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Formulation of a nevirapine co-crystal as a liquid dosage formInjety, Sahana January 2016 (has links)
Magister Pharmaceuticae - MPharm / Co-crystals are a solid phase phenomena that could enhance the physicochemical properties of an active pharmaceutical ingredient. A co-crystal has never been incorporated into a liquid dosage form with the assurance of maintaining its co-crystal state until absorption under defined conditions. This study aims to develop a liquid formulation with a nevirapine co-crystal. A protocol was developed to investigate all the five co-formers that were used to make the nevirapine co-crystals to-date. The most appropriate co-former was selected for a liquid dosage form to study the integrity and the scaling up of the co-crystal in a suspension formulation. Co-formers used were viz. saccharin, glutaric acid, salicylic acid, rac-tartaric acid and maleic acid. These were characterized according to their physical, chemical, pharmacological and pharmaceutical properties. A grading scale was used to select the most appropriate co-former for a suspension formulation. Comparatively, saccharin produced the best combination of physical, chemical, pharmacological and pharmaceutical properties, especially with regard to the particle size and the specific gravity which proved to be very useful as optimal criteria for suspension formulation. Upon selection of the ideal co-former, scale-up of the nevirapine saccharin co-crystal was performed from a small scale of 350 mg to a large scale of 5 g. Nevirapine-saccharin (NVSC) co-crystals were prepared utilizing the slow evaporation technique, using methanol as the solvent and the percentage yield of the co-crystals were > 80 %. The identity of co-crystals was confirmed using hot stage microscopy (HSM), differential scanning calorimetry (DSC), fourier transform infra- red (FTIR) and thermogravimetric analysis (TGA). Three co-crystal suspension formulations were prepared using the excipients identified in the branded, Viramune® suspension, with each formulation containing viscosity enhancers such as aerosil 200, carbopol 971G and carbopol 974P. To ascertain the co- crystal integrity in the suspension, it was filtered and the filtrate was identified with DSC and FTIR while the filtered solution was identified with ultraviolet spectroscopy (UV). The co-crystal suspension formulation with optimal pH, viscosity and assurance of co-crystal integrity was the carbopol 974P formulation. The UV and DSC of the filtrate of the suspension revealed that the co-crystal had not separated into its individual components and remained intact while in suspension form irrespective of the excipients added. This formulation proceeded to the quality control stage. It was assessed for its pH, viscosity and dissolution according to the USP 32 standards and compared to the branded nevirapine suspension, Viramune ®, presently on the market. The suspension was characterized for particle size, zeta potential and polydispersity index. The dissolution results assayed by High Performance Liquid Chromatography (HPLC) revealed a drug release of 86 % in the Viramune® suspension while the NVSC co- crystal suspension achieved a drug release of 94% within 30 minutes of dissolution. / National Research Foundation (NRF)
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