ABSTRACT
The present article utilized analytical quality by design (AQbD) methodology to optimize chromatographic conditionsfor the routine analysis of Cholecalciferol (CHL). Taguchi orthogonal array design and Box–Behnken designwere employed to screen and optimize critical method parameters for augmenting the method performance. Theoptimal chromatographic separation was attained on Eurosphere® 100-5, C8 (250 × 4.6 mm i.d., 5 μm) column in anisocratic elution mode using methanol:acetonitrile (50:50, % v/v) as mobile phase at a flow rate of 1.0 ml/minutesand photodiode array detection at 265 nm. The optimized chromatographic method was successfully validated asper International Council for Harmonisation Q2 (R1) guidelines. The method was found to be linear (r2 = 0.9993)in the range of 20–100 IU/ml. Limit of detection and limit of quantitation were found to be 10 and 20 IU/ml. Theprecision, robustness, and ruggedness values were within the acceptance limits (relative standard deviation < 2). Thepercent recovery of in-house developed 400 IU mouth dissolving tablets and marketed Tayo 60k tablets were foundto be 99.89% and 101.46%, respectively. The forced degradation products were well resolved from the main peaksuggesting the stability-indicating the power of the method. In conclusion, the AQbD-driven method is highly suitablefor analysis of CHL in bulk and pharmaceutical formulations
ABSTRACT
Tuberculosis has metamorphosized over the decades from drug resistant to multidrug resistant to the lethal extensively drug resistant forms lately. With scarce newer anti-TB drugs emerging, there is a pressing need to ameliorate the current treatment therapy by modulating the formulation approaches towards the first line treatment drugs. In the present study an attempt has been made to formulate Rifampicin (RIF), the first line treatment drug for TB as an extended release oral formulation using melt extrusion technique. The total dose of RIF was divided into two components- Immediate release (IR) pellets of RIF as the loading dose (300mg) and extended release tablet as the maintenance dose (150mg). Extrusion trials were conducted using various class of extrudable polymers (cellulose, polyvinyl acetate, polyethylene oxide, poly(meth)acrylates). Based on the preliminary findings, IR pellets were formulated using Eudragit EPO whereas hydroxylpropyl cellulose (HPC) was further explored as the matrix former. The release rate was modified using addition of hydrophilic pH independent release modifier. The formulation was characterized with respect to in vitro dissolution behavior, thermal and chemical stability, miscibility, drug-polymer interactions and surface morphology followed by stability studies. The loading dose could adequately release RIF initially whereas a combination of hydrophilic pH independent polymer of varying viscosity could successfully control RIF release over 24 hours following zero order release mechanism. The developed formulation exhibited content uniformity, physical and chemical stability over a period of six months. The application of melt extrusion for developing extended release matrices for anti-TB drugs like RIF was sought. Melt extrusion being a continuous manufacturing process could be scaled up commercially thus enhancing the feasibility of the designed formulation.