Polymer-Mediated Drug Supersaturation Controlled by Drug–Polymer Interactions Persisting in an Aqueous Environment
| Autor: | Shan Wang, Peter Serno, Wouter Tonnis, Huijun Chen, Feng Qian, Linc Chen, Yipshu Pui, Yuejie Chen |
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| Rok vydání: | 2018 |
| Předmět: |
Magnetic Resonance Spectroscopy
Polymers Pharmaceutical Science 02 engineering and technology Flory–Huggins solution theory 030226 pharmacology & pharmacy Hydrophobic effect 03 medical and health sciences 0302 clinical medicine Dynamic light scattering Spectroscopy Fourier Transform Infrared Drug Discovery Dissolution chemistry.chemical_classification Supersaturation Aqueous solution Calorimetry Differential Scanning Hydrogen bond Chemistry technology industry and agriculture Water Hydrogen Bonding Polymer 021001 nanoscience & nanotechnology Solubility Chemical engineering Molecular Medicine 0210 nano-technology Hydrophobic and Hydrophilic Interactions |
| Zdroj: | Molecular Pharmaceutics. 16:205-213 |
| ISSN: | 1543-8392 1543-8384 |
| DOI: | 10.1021/acs.molpharmaceut.8b00947 |
| Popis: | We investigated the drug-polymer interactions in nonaqueous and aqueous environments between a poorly water-soluble drug, BAY1161909 (909), and two commonly used polymers in amorphous solid dispersions, i.e., PVP and HPMC-AS. In an nonaqueous state, with a drug-polymer Flory-Huggins interaction parameter, solution NMR and FT-IR results revealed that strong specific interactions existed between 909 and PVP, while not between 909 and HPMC-AS. After prolonged moisture exposure under 95% RH, 909/PVP intermolecular interaction no longer existed, while hydrophobic interaction between 909 and HPMC-AS occurred and persisted. In an aqueous supersaturation study of 909, codissolved PVP significantly outperformed predissolved PVP in maintaining 909 supersaturation. We hypothesized that the codissolved PVP formed a specific interaction with 909, and thus, it was able to prolong 909 supersaturation before disruption of the interaction in aqueous medium, while predissolved PVP formed hydrogen bonds with water, and thus, it was no longer able to form specific interactions with 909 to prolong its supersaturation. In contrast, HPMC-AS effectively mediated 909 supersaturation through hydrophobic interaction, which became pronounced in an aqueous environment and was independent of how HPMC-AS was added. This hypothesis was supported by dynamic light scattering analysis, wherein the formation of nanosized drug/polymer aggregations was found to be correlating with the supersaturation of 909. In summary, we concluded that polymer-mediated drug supersaturation was controlled by drug-polymer interactions persisting in an aqueous environment. Therefore, the physical nature of the drug-polymer interaction as well as the dissolution kinetic of the drug and polymer are all critically important to achieve an optimal ASD formulation design. |
| Databáze: | OpenAIRE |
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