Abstract
Context and Objective: To screen various polymers through extensive preformulation investigations to ultimately obtain a lead polymer combination for designing a desirable Intravaginal Bioadhesive Polymeric Device (IBPD).
Materials and methods: 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.
Results and discussion: 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.
Conclusion: 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.