Evaluation of the polymorphic forms of ritonavir and lopinavir in raw materials and co-milled systems

Autor(es)

Pinheiro, Lucas Barboza Moreira ; Tao, Songsheng ; Culbertson, Elizabeth ; de Araujo, Gabriel Lima Barros ; Billinge, Simon J. L. ; Ferreira, Fabio Furlan

• Tipo de documento: Artigo Científico
• Fonte: International Journal of Pharmaceutics; v. 628, p. 9-pg., 2022-10-28.

Resumo

Recently, the U.S. Food and Drug Administration (FDA) approved the first oral antiviral drug to treat mild to moderate cases of coronavirus disease. The combination of nirmatrelvir with an already used protease inhibitor class drug, ritonavir, has led to Paxlovid (R). Several studies considered drug repositioning as the first trial for new drugs. The precise identification and quantification of polymorphs in raw materials and finished products are important to researchers involved in pharmaceutical development and quality control processes. In this work, we study the solid-state behavior of the antiretroviral drugs ritonavir and lopinavir in raw materials and in milled compositions. The results indicate that mixtures of ritonavir Forms I and II are found in different batches of raw materials from the same manufacturer; besides three equal crystalline samples, an amorphous batch was found in lopinavir. Furthermore, the milling process of the already amorphous lopinavir seems to facilitate the amorphization of ritonavir as well as the production of some unexpected crystalline forms of ritonavir. A phase transition of ritonavir Form I to Form II is only observed when co-milling with amorphous lopinavir. These findings reveal significant variations in phase purity of raw materials that affect the processing and solid-state properties, representing risks for the product quality. (AU)

• Processo FAPESP: 17/16499-5 - Estudo de formas polimórficas de matérias-primas de ritonavir e lopinavir com o uso da difração de raios X por pó e do método de Rietveld
• Beneficiário: Lucas Barboza Moreira Pinheiro
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 21/03640-7 - Síntese e investigação de novas formas cristalinas de agentes antineoplásicos
• Beneficiário: Fabio Furlan Ferreira
• Modalidade de apoio: Auxílio à Pesquisa - Regular