Preformulation and Vaginal Film Formulation Development of Microbicide Drug Candidate CSIC for HIV prevention
| Autor: | Phalguni Gupta, Tiantian Gong, Michael A. Parniak, Bernard J. Moncla, Wei Zhang, Phillip W. Graebing, Lisa C. Rohan, Kerry M. Empey |
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| Rok vydání: | 2017 |
| Předmět: |
Chromatography
Materials science Biocompatibility Vaginal microbicide Pharmaceutical Science Nanotechnology 02 engineering and technology Polyethylene glycol 021001 nanoscience & nanotechnology 030226 pharmacology & pharmacy Polyvinyl alcohol Dosage form Article Solvent 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine chemistry Microbicide Drug Discovery Solubility 0210 nano-technology |
| Zdroj: | Journal of pharmaceutical innovation. 12(2) |
| ISSN: | 1872-5120 |
| Popis: | 5-Chloro-3-[phenylsulfonyl] indole-2-carboxamide (CSIC) is a highly potent non-nucleoside reverse transcriptase inhibitor (NNRTI) of HIV-1 which has been shown to have a more desirable resistance profile than other NNRTIs in the development as HIV prevention strategies. This work involves generation of preformulation data for CSIC and systematic development of a cosolvent system to effectively solubilize this hydrophobic drug candidate. This system was then applied to produce a polymeric thin film solid dosage form for vaginal administration of CSIC for use in prevention of sexual acquisition of HIV. Extensive preformulation, formulation development, and film characterization studies were conducted. An HPLC method was developed for CSIC quantification. Preformulation tests included solubility, crystal properties, stability, and drug-excipient compatibility. Cytotoxicity was evaluated using both human epithelial and mouse macrophage cell lines. Ternary phase diagram methodology was used to identify a cosolvent system for CSIC solubility enhancement. Following preformulation evaluation, a CSIC film formulation was developed and manufactured using solvent casting technique. The developed film product was assessed for physicochemical properties, anti-HIV bioactivity, and Lactobacillus biocompatibility during 12-month stability testing period. Preformulation studies showed CSIC to be very stable. Due to its hydrophobicity, a cosolvent system consisting of polyethylene glycol 400, propylene glycol, and glycerin (5:2:1, w/w/w) was developed, which provided a uniform dispersion of CSIC in the film formulation. The final film product met target specifications established for vaginal microbicide application. The hydrophobic drug candidate CSIC was successfully formulated with high loading capacity in a vaginal film by means of a cosolvent system. The developed cosolvent strategy is applicable for incorporation of other hydrophobic drug candidates in the film platform. |
| Databáze: | OpenAIRE |
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