Systematic Studies in Preparation and Evaluation of Multifunctional Diluent Blend for the Preparation of Solid Dosage Forms

Abstract

Single excipient cannot posses all the desired physicochemical properties to prepare a robust and efficient drug delivery system hence there is a need for co-processing of one excipient with other. Co-processing involves combining two or more existing excipients and hence eliminates time and cost consuming safety and toxicological studies. Microcrystalline cellulose (MCC) is an excellent excipient for the production of pellets by extrusion spheronization. However, it causes slow release rate of poorly water soluble drugs from pellets. The objective of present study was to develop co-processed MCC pellets (MOMLETS) by extrusion-spheronization technique using the principle of Quality by Design (QbD). BCS class II drug (telmisartan) was layered onto it in a fluidized bed processor. Quality Target Product Profile (QTPP) and Critical Quality Attributes (CQA) for pellets were identified. Risk assessment was reported using Ishikawa diagram. Plackett Burman design was used to check the effect of seven independent variables; superdisintegrant, extruder speed, ethanol: water, spheronizer speed, extruder screen, pore former and MCC: lactose; on percentage drug release at 30 min. Pareto chart and normal probability plot were constructed to identify the significant factors. Box-Behnken design (BBD) using three most significant factors (extruder screen size, type of superdisintegrant and type of pore former) was used as an optimization design. The design space was identified in which desired quality of the pellets can be obtained. Three additional model drugs (atazanavir, eprosartan mesylate and nimesulide) were layered onto the optimized MOMLETS to prove its versatility. Variety of drugs can be layered on MOMLETS with ease of drug layering, greater accuracy and less batch-to-batch variability. The drugs were released rapidly from the drug layered pellets consisted of co-processed excipient core pellets than that of MCC core pellets. Simplicity, Industrial applicability and versatility are the main features of the present...