Formulation Development and Optimization of Delayed Release Mini-Tablets in Capsule Dosage Form Containing BCS Class I Drug

Abstract

Control drug deliveries are used to decrease the dosing frequency and enhance the effectiveness of drug. Multi-unit dosage forms like pellets and mini-tablets are widely used to deliver the drug in control manner. Mini-tablets have the diameter less than 4.0 mm. Aim of present work is to develop robust and stable product bio equivalent to innovator product. Current project carried out to identify the critical process parameters and formulation parameters that have an impact on the mini-tablets formulation by applying the QbD approach. Initially patent for the model drug X was review and bypass to formulate the mini-tablets in capsule dosage form. Critical quality attributes for the formulation as well as process were identifying based on the innovator product characterization. 3 methods were used to prepare mini-tablets (wet granulation, granulation by top spray and dry mixing approach). Out of them dry mixing and direct compression was used to prepare the mini-tablets. Based on the experimental trial it was decided to use 51μm particle size for the formulation of the mini-tablets. Size of the minitablets was decided to 2.8 mm to avoid the gastric irritation. Based on the preliminary trial 16 mini-tablets were required to deliver the 240 mg. Mini-tablets were first coated by the Eudragit L100 to provide the non-aqueous seal coating followed by the enteric coating using the Eudragit L30 D 55 which delay the release of the drug until it passes the stomach acidic environment. Prepared mini-tablets were administered by encapsulating it into the capsule shell. Based on the updated CQAs factors for the DoE trials were identify which have potential impact on the quality of the finished product. Amount of the croscarmellose sodium and magnesium stearate were consider as a potential formulation factor that have impact on the dissolution rate. Based on the DoE trial amount of croscarmellose sodium and magnesium stearate were optimized to 18.4 mg and 3.68 mg respectively. Along with the formulation factor, blending time for prelubrication and after the lubrication was identifying as a process parameters that have significant impact on the blend uniformity and assay. Based on the optimization trial results, it has been decided to finalize 15 minutes as an optimum prelubrication blending time and 5 minutes as an optimum lubrication blending time for the drug X. After the optimization of amount of croscarmellose sodium and magnesium stearate and prelubrication and lubrication blending time scale-up batch was taken to prepared mini-tabets in capsule dosage form. Finished product shows the similar drug release profile as compare to the innovator product and studied for the bio equivalence with the innovator product.