Solubility Enhancement of Some Poorly Water Soluble Drugs Using Crystal Engineering Technique

Abstract

Pharmaceutical cocrystal has gained substantial interest due to appearance of cocrystal product in the market. The aim of the present research was to increase the solubility and dissolution rate of poorly water soluble drugs through pharmaceutical cocrystal. Piroxicam and zaltoprofen were selected for the preparation of cocrystals due to their poor water solubility. The neat grinding and liquid assisted grinding method were used for the preparation of cocrystals by screening various coformers. The cocrystals were prepared in 1:1 and 1:2 molar ratio of drug and coformers. Initially, the resulting product was evaluated for the melting point and solubility. The selected potential cocrystal was further characterized and confirmed by FTIR, DSC, PXRD, SEM etc. Further, dissolution rate, flowability and stability of the selected cocrystals were also investigated. Finally, the performance of selected cocrystals was examined in the tablet dosage form using 32 factorial design. The changes in melting point and solubility provided the preliminary evidence of formation of new solid phase. In addition, the alteration in FTIR absorption, thermal behavior and PXRD pattern signaled the formation of cocrystal. Piroxicam formed cocrystal with sodium acetate and zaltoprofen with nicotinamide. The flowability of cocrystals was found superior to pure drugs. The dissolution rate of cocrystals was improved significantly as compared to original drugs and found stable. The orodispersible tablets of piroxicam cocrystals were prepared and optimized. Similarly, zaltoprofen cocrystal formulated as immediate release tablets and optimized. Hence, pharmaceutical cocrystals of piroxicam and zaltoprofen having enhanced solubility, dissolution, flowability and stability were designed, prepared and evaluated. The prepared cocrystals showed good performance in the tablet dosage form as well. newline