Ahm Musleh Uddin, Roy N Kirkwood, Kiro R Petrovski, Souha H Youssef, Baljinder Singh, Songhita Mukhopadhyay, Yunmei Song, Sanjay Garg
{"title":"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。","authors":"Ahm Musleh Uddin, Roy N Kirkwood, Kiro R Petrovski, Souha H Youssef, Baljinder Singh, Songhita Mukhopadhyay, Yunmei Song, Sanjay Garg","doi":"10.3390/pharmaceutics17091181","DOIUrl":null,"url":null,"abstract":"<p><p><b>Background/Objectives</b>: 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. <b>Methods</b>: 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 (R<sup>2</sup> = 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. <b>Results</b>: Among all tested PEs, chitosan demonstrated the best enhancement of BA permeation. It achieved the highest flux (J) (0.64 ± 0.03 × 10<sup>-2</sup> µg/cm<sup>2</sup>·h) and apparent permeability coefficient (P<sub>app</sub>) (16.20 ± 0.84 × 10<sup>-5</sup> cm/h), both of which were statistically significantly higher (<i>p</i> < 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. <b>Conclusions</b>: 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.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 9","pages":""},"PeriodicalIF":5.5000,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473407/pdf/","citationCount":"0","resultStr":"{\"title\":\"Evaluation of Permeation Enhancers for Vaginal Delivery of Buserelin Acetate Using a Validated Chromatographic Method and Ex Vivo Porcine Model.\",\"authors\":\"Ahm Musleh Uddin, Roy N Kirkwood, Kiro R Petrovski, Souha H Youssef, Baljinder Singh, Songhita Mukhopadhyay, Yunmei Song, Sanjay Garg\",\"doi\":\"10.3390/pharmaceutics17091181\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p><b>Background/Objectives</b>: 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. <b>Methods</b>: 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 (R<sup>2</sup> = 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. <b>Results</b>: Among all tested PEs, chitosan demonstrated the best enhancement of BA permeation. It achieved the highest flux (J) (0.64 ± 0.03 × 10<sup>-2</sup> µg/cm<sup>2</sup>·h) and apparent permeability coefficient (P<sub>app</sub>) (16.20 ± 0.84 × 10<sup>-5</sup> cm/h), both of which were statistically significantly higher (<i>p</i> < 0.05) than those of all other enhancer groups. 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Evaluation of Permeation Enhancers for Vaginal Delivery of Buserelin Acetate Using a Validated Chromatographic Method and Ex Vivo Porcine Model.
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 (Papp) (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.
PharmaceuticsPharmacology, 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.