Hexyl alginate derivative, an amphiphilic innovative buccal film-forming material of promising mechanical and release characteristics for the improvement of repaglinide bioavailability
Open Access
- 1 March 2019
- journal article
- research article
- Published by Taylor & Francis Ltd in Drug Design, Development and Therapy
- Vol. ume 13, 925-940
- https://doi.org/10.2147/dddt.s196425
Abstract
Background: Association of long hydrocarbon chain with alginate molecule imparts surface active properties and increases chain flexibility. Purpose: This work studied the efficacy of synthesized hexyl alginate derivative as a film-forming material with unique amphiphilic and mechanical properties for the preparation of rapidly disintegrating repaglinide oral films with higher drug release rate and improved bioavailability. Methods: Alginate hexyl amide derivative was prepared and used in the formulation of oral films by solvent casting technique. Using Box–Behnken experimental design, formulations were optimized at different polymer, plasticizer, and disintegrant levels as independent variables for maximum drug release rate, higher tensile strength, and shortest disintegration time as responses. Optimized film formulae were fully evaluated and subjected to further in vivo bioavailability studies in rabbits. Results: Higher dependency of response results on the selected variables was observed. Optimized formula showed satisfactory tensile strength (145.862 g/cm2), rapid disintegration (22.2 seconds), and higher drug release rate (97.799% within 30 minutes). The drug bioavailability was significantly improved in comparison with plain drug and conventional alginate oral films, where the AUC and Cmax values reached 296.072 µg.h/mL and 116.932 µg/mL in comparison with 164.917 µg.h/mL and 56.568 µg/mL for alginate film and 95.368 µg.h/mL and 31.925 µg/mL for plain drug, respectively. Tmax also showed significant reduction to be only 30 minutes in comparison with 60 minutes for other forms. Conclusion: This led to the final conclusion that the synthesized alginate derivative is an innovative promising film-forming material with unique mechanical and drug release properties for application in buccal drug delivery especially of Biopharmaceutics Classification System (BCS) class II drugs to increase solubility and improve bioavailability.Keywords
This publication has 35 references indexed in Scilit:
- Chemical Modification of PolysaccharidesISRN Organic Chemistry, 2013
- A review of polysaccharide cytotoxic drug conjugates for cancer therapyCarbohydrate Polymers, 2013
- Alginate derivatization: A review of chemistry, properties and applicationsBiomaterials, 2012
- Targeted polymeric therapeutic nanoparticles: design, development and clinical translationChemical Society Reviews, 2012
- The mechanisms of drug release in poly(lactic-co-glycolic acid)-based drug delivery systems—A reviewInternational Journal of Pharmaceutics, 2011
- Development and optimization of solid lipid nanoparticle formulation for ophthalmic delivery of chloramphenicol using a Box-Behnken designInternational Journal of Nanomedicine, 2011
- Marine Polysaccharides in Pharmaceutical Applications: An OverviewMarine Drugs, 2010
- Precise engineering of targeted nanoparticles by using self-assembled biointegrated block copolymersProceedings of the National Academy of Sciences of the United States of America, 2008
- Polyionic hydrocolloids for the intestinal delivery of protein drugs: Alginate and chitosan — a reviewJournal of Controlled Release, 2006
- Nanoparticle-Aptamer BioconjugatesCancer Research, 2004