Drug-Excipient Compatibility Study Through a Novel Vial-in-Vial Experimental Setup: A Benchmark Study.

Abstract

Drug-excipient compatibility study (DECS) is one of the critical steps during pre-formulation studies to select the appropriate excipient to obtain a stable formulation/dosage form. As such, there is no recommended guideline for DECS. Further, the previously reported studies and protocols followed by various pharmaceutical industries are very lengthy and laborious. Therefore, to improve the existing study strategies and rapid screening of suitable excipients during formulation development, a novel vial-in-vial approach has been proposed. The devised approach was compared with the previously reported conventional approaches using six different drugs with multiple marketed formulations from different manufacturers for each drug. To validate the proposed novel approach, several reported strategies/methodologies have been executed such as exposure of formulations with and without primary packaging, crushed blend with and without water, and/or acetonitrile at accelerated stability condition of 40°C/75% RH for 3 to 6months and compared with the novel approach. Eventually, all the samples were subjected to HPLC analysis to evaluate the degradation behaviour. The results suggested that the novel approach demonstrated discriminating results with significant degradation as compared to the conventional approaches. Consequently, exercising this methodology for screening the excipients is expected to shorten the drug development cycle by many folds. Moreover, it has also been anticipated that the developed novel approach would prevent the occurrence of late-stage surprises during stability studies.