Plantago ovata F. Mucilage-Alginate Mucoadhesive Beads for Controlled Release of Glibenclamide: Development, Optimization, and In Vitro-In Vivo Evaluation
The current study deals with the development and optimization of ispaghula (Plantago ovata F.) husk mucilage- (IHM-) alginate mucoadhesive beads containing glibenclamide by ionotropic gelation technique. The effects of sodium alginate (SA) to IHM and cross-linker (CaCl2) concentration on the drug encapsulation efficiency (DEE, %), as well as cumulative drug release after 10 hours ( , %), were optimized using 32 factorial design based on response surface methodology. The observed responses were coincided well with the predicted values by the experimental design. The optimized mucoadhesive beads exhibited % w/w of DEE and good mucoadhesivity with the biological membrane in wash-off test and sustained drug release profile over 10 hours. The beads were also characterized by SEM and FTIR analyses. The in vitro drug release from these beads was followed by controlled release (zero-order) pattern with super case-II transport mechanism. The optimized glibenclamide-loaded IHM-alginate mucoadhesive beads showed significant antidiabetic effect in alloxan-induced diabetic rats over prolonged period after oral administration. 1. Introduction The mucoadhesive polymer containing oral drug delivery systems has the capacity to prolong residence time of drugs at the absorption site and facilitate intimate contact with underlying absorptive surface to enhance bioavailability [1]. Polymers used in the mucoadhesive formulations include natural, semisynthetic, and synthetic ones. In recent years, a growing interest has been identified in the development of natural polymer-based drug delivery systems due to their biodegradability, biocompatibility, aqueous solubility, swelling ability, easy availability, and cost-effectiveness [2]. Amongst various natural polymers, alginates have been widely used in the development of drug delivery applications [3–6]. It is obtained from Laminaria hyperborean, Ascophullum nodosum, and Macrocystis pyrifera [1]. It is composed of linear copolymers of two monomeric units, that is, β-D-mannuronic acid and α-L-guluronic acid [7]. Sodium alginate (SA) undergoes ionotropic-gelation by Ca2+ to form calcium alginate due to an ionic interaction between carboxylic acid groups of alginate chain and Ca2+ [8]. Sodium alginate has mucoadhesive property; however, the cross-linked alginates are usually fragile [9, 10]. Therefore, blending of different mucoadhesive polymers is one of the most popular approaches to formulate ionotropically cross-linked alginate-based mucoadhesive beads [9, 11, 12]. Again, blending with suitable polymers, may improve the drug
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