药物加入胶束对降低格列齐芬和美洛昔康在中空纤维膜上的渗透率的影响

IF 3.7 3区 医学 Q2 CHEMISTRY, MEDICINAL Journal of pharmaceutical sciences Pub Date : 2024-10-17 DOI:10.1016/j.xphs.2024.10.017
Roshni P Patel, Lynne S Taylor, James E Polli
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引用次数: 0

摘要

中空纤维膜(HFM)是溶解/渗透系统中潜在的渗透元件,以前曾对其进行过表征。研究的两个目的是评估胶束化对药物在中空纤维膜上渗透的影响,并从以下三种模式中确定首选渗透模式:仅从游离药物中渗透、从游离药物和胶束结合药物中渗透,以及通过胶束穿梭增强渗透。在不饱和药物条件下,使用格列齐芬和亲水性较强的药物美洛昔康,在添加或不添加表面活性剂[十二烷基硫酸钠、聚山梨醇酯 80 和聚氧乙烯(10)十二烷基醚]的情况下进行了高频渗透研究。与美洛昔康相比,吉西福林的胶束掺入程度更高,因此吉西福林通量的下降程度也比美洛昔康更大。只从游离药物渗透格列齐芬的模型被否定,因为在高频通量研究中,格列齐芬的通量要求游离药物比溶解度研究支持的高出约 5-20 倍,具体取决于表面活性剂。在截留分子量为 10KDa 的 HFM 中,游离格列齐芬和胶束结合格列齐芬的渗透性比游离药物的渗透性低约 5 倍,因此成功地适应了观察到的通量。尽管该模型能够容纳通量数据,并提供与其他设置相似的水边界层厚度,但胶束穿梭产生的渗透增强效应并不是首选的解释。
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Impact of drug incorporation into micelle on reduced griseofulvin and meloxicam permeation across a hollow fiber membrane.

A hollow fiber membrane (HFM) was previously characterized as a potential permeation component of a dissolution/permeation system. Two objectives were to assess the impact of micellization on drug permeation across HFM and identify a preferred permeation model from three models: permeation from only free drug, permeation from both free drug and micelle-bound drug, and permeation with enhancement from micelle shuttling. HFM studies were conducted under unsaturated drug conditions, using griseofulvin and the more hydrophilic drug meloxicam, with and without surfactant [sodium lauryl sulfate, polysorbate 80, and polyoxyethylene (10) lauryl ether]. Griseofulvin was micelle incorporated to a greater extent than meloxicam, such that griseofulvin flux decreased to a greater extent than for meloxicam. The griseofulvin permeation model from only free drug was rejected, since griseofulvin flux required free drug to be about 5-20 fold higher in HFM flux studies than supported by solubility studies, depending on surfactant. Permeation from both free griseofulvin and micelle-bound griseofulvin successfully accommodated observed flux, where micelle permeability was about 5-fold lower than free drug permeability for HFM with 10KDa MWCO. Permeation with enhancement from micelle shuttling was not the preferred explanation, although the model accommodated flux data and provided aqueous boundary layer thicknesses similar to other setups.

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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
A Survey of Solid Form Landscape: Trends in Occurrence and Distribution of Various Solid Forms and Challenges in Solid Form Selection. Impact of Surfactants on Solution Behavior and Membrane Transport of Amorphous Solid Dispersions. Insights into pharmaceutical co-crystallization using coherent Raman microscopy. β-Cyclodextrin Derivatives Bind Aromatic Side Chains of the Cyclic Peptide Lanreotide. Bioavailability Improvement by Atomic Layer Coating: Fenofibrate A Case Study.
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