Pamlényi Krisztián, Rayya Hala, Hassan Alharith A A, Jójárt-Laczkovich Orsolya, Sovány Tamás, Pintye-Hódi Klára, Regdon Géza, Kristó Katalin
Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, Eötvös u. 6., H-6720 Szeged, Hungary.
Pharmaceutics. 2025 Mar 22;17(4):401. doi: 10.3390/pharmaceutics17040401.
Captopril (CAP), an angiotensin-converting enzyme inhibitor (ACEI), is widely prescribed for managing hypertension, heart failure, and related conditions. When administered orally, CAP undergoes hepatic metabolism, resulting in a bioavailability of 60-75%. However, to bypass the first-pass metabolism and other limitations of the oral route, mucoadhesive buccal films have gained attention as a promising alternative with several advantages. The aim of this work was the formulation and optimization of chitosan-ascorbate mucoadhesive films for buccal delivery of CAP for the management of a hypertension crisis (10 mg and 20 mg) by employing quality by design (QbD) principles and the design of experiment (DoE) approach. : In the present work, chitosan (CHI) was selected as a film-forming agent due to its permeability-enhancing properties, which could be further improved through salification with ascorbic acid (AA). The polymer films were prepared by the solvent casting method. : The optimized CAP-loaded formula showed appropriate in vitro mucoadhesion force (>15 N) and breaking hardness (>14 N). The different CAP-containing films had a high drug content (>95%) with homogeneous drug distribution, thus complying with the requirements of Pharmacopeia. FT-IR and RAMAN spectroscopy analyses demonstrated successful incorporation of the drug, and interaction was observed between the excipients of the films, especially in the form of hydrogen bonds. The dissolution test showed immediate release of the API with a similar release pattern from both concentrations of CAP-loaded films. : The properties of the prepared films met the predetermined critical quality attribute requirements. The optimized formula of CHI 1.4%, AA 2.5%, and glycerol 0.3% appears to be a promising buccal drug delivery system for CAP.
卡托普利（CAP）是一种血管紧张素转换酶抑制剂（ACEI），广泛用于治疗高血压、心力衰竭及相关病症。口服给药时，CAP会经历肝脏代谢，生物利用度为60 - 75%。然而，为了绕过首过代谢和口服途径的其他局限性，粘膜粘附性口腔膜作为一种有前景的替代方法受到关注，它具有多个优点。本研究的目的是采用质量源于设计（QbD）原则和实验设计（DoE）方法，制备并优化用于口腔递送CAP以治疗高血压危象（10毫克和20毫克）的壳聚糖 - 抗坏血酸盐粘膜粘附膜。在本研究中，壳聚糖（CHI）因其增强通透性的特性被选作成膜剂，通过与抗坏血酸（AA）成盐可进一步改善其性能。聚合物膜采用溶剂浇铸法制备。优化后的载CAP配方显示出合适的体外粘膜粘附力（>15 N）和断裂硬度（>14 N）。不同的含CAP膜具有高药物含量（>95%）且药物分布均匀，因此符合药典要求。傅里叶变换红外光谱（FT - IR）和拉曼光谱分析表明药物成功载入，并且观察到膜的辅料之间存在相互作用，尤其是以氢键形式存在。溶出试验表明活性药物成分（API）即刻释放，两种浓度的载CAP膜具有相似的释放模式。所制备膜的性能满足预定的关键质量属性要求。1.4% CHI、2.5% AA和0.3%甘油的优化配方似乎是一种有前景的CAP口腔给药系统。
