Impact of Polymer Type on Thermal Degradation of Amorphous Solid Dispersions Containing Ritonavir

Autor(es)

de Alvarenga, Jr., Benedito Roberto ^{[1, 2]} ; Moseson, Dana E. ^[1] ; Carneiro, Renato Lajarim ^[2] ; Taylor, Lynne S. ^[1]

Afiliação do(s) autor(es)

^[1] Purdue Univ, Coll Pharm, Dept Ind & Phys Pharm, W Lafayette, IN 47907 - USA

^[2] Univ Fed Sao Carlos, Dept Chem, BR-13560905 Sao Carlos, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: MOLECULAR PHARMACEUTICS; DEC 2021.
• Citações Web of Science: 0

Resumo

High-temperature exposure during hot melt extrusion processing of amorphous solid dispersions may result in thermal degradation of the drug. Polymer type may influence the extent of degradation, although the underlying mechanisms are poorly understood. In this study, the model compound, ritonavir (T-m = 126 degrees C), undergoes thermal degradation upon high-temperature exposure. The extent of degradation of ritonavir in amorphous solid dispersions (ASDs) formulated with poly(vinylpyrrolidone) (PVP), poly(vinylpyrrolidone vinyl acetate copolymer (PVP/VA), hydroxypropyl methylcellulose acetate succinate (HPMCAS), and hydroxypropyl methylcellulose (HPMC) following isothermal heating and hot melt extrusion was evaluated, and mechanisms related to molecular mobility and intermolecular interactions were assessed. Liquid chromatography-mass spectrometry (LC-MS/MS) studies were used to determine the degradation products and pathways and ultimately the drug- polymer compatibility. The dominant degradation product of ritonavir was the result of a dehydration reaction, which then catalyzed a series of hydrolysis reactions to generate additional degradation products, some newly reported. This reaction series led to accelerated degradation rates with protic polymers, HPMCAS and HPMC, while ASDs with aprotic polymers, PVP and PVP/VA, had reduced degradation rates. This work has implications for understanding mechanisms of thermal degradation and drug-polymer compatibility with respect to the thermal stability of amorphous solid dispersions. (AU)

• Processo FAPESP: 19/22048-1 - Avaliação dos produtos de degradação do medicamento antirretroviral Ritonavir durante processo de extrusão a quente (HME)
• Beneficiário: Benedito Roberto de Alvarenga Junior
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado
• Processo FAPESP: 17/13095-0 - Planejamento experimental aplicado a estudos de degradação forçada dos fármacos Nitazoxanida e Sofosbuvir
• Beneficiário: Benedito Roberto de Alvarenga Junior
• Modalidade de apoio: Bolsas no Brasil - Doutorado