpps29745.
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PURPOSE: The U.S. Pharmacopeia defines excipients as substances other than the active pharmaceutic ingredient (API) that are added in a drug delivery system in order to aid in the manufacturing process and enhance stability, bioavailability, safety, effectiveness and delivery of the drug. The 1968 phenytoin intoxication outbreak in Brisbane, Australia, is a classic example of an API–excipient interaction. When administered with CaSO4 the absorption of phenytoin was reduced due to an interaction between the API and the excipient. When CaSO4 was replaced by lactose, the amount of drug absorbed was much higher, resulting in the observed intoxication. It was hypothesized that phenytoin was converted to a calcium salt prior to ingestion. The purpose of this study was to mechanistically investigate the interactions between excipients and phenytoin to confirm the hypothesis of the previous reports. METHODS: Titration experiments with phenytoin and calcium salt were performed. Isothermal micro calorimetry was used to determine incompatibilities between excipients, phenytoin and milk. NMR was used to characterize the compounds. Dissolution tests containing CaSO4, lactose or sorbitol as excipients were also performed. Both Canadian and United States of America commercially available capsules were tested with milk and water. RESULTS: The calorimeter results indicate that phenytoin sodium interacts with CaSO4 in aqueous media and the dissolution profile of CaSO4 containing capsules showed a reduced dissolution rate. In addition, phenytoin sodium also interacts with lactose through a Maillard reaction that can occur at body temperature. Likewise, commercial Phenytoin sodium products interacted with milk and the products containing lactose showed browning in water. CONCLUSION: In Canada and the USA, the reference product contains lactose as an excipient in the formulation, whereas the Canadian generic formulations do not contain lactose. Any clinical relevance of these difference has not been determined. A new incompatibility between phenytoin and lactose has been discovered and an incompatibility with calcium was confirmed, which may have implications in regard to excipients and food effects. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.
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Paul, McCague, Brennan Hilary, and Wallace Scott. "P13 Medication use and excipient exposure in paediatrics in a secondary care setting." Archives of Disease in Childhood 103, no. 2 (January 19, 2018): e1.17-e1. http://dx.doi.org/10.1136/archdischild-2017-314584.24.
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Background and aimPaediatric patients are widely exposed to a range of excipients which may cause harm to this vulnerable patient group. Legal requirement to disclose quantitative information on excipients changed in 2010,2 however, since most formulations were licensed prior to this date, there is a lack of potentially critical information available to currently practising pharmacists and clinicians. The aim of this study was to quantify excipient exposure to children in a secondary care setting.MethodA cohort study was conducted within Altnagelvin Area Hospital Paediatric Ward (Northern Ireland, Western Health and Social Care Trust) in January 2017. Medicines prescribed to patients throughout the study were recorded and exposure to ethanol, sodium benzoate and propylparaben was quantified.Exposure was then compared to proposed safe limits. Off-label and unlicensed use of medicines was assessed as a secondary aim. This study was classified as a service evaluation and ethical approval was not required.ResultsA total of 91 patients were enrolled in the study. Patient age ranged from 5 days to 15 years. The mean number of items prescribed per patient was 3.0. Analysis revealed that 75.8% of patients were exposed to ≥1 excipient of interest including ethanol, sodium benzoate and propylparabens. Excipient safety levels as proposed by the European Medicines Agency or World Health Organisation (where available) were not exceeded.Quantitative excipient information were not available for two products. There was both off-label and unlicensed use ofmedicines, with off-label prescribing (9.6%) being more common than the use of unlicensed medicines (0.4%).ConclusionThe paediatric population is exposed to potentially harmful excipients contained in commonly prescribed medicines. Although exposure within this study falls within existing safety limits, further research into paediatric specific safe exposure limits are required. It is notable that despite contacting themanufacturer, quantitative excipient information were not available for two products. Safety limits when considered together with quantitative excipient information will allow clinicians to complete an informed risk-benefit analysis for paediatric patients.ReferencesTulec C. Paediatric formulations in practice. In Costello I, Long PF, Wong IK, Tulec C, Yeung V (Ed.), Paediatric drug handling 2007:pp. 43–74. London: Pharmaceutical Press.European Commission. A guideline on summary of product characteristics [Online]2009;2:1–29. http://ec.europa.eu/health//sites/health/files/files/eudralex/vol-2/c/smpc_guideline_rev2_en.pdf [Accessed: 14th April 2017].
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Pani, Nihar, Lila Nath, and Sujata Acharya. "Compatibility studies of nateglinide with excipients in immediate release tablets." Acta Pharmaceutica 61, no. 2 (June 1, 2011): 237–47. http://dx.doi.org/10.2478/v10007-011-0016-4.
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Compatibility studies of nateglinide with excipients in immediate release tabletsExperiments were done to assess the compatibility of nateglinide with selected excipients in the development of immediate release tablets of nateglinide by thermal and isothermal stress testing (IST) techniques. To evaluate the drug-excipient compatibility, different techniques such as differential scanning calorimetric (DSC) study, infra-red (IR) spectrophotometric study and isothermal stress testing were adopted. The results of DSC study showed that magnesium stearate exhibited some interaction with nateglinide. However, the results of IR, and IST studies showed that all the excipients used in the formula were compatible with nateglinide. Optimized formulations developed using the compatible excipients were found to be stable over 3 months of accelerated stability studies (40 ± 2°C and 75 ± 5% RH). Overall, compatibility of excipients with nateglinide was successfully evaluated using a combination of thermal and IST methods and the formulations developed using the compatible excipients were found to be stable.
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Dornelas, Camila B., Daniel K. Resende, Maria Inês B. Tavares, Ailton S. Gomes, and Lúcio M. Cabral. "Preparação e avaliação reacional de nanocompósitos de PVP K-30 - montmorilonita (natural e organicamente modificada) por difração de raios X." Polímeros 18, no. 2 (June 2008): 187–92. http://dx.doi.org/10.1590/s0104-14282008000200017.
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Em estudo anterior foi utilizado o conceito de nanocompósito para aplicações farmacêuticas, mais especificamente na liberação controlada de fármacos. Um nanocompósito polímero (PVP K-30) - silicato lamelar (argila organofílica, OMMT) foi preparado por solução, em diclorometano, e a sua avaliação como excipiente farmacêutico foi realizada com sucesso. Neste trabalho, um estudo do tempo reacional foi realizado (12, 48 e 72 horas), tendo sido observado, através de difração de raios X (DRX), um valor de espaçamento interlamelar máximo em 12 horas. Este resultado motivou um estudo mais detalhado a respeito deste processo de intercalação. Para tal, e em razão da solubilidade da PVP, foi avaliado, também, um sistema mais simples, com a argila sódica (MMT), não tratada, em água. Em ambos os sistemas, PVP-OMMT e PVP-MMT, foi realizada uma varredura de tempos reacionais (de 15 minutos a 72 horas), nas proporções de 2:1, 1:1 e 1:2, para caracterização por DRX. As análises sugerem a formação dos nanocompósitos em até 1 hora de reação, resultado atribuído à estrutura amídica da PVP, capaz de estabilizar as lamelas negativamente carregadas da argila.
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de Salvi, Simone T. B., Diego Luiz Tita, Carlos de O. Paiva-Santos, and Selma G. Antonio. "Characterization of hydrochlorothiazide in solid formulations." Powder Diffraction 30, S1 (May 4, 2015): S127—S130. http://dx.doi.org/10.1017/s0885715615000226.
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Hydrochlorothiazide (HCTZ) is a diuretic used for the treatment of blood pressure (hypertension). HCTZ has two anhydrous polymorphs denoted as Forms I and II. Aiming at solid-state characterization, X-ray powder diffraction (XRPD) is known to be a powerful technique which has been successfully applied in investigating polymorphism in medicines. In this work, three tablets of HCTZ (a reference and two generic) were analyzed. The data were collected using Rigaku RINT2000 diffractometer copper rotate anode. The Rietveld method (RM) was applied for the characterization of HCTZ polymorphic form. For the crystalline excipients where the crystal structure is known, their phases were identified by the RM either. The results showed that all the tablets exhibit Form I of HCTZ, while the excipient lactose monohydrate is found to exhibit the crystalline form. One of the generics is also found to exhibit the excipient sodium lauryl sulfate (SLS) in the crystalline form. Therefore, the RM and XRPD are an efficient methodology for characterization of the crystalline Form I of the active principle of HCTZ and crystalline excipients lactose monohydrate and SLS in solid formulations. It is also interesting to observe excipients not described in the package insert of the medicament.
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Benabbas, Rihab, Noelia M. Sanchez-Ballester, Adrien Aubert, Tahmer Sharkawi, Bernard Bataille, and Ian Soulairol. "Performance Evaluation of a Novel Biosourced Co-Processed Excipient in Direct Compression and Drug Release." Polymers 13, no. 6 (March 23, 2021): 988. http://dx.doi.org/10.3390/polym13060988.
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This study exposes the potential usefulness of a new co-processed excipient, composed of alginic acid and microcrystalline cellulose (Cop AA-MCC), for the preparation of immediate drug release tablets by direct compression. Evaluation of the physical and mechanical properties as well as the disintegration behavior of Cop AA-MCC in comparison to commercial co-processed excipients (Cellactose®, Ludipress®, Prosolv® SMCC HD90 and Prosolv® ODT) and to the physical mixture of the native excipients (MCC and AA), was carried out. The obtained results illustrate the good performance of Cop AA-MCC in terms of powder flowability, tablet tensile strength, compressibility, and disintegration time. Although, this new co-processed excipient showed a slightly high lubricant sensitivity, which was explained by its more plastic than fragmentary deformation behavior, it presented a low lubricant requirement due to the remarkably low ejection force observed during compression. Compression speed and dwell time seemed not to affect significantly the tabletability of Cop AA-MCC. The study exposed evenly the performance of Cop AA-MCC compared to Prosolv® ODT, in terms of tabletability and dissolution rate of Melatonin. Cop AA-MCC presented comparable hardness, lower dilution potential, higher lubricant sensitivity, lower ejection force, and faster Melatonin’s release time than Prosolv® ODT. In summary, Cop AA-MCC exhibited interesting physical, mechanical, and biopharmaceutical properties, which demonstrate its concurrence to commercially available co-processed excipients. Furthermore, the simplicity of its composition and the scalability of its elaboration makes this multifunctional excipient highly recommended for direct compression.
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Santos, Ana, Francisco Veiga, and Ana Figueiras. "Dendrimers as Pharmaceutical Excipients: Synthesis, Properties, Toxicity and Biomedical Applications." Materials 13, no. 1 (December 21, 2019): 65. http://dx.doi.org/10.3390/ma13010065.
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The European Medicines Agency (EMA) and the Current Good Manufacturing Practices (cGMP) in the United States of America, define excipient as the constituents of the pharmaceutical form other than the active ingredient, i.e., any component that is intended to furnish pharmacological activity. Although dendrimers do not have a pharmacopoeia monograph and, therefore, cannot be recognized as a pharmaceutical excipient, these nanostructures have received enormous attention from researchers. Due to their unique properties, like the nanoscale uniform size, a high degree of branching, polyvalency, aqueous solubility, internal cavities, and biocompatibility, dendrimers are ideal as active excipients, enhancing the solubility of poorly water-soluble drugs. The fact that the dendrimer’s properties are controllable during their synthesis render them promising agents for drug-delivery applications in several pharmaceutical formulations. Additionally, dendrimers can be used for reducing the drug toxicity and for the enhancement of the drug efficacy. This review aims to discuss the properties that turn dendrimers into pharmaceutical excipients and their potential applications in the pharmaceutical and biomedical fields.
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Domínguez-Robles, Stewart, Rendl, González, Donnelly, and Larrañeta. "Lignin and Cellulose Blends as Pharmaceutical Excipient for Tablet Manufacturing via Direct Compression." Biomolecules 9, no. 9 (August 28, 2019): 423. http://dx.doi.org/10.3390/biom9090423.
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Extensive efforts are being made to find alternative uses for lignin (LIG). In the present work the use of this biopolymer as excipient to prepare tablets was studied. For this purpose, LIG was combined with microcrystalline cellulose (MCC) and used as excipients to prepare directly compressed tablets containing a model drug, tetracycline (TC). The excipients contained different concentrations of LIG: 100%, 75%, 50%, 25% and 0% (w/w). Two different compression forces were used (two and five tonnes). When formulations were prepared using LIG as the only excipient, tablets were formed, but they showed lower densities and crushing strength than the ones obtained with only MCC or LIG/MCC blends. Moreover, tablets prepared using five tonnes of compression force showed TC releases ranging from 40% to 70% of the drug loading. On the other hand, the tablets prepared using two tonnes of compression force showed a faster and more efficient TC release, between 60% and 90%. The presence of LIG in the tablets modified significantly the release profile and the maximum amount of TC released. Finally, a DPPH (2,2-diphenyl-1-picrylhydrozyl) assay was performed to confirm that the presence of LIG provided antioxidant properties to the formulations. Accordingly, LIG has potential as a pharmaceutical excipient.
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Oleksii, Yakovenko, Kolisnyk Tetiana, Ruban Lena, and Fil Natalia. "Formulation development of anti-stress compressed lozenges using a fractional factorial Latin cube design and ANOVA approach." Česká a slovenská farmacie 70, no. 1 (2021): 66–78. http://dx.doi.org/10.5817/csf2021-2-66.
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The aim of this work was to develop anti-stress compressed lozenges containing 100 mg of glycine and 250 mg of magnesium citrate obtained by the direct compression method. To choose optimal excipient composition providing the sufficient pharmaco-technical properties of the tablet blend, mechanical strength of tablets and non-disintegrating, slow-dissolving behavior of compressed lozenges during sucking, 27 experimental formulations according to fractional factorial Latin cube design were prepared and tested. The excipients used in the study were: Mannogem® EZ, Cellactose® 80 and GalenIQ™ 721 (fillers); Plasdone™ S-630, Kollidon® 90 F and Avicel® PH-101 (dry binders); Metolose® 90SH-4000SR and guar gum (gel-forming binders); PRUV®, Neusilin® US2, and Compritol® 888 CG ATO (antifriction excipients). The following parameters were investigated as responses: bulk density, Carr’s index, friability, resistance to crushing, and in vitro disintegration time. ANOVA approach was applied for statistical processing, which allowed to reveal the individual effects of each excipient and several interaction effects observed for the excipient amounts used in this study. Isomalt (GalenIQ™ 721), copovidone (Plasdone™ S-630), and glyceryl behenate (Compritol® 888 CG ATO) were selected to be incorporated in the final formulation of compressed lozenges.
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Khan, Dilawar, Daniel Kirby, Simon Bryson, Maryam Shah, and Mohammed Afzal. "P23 Accelerating and de-risking the production of paediatric oral formulations." Archives of Disease in Childhood 105, no. 9 (August 19, 2020): e18.1-e18. http://dx.doi.org/10.1136/archdischild-2020-nppg.32.
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Background & AimAs part of the EU paediatric regulation, the paediatric use marketing authorisation (PUMA) was introduced, with an aim to stimulate research in existing compounds that are off-patent and/or to help transform known off-label use into authorised use.1 However, success has been limited, with only a few products gaining a PUMA, such as Sialanar 320 micrograms/mL glycopyrronium (equivalent to 400 micrograms/mL glycopyrronium bromide). A distinct challenge to overcome in this area is the development of more ‘age appropriate formulations’, particularly with an excipient composition and load that is suitable for paediatric patients. This project aims to establish an excipient screening platform, supplemented with analytical characterisation of materials, which will act as a decision making tool to accelerate and de-risk the production of age appropriate paediatric medicines.MethodTo develop this excipient screening platform, a list of drugs that require an age appropriate formulation was produced using the ‘needs for paediatric medicines’ documents provided by the European medicines agency (EMA),2whilst common problematic excipients in paediatrics were identified using an EMA reflection paper.3 Literature and prescribing data were also reviewed to ensure drugs selected would benefit from an age appropriate formulation. Differential scanning calorimetry (DSC) to determine compatibility of selected drugs with widely used excipients was carried out using a TA DSCQ200 instrument (TA Instruments, New Castle, DE) with TA Instruments Universal Analysis 2000 software. Data was collected under nitrogen atmosphere (50 mL min−1) using pierced flat-bottomed TZero aluminium pans (sample mass about 2 mg) and heating rate of 10 °C min−1 in the range from 50 to 400°C. For samples containing both the drug and an excipient, 1 mg of each was measured out and gently mixed with a spatula for one minute.ResultsThe most common class of drugs identified as requiring age appropriate formulations were related to cardiovascular disorders and neurology, whilst the majority of drugs identified also exhibit poor aqueous solubilities. Some identified problematic excipients include ethanol, sodium benzoate and sorbitol; however, these excipients may still be used in paediatric formulations, as long as they are below certain concentrations (for example, ethanol concentration should not exceed 0.5% w/v for under 6 years old). Two drugs identified through the initial screening, carvedilol and nifedipine, were analysed by DSC, alone and then alongside starch from corn and starch 1500; the resulting DSC curves showed no changes in peak size, position (peak onset temperatures for nifedipine and carvedilol were observed at 173.2°C and 117.3°C, respectively) and shape, as well as no additional peaks, therefore suggesting compatibility between the tested samples.ConclusionThis first phase of the development of an excipient screening platform will continue to scan several different excipients with selected active pharmaceutical ingredients (APIs) in order to create compatibility profiles. The excipient screening platform generated will accelerate and de-risk the production of age appropriate formulations, as it would allow screening for potential incompatibilities and acceptability, alongside informing formulation of appropriate oral paediatric dosage forms.ReferencesEuropean Commission. State of Paediatric Medicines in the EU. 10 years of the EU Paediatric Regulation. COM (2017) 626. Available at: https://ec.europa.eu/health/sites/health/files/files/paediatrics/docs/2017_childrensmedicines_report_en.pdfNeeds for paediatric medicines - European Medicines Agency [Internet]. 2019 [cited 28 June 2019]. Available from: https://www.ema.europa.eu/en/human-regulatory/research-development/paediatric-medicines/needs-paediatric-medicinesReflection paper: formulations of choice for the paediatric population [Internet]. European Medicines Agency. 2019 [cited 28 June 2019]. Available from: https://www.ema.europa.eu/en/documents/scientific-guideline/reflection-paper-formulations-choice-paediatric-population_en.pdf
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Tian, Beiqian, Zhiyong Ding, Shuyi Zong, Jinyue Yang, Na Wang, Ting Wang, Xin Huang, and Hongxun Hao. "Manipulation of Pharmaceutical Polymorphic Transformation Process Using Excipients." Current Pharmaceutical Design 26, no. 21 (June 24, 2020): 2553–63. http://dx.doi.org/10.2174/1381612826666200213122302.
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Background: In the pharmaceutical field, it is vital to ensure a consistent product containing a single solid-state form of the active pharmaceutical ingredient (API) in the drug product. However, some APIs are suffering from the risk of transformation of their target forms during processing, formulation and storage. Methods: The purpose of this review is to summarize the relevant category of excipients and demonstrate the availability and importance of using excipients as a key strategy to manipulate pharmaceutical polymorphic transformation. Results: The excipient effects on solvent-mediated phase transformations, solid-state transitions and amorphous crystallization are significant. Common pharmaceutical excipients including amino acids and derivatives, surfactants, and various polymers and their different manipulation effects were summarized and discussed. Conclusion: Appropriate use of excipients plays a role in manipulating polymorphic transformation process of corresponding APIs, with a promising application of guaranteeing the stability and effectiveness of drug dosage forms.
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Rouaz, Khadija, Blanca Chiclana-Rodríguez, Anna Nardi-Ricart, Marc Suñé-Pou, Dèbora Mercadé-Frutos, Josep María Suñé-Negre, Pilar Pérez-Lozano, and Encarna García-Montoya. "Excipients in the Paediatric Population: A Review." Pharmaceutics 13, no. 3 (March 13, 2021): 387. http://dx.doi.org/10.3390/pharmaceutics13030387.
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This theoretical study seeks to critically review the use of excipients in the paediatric population. This study is based on the rules and recommendations of European and American drug regulatory agencies. On the one hand, this review describes the most frequent excipients used in paediatric medicine formulations, identifying the compounds that scientific literature has marked as potentially harmful regarding the side effects generated after exposure. On the other hand, this review also highlights the importance of carrying out safety -checks on the excipients, which, in most cases, are linked to toxicity studies. An excipient in the compilation of paediatric population databases is expected to target safety and toxicity, as in the STEP database. Finally, a promising pharmaceutical form for child population, ODT (Orally Disintegrating Tablets), will be studied.
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Zupanets, Kateryna O., Sergii K. Shebeko, Kseniia L. Ratushna, and Oleksandr V. Katilov. "Cumulative Risks of Excipients in Pediatric Phytomucolytic Syrups: The Implications for Pharmacy Practice." Scientia Pharmaceutica 89, no. 3 (July 5, 2021): 32. http://dx.doi.org/10.3390/scipharm89030032.
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Expectorant phytomucolytic syrups are widely used pediatric OTC-medicines. Physicians, pediatricians, and pharmacists are traditionally concerned with the efficacy of the active ingredients in cough syrups, and rarely consider the safety aspects of excipients that however are not absolutely “inactive” and are proved to initiate some negative reactions and interactions with other drugs. This paper presents a review, categorization, and comparative analysis of the safety profile of excipients contained in the 22 best-selling OTC pediatric phytomucolytic syrups available in pharmaceutical markets in Ukraine and Germany and proposes an approach to the consideration of the excipients’ safety risks for a pharmacist in the process of pharmaceutical care. The study has revealed that only one of the twenty-two analyzed syrups does not contain any potentially harmful excipients. The results of this analysis were used for developing a specific decision tool for pharmacists that can be used for minimizing excipient-initiated reactions when delivering OTC phytomucolytic syrups for children.
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Schlich, Michele, Francesco Lai, Anna Maria Fadda, Chiara Sinico, and Elena Pini. "Drug-Excipients Compatibility Studies in Proniosomal Formulation: A Case Study with Resveratrol." Journal of Nanoscience and Nanotechnology 21, no. 5 (May 1, 2021): 2917–21. http://dx.doi.org/10.1166/jnn.2021.19056.
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Proniosomal drug delivery system is one of the advancements in nanotechnology. Similarly to traditional dosage forms, chemical and physical compatibility of proniosomes components with the active ingredient(s) is a key step in the preformulation process of such systems. In this work, the compatibility of resveratrol with selected excipients in the development of proniosomal formulation was investigated by thermal and spectroscopic techniques. To evaluate the drug-excipient compatibility, different techniques such as differential scanning calorimetric study, attenuated total reflectance Fourier transform infrared spectroscopy study and powder X-ray diffraction were adopted. The results showed that the excipients used in the formulation were compatible with resveratrol.
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Ramesh, Kanteti V. R. N. S., Hemant Yadav, and Omar Sarheed. "Safety of Pharmaceutical Excipients and Regulatory Issues." Applied Clinical Research, Clinical Trials and Regulatory Affairs 6, no. 2 (July 3, 2019): 86–98. http://dx.doi.org/10.2174/2213476x05666181105123750.
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Background:Pharmaceutical excipients are critical in the formulation of any dosage form. Not many additives employed in the drug product manufacture have properties, which meet the desired qualities that the finished product must have. Therefore, it is mandatory to mix the drug substance with other substances to overcome the deficiencies. As a result, almost all pharmaceutical products are mixtures of active pharmaceutical ingredient and additives. So, there is a compelling need of these substances and normally they occupy the major part of any drug product. Excipients are of different chemical categories that have varying physicochemical properties like solubility, miscibility and the nature and source of these materials vary. With growing number of pharmaceutical excipients and polymers, the question of evaluating their toxicity is becoming a complex issue. Many polymers and novel excipients are now available in the market and with their diverse chemical nature and different sources and presence of impurities and their adverse effects will further complicate the safety profiling of these excipients.Conclusion:This review article will discuss the unwanted biological activities of some commonly used excipients and issues of the supply of the pharmaceutical excipients that need to be highly regulated and monitored to ensure availability of quality and pure excipient compounds.
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Barros, Ilka de Carvalho, Lécia Maria da Silva Freire, José Lamartine Soares Sobrinho, Edson Cavalcanti Silva Filho, and Lívio César Cunha Nunes. "Development and Evaluation of Capsule of Sodium Diclofenac and Paracetamol Using Mesocarp Babassu Powder as Excipient - Part II." Materials Science Forum 869 (August 2016): 849–53. http://dx.doi.org/10.4028/www.scientific.net/msf.869.849.
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The capsules are pharmaceutical forms extremely versatile used to administer drugs orally, thus demonstrating the relevance of search for new excipients. Therefore, it was aimed to demonstrate the technological feasibility of babassu mesocarp powder (MB) as an excipient in development of diclofenac capsules 50mg and paracetamol 500 mg. Two lots of capsule were produced for each active ingredient separately using MB and microcrystalline cellulose (MC) as an excipient. The analytical results of quality control of all lots remained within the limits accepted by the Brazilian Pharmacopoeia. Although the values of dissolution time coming from lots of CM and MB, the statistical analysis revealed that lots manufactured with MB showed a profile of release superior to CM, demonstrating the potential of MB as an excipient once the lots produced with MB showed a disintegration and dissolution equivalent to those obtained with CM lots.
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Wu, Yongmei, Jaquan Levons, Ajit S. Narang, Krishnaswamy Raghavan, and Venkatramana M. Rao. "Reactive Impurities in Excipients: Profiling, Identification and Mitigation of Drug–Excipient Incompatibility." AAPS PharmSciTech 12, no. 4 (September 27, 2011): 1248–63. http://dx.doi.org/10.1208/s12249-011-9677-z.
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