The primary purpose of the present study was to apply the quality by design approach to the formulation of the somatostatin analog (SSA) cyphetrylin dosage form. Experimental investigations of cyphetrylin activity in vivo showed that its oral administration is optimal. For better patient compliance and product quality, an interdisciplinary team identified the quality target product profile and determined the critical quality attributes (CQAs) related to product safety and efficacy. On the basis of our own in vitro/in vivo nonclinical data and experience of SSA medicinal use, we estimated the criticality of each CQA by a specially created scale. Because of the minimal quantity of the active substance in the tablet, the assay and uniformity of content are defined as the most CQAs. Estimation of the manufacturing process by methods of the risk analysis and mitigation matrix and failure mode effect analysis allowed us to determine the effects of process unit operations on final product in-process CQAs and to characterize the granulation and compression as the most critical steps. It has been shown that the moisture content of granulate is the most significant in-process CQA, which affects the disintegration and resistance to crushing of tablets and their microbial limits.
Key words: Key words: somatostatin analogue, quality by design, quality target product profile, critical quality attributes, risk assessment, tablet
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