Impact of colloidal drug-rich droplet size and amorphous solubility on drug membrane permeability: A comprehensive analysis.

IF 3.7 3区 医学 Q2 CHEMISTRY, MEDICINAL Journal of pharmaceutical sciences Pub Date : 2025-01-01 Epub Date: 2024-06-26 DOI:10.1016/j.xphs.2024.06.017
Keisuke Ueda, Shiryu Takemoto, Kenjirou Higashi, Kunikazu Moribe
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Abstract

This study aimed to investigate the impact of amorphous solubility and colloidal drug-rich droplets on drug absorption. The amorphous solubility of cilnidipine (CND) in AS-HF grade of hypromellose acetate succinate (HPMC-AS) solution was significantly reduced compared to that in non-polymer solution due to AS-HF partitioning into the CND-rich phase. In contrast, AS-LF grade of HPMC-AS has minimal effect on the amorphous solubility. The size of colloidal CND-rich droplets formed in the CND-supersaturated solution was less than 100 nm in the presence of AS-HF, while 200-450 nm in the presence of AS-LF. When the CND concentrations were near the amorphous solubility, CND membrane flux was reduced in the presence of AS-HF due to the decrease in the amorphous solubility of CND. However, the CND flux increased with the increase in CND-rich droplets, especially in the AS-HF solution. The size reduction of the CND-rich droplets led to their effective diffusion into the unstirred water layer, enhancing CND flux. In higher CND concentration regions, the CND flux became higher in the AS-HF solution than in the AS-LF solution. Thus, it is essential to elucidate the drug concentration-dependent impact of the colloidal drug-rich droplets on the drug absorption performance to optimize supersaturating formulations.

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富含药物的胶体液滴大小和无定形溶解度对药物膜渗透性的影响:综合分析
本研究旨在探讨无定形溶解度和胶体药物富集液滴对药物吸收的影响。与非聚合物溶液相比,西尼地平(CND)在AS-HF级醋酸琥珀酸异丁烯酸羟丙甲纤维素(HPMC-AS)溶液中的无定形溶解度明显降低,原因是AS-HF分配到了富含CND的相中。相反,AS-LF 级 HPMC-AS 对无定形溶解度的影响很小。在有 AS-HF 的情况下,CND 过饱和溶液中形成的富含 CND 的胶体液滴的尺寸小于 100 nm,而在有 AS-LF 的情况下则为 200-450 nm。当 CND 浓度接近无定形溶解度时,由于 CND 的无定形溶解度降低,AS-HF 存在时 CND 膜通量减少。然而,CND 通量随着富含 CND 的液滴的增加而增加,尤其是在 AS-HF 溶液中。富含 CND 的液滴尺寸减小,导致其有效扩散到未搅拌的水层中,从而提高了 CND 通量。在 CND 浓度较高的区域,AS-HF 溶液中的 CND 通量高于 AS-LF 溶液。因此,阐明富含药物的胶体液滴对药物吸收性能的影响与药物浓度有关,对于优化过饱和制剂至关重要。
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来源期刊
CiteScore
7.30
自引率
13.20%
发文量
367
审稿时长
33 days
期刊介绍: The Journal of Pharmaceutical Sciences will publish original research papers, original research notes, invited topical reviews (including Minireviews), and editorial commentary and news. The area of focus shall be concepts in basic pharmaceutical science and such topics as chemical processing of pharmaceuticals, including crystallization, lyophilization, chemical stability of drugs, pharmacokinetics, biopharmaceutics, pharmacodynamics, pro-drug developments, metabolic disposition of bioactive agents, dosage form design, protein-peptide chemistry and biotechnology specifically as these relate to pharmaceutical technology, and targeted drug delivery.
期刊最新文献
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