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

Purpose Oral direct compressible tablets are the most frequentlyused drug products. Manufacturing of tablets requiresdesign and development of formulations, which need a numberof excipients. The choice of excipients depends on theconcentration, manufacturability, stability, and bioavailabilityof the active pharmaceutical ingredients (APIs). At MIT, wedeveloped a miniature platform for on-demand manufacturingof direct compressible tablets. This study investigated howformulations could be simplified to use a small number ofexcipients for a number of different API’s in which long termstability is not required.Method Direct compressible tablets of five pharmaceuticaldrugs, Diazepam, Diphenhydramine HCl, DoxycyclineMonohydrate, Ibuprofen, and CiprofloxacinHCl, with differentdrug loadings, were made using direct compression in anautomated small scale system.. The critical quality attributes(CQA) of the tablets were assessed for the quality standards setby the United States Pharmacopeia (USP).Results This miniature system can manufacture tablets - ondemandfrom crystalline API using the minimum number ofexcipients required for drug product performance. All drugtablets met USP quality standards after manufacturing andafter 2 weeks of accelerated stability test, except for slightlylower drug release for Ibuprofen.Conclusions On-demand tablets manufacturing where thereis no need for long term stability using a flexible, miniature,automated (integrated) system will simplify pharmaceuticalformulation design compared to traditional formulations.This advancement will offer substantial economic benefits bydecreasing product time-to-market and enhancing quality.