Compatibility Study

Compatibility study (based on microenvironmental pH and isothermal stress testing) of Febuxostat was carried out with selected excipients (Microcrystalline cellulose (MCC), Mannitol, Lactose, Hydroxypropyl-β-cyclodextrin (HP-β-CD), Polyethylene glycol(PEG) 6000, Polyvinyl pyrollidoneK30, Eudragit EPO, Sodium starch glycollate, Croscarmellose sodium (CCMC), Sodium lauryl sulphate, Magnesium stearate (MgS), Sodium steryl fumarate, Aerosil 200 and Purified talc) using FTIR and HPLC. Among them, Aerosil 200, MgS, Purified talc, Lactose and MCC were selected for the formulation of Febuxostat tablet. Three different polymers viz. PEG 6000, HP-b-CD and CCMC were selected as independent variables to enhance the dissolution rate by their complexation. Fifteen formulations obtained from Box Behnken design (BBD) (Minitab 16) were prepared through kneading method. Contour plot suggested CCMC (13.01mg) and HP-b-CD (65.45mg) excluding PEG 6000 for optimized formulation. Drug release profile of optimized formulation compared separately with formulation without filler, without polymer, physical mixture and a marketed product using similarity (fs) and dissimilarity (fd) factors showed similarity with marketed product. Similarly, similarity and dissimilarity factors for formulation without filler and optimized formulation was obtained within the range (fs= 82.34 and fd=5.42) indicating that the filler does not have any effect on the drug release. fs and fd for formulation without polymer and physical mixture lied outside the range suggesting the importance of the polymer complexation in the formulation. An accurate, simple, precise and robust reversed-phase liquid chromatographic method was developed for the estimation of Febuxostat. Furthermore, solid state characterization evaluated by FTIR showed that complexation between the polymers has occurred in the optimized formulation.

The purpose of this study was to formulate a stable parenteral formulation of Palonosetron HCl 0.05 mg/mL which is pharmaceutically equivalent to Reference Drug Product. Preformulation study was performed to evaluate the compatibility of product with materials which come in contact with the product during manufacturing. Compatibility study was carried out with metal, silicon tubes, PVDF filters and stoppers. Thermal cycling and photostabilty study were also performed to ensure the stability of the product. Palonosetron injection was formulated by dissolving the API and excipients in WFI in a S.S vessel under continuous stirring. Stability studies at different conditions were also performed. Compatibility study results indicate that drug product was compatible with the product contact materials. Thermal cycling and photostabilty data indicates that there was no significant degradation in the formulation. As a part of Sterilization cycle development, terminal sterilization was performed at 1210C for 15, 20 and 30 minutes time intervals and finalized cycle was 20 minutes. A stable Palonosetron Injection was developed and evaluated. Compatibility and accelerated stability studies at different conditions were performed and it can be concluded that the product is compatible with product contact materials, thermal and photostable.