Advanced preformulation investigations for the development of a lead intravaginal bioadhesive polymeric device

To screen various polymers through extensive preformulation investigations to ultimately obtain a lead polymer combination for designing a desirable Intravaginal Bioadhesive Polymeric Device (IBPD).

Hydrophilic and hydrophobic polymers (18) at different combinations were blended and compressed into 62 caplet-shaped devices at 5 tons, one of the hydrophilic polymers being a modified synthetic product of polyamide 6,10 ((m)PA 6,10). Two sets of crosslinked PAA-based caplets comprising either allyl-sucrose (AS-PAA) or allyl-penta-erythritol (APE-PAA) were explored. The devices were subjected to in-process validation tests and thereafter to preformulation investigational screening {equilibrium swelling ratio (ESR) being a screening parameter}, using a One Variable at a Time (OVAT) approach. Molecular mechanics force field simulations in both vacuum and solvated systems were conducted to investigate the influence of addition and subsequent replacement of a polymer(s) on the spatial disposition and energetic profile of the sterically constrained and geometrically optimized multi-polymeric complex, IBPD.

The developed devices were sufficiently strong (longitudinal crushing force:286 ± 0.01 N; mean weight:600 ± 0.48 mg; mean friability:0.31 ± 0.04%). Through OVAT approach, 15 lead formulations with minimal swelling tendencies (ESRs ranging from 0.011 to 0.084) were obtained out of 62 formulations. F62 {i.e. (m)PA 6,10, (150 mg), PLGA (400 mg), EC (200 mg), PVA (25 mg) and PAA (25 mg)} displayed minimal swelling tendency and therefore the highest stability. The highly stabilized conformation of the final in silico IBPD polymeric assembly PLGA-(m)PA6,10-PVA-PAA-EC corroborated the experimental results in terms of preformulation investigational screening using the OVAT approach.

The results obtained suggest that (m)PA 6,10, PLGA, EC, PVA and PAA at an appropriate weight ratio may be suitable for development of an IBPD.