Optimization of the composition of the anti-inflammatory drug Piron

Introduction. The original Russian pharmaceutical substance Piron belongs to the group of nonsteroidal anti-inflammatory drugs. Its dosage form (50-mg tablets) has been designed for the treatment of musculoskeletal system diseases. Objective: to optimize the composition of 50-mg film-coated Piron tablets in order to increase the release of the pharmaceutical substance from the tablets into the dissolution medium. Material and methods. The composition of the tablets was optimized by incorporating the disintegrants of various chemical compositions. The release of the active ingredient was assessed in accordance with the requirements of the 14th Edition of the State Pharmacopoeia of the Russian Federation. The dissolution test was carried out on an RC-3 paddle mixer. Quantitative determination was performed using an HPLC system based on a Shimadzu modular chromatograph (Japan). Results. A number of compositions for direct compression were designed and tested, where disintegrants (crospovidone, croscarmellose sodium, and pregelatinized starch) and silicon dioxide (Aerosil) were additionally incorporated in various combinations. The degree of transition of the active substance into the solution was quantified by HPLC and a relationship was determined between the release of Piron into the dissolution medium and the proportion of various disintegrants in the composition of tablets. The optimal composition of the solid dosage form was established and a pilot batch of tablet cores was obtained using a ZP-9 rotary tablet press. The quantity of the active ingredient passing from the tablets of this composition into the solution was found to be 98%. Conclusion. The investigators have designed the optimized composition of 50-mg film-coated Piron tablets with the increased release of the active ingredient, which contains a combination of two disintegrants: croscarmellose sodium and pregelatinized starch. The chosen excipients considerably improve the release of the substance from the dosage form as compared to the baseline values.

nonsteroidal anti-inflammatory drugs (NSAIDs), release, disintegrants, dissolution