Komanduri Neeraja, Almutairi Mashan, Elkanayati Rasha M, Dumpa Nagireddy, Butreddy Arun, Bandari Suresh, Repka Michael A
Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, Oxford, MS 38677, USA.
Department of Pharmaceutics, College of Pharmacy, University of Hail, Hail 81442, Saudi Arabia.
Pharmaceutics. 2025 Mar 25;17(4):413. doi: 10.3390/pharmaceutics17040413.
This study aimed to develop and evaluate taste-masked theophylline pellets using hot-melt extrusion (HME) technology. Additionally, the study evaluates the efficacy of various taste-masking polymers by comparing three pH-dependent polymers, Kollicoat Smartseal 100P, Eudragit EPO, and Kollicoat MAE 100-55, in masking taste and optimizing drug release. Formulations were designed with varying drug loads (10%, 20%, and 30%) and plasticizer concentrations (20% and 30% PEG 1500). Lead formulations were characterized using differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), bitter threshold level, and in vitro release testing. Stability was assessed under accelerated conditions (40 °C ± 2 °C and 75% ± 5% RH) for three months. DSC confirmed homogenous dispersion of the drug within the polymer matrix. The optimized formulation comprising 20% theophylline, 20% PEG 1500, and 60% Kollicoat Smartseal 100P demonstrated effective taste masking, releasing only 1.1% of the drug in simulated salivary fluid (SSF) within two minutes, significantly lower than the pure drug (29.5%, < 0.05), Kollicoat MAE 100-55 (2.8%, < 0.05), and comparable to Eudragit EPO (2.1%, > 0.05). Solubility studies further confirmed that theophylline release from the lead formulations remained well below its reported bitter threshold, which could prevent taste perception and mitigate bitterness. In gastric fluid, complete drug release was achieved from Kollicoat Smartseal 100P and Eudragit EPO, while Kollicoat MAE 100-55 exhibited limited release. Stability studies showed that the Kollicoat Smartseal 100P formulation maintained its texture, taste-masking efficacy, and dissolution profile under accelerated conditions. The study demonstrates the novel exploration of Kollicoat Smartseal 100P for HME application, and its effectiveness in achieving robust taste masking for theophylline, improving patient compliance, particularly in pediatric and geriatric populations.
本研究旨在利用热熔挤出（HME）技术开发并评估掩味型茶碱微丸。此外，该研究通过比较三种pH依赖性聚合物（Kollicoat Smartseal 100P、Eudragit EPO和Kollicoat MAE 100 - 55）在掩味和优化药物释放方面的效果，评估了各种掩味聚合物的功效。设计了不同药物负载量（10%、20%和30%）和增塑剂浓度（20%和30%聚乙二醇1500）的制剂。采用差示扫描量热法（DSC）、傅里叶变换红外光谱法（FTIR）、苦味阈值水平和体外释放试验对先导制剂进行表征。在加速条件（40℃±2℃和75%±5%相对湿度）下评估稳定性，为期三个月。DSC证实药物在聚合物基质中均匀分散。包含20%茶碱、20%聚乙二醇1500和60% Kollicoat Smartseal 100P的优化制剂显示出有效的掩味效果，在模拟唾液（SSF）中两分钟内仅释放1.1%的药物，显著低于纯药物（29.5%，<0.05）、Kollicoat MAE 100 - 55（2.8%，<0.05），与Eudragit EPO（2.1%，>0.05）相当。溶解度研究进一步证实，先导制剂中茶碱的释放量仍远低于其报道的苦味阈值，这可以防止味觉感知并减轻苦味。在胃液中，Kollicoat Smartseal 100P和Eudragit EPO实现了药物的完全释放，而Kollicoat MAE 100 - 55表现出有限的释放。稳定性研究表明，Kollicoat Smartseal 100P制剂在加速条件下保持了其质地、掩味功效和溶出曲线。该研究展示了对Kollicoat Smartseal 100P在HME应用中的新探索，以及其在为茶碱实现强大掩味效果、提高患者顺应性方面的有效性，特别是在儿科和老年人群中。
