Evaluation of Permeation Enhancers for Vaginal Delivery of Buserelin Acetate Using a Validated Chromatographic Method and Ex Vivo Porcine Model.

IF 5.5 3区医学 Q1 PHARMACOLOGY & PHARMACY

Pharmaceutics Pub Date : 2025-09-11 DOI:10.3390/pharmaceutics17091181

Ahm Musleh Uddin, Roy N Kirkwood, Kiro R Petrovski, Souha H Youssef, Baljinder Singh, Songhita Mukhopadhyay, Yunmei Song, Sanjay Garg

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Abstract

Background/Objectives: This study aimed to enhance the vaginal permeation of buserelin acetate (BA), a synthetic gonadotropin-releasing hormone (GnRH) analogue, by evaluating various permeation enhancers (PEs) using a validated reversed-phase high-performance liquid chromatography (RP-HPLC) method and an ex vivo porcine vaginal model. Methods: A robust RP-HPLC method was developed and validated according to ICH Q2 (R2) guidelines to enable accurate quantification of BA in permeation samples. The analytical method demonstrated high specificity, linearity (R² = 0.9999), accuracy (98-102%), precision (%RSD < 2%), robustness, and stability. Using this method, ex vivo permeation studies were conducted with six different PEs: 2-hydroxypropyl-β-cyclodextrin, sodium dodecyl sulfate, poloxamer 188, Span 80, Tween 80, and chitosan. Results: Among all tested PEs, chitosan demonstrated the best enhancement of BA permeation. It achieved the highest flux (J) (0.64 ± 0.03 × 10^-2 µg/cm²·h) and apparent permeability coefficient (P_app) (16.20 ± 0.84 × 10^-5 cm/h), both of which were statistically significantly higher (p < 0.05) than those of all other enhancer groups. Kinetic modelling indicated a non-Fickian, biphasic permeation mechanism best described by the Makoid-Banakar model. Conclusions: These findings highlight chitosan's potential as an effective intravaginal delivery vehicle for peptide therapeutics and establish the validated HPLC method as a reliable platform for future formulation development and translational studies in mucosal drug delivery.

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用有效的色谱法和离体猪模型评价醋酸布瑟林阴道给药的渗透促进剂。

背景/目的：本研究旨在通过反相高效液相色谱法（RP-HPLC）和离体猪阴道模型，评价不同的促性腺激素释放激素（GnRH）类似物醋酸布丝林（BA）对阴道的渗透作用。方法：根据ICH Q2 （R2）指南，建立了一种可靠的反相高效液相色谱（RP-HPLC）方法，以准确定量渗透样品中的BA。分析方法具有较高的特异性、线性度（R2 = 0.9999）、准确度（98 ~ 102%）、精密度（%RSD < 2%）、鲁棒性和稳定性。采用该方法对6种不同的pe进行了体外渗透研究：2-羟丙基-β-环糊精、十二烷基硫酸钠、波洛沙姆188、Span 80、Tween 80和壳聚糖。结果：在所有pe中，壳聚糖对BA渗透的促进效果最好。其通量(J)最高（0.64±0.03 × 10-2µg/cm2·h），表观渗透系数（Papp）最高（16.20±0.84 × 10-5 cm/h），均显著高于其他增强剂组（p < 0.05）。动力学模型表明，Makoid-Banakar模型最好地描述了非菲克式的双相渗透机制。结论：这些发现突出了壳聚糖作为一种有效的多肽治疗阴道内递送载体的潜力，并建立了有效的高效液相色谱方法，为未来的配方开发和粘膜药物递送的转化研究提供了可靠的平台。

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来源期刊

Pharmaceutics Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science

CiteScore

7.90

自引率

11.10%

发文量

2379

审稿时长

16.41 days

期刊介绍： Pharmaceutics (ISSN 1999-4923) is an open access journal which provides an advanced forum for the science and technology of pharmaceutics and biopharmaceutics. It publishes reviews, regular research papers, communications, and short notes. Covered topics include pharmacokinetics, toxicokinetics, pharmacodynamics, pharmacogenetics and pharmacogenomics, and pharmaceutical formulation. Our aim is to encourage scientists to publish their experimental and theoretical details in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced.