Characterization of the Rheological, Mucoadhesive, and Drug Release Properties of Highly Structured Gel Platforms for Intravaginal Drug Delivery

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• 作者：Gavin P. Andrews ; Louise Donnelly ; David S. Jones ; Rhonda M. Curran ; Ryan J. Morrow ; A. David Woolfson ; R. Karl Malcolm
• 刊名：Biomacromolecules
• 出版年：2009
• 出版时间：September 14, 2009
• 年：2009
• 卷：10
• 期：9
• 页码：2427-2435
• 全文大小：208K
• 年卷期：v.10,no.9(September 14, 2009)
• ISSN：1526-4602

文摘

This investigation describes the formulation and characterization of rheologically structured vehicles (RSVs) designed for improved drug delivery to the vagina. Interactive, multicomponent, polymeric platforms were manufactured containing hydroxyethylcellulose (HEC, 5% w/w) polyvinylpyrrolidone (PVP, 4% w/w), Pluronic (PL, 0 or 10% w/w), and either polycarbophil (PC, 3% w/w) or poly(methylvinylether-co-maleic anhydride) (Gantrez S97, 3% w/w) as a mucoadhesive agent. The rheological (torsional and dynamic), mechanical (compressional), and mucoadhesive properties were characterized and shown to be dependent upon the mucoadhesive agent used and the inclusion/exclusion of PL. The dynamic rheological properties of the gel platforms were also assessed following dilution with simulated vaginal fluid (to mimic in vivo dilution). RSVs containing PC were more rheologically structured than comparator formulations containing GAN. This trend was also reflected in formulation hardness, compressibility, consistency, and syringeability. Moreover, formulations containing PL (10% w/w) were more rheologically structured than formulations devoid of PL. Dilution with simulated vaginal fluids significantly decreased rheological structure, although RSVs still retained a highly elastic structure (G′ > G′′ and tan δ < 1). Furthermore, RSVs exhibited sustained drug release properties that were shown to be dependent upon their rheological structure. It is considered that these semisolid drug delivery systems may be useful as site-retentive platforms for the sustained delivery of therapeutic agents to the vagina.