Kozakiewicz-Latała Marta, Dyba Aleksandra J, Marciniak Dominik, Szymczyk-Ziółkowska Patrycja, Cieszko Mieczysław, Nartowski Karol P, Nowak Maciej, Karolewicz Bożena
Department of Drug Form Technology, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211, Wroclaw, Poland.
Centre for Advanced Manufacturing Technologies (CAMT/FPC), Wroclaw University of Science and Technology, Lukasiewicza 5, 50-371 Wroclaw, Poland.
Int J Pharm. 2024 Nov 15;665:124666. doi: 10.1016/j.ijpharm.2024.124666. Epub 2024 Sep 13.
In the majority of pharmaceutical applications, polymers are employed extensively in a diverse range of pharmaceutical products, serving as indispensable components of contemporary solid oral dosage forms. A comprehensive understanding of the properties of polymers and selection the appropriate methods of characterization is essential for the design and development of novel drug delivery systems and manufacturing processes. Orally disintegrating film (ODF) formulations are considered to be a potential substitute to traditional oral dosage forms and an alternative method of drug administration for children and uncooperative adult patients, including those with swallowing difficulties. A multitude of pharmaceutical formulations with varying mechanical and biopharmaceutical properties have emerged from the modification of the original polymeric bulk. Here we propose different formulation approaches, i.e. solvent casting (SC), 3D printing (3DP), electrospinning (ES), and lyophilization (LP) that enabled us to adjust the disintegration time and the release profile of poorly water soluble haloperidol (HAL, BCS class II) from PVA (polyvinyl alcohol) based polymer films while maintaining similar hydrogel composition. In this study, the solubility of haloperidol in aqueous solution was improved by the addition of lactic acid. The prepared films were evaluated for their morphology (SEM, micro-CT), physicochemical and biopharmaceutical properties. TMDSC, TGA and PXRD were employed for extensive thermal and structural analysis of fabricated materials and their stability. These results allowed us to establish correlations between preparation technology, structural characteristics and properties of PVA films and to adapt the suitable manufacturing technique of the ODFs to achieve appropriate HAL dissolution behaviour.
在大多数药物应用中，聚合物被广泛用于各种药品中，是当代固体口服剂型不可或缺的组成部分。全面了解聚合物的性质并选择合适的表征方法对于新型药物递送系统的设计、开发以及制造工艺至关重要。口腔崩解膜（ODF）制剂被认为是传统口服剂型的潜在替代品，也是儿童和不合作成年患者（包括吞咽困难患者）的一种替代给药方法。通过对原始聚合物本体进行改性，出现了多种具有不同机械和生物药剂学性质的药物制剂。在此，我们提出了不同的制剂方法，即溶剂浇铸（SC）、3D打印（3DP）、静电纺丝（ES）和冻干（LP），这些方法使我们能够在保持相似水凝胶组成的同时，调节难溶性氟哌啶醇（HAL，BCS II类）从基于聚乙烯醇（PVA）的聚合物薄膜中的崩解时间和释放曲线。在本研究中，通过添加乳酸提高了氟哌啶醇在水溶液中的溶解度。对制备的薄膜进行了形态学（扫描电子显微镜、微型计算机断层扫描）、物理化学和生物药剂学性质的评估。采用调制式差示扫描量热法、热重分析法和粉末X射线衍射法对制备材料及其稳定性进行了广泛的热分析和结构分析。这些结果使我们能够建立PVA薄膜的制备技术、结构特征与性能之间的相关性，并采用合适的ODF制造技术以实现氟哌啶醇的适当溶解行为。
