Quality by Design Based Pharmaceutical Development Report of Cost-effective Dexamethasone Tablets, 20 mg for Regulatory Submission

Abstract

Aim: In this research, the pharmaceutical development report of Dexamethasone tablets, 20 mg has been discussed in-detail with all relevant sections in sufficiency thus making it eligible to be filed with a regulatory agency. Scheme: The overall work flow and the report compilation was done similar to an Abbreviated    New Drug Application (ANDA). The Quality Target Product Profile (QTPP) is HEMADY™ (Dexamethasone) Tablets, 20 mg manufactured for Dexcel Pharma Technologies Ltd, Israel and distributed by Acrotech Biopharma Inc, USA. The complete development work was done by Quality by Design (QbD) approach. The composition of drug product was kept similar to the brand product with Lactose Monohydrate as diluent; Corn Starch as binder and disintegrant; Povidone as binder; Sodium Starch Glycollate Type A as disintegrant and Magnesium Stearate as Lubricant. A simple direct blending and compression process was followed to manufacture the drug product. Optimization: The particle size distribution (PSD) of Active Pharmaceutical Ingredient (API) was identified as Critical Material Attribute (CMA) – micronized API less than 10 microns needed to achieve Bio-equivalence with the brand product. The blending time was identified as Critical Process Parameter (CPP)–blending time of 15 minutes in Pre-lubrication stage and 5 minutes in Lubrication stage was finalized. The blend flow, hardness and dissolution were identified as Critical Quality Attribute (CQA). Results and Conclusion: The manufactured product was found to be stable in bottle and blister pack at International Council for Harmonization (ICH) recommended accelerated stability storage condition at 40°C ± 2°C / 75%RH ± 5% RH for 6 months. The product was found bio-equivalent with the brand product under Fast & Fed condition. To further enable seamless and quality manufacturing of the drug product, systems and controls are put in-place for Microbiological attributes; Control strategy; Product lifecycle management and continuous improvement.