In vivo evaluation of an Ultra-fast Disintegrating Wafer matrix: A molecular simulation approach to the ora-mucoadhesivity

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• 作者：Deshika Reddy^a ; Yahya E. Choonara^a ; Pradeep Kumar^a ; Mershen Govender^a ; Sunaina Indermun^a ; Lisa C. du Toit^a ; Leith C.R. Meyer^b ; Viness Pillay^a ; ^{viness.pillay@wits.ac.za}
• 关键词：Oramucosal drug delivery ; Wafer matrix ; Rapid disintegration ; In vivo permeabilty ; Molecular modeling ; Mucoadhesivity
• 刊名：Journal of Drug Delivery Science and Technology
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：37
• 期：Complete
• 页码：123-133
• 全文大小：1714 K
• 卷排序：37

文摘

The purpose of this study was to design and evaluate the performance of an Ultra-fast Disintegrating Wafer (U-D-WAF) loaded with highly water soluble diphenhydramine hydrochloride (DPH) through the oramucosa of the Large White Pig model. For the first time this work explored the oramucosivity of the U-D-WAF by detailed molecular modeling of the matrix on buccal tissue in order to mechanistically deduce the mucodhesivity. The U-D-WAF was formulated using a blend of hydroxypropylcellulose, poly(acrylic) acid, sodium starch glycolate and β –cyclodextrin in accordance with a Box-Benkhen experimental design for optimization prior to ex vivo permeation and in vivo release studies in the Large White Pig. Molecular simulation studies assess the mucoadhesivity of the U-D-WAF to the oramucosa. A mean Drug Entrapment Efficiency of 72.96 ± 4.32%, disintegration time of 29.33 ± 15.91 s and drug release after 60 s of 86.32 ± 20.37% was recorded. Ex vivo permeation studies revealed cumulative drug permeation of 86.32 ± 20.34% 60 s after onset. In vivo evaluation of the optimized U-D-WAF had a Cmax = 59 μgL−1 approximately 300 s after administration. The ultrafast disintegration of the U-D-WAF matrix with desirable mucoadhesivity in in vitro and in vivo studies makes it suitable for effective and rapid oramucosal drug delivery.