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

Abstract

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.

Formulation Development and Evaluation of Innovative Two-Polymer (SR-2P) Bioadhesive Vaginal Gel

“…Polymer-based gel systems are widely used in formulation development of oral, dental, dermatological, vaginal, and ophthalmic applications (13,14). The gel-based formulations are easy to apply, easy to manufacture on a large scale, and have enhanced patient compliance.…”

“…The gel-based formulations are easy to apply, easy to manufacture on a large scale, and have enhanced patient compliance. Furthermore, these aqueousbased systems display reduced irritancy, which is essential for application to vaginal membranes (13,14). It is understood from the published literature that development of viable semisolid drug delivery platforms for vaginal application requires a fundamental understanding of their rheological, textural, and mucoadhesive properties within the vaginal cavity (15).…”

“…Adhesion mode was used to measure peak force required to detach placebo gel formulation from isolated mini pig vaginal tissue application are critical for the development of vaginal gels (16). Mucoadhesive polymers based on acrylic acid and celluloses have been reported to destabilize during dilution resulting in subsequent loss of gel adherence to the vaginal cavity (13,14,16). Mucoadhesive property exhibited by these acrylic acid cellulosic-based polymers alone is not sufficient to resist dilution and coital stress effects (13,14).…”

“…Mucoadhesive polymers based on acrylic acid and celluloses have been reported to destabilize during dilution resulting in subsequent loss of gel adherence to the vaginal cavity (13,14,16). Mucoadhesive property exhibited by these acrylic acid cellulosic-based polymers alone is not sufficient to resist dilution and coital stress effects (13,14). Research and development efforts are underway for the development of optimum vaginal gel formulations that exhibit non-Newtonian characteristics and possess shear thinning properties, so that they are easy to apply.…”

“…In addition, these optimum gels should be resistant to in vivo vaginal dilution and maintain structural integrity in spite of coital stress. In addition to the abovementioned gel characteristics, bioadhesivity of the formulation is critical for the prolonged retention and optimal exposure of the therapeutics in the vaginal cavity (13,14). The present study aims to identify placebo gels possessing all the abovementioned characteristics as suitable depot for anti-HIV/HSV agents, for use as microbicides.…”