Application Of D-Optimal Mixture Design In The Development Of Nanocarrier-Based Darifenacin Hydrobromide Gel
- 1 February 2023
- journal article
- Published by Bentham Science Publishers Ltd. in Recent Advances in Drug Delivery and Formulation
Abstract
Background: Darifenacin hydrobromide, a BCS Class II drug, is poorly bioavailable due to extensive first-pass metabolism. The present study is an attempt to investigate an alternative route of drug delivery by developing a nanometric microemulsion-based transdermal gel for the management of an overactive bladder. Method: Oil, surfactant, and cosurfactant were selected based on the solubility of the drug, and surfactant: cosurfactant in surfactant mixture (Smix) was selected at a 1:1 ratio as inferred from the pseudo ternary phase diagram. The D-optimal mixture design was used to optimize the o/w microemulsion wherein the globule size and zeta potential were selected as dependable variables. The prepared microemulsions were also characterized for various physico-chemical properties like transmittance, conductivity, and TEM. The optimized microemulsion was gelled using Carbopol 934 P and assessed for drug release in-vitro and ex-vivo, viscosity, spreadability, pH, etc. Results: Drug excipient compatibility studies showed that the drug was compatible with formulation components. The optimized microemulsion showed a globule size of less than 50 nm and a high zeta potential of -20.56 mV. The ME gel could sustain the drug release for 8 hours as reflected in in-vitro and ex-vivo skin permeation and retention studies. The accelerated stability study showed no significant change in applied storage conditions. Conclusion: An effective, stable, non-invasive microemulsion gel containing darifenacin hydrobromide was developed. The achieved merits could translate into increased bioavailability and dose reduction. Further confirmatory in-vivo studies on this novel formulation, which is a cost-effective & industrially scalable option, can improve the pharmacoeconomics of overactive bladder management.Keywords
Funding Information
- SSIP, Government Gujarat, India (GKS/SSIP/SOIC Phase 7/SOIC 2020-2021/SO/957)
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