On-Demand Manufacturing of Direct Compressible Tablets: Can Formulation Be Simplified?

Abstract

Oral direct compressible tablets are the most frequently used drug products. Manufacturing of tablets requires design and development of formulations, which need a number of excipients. The choice of excipients depends on the concentration, manufacturability, stability, and bioavailability of the active pharmaceutical ingredients (APIs). At MIT, we developed a miniature platform for on-demand manufacturing of direct compressible tablets. This study investigated how formulations could be simplified to use a small number of excipients for a number of different API’s in which long term stability is not required. Direct compressible tablets of five pharmaceutical drugs, Diazepam, Diphenhydramine HCl, Doxycycline Monohydrate, Ibuprofen, and Ciprofloxacin HCl, with different drug loadings, were made using direct compression in an automated small scale system.. The critical quality attributes (CQA) of the tablets were assessed for the quality standards set by the United States Pharmacopeia (USP). This miniature system can manufacture tablets - on-demand from crystalline API using the minimum number of excipients required for drug product performance. All drug tablets met USP quality standards after manufacturing and after 2 weeks of accelerated stability test, except for slightly lower drug release for Ibuprofen. On-demand tablets manufacturing where there is no need for long term stability using a flexible, miniature, automated (integrated) system will simplify pharmaceutical formulation design compared to traditional formulations. This advancement will offer substantial economic benefits by decreasing product time-to-market and enhancing quality.