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Journal articles on the topic 'Absorption enhancers'

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Published: 4 June 2021

Last updated: 3 February 2022

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1

Maher, Casettari, and Illum. "Transmucosal Absorption Enhancers in the Drug Delivery Field." Pharmaceutics 11, no. 7 (July 15, 2019): 339. http://dx.doi.org/10.3390/pharmaceutics11070339.

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Drug delivery systems that safely and consistently improve transport of poorly absorbed compounds across epithelial barriers are highly sought within the drug delivery field. The use of chemical permeation enhancers is one of the simplest and widely tested approaches to improve transmucosal permeability via oral, nasal, buccal, ocular and pulmonary routes. To date, only a small number of permeation enhancers have progressed to clinical trials, and only one product that includes a permeation enhancer has reached the pharmaceutical market. This editorial is an introduction to the special issue entitled Transmucosal Absorption Enhancers in the Drug Delivery Field (https://www.mdpi.com/journal/pharmaceutics/special_issues/transmucosal_absorption_enhancers). The guest editors outline the scope of the issue, reflect on the results and the conclusions of the 19 articles published in the issue and provide an outlook on the use of permeation enhancers in the drug delivery field.

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2

Steyn, Dewald, Lissinda Hester Du Plessis, and Awie Kotze. "Nasal Delivery of Recombinant Human Growth Hormone: In Vivo Evaluation with Pheroid™ Technology and N-Trimethyl Chitosan Chloride." Journal of Pharmacy & Pharmaceutical Sciences 13, no. 2 (August 7, 2010): 263. http://dx.doi.org/10.18433/j3cs3f.

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Purpose. It was the aim of this study to investigate the possible enhancement of the absorption of recombinant human growth hormone (rhGH) in the nasal cavity, in the presence of a polymeric absorption enhancer, N-trimethyl chitosan chloride (TMC) and a fatty acid-based delivery system, Pheroid™. Methods. Two types of Pheroid™ formulations, Pheroid™ vesicles and Pheroid™ microsponges were characterized and evaluated with regard to particle size and morphology. In vivo bioavailability studies in rats were performed and the nasal bioavailability of Pheroid™ vesicles and Pheroid ™microsponges were compared relative to subcutaneous administration. The results were also compared with different N-trimethyl chitosan chloride (TMC) formulations, TMC H-L and TMC H-H, well studied absorption enhancers. Results. Pheroid™ vesicles and Pheroid™ microsponges showed a size distribution of approxiamately 2-3 µm and 3-4 µm for Pheroid™ vesicles and Pheroid™ microsponges respectively. Using specific RIA, the relative bioavailability of rhGH after comparison with subcutaneous injection was determined to be 38.9, 128.5, 39.9, 136.3, and 8.3 % for Pheroid™ microsponges, Pheroid™ vesicles, TMC H-H, TMC H-L and control group (intranasal rhGH alone), respectively. All the enhancers showed significant absorption enhancement (P < 0.05) with the highest effect observed with TMC H-L. Conclusion. All the enhancers may have promising potential as safe and effective nasal absorption enhancers of rhGH.

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3

Carpentieri-Rodrigues, Letícia Norma, Juliana Modolo Zanluchi, and Ivanna Hinke Grebogi. "Percutaneous absorption enhancers: mechanisms and potential." Brazilian Archives of Biology and Technology 50, no. 6 (November 2007): 949–61. http://dx.doi.org/10.1590/s1516-89132007000700006.

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Transdermal applications of drugs present many advantages in terms of absorption, however this is not easily obtained through the transdermal route. The principle barrier is the stratum corneum and one of the strategies that have been found to promote cutaneous drug penetration is through the use of absorption enhancers. Many substances have been identified as absorption enhancers. Although the list of substances that promote absorption is growing, in most cases, there is a direct correlation between the effects of absorption enhancers and their skin toxicity. The use of these substances depends therefore on studies which focus on local and systemic toxicity, as well as action mechanisms.

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4

Aungst, Bruce J. "Absorption Enhancers: Applications and Advances." AAPS Journal 14, no. 1 (November 22, 2011): 10–18. http://dx.doi.org/10.1208/s12248-011-9307-4.

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5

Davis, Stanley S., and Lisbeth Illum. "Absorption Enhancers for Nasal Drug Delivery." Clinical Pharmacokinetics 42, no. 13 (2003): 1107–28. http://dx.doi.org/10.2165/00003088-200342130-00003.

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6

de Boer, A. G., E. J. van Hoogdalem, and D. D. Breimer. "Improvement of drug absorption through enhancers." European Journal of Drug Metabolism and Pharmacokinetics 15, no. 2 (April 1990): 155–57. http://dx.doi.org/10.1007/bf03190198.

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7

Hussain, Alamdar, John J. Arnold, Mansoor A. Khan, and Fakhrul Ahsan. "Absorption enhancers in pulmonary protein delivery." Journal of Controlled Release 94, no. 1 (January 2004): 15–24. http://dx.doi.org/10.1016/j.jconrel.2003.10.001.

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8

Patil, Nilam H., and Padma V. Devarajan. "Enhanced insulin absorption from sublingual microemulsions: effect of permeation enhancers." Drug Delivery and Translational Research 4, no. 5-6 (October 29, 2014): 429–38. http://dx.doi.org/10.1007/s13346-014-0205-z.

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9

Shah, Pranav, Viral Jogani, Pushpa Mishra, Anil Kumar Mishra, Tamishraha Bagchi, and Ambikanandan Misra. "Modulation of Ganciclovir Intestinal Absorption in Presence of Absorption Enhancers." Journal of Pharmaceutical Sciences 96, no. 10 (October 2007): 2710–22. http://dx.doi.org/10.1002/jps.20888.

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10

Chavanpatil, Mahesh D., and Pradeep R. Vavia. "The influence of absorption enhancers on nasal absorption of acyclovir." European Journal of Pharmaceutics and Biopharmaceutics 57, no. 3 (May 2004): 483–87. http://dx.doi.org/10.1016/j.ejpb.2004.01.001.

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11

Jiang, Cui-Ping, Xin He, Xiao-Lin Yang, Su-Li Zhang, Hui Li, Zi-Jing Song, Chun-Feng Zhang, Zhong-Lin Yang, and Ping Li. "Intestinal Absorptive Transport of Genkwanin from Flos genkwa Using a Single-Pass Intestinal Perfusion Rat Model." American Journal of Chinese Medicine 42, no. 02 (January 2014): 349–59. http://dx.doi.org/10.1142/s0192415x14500232.

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To investigate the absorptive transport behavior of genkwanin and the beneficial effects of monoterpene enhancers with different functional groups, the single-pass intestinal perfusion (SPIP) of rats was used. The results showed that genkwanin was segmentally-dependent and the best absorptive site was the duodenum. The effective permeability coefficient (P eff ) was 1.97 × 10-4 cm/s and the absorption rate constant (Ka) was 0.62 × 10-2 s-1. Transepithelial transportation descended with increasing concentrations of genkwanin. This was a 1.4-fold increase in P eff by probenecid, whereas a 1.4-fold or 1.6-fold decrease was observed by verapamil and pantoprazole, respectively. Furthermore, among the absorption enhancers, the enhancement with carbonyl (camphor and menthone) was higher than that with hydroxyl (borneol and menthol). The concentration-independent permeability and enhancement by coperfusion of probenecid indicated that genkwanin was transported by both passive diffusion and multidrug resistance protein (MDR)-mediated efflux mechanisms.

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12

Alama, Tammam, Kosuke Kusamori, Masaki Morishita, Hidemasa Katsumi, Toshiyasu Sakane, and Akira Yamamoto. "Mechanistic Studies on the Absorption-Enhancing Effects of Gemini Surfactant on the Intestinal Absorption of Poorly Absorbed Hydrophilic Drugs in Rats." Pharmaceutics 11, no. 4 (April 7, 2019): 170. http://dx.doi.org/10.3390/pharmaceutics11040170.

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Generally, the use of absorption enhancers might be the most effective approaches to ameliorate the enteric absorption of poorly absorbed substances. Among numerous absorption enhancers, we already reported that a gemini surfactant, sodium dilauramidoglutamide lysine (SLG-30) with two hydrophobic and two hydrophilic moieties, is a novel and promising adjuvant with a high potency in improving the absorption safely. Here, we examined and elucidated the absorption-improving mechanisms of SLG-30 in the enteric absorption of substances. SLG-30 increased the intestinal absorption of 5(6)-carboxyfluorescein (CF) to a greater level than the typical absorption enhancers, including sodium glycocholate and sodium laurate, as evaluated by an in situ closed-loop method. Furthermore, SLG-30 significantly lowered the fluorescence anisotropy of dansyl chloride (DNS-Cl), suggesting that it might increase the fluidity of protein sections in the intestinal cell membranes. Moreover, SLG-30 significantly lowered the transepithelial-electrical resistance (TEER) values of Caco-2 cells, suggesting that it might open the tight junctions (TJs) between the enteric epithelial cells. Additionally, the levels of claudin-1 and claudin-4 expression decreased in the presence of SLG-30. These outcomes propose that SLG-30 might improve the enteric transport of poorly absorbed substances through both transcellular and paracellular routes.

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13

Tamiwa, Hideyuki, and Mariko Takeda-Morishita. "Development of mucosal absorption enhancers used biopharmaceuticals." Drug Delivery System 35, no. 1 (January 25, 2020): 10–19. http://dx.doi.org/10.2745/dds.35.10.

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14

Thein Maw, May Phyu, Panadda Phattanawasin, Chanokporn Sukonpan, and Nusara Piyapolrungroj. "Possible Intestinal Absorption Enhancers from Citrus hystrix." E3S Web of Conferences 141 (2020): 02003. http://dx.doi.org/10.1051/e3sconf/202014102003.

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Bioavailability of orally administered drugs is regulated by P-gp, a member of the ATP binding cassette transporter families. It expresses at the apical surface of epithelial cells and effluxs out several clinically important drugs resulting in decreased absorption and bioavailability. In recent years, the utilization of bioenhancer to increase the bioavailability of drugs has extensively studied. The objective of this study was to evaluate the potential of the compounds found in Citrus hystrix as a bioenhancer for orally administered drugs by modulation of P-gp function. The modulation effects of fruit extracts and isolated pure compounds on P-gp were investigated by uptake assay of the P-gp substrate calcein-AM in Caco-2, LLC-PK1 and LLC-GA5-COL300 cell lines. The results show that the extract from the flavedo part remarkably increased calcein-AM uptake in Caco-2 and LLC-GA5-COL300 cell lines. Among five furanocoumarins identified, 6’,7’-epoxybergamottin, 6’,7’-dihydroxybergamottin and oxypeucedanin significantly enhanced calcein-AM uptake in LLC-GA5-COL300 in a concentration-dependent manner, indicating strongly inhibition effects on P-gp function. Taken together, 6’,7’-epoxybergamottin, 6’,7’-dihydroxybergamottin and oxypeucedanin could be employed as the potential intestinal bioenhancer to improve the bioavailability of P-gp substrate drugs. However, further studies including in vivo studies should be performed to confirm these findings.

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15

Burgalassi, Susi, Patrizia Chetoni, Laura Dini, Marcela Najarro, Daniela Monti, Paolo Morelli, and M. Saettone. "Effect of Permeation Enhancers on Buccal Absorption." Arzneimittelforschung 56, no. 07 (December 22, 2011): 561–67. http://dx.doi.org/10.1055/s-0031-1296752.

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16

Takanashi, Yuki, Kimio Higashiyama, Hideaki Komiya, Kozo Takayama, and Tsuneji Nagai. "Thiomenthol Derivatives as Novel Percutaneous Absorption Enhancers." Drug Development and Industrial Pharmacy 25, no. 1 (January 1999): 89–94. http://dx.doi.org/10.1081/ddc-100102146.

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17

Chiou, George C. Y., and Ching Yao Chuang. "Improvement of Systemic Absorption of Insulin Through Eyes with Absorption Enhancers." Journal of Pharmaceutical Sciences 78, no. 10 (October 1989): 815–18. http://dx.doi.org/10.1002/jps.2600781007.

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18

Yamamoto, Akira, Takuya Fujita, and Shozo Muranishi. "Pulmonary absorption enhancement of peptides by absorption enhancers and protease inhibitors." Journal of Controlled Release 41, no. 1-2 (August 1996): 57–67. http://dx.doi.org/10.1016/0168-3659(96)01480-0.

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19

Chandler, S. G., N. W. Thomas, and l. Illum. "Nasal absorption in the rat: IV. Membrane activity of absorption enhancers." International Journal of Pharmaceutics 117, no. 2 (April 1995): 139–46. http://dx.doi.org/10.1016/0378-5173(94)00308-r.

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20

Fuh, Yuh-Ming, Dinh-Chuong Pham, and Ching-Feng Weng. "Effects of Sting Plant Extracts as Penetration Enhancers on Transdermal Delivery of Hypoglycemic Compounds." Medicina 55, no. 5 (May 7, 2019): 121. http://dx.doi.org/10.3390/medicina55050121.

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Background and objectives: The percutaneous route is an interesting and inventive investigation field of drug delivery. However, it is challenging for drug molecules to pass through the skins surface, which is a characterized by its permeability barrier. The purpose of this study is to look at the effect of some penetration enhancers on in vivo permeation of insulin and insulin sensitizers (curcumin and rutin) through diabetes-induced mouse skin. Materials and Methods: Sting crude extracts of Dendrocnide meyeniana, Urtica thunbergiana Sieb. and Zucc, and Alocasia odora (Lodd.) Spach were used as the penetration enhancers. Mouse skin irritation was tested by smearing the enhancers for the measurements at different time points and the cell viability of the HaCaT human skin keratinocytes, which was determined by Trypan blue exclusion and MTT assays to evaluate human biosafety for these extracts after the mouse skin permeation experiments. Results: All enhancers induced a slight erythema without edema on the mouse skin that completely recovered after 6 h from the enhancer smears as compared with normal mouse skin. Furthermore, no damaged cells were found in the HaCaT keratinocytes under sting crude extract treatments. The blood sugar level in the diabetic mice treated with the insulin or insulin sensitizers, decreased significantly (p < 0.05) in the presence of enhancers. The area under the curve (AUC) values of transdermal drug delivery (TDD) ranged from 42,000 ± 5000 mg/dL x min without enhancers, to 30,000 ± 2000 mg/dL x min in the presence of enhancers. Conclusions: This study exhibited that natural plant extracts could be preferred over the chemically synthesized molecules and are safe and potent penetration enhancers for stimulating the transdermal absorption of drugs.

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21

Di Prima, Giulia, Mariano Licciardi, Flavia Bongiovì, Giovanna Pitarresi, and Gaetano Giammona. "Inulin-Based Polymeric Micelles Functionalized with Ocular Permeation Enhancers: Improvement of Dexamethasone Permeation/Penetration through Bovine Corneas." Pharmaceutics 13, no. 9 (September 9, 2021): 1431. http://dx.doi.org/10.3390/pharmaceutics13091431.

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Ophthalmic drug delivery is still a challenge due to the protective barriers of the eye. A common strategy to promote drug absorption is the use of ocular permeation enhancers, while an innovative approach is the use of polymeric micelles. In the present work, the two mentioned approaches were coupled by conjugating ocular permeation enhancers (PEG2000, carnitine, creatine, taurine) to an inulin-based co-polymer (INU-EDA-RA) in order to obtain self-assembling biopolymers with permeation enhancer properties for the hydrophobic drug dexamethasone (DEX). Inulin derivatives were properly synthetized, were found to expose about 2% mol/mol of enhancer molecules in the side chain, and resulted able to self-assemble at various concentrations by varying the pH and the ionic strength of the medium. Moreover, the ability of polymeric micelles to load dexamethasone was demonstrated, and size, mucoadhesiveness, and cytocompatibility against HCE cells were evaluated. Furthermore, the efficacy of the permeation enhancer was evaluated by ex vivo permeation studies to determine the performance of the used enhancers, which resulted in PEG2000 > CAR > TAU > CRE, while entrapment ability studies resulted in CAR > TAU > PEG2000 > CRE, both for fluorescent-labelled and DEX-loaded micelles. Finally, an increase in terms of calculated Kp and Ac parameters was demonstrated, compared with the values calculated for DEX suspension.

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22

Ghadiri, Maliheh, Paul Young, and Daniela Traini. "Strategies to Enhance Drug Absorption via Nasal and Pulmonary Routes." Pharmaceutics 11, no. 3 (March 11, 2019): 113. http://dx.doi.org/10.3390/pharmaceutics11030113.

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New therapeutic agents such as proteins, peptides, and nucleic acid-based agents are being developed every year, making it vital to find a non-invasive route such as nasal or pulmonary for their administration. However, a major concern for some of these newly developed therapeutic agents is their poor absorption. Therefore, absorption enhancers have been investigated to address this major administration problem. This paper describes the basic concepts of transmucosal administration of drugs, and in particular the use of the pulmonary or nasal routes for administration of drugs with poor absorption. Strategies for the exploitation of absorption enhancers for the improvement of pulmonary or nasal administration are discussed, including use of surfactants, cyclodextrins, protease inhibitors, and tight junction modulators, as well as application of carriers such as liposomes and nanoparticles.

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23

Thanou, M., J. C. Verhoef, and H. E. Junginger. "Chitosan and its derivatives as intestinal absorption enhancers." Advanced Drug Delivery Reviews 50 (October 2001): S91—S101. http://dx.doi.org/10.1016/s0169-409x(01)00180-6.

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24

Furrer, Pascal, Joachim Michael Mayer, Bernard Plazonnet, and Robert Gurny. "Ocular tolerance of absorption enhancers in ophthalmic preparations." AAPS PharmSci 4, no. 1 (March 2002): 6–10. http://dx.doi.org/10.1208/ps040102.

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25

Schipper, Nicolaas G. M., Kjell M. Vårum, Patric Stenberg, Göran Ocklind, Hans Lennernäs, and Per Artursson. "Chitosans as absorption enhancers of poorly absorbable drugs." European Journal of Pharmaceutical Sciences 8, no. 4 (August 1999): 335–43. http://dx.doi.org/10.1016/s0928-0987(99)00032-9.

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26

Rosenthal, Rita, Miriam S. Heydt, Maren Amasheh, Christoph Stein, Michael Fromm, and Salah Amasheh. "Analysis of absorption enhancers in epithelial cell models." Annals of the New York Academy of Sciences 1258, no. 1 (June 25, 2012): 86–92. http://dx.doi.org/10.1111/j.1749-6632.2012.06562.x.

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27

Kondoh, Masuo, and Kiyohito Yagi. "Progress in absorption enhancers based on tight junction." Expert Opinion on Drug Delivery 4, no. 3 (May 2007): 275–86. http://dx.doi.org/10.1517/17425247.4.3.275.

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28

Enslin, Gill M., Josias H. Hamman, and Awie F. Kotzé. "Intestinal Drug Absorption Enhancers: Synergistic Effects of Combinations." Drug Development and Industrial Pharmacy 34, no. 12 (January 2008): 1343–49. http://dx.doi.org/10.1080/03639040802098185.

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29

Samanthula, Kumara Swamy, Shobha Rani Satla, and Agaiah Goud Bairi. "Bioadhesive polymers, permeation enhancers and types of dosage forms for buccal drug delivery." Journal of Drug Delivery and Therapeutics 11, no. 1 (January 15, 2021): 138–45. http://dx.doi.org/10.22270/jddt.v11i1.4495.

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The buccal delivery is defined as the drug administration through the mucosal membranes lining the cheeks (buccal mucosa). The main impediment to the use of many hydrophilic macromolecular drugs as potential therapeutic agents is their inadequate and erratic oral absorption. Based on our current understanding of biochemical and physiological aspects of absorption and metabolism of many biotechnologically produced drugs, they cannot be delivered effectively through the conventional oral route. Because after oral administration many drugs are subjected to pre-systemic clearance extensive in the liver, which often leads to a lack of significant correlation between membrane permeability, absorption and bioavailability. Difficulties associated with the parenteral delivery and poor oral bioavailability provided the impetus for exploring alternative routes for the delivery of such drugs. This review covers the advantages, disadvantages of buccal delivery, drug and excipient selection especially bioadhesive polymers and permeation enhancers, and further a list of drugs developed as various dosage forms for buccal route of administration. Keywords: Buccal delivery, bioadhesive/mucoadhesive, permeation enhancer, dosage forms.

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30

Lu, Juan, Nannan Li, Yaochun Gao, Nan Li, Yifei Guo, Haitao Liu, Xi Chen, Chunyan Zhu, Zhengqi Dong, and Akira Yamamoto. "The Effect of Absorption-Enhancement and the Mechanism of the PAMAM Dendrimer on Poorly Absorbable Drugs." Molecules 23, no. 8 (August 10, 2018): 2001. http://dx.doi.org/10.3390/molecules23082001.

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The polyamidoamine (PAMAM) dendrimer is a highly efficient absorption promoter. In the present study, we studied the absorption-enhancing effects and the mechanism of PAMAM dendrimers with generation 0 to generation 3 (G0–G3) and concentrations (0.1–1.0%) on the pulmonary absorption of macromolecules. The absorption-enhancing mechanisms were elucidated by microarray, western blotting analysis, and PCR. Fluorescein isothiocyanate-labeled dextrans (FDs) with various molecular weights were used as model drugs of poorly absorbable drugs. The absorption-enhancing effects of PAMAM dendrimers on the pulmonary absorption of FDs were in a generation- and concentration-dependent manner. The G3 PAMAM dendrimer with high effectiveness was considered to the best absorption enhancer for improving the pulmonary absorption of FDs. G3 PAMAM dendrimers at three different concentrations were non-toxic to Calu-3 cells. Based on the consideration between efficacy and cost, the 0.1% G3 PAMAM dendrimer was selected for subsequent studies. The results showed that treatment with a 0.1% G3 PAMAM dendrimer could increase the secretion of organic cation transporters (OCTs), OCT1, OCT2, and OCT3, which might be related to the absorption-enhancing mechanisms of the pulmonary absorption of FDs. These findings suggested that PAMAM dendrimers might be potentially safe absorption enhancers for improving absorption of FDs by increasing the secretion of OCT1, OCT2, and OCT3.

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31

Sasaki, Isao, Takashi Tamura, Takuya Fujita, Akira Yamamoto, and Shozo Muranishi. "Improvement of intestinal absorption of azetirelin, a new TRH analogue, by absorption enhancers." Drug Delivery System 9, no. 3 (1994): 193–97. http://dx.doi.org/10.2745/dds.9.193.

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32

Donnelly, Andrew, I. W. Kellaway, G. Taylor, and M. Gibson. "Absorption Enhancers as Tools to Determine the Route of Nasal Absorption of Peptides." Journal of Drug Targeting 5, no. 2 (January 1998): 121–27. http://dx.doi.org/10.3109/10611869808995865.

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33

Angelo, Robert, Kathleen Rousseau, Marshall Grant, Andrea Leone-Bay, and Peter Richardson. "Technosphere® Insulin: Defining the Role of Technosphere Particles at the Cellular Level." Journal of Diabetes Science and Technology 3, no. 3 (May 2009): 545–54. http://dx.doi.org/10.1177/193229680900300320.

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Background: Technosphere® Insulin (TI) is a novel inhalation powder for the treatment of diabetes mellitus. Technosphere Insulin delivers insulin with an ultra rapid pharmacokinetic profile that is distinctly different from all other insulin products but similar to natural insulin release. Such rapid absorption is often associated with penetration enhancers that disrupt cellular integrity. Methods: Technosphere Insulin was compared to a panel of known penetration enhancers in vitro using the Calu-3 lung cell line to investigate the effects of TI on insulin transport. Results: Measures of tight junction integrity such as transepithelial electrical resistance, Lucifer yellow permeability, and F-actin staining patterns were all unaffected by TI. Cell viability and plasma membrane integrity were also not affected by TI. In contrast, cells treated with comparable (or lower) concentrations of penetration enhancers showed elevated Lucifer yellow permeability, disruption of the F-actin network, reduced cell viability, and compromised plasma membranes. Conclusions: These results demonstrate that TI is not cytotoxic in an in vitro human lung cell model and does not function as a penetration enhancer. Furthermore, TI does not appear to affect the transport of insulin across cellular barriers.

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34

Dahlgren, David, Maria-Jose Cano-Cebrián, Tobias Olander, Mikael Hedeland, Markus Sjöblom, and Hans Lennernäs. "Regional Intestinal Drug Permeability and Effects of Permeation Enhancers in Rat." Pharmaceutics 12, no. 3 (March 8, 2020): 242. http://dx.doi.org/10.3390/pharmaceutics12030242.

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Sufficient colonic absorption is necessary for all systemically acting drugs in dosage forms that release the drug in the large intestine. Preclinically, colonic absorption is often investigated using the rat single-pass intestinal perfusion model. This model can determine intestinal permeability based on luminal drug disappearance, as well as the effect of permeation enhancers on drug permeability. However, it is uncertain how accurate the rat single-pass intestinal perfusion model predicts regional intestinal permeability and absorption in human. There is also a shortage of systematic in vivo investigations of the direct effect of permeation enhancers in the small and large intestine. In this rat single-pass intestinal perfusion study, the jejunal and colonic permeability of two low permeability drugs (atenolol and enalaprilat) and two high-permeability ones (ketoprofen and metoprolol) was determined based on plasma appearance. These values were compared to already available corresponding human data from a study conducted in our lab. The colonic effect of four permeation enhancers—sodium dodecyl sulfate, chitosan, ethylenediaminetetraacetic acid (EDTA), and caprate—on drug permeability and transport of chromium EDTA (an established clinical marker for intestinal barrier integrity) was determined. There was no difference in jejunal and colonic permeability determined from plasma appearance data of any of the four model drugs. This questions the validity of the rat single-pass intestinal perfusion model for predicting human regional intestinal permeability. It was also shown that the effect of permeation enhancers on drug permeability in the colon was similar to previously reported data from the rat jejunum, whereas the transport of chromium EDTA was significantly higher (p < 0.05) in the colon than in jejunum. Therefore, the use of permeation enhancers for increasing colonic drug permeability has greater risks than potential medical rewards, as indicated by the higher permeation of chromium EDTA compared to the drugs.

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35

Onyeji, Cyprian O., Amusa S. Adebayo, and Chinedum P. Babalola. "Effects of absorption enhancers in chloroquine suppository formulations: I." European Journal of Pharmaceutical Sciences 9, no. 2 (December 1999): 131–36. http://dx.doi.org/10.1016/s0928-0987(99)00053-6.

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36

GARCÍA-ARIETA, Alfredo, Santiago TORRADO-SANTIAGO, Luis GOYA, and Juan José TORRADO. "Spray-Dried Powders as Nasal Absorption Enhancers of Cyanocobalamin." Biological & Pharmaceutical Bulletin 24, no. 12 (2001): 1411–16. http://dx.doi.org/10.1248/bpb.24.1411.

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37

Merkus, F. W. H. M., N. G. M. Schipper, W. A. J. J. Hermens, S. G. Romeijn, and J. C. Verhoef. "Absorption enhancers in nasal drug delivery: efficacy and safety." Journal of Controlled Release 24, no. 1-3 (May 1993): 201–8. http://dx.doi.org/10.1016/0168-3659(93)90179-9.

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38

Zambito, Ylenia, Gloria Uccello-Barretta, Chiara Zaino, Federica Balzano, and Giacomo Di Colo. "Novel transmucosal absorption enhancers obtained by aminoalkylation of chitosan." European Journal of Pharmaceutical Sciences 29, no. 5 (December 2006): 460–69. http://dx.doi.org/10.1016/j.ejps.2006.09.001.

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39

Na, Lidong, Shirui Mao, Juan Wang, and Wei Sun. "Comparison of different absorption enhancers on the intranasal absorption of isosorbide dinitrate in rats." International Journal of Pharmaceutics 397, no. 1-2 (September 2010): 59–66. http://dx.doi.org/10.1016/j.ijpharm.2010.06.048.

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Merkus, Frans W. H. M., Nicolaas G. M. Schipper, and J. Coos Verhoef. "The influence of absorption enhancers on intranasal insulin absorption in normal and diabetic subjects." Journal of Controlled Release 41, no. 1-2 (August 1996): 69–75. http://dx.doi.org/10.1016/0168-3659(96)01357-0.

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Chandler, Susan G., Lisbeth Ilium, and Norman W. Thomas. "Nasal absorption in rats. II. Effect of enhancers on insulin absorption and nasal histology." International Journal of Pharmaceutics 76, no. 1-2 (September 1991): 61–70. http://dx.doi.org/10.1016/0378-5173(91)90344-n.

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del Rio-Sancho, S., C. E. Serna-Jiménez, M. A. Calatayud-Pascual, C. Balaguer-Fernández, A. Femenía-Font, V. Merino, and A. López-Castellano. "Transdermal absorption of memantine – Effect of chemical enhancers, iontophoresis, and role of enhancer lipophilicity." European Journal of Pharmaceutics and Biopharmaceutics 82, no. 1 (September 2012): 164–70. http://dx.doi.org/10.1016/j.ejpb.2012.06.005.

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Teucher, Olivares, and Cori. "Enhancers of Iron Absorption: Ascorbic Acid and other Organic Acids." International Journal for Vitamin and Nutrition Research 74, no. 6 (November 1, 2004): 403–19. http://dx.doi.org/10.1024/0300-9831.74.6.403.

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Abstract:

Ascorbic acid (AA), with its reducing and chelating properties, is the most efficient enhancer of non-heme iron absorption when its stability in the food vehicle is ensured. The number of studies investigating the effect of AA on ferrous sulfate absorption far outweighs that of other iron fortificants. The promotion of iron absorption in the presence of AA is more pronounced in meals containing inhibitors of iron absorption. Meals containing low to medium levels of inhibitors require the addition of AA at a molar ratio of 2:1 (e.g., 20 mg 3 mg iron). To promote absorption in the presence of high levels of inhibitors, AA needs to be added at a molar ratio in excess of 4:1, which may be impractical. The effectiveness of AA in promoting absorption from less soluble compounds, such as ferrous fumarate and elemental iron, requires further investigation. The instability of AA during food processing, storage, and cooking, and the possibility of unwanted sensory changes limits the number of suitable food vehicles for AA, whether used as vitamin fortificant or as an iron enhancer. Suitable vehicles include dry-blended foods, such as complementary, precooked cereal-based infant foods, powdered milk, and other dry beverage products made for reconstitution that are packaged, stored, and prepared in a way that maximizes retention of this vitamin. The consumption of natural sources of Vitamin C (fruits and vegetables) with iron-fortified dry blended foods is also recommended. Encapsulation can mitigate some of the AA losses during processing and storage, but these interventions will also add cost. In addition, the bioavailability of encapsulated iron in the presence/absence of AA will need careful assessment in human clinical trials. The long-term effect of high AA intake on iron status may be less than predicted from single meal studies. The hypothesis that an overall increase of dietary AA intake, or fortification of some foods commonly consumed with the main meal with AA alone, may be as effective as the fortification of the same food vehicle with AA and iron, merits further investigation. This must involve the consideration of practicalities of implementation. To date, programs based on iron and AA fortification of infant formulas and cow's milk provide the strongest evidence for the efficacy of AA fortification. Present results suggest that the effect of organic acids, as measured by in vitro and in vivo methods, is dependent on the source of iron, the type and concentration of organic acid, pH, processing methods, and the food matrix. The iron absorption-enhancing effect of AA is more potent than that of other organic acids due to its ability to reduce ferric to ferrous iron. Based on the limited data available, other organic acids may only be effective at ratios of acid to iron in excess of 100 molar. This would translate into the minimum presence/addition of 1 g citric acid to a meal containing 3 mg iron. Further characterization of the effectiveness of various organic acids in promoting iron absorption is required, in particular with respect to the optimal molar ratio of organic acid to iron, and associated feasibility for food application purposes. The suggested amount of any organic acid required to produce a nutritional benefit will result in unwanted organoleptic changes in most foods, thus limiting its application to a small number of food vehicles (e.g., condiments, beverages). However, fermented foods that already contain high levels of organic acid may be suitable iron fortification vehicles.

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Pillay, Viness, Angus R. Hibbins, Yahya E. Choonara, Lisa C. du Toit, Pradeep Kumar, and Valence M. K. Ndesendo. "Orally Administered Therapeutic Peptide Delivery: Enhanced Absorption Through the Small Intestine Using Permeation Enhancers." International Journal of Peptide Research and Therapeutics 18, no. 3 (April 22, 2012): 259–80. http://dx.doi.org/10.1007/s10989-012-9299-7.

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Yu, Qinghua, Pengcheng Li, and Qian Yang. "Improving the absorption of earthworm fibrinolytic enzymes with mucosal enhancers." Pharmaceutical Biology 48, no. 7 (June 3, 2010): 816–21. http://dx.doi.org/10.3109/13880200903283681.

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Woodford, Roger, and Brian W. Barry. "Penetration Enhancers and the Percutaneous Absorption of Drugs: An Update." Journal of Toxicology: Cutaneous and Ocular Toxicology 5, no. 3 (January 1986): 167–77. http://dx.doi.org/10.3109/15569528609030991.

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Pr̆iborský, J., K. Takayama, E. Mühlbachová, and T. Nagai. "Effect of penetration enhancers on percutaneous absorption of flufenamic acid." European Journal of Pharmacology 183, no. 2 (July 1990): 385. http://dx.doi.org/10.1016/0014-2999(90)93262-o.

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Gleeson, John P., Sinéad M. Ryan, and David J. Brayden. "Oral delivery strategies for nutraceuticals: Delivery vehicles and absorption enhancers." Trends in Food Science & Technology 53 (July 2016): 90–101. http://dx.doi.org/10.1016/j.tifs.2016.05.007.

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Beskid, George, Joel Unowsky, Charanjit R. Behl, Jo Ann Siebelist, Jacques L. Tossounian, Carolyn M. McGarry, Navnit H. Shah, and Roy Cleeland. "Enteral, Oral, and Rectal Absorption of Ceftriaxone Using Glyceride Enhancers." Chemotherapy 34, no. 2 (1988): 77–84. http://dx.doi.org/10.1159/000238551.

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SAKAI, MICHINORI, TERUKO IMAI, HIROSHI OHTAKE, and MASAKI OTAGIRI. "Biopharmaceutics: Cytotoxicity of Absorption Enhancers in Caco-2 Cell Monolayers." Journal of Pharmacy and Pharmacology 50, no. 10 (October 1998): 1101–8. http://dx.doi.org/10.1111/j.2042-7158.1998.tb03319.x.

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