A Comprehensive Development Strategy in Buccal Drug Delivery

Abstract

Abstract. This work combines several methods in an integrated strategy to develop a matrix for buccal administration. For this purpose, tablets containing selected mucoadhesive polymers loaded with a model drug (omeprazole), free or in a complexed form with cyclodextrins, and in the absence and presence of alkali agents were subjected to a battery of tests. Mucoadhesion studies, including simple factorial analysis, in vitro release studies with both model-dependent and model-independent analysis, and permeation studies were performed. Mucoadhesive profiles indicated that the presence of the drug decreases the mucoadhesion profile, probably due its hydrophobic character. In tablets loaded with the drug complexed with β-cyclodextrin or methyl-β-cyclodextrin, better results were obtained with the methylated derivative. This effect was attributed to the fact that in the case of β-cyclodextrin, more hydroxyl groups are available to interact with the mucoadhesive polymers, thus decreasing the mucoadhesion performance. The same result was observed in presence of the alkali agent (L-arginine), in this case due to the excessive hydrophilic character of L-arginine. Drug release from tablets was also evaluated, and results suggested that the dissolution profile with best characteristics was observed in the matrix loaded with omeprazole complexed with methyl-β-cyclodextrin in the presence of L-arginine. Several mathematical models were applied to the dissolution curves, indicating that the release of the drug, in free or in complexed state, from the mucoadhesive matrices followed a super case II transport, as established on the basis of the Korsmeyer-Peppas function. The feasibility of drug buccal administration was assessed by permeation experiments on porcine buccal mucosa. The amount of drug permeated from mucoadhesive tablets presented a maximum value for the system containing drug complexed with the methylated cyclodextrin derivative in presence of L-arginine. According to these results, the system containing the selected polymer mixture and the drug complexed with methyl-β-cyclodextrin in presence of L-arginine showed a great potential as a buccal drug delivery formulation, in which a good compromise among mucoadhesion, dissolution, and permeation properties was achieved.

Design and in Vitro Evaluation of Floating Drug Delivery System of Glipizide Using Combination of Natural Mucilages and Synthetic Polymers

“…It might be a combination of CE and HPMC exhibited mucin interaction strongly. Typically, good wetting and swelling properties should correlate to good mucoadhesion, however only up to a certain point; polymer swelling behavior is essential for the exposure of the bioadhesive sites for the formation of strong hydrogen bonding and important character for uniform and sustained release of the drug and effective mucoadhesion [36,37]. Therefore, based on the results of the In vitro buoyancy, in vitro drug release, in vitro bioadhesive studies and cost-effectiveness of CE compared to FG; F7 has been selected as the final formulation.…”

“…Followed by mucoadhesive strength and mucoadhesive detachment force was recorded. 3 tablets randomly selected from each formulation and employed on fresh mucosa [36,37].…”

Buccal Dosage Forms: General Considerations for Pediatric Patients

“…Such absorption enhancers have the advantage of keeping hydrophobic molecules in solution by forming an inclusion complex molecule-cyclodextrin (106). Another mechanism for permeation enhancement is due to lipid extraction by forming inclusion complexes with cell membrane lipids (107). A study has shown how dimethylated β-cyclodextrin at 2.5% and 5% helped increasing the amount of PEG-4000 transported across Caco-2 monolayers (108).…”

The Application of Factorial Experimental Design in Capsule Coating for Potential Colon Targeting of an Antiamebic Drug

“…This means characteristic relaxation-controlled release due to reduction in attractive forces between polymer chains [23]. In other words drug release was strongly influenced by the relaxation rate of polymer chains and their erosion [23,24,25].…”

“…British Journal of Pharmaceutical Research, 4(24):[2711][2712][2713][2714][2715][2716][2717][2718][2719][2720][2721][2722][2723][2724][2725][2726][2727][2728] 2014 …”