Mucoadhesive Microspheres for Gastroretentive Delivery of Acyclovir: In Vitro and In Vivo Evaluation
Journal Title: The AAPS Journal - Year 2008, Vol 10, Issue 2
Abstract
The aim of the present investigation was to evaluate the potential use of mucoadhesive microspheres for gastroretentive delivery of acyclovir. Chitosan, thiolated chitosan, Carbopol 71G and Methocel K15M were used as mucoadhesive polymers. Microsphere formulations were prepared using emulsion-chemical crosslinking technique and evaluated in vitro, ex-vivo and in-vivo. Gelatin capsules containing drug powder showed complete dissolution (90.5 ± 3.6%) in 1 h. The release of drug was prolonged to 12 h (78.8 ± 3.9) when incorporated into mucoadhesive microspheres. The poor bioavailability of acyclovir is attributed to short retention of its dosage form at the absorption sites (in upper gastrointestinal tract to duodenum and jejunum). The results of mucoadhesion study showed better retention of thiolated chitosan microspheres (8.0 ± 0.8 h) in duodenal and jejunum regions of intestine. The results of qualitative and quantitative GI distribution study also showed significant higher retention of mucoadhesive microspheres in upper GI tract. Pharmacokinetic study revealed that administration of mucoadhesive microspheres could maintain measurable plasma concentration of acyclovir through 24 h, as compared to 5 h after its administration in solution form. Thiolated chitosan microsphere showed superiority over the other formulations as observed with nearly 4.0-fold higher AUC0–24 value (1,090 ± 51 ng h/ml) in comparison to drug solution (281 ± 28 ng h/ml). Overall, the result indicated prolonged delivery with significant improvement in oral bioavailability of acyclovir from mucoadhesive microspheres due to enhanced retention in the upper GI tract.
Authors and Affiliations
Sumeet Dhaliwal, Subheet Jain, Hardevinder P. Singh, A. K. Tiwary
Keywords
Related Articles
- EP ID EP681549
- DOI 10.1208/s12248-008-9039-2
- Views 77
- Downloads 0
Handling Data Below the Limit of Quantification in Mixed Effect Models
The purpose of this study is to investigate the impact of observations below the limit of quantification (BQL) occurring in three distinctly different ways and assess the best method for prevention of bias in parameter e...
Molecular Mechanisms of Silibinin-Mediated Cancer Chemoprevention with Major Emphasis on Prostate Cancer
Despite advances in early detection, prostate cancer remains the second highest cancer mortality in American men, and even successful interventions are associated with enormous health care costs as well as prolonged dele...
Statistics on BCS Classification of Generic Drug Products Approved Between 2000 and 2011 in the USA
The Biopharmaceutics Classification system (BCS) classifies drug substances based on aqueous solubility and intestinal permeability. The objective of this study was to use the World Health Organization Model List of Esse...
Pharmacodynamic Model of Hepcidin Regulation of Iron Homeostasis in Cynomolgus Monkeys
The online version of this article (doi:10.1208/s12248-016-9886-1) contains supplementary material, which is available to authorized users.
Issues and Challenges of Subvisible and Submicron Particulate Analysis in Protein Solutions
The online version of this article (doi:10.1208/s12248-012-9335-8) contains supplementary material, which is available to authorized users.