Literatura académica sobre el tema "Felodipine"

Calcium entry blockers, such as felodipine, increase natriuresis without increasing kaliuresis. Since these drugs acutely increase plasma renin activity without a concomitant change of aldosterone, inhibition of such stimulated aldosterone release might explain the absence of kaliuresis. In a randomized crossover study in 12 male volunteers, we compared the effects of simultaneously administered exogenous aldosterone and felodipine with the effects of either felodipine or aldosterone alone. Felodipine infusion decreased blood pressure, increased renal plasma flow, and induced natriuresis without kaliuresis. Aldosterone alone reduced sodium excretion and increased potassium excretion without influencing hemodynamics. Addition of aldosterone to felodipine attenuated its natriuretic effect and induced a kaliuresis, which clearly exceeded the rise of potassium excretion during aldosterone alone [delta% fractional excretion of K+ +42 +/- 12 with felodipine+aldosterone and +7 +/- 8% with aldosterone alone; means +/- SE, P < 0.02]. Our data suggest that felodipine-mediated inhibition of stimulated aldosterone release is essential for the absence of kaliuresis with felodipine. In addition, the pronounced kaliuresis with aldosterone during felodipine is in keeping with increased distal sodium delivery due to a proximal tubular action of felodipine.

In recent years the pharmaceutical industry has seen a rise in the number of drug compounds with low aqueous solubility, and consequently poor oral bioavailablility. One potential solution to this problem is to formulate such compounds as solid dispersions, whereby the drug is dispersed in a carrier matrix in the solid state. In this thesis, the hypothesis that a number of drug-drug and drug-polymer intermolecular interactions influence the physical stability and dissolution performance of solid dispersions is considered. The aim is to use correlations between drug molecular structure and solid dispersion performance to develop a platform to rapidly assess whether drug compounds will have favourable properties when formulated as a solid dispersion. Amorphous felodipine/copovidone solid dispersions are used as a model system to develop a suitable testing regime with regards to physical stability and dissolution performance. A laser light scattering technique developed in this work shows that morphological changes in felodipine/copovidone films exposed to water are due to polymer swelling. A combination of dissolution testing methodologies is also used to suggest a mechanism for the dissolution of bulk solid dispersion samples. Contributions of individual functional groups in the felodipine analogues to the physical stability and dissolution performance of their amorphous solid dispersions are assessed. Blocking of the felodipine amine hydrogen-bond-donor with an N-methyl, and the removal of chlorine substituents are both shown to reduce the physical stability of the solid dispersions. Correlations between molecular descriptors and data from the above experiments show that drug compounds are more likely to crystallise from solid dispersions with copovidone if they have a low log P, low relative molecular mass and low polarizability. Such correlations can form the basis of a screening method for the molecular design of analogous drug compounds likely to form high-performance solid dispersions with copovidone.

Thesis (Ph. D.)--School of Pharmacy and Dept. of Chemistry. University of Missouri--Kansas City, 2005.
"A dissertation in pharmaceutical sciences and chemistry." Advisor: Steven H. Neau and Thomas P. Johnston. Typescript. Vita. Description based on contents viewed Mar. 12, 2007; title from "catalog record" of the print edition. Includes bibliographical references (leaves 97-108). Online version of the print edition.

The feasibility of the injection moulding (IM) was explored for the development of novel drug delivery systems. Controlled release formulations were developed using a substituted cellulose derivative, hydroxypropyl methyl cellulose acetate succinate (HPMCAS) and a graft co-polymer (Soluplus®). BCS class II drugs ibuprofen and the felodipine were selected based on their physicochemical properties. In the present work, a homogenous dispersion of drugs in the polymer matrices was achieved using Hot Melt Extrusion (HME) and extruded pellets obtained were used for the development of the injection moulded systems. Four systems were developed using the IM consisting of ibuprofen-HPMCAS, ibuprofen-Soluplus®, felodipine-PEO-HPMCAS and felodipine-Soluplus®. The ibuprofen acts as a good plasticiser compared to felodipine therefore, felodipine containing IM systems required a plasticiser (PEO) when processed with HPMCAS. The analysis of extruded pellets and injection moulded systems using modulated DSC (MDSC) and Raman spectroscopy confirmed the formation of an amorphous molecular dispersion (i.e solid solution) in the case of all four systems. The phase separation behaviour and the amorphous stability of the systems was studied at various stress conditions. This revealed the “surface crystallisation” behaviour of the ibuprofen-HPMCAS systems. Temperature-composition phase diagram constructed based on the melting point depression and the Flory-Huggins lattice solution theory provided the explanation for the phase separation and crystallisation behaviour of ibuprofen-HPMCAS systems. The advanced characterisation techniques like DMA, 2D XRD and 3D laser microscopy provided the detailed understanding of crystal habits, phase seperation and surface crystallisation. The significant effect of the stress conditions on the rate of shrinkage was observed where, higher shrinkage tendency of a HPMCAS IM system was observed compared to Soluplus® IM systems. The extruded pellets provided the faster drug release compared to the moulded tablets suggests the effect of particle size as well as the densification during IM on the dissolution rate of the dosage form. The nature of the polymer and processing history were the contributing factors for the dissolution of the dosage forms.
The thesis is hardbound in two volumes. Volume II starts at Chapter 5, page 135.

The feasibility of the injection moulding (IM) was explored for the development of novel drug delivery systems. Controlled release formulations were developed using a substituted cellulose derivative, hydroxypropyl methyl cellulose acetate succinate (HPMCAS) and a graft co-polymer (Soluplus®). BCS class II drugs ibuprofen and the felodipine were selected based on their physicochemical properties. In the present work, a homogenous dispersion of drugs in the polymer matrices was achieved using Hot Melt Extrusion (HME) and extruded pellets obtained were used for the development of the injection moulded systems. Four systems were developed using the IM consisting of ibuprofen-HPMCAS, ibuprofen-Soluplus®, felodipine-PEO-HPMCAS and felodipine-Soluplus®. The ibuprofen acts as a good plasticiser compared to felodipine therefore, felodipine containing IM systems required a plasticiser (PEO) when processed with HPMCAS. The analysis of extruded pellets and injection moulded systems using modulated DSC (MDSC) and Raman spectroscopy confirmed the formation of an amorphous molecular dispersion (i.e solid solution) in the case of all four systems. The phase separation behaviour and the amorphous stability of the systems was studied at various stress conditions. This revealed the “surface crystallisation” behaviour of the ibuprofen-HPMCAS systems. Temperature-composition phase diagram constructed based on the melting point depression and the Flory-Huggins lattice solution theory provided the explanation for the phase separation and crystallisation behaviour of ibuprofen-HPMCAS systems. The advanced characterisation techniques like DMA, 2D XRD and 3D laser microscopy provided the detailed understanding of crystal habits, phase seperation and surface crystallisation. The significant effect of the stress conditions on the rate of shrinkage was observed where, higher shrinkage tendency of a HPMCAS IM system was observed compared to Soluplus® IM systems. The extruded pellets provided the faster drug release compared to the moulded tablets suggests the effect of particle size as well as the densification during IM on the dissolution rate of the dosage form. The nature of the polymer and processing history were the contributing factors for the dissolution of the dosage forms.

Orientador: Gilberto de Nucci
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
Made available in DSpace on 2018-08-06T06:05:33Z (GMT). No. of bitstreams: 1 Miglioranca_LuisHenrique_M.pdf: 3126825 bytes, checksum: 2c21ff2875a4ccdf7b161478ecc7b5a3 (MD5) Previous issue date: 2005
Resumo: Foi desenvolvido um método rápido, sensível, robusto e específico para determinação e quantificação da felodipina, em plasma sanguíneo humano por cromatografia líquida acoplada com espectrometria de massas usando nimodipina como padrão interno. A felodipina foi extraída em plasma humano, utilizando o procedimento de extração líquido/líquido com éter dietílicolhexano (80:20 v/v) como eluente. O método inclui uma corrida cromatográfica de 5 minutos usando uma coluna analítica Cg(100 mm x 4,6 mm d.i.) e a curva de calibração foi linear de 0,02 nglmL a 10 ng/mL (r2 > 0,994). A precisão entre as corridas, determinadas pelo desvio padrão relativo de replicatas dos controles de qualidades, foi 5,7% (0,06 ng/mL), 7,1% (0,6 ng/mL) e 6,8% (7,5 ng/mL). A exatidão entre as corridas foi:!: 0;2,1 e 3,1% para as concentrações acima mencionadas, respectivamente
Abstract: A rapid, sensitive,robust and specificmethodwas developed for the determinationand quantitation of felodipine, in human blood plasma by liquid chromatography coupled with tandem mass spectrometryusing nimodipine as internalstandardoFelodipinewas extractedfrom 0.5mL human plasma by use of a liquid/liquidprocedureusing diethyIetherlhexane(80/20:v/v) as eluent. The method inc1uded a chromatographicrun of 5 minutes using a Cs analytical column (100 mm x 406mm iod.)and the calibrationcurve was linear over the range from 0.02 nglmL to 10nglmL(~ > 0.994). The between-run precision, determined as relative standard deviation ofreplicate qualitycontroIs,was 5.7%(0.06 ng/mL),7.1% (0.6ng/mL)and 6.8% (7.5 ng/mL). The between-runaccuracy was :I: 0, 2.1 and 3.1% for the above-mentioned concentrations,respectively
Mestrado
Mestre em Farmacologia

博士
國防醫學院
醫學科學研究所
94
Felodipine (FLD) is a poorly water-soluble drug. To improve its dissolution rate, we used the rapid expansion of supercritical solutions (RESS) technique to prepare micronized FLD drug particles, which we encapsulated in poly-(ethylene glycol) 4000 (PEG 4000). We characterized the physical properties of the encapsulated drug particles by a variety of analytical methods, including optical light microscopy, scanning electron microscopy (SEM), differential scanning calorimetry (DSC) powder X-ray diffraction (powder-XRD) and fourier transform infrared (FT-IR), and studied the dissolution behavior of FLD in the microparticles. The supercritical condition of micronized FLD occurred at a relatively high pressure and moderate temperature. FLD–PEG 4000 microparticles compared well with micronized FLD. RESS was effective in reducing the particle size of FLD; we observed spot-shaped micronized FLD and popcorn-shaped FLD–PEG 4000 microparticles. The particulate properties of the microparticles included a narrow distribution and uniform size. The results of thermodynamic analysis and FT-IR showed no molecular interaction between FLD and PEG 4000 molecules, neither polymorphism nor amorphous state in the micronized FLD or FLD–PEG 4000 microparticles. FLD–PEG 4000 microparticles had a significantly faster drug dissolution rate than micronized FLD. These data show that RESS can be used to prepare FLD–PEG 4000 microparticles with small particle size (2–6 µm) and enhanced dissolution rate. Additionally, the in vitro and in vivo evaluation of felodipine microparticles for tablet formulation is also to explore in this study.

碩士
高雄醫學大學
醫務管理學研究所碩士在職專班
98
Objectives The trend of medical costs keeps rising over the years. Of the all expenses, drug expenditure accounts for around 1/4 and NHI Taiwan has implemented the routine drug price surveys for 6 times to suppress it since the first time on 04/01/2000. For this purpose, to analyze the impacts of the policy of regular drug price surveys on prescribed oral medication, single –component and single-purpose cardiovascular drug Felodipine is used for probing the drug consumption for the first 5 price adjustments, in order to provide NHI Taiwan the reference and the revision of cost controls. Methods The study is of a retrospective longitudinal basis which period of inferential statistics is from 04/01/2000 to 12/31/2008. Utilizing national health insurance research database, OPD & Hospitalization being at the ratio of 500:1 & 20:1 respectively from the randomly sampled secondary data files, yielded from National Health Research Institutes constitutes Taiwan’s medical consumption database of drugs. Prescribed drugs in accordance with ingredient name “Felodipine” are in the grand total of 12, and through proper exclusion and reformation of the database afterwards, 75970 data-sets meet the standards for analyses eventually. SPSS for Windows is used for statistical analyses, which involves Independent-Samples T-test, One-Way ANOVA, Linear Regression, Logistic Regression, and Generalized Estimating Equations for data analyses and verification of hypotheses. Results Generalized estimating equations are particularly utilized to deal with time effect through repeated measures of regular drug price surveys for 6 times as well as to examine drug consumption in number and amount during a specific period of time, and by using the results of the repeated measures to precisely compute the model outcomes for each predictor. Research findings: By control of other predictors in separate models of distinct dependent variables— (1) only the drug doses in average number per physician order (p=0.521), and rate cuts of drug prices in average number (p=0.433) and average amount (p=0.906) show no statistical significance respectively, other predictors of each model all revealing significant differences both in drug consumption of number and amount. (2) only the drug doses (p=0.983) and hospital ownership (p=0.789) prove no statistical significance towards decision making of physician order on brand name or generic drugs, while the other predictors do influence the behavior how a doctor prescribes, presenting significant differences. 1. Average number affected by predictors: (1) Result of average number affected by hospital ownership shows clinics > public hospitals > profit hospitals > private hospitals, which means clinics consume the most Felodipine drug in average number. (2) Based on hospital contract type, the consequence of average number presents medical centers > regional hospitals > area hospitals > clinics; in other words, medical center dominates over the others in Felodipine drug consumption of average number. 2. Average amount affected by predictors: (1) Result of average amount affected by hospital ownership shows clinics > public hospitals > profit hospitals > private hospitals. (2) Based on hospital contract type, the consequence of average number presents medical centers > regional hospitals > area hospitals > clinics, to clinics however, regional hospitals reveal no significant differences (p=0.55). 3. Average number per physician order affected by predictors: (1) Result of average number per physician order affected by hospital ownership shows clinics > profit hospitals > public hospitals > private hospitals, but there is no significant differences (p=0.209) of private versus public hospitals. (2) Based on hospital contract type, the consequence of average number per physician order presents clinics > medical centers > regional hospitals > area hospitals, to medical centers however, regional hospitals prove no significant difference (p=0.572). 4. Average amount per physician order affected by predictors: (1) Average amount per physician order of brand name drugs is much higher than that of generic drugs; if generic drugs are used, that would be saving 70 NTD compared to the use of brand name drugs. (2) Based on hospital ownership, the consequence of average amount per physician order indicates clinics > profit hospitals > public hospitals > private hospitals, to public hospitals however, private hospitals show no significant differences (p=0.082). (3) Result of average amount per physician order affected by hospital contract type indicates clinics > medical centers > regional hospitals > area hospitals, but there is no significant differences (p=0.584) of clinics versus medical centers. (4) Although higher Felodipine average number per physician order is presented in late periods, but average amount per physician order is much relatively less. (5) Rate cuts of drug prices to average amount per physician order indicate a significantly negative correlation, in other words, average amount per physician order less 1.63 NTD while drug prices cut 1%. 5. Predictive model of prescribing bias on brand name or generic drugs: (1) Drug doses do not influence the prescribing bias on brand name or generic drugs. (2) Based on hospital contract type, the outcome of prescribing bias on generic drugs points out clinics > regional hospitals > area hospitals > medical centers, to clinics however, regional hospitals signify no significant differences (p=0.156). (3) According to intervals of drug price adjustment, we conclude that the later the interval is, the higher probability the generic drugs will be chosen. (4) After the consideration of time effect and the control of other variables in the model, probability of prescribing bias on generic drugs will be 0.06-fold reduction while drug prices cut 1%, in another word, a decrease of 6% (p=0.021). Conclusions and suggestions A word spreads among people in pharmaceutical industry: “Price is the most precious for drug, just like its life!”. NHI Taiwan utilizes powerful routine drug price surveys to restrain drug expenses from rising up all the time. But excessive cuts of the drug price will result in benefit instead specially for new and costly drugs on patent sometimes, and cause the negative feedback of drug expenses to grow conceivably. It is like the both ends of a balance, and weighing “price” and “quantity” is in need of meticulous deliberation by NHI Taiwan. In view of the mentioned above, particularly proposing two suggestions for policy makers as the following: 1. To consider the recommendation by “Council For Economic Planning And Development” that a standard of reasonable drug expenses accounts for 24.3% of medical expenditure, and only to adjust drug prices while drug expenses exceed the goal. 2. To consider the recommendation by “Department of Health, Executive Yuan, R.O.C.” that drug and medical costs should have the same degree of growth rate, and only to adjust drug prices while drug expenses exceed the goal.

No
OBJECTIVES: To compare the properties of solid dispersions of felodipine for oral bioavailability enhancement using two different polymers, polyvinylpyrrolidone (PVP) and hydroxypropyl methylcellulose acetate succinate (HPMCAS), by hot-melt extrusion (HME) and spray drying. METHODS: Felodipine solid dispersions were prepared by HME and spray drying techniques. PVP and HPMCAS were used as polymer matrices at different drug : polymer ratios (1 : 1, 1 : 2 and 1 : 3). Detailed characterization was performed using differential scanning calorimetry, powder X-ray diffractometry, scanning electron microscopy and in-vitro dissolution testing. Dissolution profiles were evaluated in the presence of sodium dodecyl sulphate. Stability of different solid dispersions was studied under accelerated conditions (40 degrees C/75% RH) over 8 weeks. KEY FINDINGS: Spray-dried formulations were found to release felodipine faster than melt extruded formulations for both polymer matrices. Solid dispersions containing HMPCAS exhibited higher drug release rates and better wettability than those produced with a PVP matrix. No significant differences in stability were observed except with HPMCAS at a 1 : 1 ratio, where crystallization was detected in spray-dried formulations. CONCLUSIONS: Solid dispersions of felodipine produced by spray drying exhibited more rapid drug release than corresponding melt extruded formulations, although in some cases improved stability was observed for melt extruded formulations.