Ashwinee Kumar Shrestha

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.

Present study was carried out to study compatibility of Atorvstatin Calcium (ATR) and Telmisartan (TEL) with selected generally regarded as safe (GRAS) excipients and to prepare bilayer tablet. Isothermal stress testing was performed in binary mixtures which was subjected to 50°C for 4 weeks. Isothermal stressed samples were evaluated with RP-HPLC method and FTIR analysis. A trial was conducted with single disintegrant and diluent with direct compression technique and in-vitro dissolution was carried out. To improve the release profile of ATR layer, multiple disintegrants were used namely croscarmellose sodium (CCS), sodium starch glycolate (SSG)  and crosprovidone (CP). These disintegrants were taken as variable in Box-behnken design (BBD) in Minitab 16.2.3.0. The tablets were prepared from obtained design formulations by direct compression. Similarly, Telmisartan layer was prepared by wet granulation technique. TEL was treated with alkalizing agent, sodium hydroxide in stoichiometrical proportion. Croscarmellose sodium, sodium starch glycolate and crosprovidone were taken as variable and subjected to BBD. Intra and extra granulation was done with mixtures of disintegrants. Optimized formulation as per response surface optimizer in Minitab 16 contains be 10.0 mg of SSG, 7.36 mg of CP and 10.0 mg of CCS per tablet for ATR layer. Similarly in case of TEL tablet, it was found that as concentration of SSG, CP and CCS increases, the release of drug also increases. When multiple disintegrants were used in the combination, better release was obtained. Optimize formulation as per response surface optimizer in Minitab 16  contains 22.03 mg of SSG, 15 mg of CP and 15 mg of CCS per tablet for Telmisartan layer. Bilayer tablet was prepared with this optimized formulation in 10 station compression machine. The prepared bilayer tablet was further evaluated and in-vitro dissolution were compared with market products. Thus, the conversion of salt form, optimized combination of disintegrants, use of polyvinyl pyrrolidone K-30 as carrier, intra and extra granulation was observed to be effective in release of TEL from the dosage form where as only the optimized combination of disintegrants was  sufficient for release of ATR from the dosage form.