Abstract

Purpose: Cocrystallisation of drug with coformers is a promising approach to alter the solid sate properties of drug substances like solubility and dissolution. The objective of the present work was to prepare, formulate and evaluate the piroxicam cocrystal by screening various coformers.Methods: Cocrystals of piroxicam were prepared by dry grinding method. The melting point and solubility of crystalline phase was determined. The potential cocrystal was characterized by DSC, IR, XRPD. Other pharmaceutical properties like solubility and dissolution rate were also evaluated. Orodispersible tablets of piroxicam cocrystal were formulated, optimized and evaluated using 32 factorial design.Results: Cocrystals of piroxicam-sodium acetate revealed the variation in melting points and solubility. The cocrystals were obtained in 1:1 ratio with sodium acetate. The analysis of Infrared explicitly indicated the shifting of characteristic bands of piroxicam. The X-Ray Powder Diffraction pattern denoted the crystallinity of cocrystals and noteworthy difference in 2θ value of intense peaks. Differential scanning calorimetry spectra of cocrystals indicated altered endotherms corresponding to melting point. The pH solubility profile of piroxicam showed sigmoidal curve, which authenticated the pKa-dependent solubility. Piroxicam cocrystals also exhibited a similar pH-solubility profile. The cocrystals exhibited faster dissolution rate owing to cocrystallization as evident from 30% increase in the extent of dissolution. The orodispersible tablets of piroxicam cocrystals were successfully prepared by direct compression method using crosscarmelose sodium as superdisintegrant with improved disintegration time (30 sec) and dissolution rate.Conclusion: The piroxicam cocrystal with modified properties was prepared with sodium acetate and formulated as orodispersible tablets having faster disintegration and greater dissolution rate.

Highlights

  • The solubility and dissolution rate of drugs is a decisive factor after oral administration for rate and extent of absorption

  • Sodium acetate successfully interacted with piroxicam, giving novel cocrystal form

  • The obtained piroxicam cocrystal was subjected to physichochemical evaluation and orodispersible tablet formulation

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Summary

Introduction

The solubility and dissolution rate of drugs is a decisive factor after oral administration for rate and extent of absorption This factor offers key challenge for the development and formulation of effective drug in the pharmaceutical industry. The cocrystals of piroxicam were reported with different carboxylic acid by solution crystallization, melt crystallization and solvent drop grinding method.[5,6,7] Piroxicam is nonsteroidal anti-inflammatory BCS class II drug with prevalent solubility problem. It takes about 3-5 hrs to reach peak plasma concentration after oral administration. It is indicated for acute or long-term use in the relief of signs and symptoms of osteoarthritis and rheumatoid arthritis.[8,9,10,11,12]

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