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Direct NMR Monitoring of Phase Separation Behavior of Highly Supersaturated Nifedipine Solution Stabilized with Hypromellose Derivatives.
Ueda, Keisuke; Higashi, Kenjirou; Moribe, Kunikazu.
Afiliação
  • Ueda K; Graduate School of Pharmaceutical Sciences, Chiba University , 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.
  • Higashi K; Graduate School of Pharmaceutical Sciences, Chiba University , 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.
  • Moribe K; Graduate School of Pharmaceutical Sciences, Chiba University , 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.
Mol Pharm ; 14(7): 2314-2322, 2017 07 03.
Article em En | MEDLINE | ID: mdl-28558250
We investigated the phase separation behavior and maintenance mechanism of the supersaturated state of poorly water-soluble nifedipine (NIF) in hypromellose (HPMC) derivative solutions. Highly supersaturated NIF formed NIF-rich nanodroplets through phase separation from aqueous solution containing HPMC derivative. Dissolvable NIF concentration in the bulk water phase was limited by the phase separation of NIF from the aqueous solution. HPMC derivatives stabilized the NIF-rich nanodroplets and maintained the NIF supersaturation with phase-separated NIF for several hours. The size of the NIF-rich phase was different depending on the HPMC derivatives dissolved in aqueous solution, although the droplet size had no correlation with the time for which NIF supersaturation was maintained without NIF crystallization. HPMC acetate and HPMC acetate succinate (HPMC-AS) effectively maintained the NIF supersaturation containing phase-separated NIF compared with HPMC. Furthermore, HPMC-AS stabilized NIF supersaturation more effectively in acidic conditions. Solution 1H NMR measurements of NIF-supersaturated solution revealed that HPMC derivatives distributed into the NIF-rich phase during the phase separation of NIF from the aqueous solution. The hydrophobicity of HPMC derivative strongly affected its distribution into the NIF-rich phase. Moreover, the distribution of HPMC-AS into the NIF-rich phase was promoted at lower pH due to the lower aqueous solubility of HPMC-AS. The distribution of a large amount of HPMC derivatives into NIF-rich phase induced the strong inhibition of NIF crystallization from the NIF-rich phase. Polymer distribution into the drug-rich phase directly monitored by solution NMR technique can be a useful index for the stabilization efficiency of drug-supersaturated solution containing a drug-rich phase.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Nifedipino / Espectroscopia de Ressonância Magnética / Derivados da Hipromelose Idioma: En Revista: Mol Pharm Assunto da revista: BIOLOGIA MOLECULAR / FARMACIA / FARMACOLOGIA Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Japão

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Nifedipino / Espectroscopia de Ressonância Magnética / Derivados da Hipromelose Idioma: En Revista: Mol Pharm Assunto da revista: BIOLOGIA MOLECULAR / FARMACIA / FARMACOLOGIA Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Japão