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Designing a Novel Coamorphous Salt Formulation of Telmisartan with Amlodipine to Enhance Permeability and Oral Absorption.
Hatanaka, Yuta; Uchiyama, Hiromasa; Kaneko, Shun; Ueda, Keisuke; Higashi, Kenjirou; Moribe, Kunikazu; Furukawa, Shingo; Takase, Mai; Yamanaka, Shinya; Kadota, Kazunori; Tozuka, Yuichi.
Afiliación
  • Hatanaka Y; Department of Formulation Design and Pharmaceutical Technology, Faculty of Pharmacy, Osaka Medical and Pharmaceutical University, Osaka 569-1094, Japan.
  • Uchiyama H; Department of Formulation Design and Pharmaceutical Technology, Faculty of Pharmacy, Osaka Medical and Pharmaceutical University, Osaka 569-1094, Japan.
  • Kaneko S; Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, Japan.
  • Ueda K; Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, Japan.
  • Higashi K; Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, Japan.
  • Moribe K; Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, Japan.
  • Furukawa S; Division of Applied Sciences, Muroran Institute of Technology, Muroran 050-8585, Japan.
  • Takase M; Division of Applied Sciences, Muroran Institute of Technology, Muroran 050-8585, Japan.
  • Yamanaka S; Division of Applied Sciences, Muroran Institute of Technology, Muroran 050-8585, Japan.
  • Kadota K; Department of Formulation Design and Pharmaceutical Technology, Faculty of Pharmacy, Osaka Medical and Pharmaceutical University, Osaka 569-1094, Japan.
  • Tozuka Y; Department of Formulation Design and Pharmaceutical Technology, Faculty of Pharmacy, Osaka Medical and Pharmaceutical University, Osaka 569-1094, Japan.
Mol Pharm ; 20(8): 4071-4085, 2023 08 07.
Article en En | MEDLINE | ID: mdl-37498232
Coamorphous formulation is a useful approach for enhancing the solubility of poorly water-soluble drugs via intermolecular interactions. In this study, a hydrogen-bonding-based coamorphous system was developed to improve drug solubility, but it barely changed the apparent permeability (Papp) of the drug. This study aimed to design a novel coamorphous salt using ionic interactions to improve drug permeability and absorption. Telmisartan (TMS), with an acidic group, was used to form a coamorphous salt with basic amlodipine (AML). Evaluation of the physicochemical properties confirmed the formation of a coamorphous salt via ionic interactions between the amine group of AML and the carboxyl group of TMS at a molar ratio of 1:1. The coamorphous salt of TMS/AML enhanced the partitioning of both drugs into octanol, indicating increased lipophilicity owing to the interaction between TMS and AML. The coamorphous salt dramatically enhanced TMS solubility (99.8 times that of untreated TMS) and decreased AML solubility owing to the interaction between TMS and AML. Although the coamorphous salt showed a decreased Papp in the permeation study in the presence of a thicker unstirred water layer (UWL) without stirring, Papp increased in the presence of a thinner UWL with stirring. The oral absorption of TMS from the coamorphous salt increased by up to 4.1 times compared to that of untreated TMS, whereas that of AML remained unchanged. Although the coamorphous salt with increased lipophilicity has a disadvantage in terms of diffusion through the UWL, the UWL is thin in human/animal bodies owing to the peristaltic action of the digestive tract. Dissociation of the coamorphous salt on the membrane surface could contribute to the partitioning of the neutral form of drugs to the membrane cells compared with untreated drugs. As a result, coamorphous salt formation has the advantage of improving the membrane permeation and oral absorption of TMS, owing to the enhanced solubility and supply of membrane-permeable free TMS on the surface of the membrane.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia Mieloide Aguda / Amlodipino Límite: Animals / Humans Idioma: En Revista: Mol Pharm Asunto de la revista: BIOLOGIA MOLECULAR / FARMACIA / FARMACOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia Mieloide Aguda / Amlodipino Límite: Animals / Humans Idioma: En Revista: Mol Pharm Asunto de la revista: BIOLOGIA MOLECULAR / FARMACIA / FARMACOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos