Compatibility Study of Atorvastatin Calcium and Telmisartan with Selected Excipients and Formulation of a Bilayer Tablet Using Box Behnken Design

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.