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The Influence of Gastrointestinal Biomolecules on Solid-State Transformations in Pharmaceutical Particulates.
Aljabbari, Anas; Kihara, Shinji; Rades, Thomas; Boyd, Ben J; Be Rzins, Ka Rlis.
Afiliação
  • Aljabbari A; Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2100, Denmark.
  • Kihara S; Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2100, Denmark.
  • Rades T; Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2100, Denmark.
  • Boyd BJ; Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2100, Denmark.
  • Be Rzins KR; Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Parkville 3052, Victoria, Australia.
Mol Pharm ; 20(8): 4297-4306, 2023 08 07.
Article em En | MEDLINE | ID: mdl-37491730
Adsorption of gut relevant biomolecules onto particles after oral administration of solid oral dosage forms is expected to form a "gastrointestinal corona", which could influence solution-mediated solid-state transformations on exposure of drug particles to gastrointestinal fluids. Low-frequency Raman (LFR) spectroscopy was used in this study to investigate in situ solid-state phase transformations under biorelevant temperature and pH conditions along with the presence of biomolecules. Melt-quenched amorphous indomethacin was used as a model solid particulate, and its solid-state behavior was evaluated at 37 °C and pH 1.2-6.8 with or without the presence of typical bile salt/phospholipid mixtures emulating fed-state conditions. Overall, a change in the solid-state transformation pathway from amorphous to crystalline drug was observed, where an intermediate ε-form that initially formed at pH 6.8 was suppressed by the addition of endogenous gastrointestinal biomolecules. These solid-state changes were corroborated using time-resolved synchrotron small- and wide-angle X-ray scattering (SAXS/WAXS). Additionally, the bile salt and phospholipid mixture partly prevented the otherwise strong aggregation between drug particles at more acidic conditions (pH ≤ 4.5) and helped to shift the balance against the intrinsic hydrophobicity of indomethacin as well as the plasticization effect brought about by the physiological temperature (i.e., the stickiness arising from the supercooled liquid state at 37 °C). The overall results highlight the importance of evaluating the impact that endogenous biomolecules may have on the solid-state characteristics of drug molecules in dissolution media, where analytical tools such as LFR spectroscopy can serve as an attractive avenue for accessing time-resolved solid-state information on time-scales that are difficult to achieve with other techniques such as X-ray diffraction.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fosfolipídeos / Indometacina Tipo de estudo: Prognostic_studies Idioma: En Revista: Mol Pharm Assunto da revista: BIOLOGIA MOLECULAR / FARMACIA / FARMACOLOGIA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Dinamarca

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fosfolipídeos / Indometacina Tipo de estudo: Prognostic_studies Idioma: En Revista: Mol Pharm Assunto da revista: BIOLOGIA MOLECULAR / FARMACIA / FARMACOLOGIA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Dinamarca