Towards Rational Excipient Selection: Assessing Lactose-Based Co-Processed Excipients with APIs of Differing Solubilities

This research was designed to systematically investigate the performance of three lactose-based co-processed excipients (CPEs): SuperTab® 40LL, StarLac®, and MicroceLac® 100 in immediate-release tablet formulations prepared by direct compression. The objective was to evaluate their suitability with drugs of varying solubility and mechanical properties and provide practical guidance for excipient selection in tablet formulation. Each co-processed excipient (CPE) was evaluated for flowability, tabletability, compressibility and compactibility. Formulations were prepared using four model drugs (promethazine, theophylline, hydrocortisone, and paracetamol) at drug loadings of 20 and 30% w/w. A single-punch tablet press was employed to prepare the tablets and were evaluated under harmonised conditions for strength, friability, disintegration and dissolution. Different performance profiles were observed among the excipients. SuperTab® 40LL exhibited the strongest flow properties. StarLac® demonstrated superior disintegration speed and dissolution performance but had the weakest tensile strength, failing friability testing at 30% paracetamol loading. MicroceLac® 100 demonstrated enhanced mechanical strength and compactibility, coupled with consistently low friability values for all APIs tested, but generally failed British Pharmacopoeia criteria for disintegration and dissolution. Regardless of the excipient used, tablets containing hydrocortisone exhibited the poorest disintegration and dissolution. Overall, most formulations complied with friability specifications, confirming good manufacturability. Excipient performance depended on API properties, drug loading, and formulation strategy. StarLac® provides optimal performance in terms of fast disintegration and high dissolution rates, SuperTab® 40LL improves flow, and MicroceLac® 100 enhances mechanical strength. This comparative evaluation provides a framework for rational excipient selection and supports Quality-by-Design approaches in tablet formulation.