Eudragit®EPO包被固体分散型盐酸氯他弗林小儿速释微丸的研制与优化

IF 2.7 4区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of Pharmaceutical Innovation Pub Date : 2025-09-16 DOI:10.1007/s12247-025-10080-x

Hitarthi Patel, Mitali Upadhyay, Meenakshi Patel

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引用次数: 0

摘要

目的：为解决盐酸氯他弗林（DHC）水溶性差、口感苦、给药灵活等问题，开发一种儿童友好型速释微丸制剂。目的是提高溶解度，保证药物快速释放，同时掩盖药物的苦味。方法以聚乙二醇4000和聚乙二醇6000为原料，采用溶剂蒸发法制备DHC固体分散体。用挤压滚圆法将这些转化为球团，用MCC（微晶纤维素）作为球团剂，用Eudragit®EPO涂层掩盖味道。采用2³析因设计优化关键变量：球化速度、PEG类型和超崩解剂浓度。对优化后的批药进行理化性质、崩解、药物含量、体外胃和口腔pH释放、动力学建模等评价。结果DHP6为DHC与PEG 4000（1:2）的固体分散体，10%的强力崩解剂，球化速度为7000 rpm。制粒粒度为0.78±0.02 mm， t85为15±3.25 min，崩解时间为0.83±0.04 min。该微球具有良好的流动性（休止角为12.04°，豪斯纳比为1.01）、脆性（0.12±0.004%）和硬度（0.55±0.25 g/cm²）。体外释放研究表明，在0.1 N HCl中15分钟内释放85%的药物，在模拟唾液液中释放几乎可以忽略不计，证实了有效的味觉掩蔽。释放动力学符合Korsmeyer-Peppas模型（R²= 0.9862），为扩散控制释放。结论研制的DHC速释微丸具有溶解度好、胃释放快、掩味效果好等特点，是治疗小儿腹痛的理想剂型。优化后的配方（DHP6）表现出强大的物理化学和性能特征，支持其在儿科使用的潜力。

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Development and Optimization of Eudragit® EPO Coated Solid Dispersion-Based Immediate-Release Pellets of Drotaverine Hydrochloride for Pediatric use

Purpose

The study aimed to develop a pediatric-friendly, immediate-release pellet formulation of Drotaverine Hydrochloride (DHC) to address issues related to poor aqueous solubility, bitter taste, and dosing flexibility in children. The objective was to enhance solubility and ensure rapid drug release while masking the bitter taste of drug.

Method

Solid dispersions of DHC were prepared using Polyethylene Glycol (PEG) 4000 and PEG 6000 via the solvent evaporation technique. These were converted into pellets using extrusion–spheronization, with MCC (Microcrystalline Cellulose), as the pelletizing agent and Eudragit^® EPO coating for taste masking. A 2³ factorial design was employed to optimize critical variables: spheronization speed, PEG type, and superdisintegrant concentration. The optimized batch was evaluated for physicochemical properties, disintegration, drug content, in vitro drug release in both gastric and oral pH, and kinetic modeling.

Results

The optimized formulation (DHP6) comprised a solid dispersion of DHC with PEG 4000 (1:2 ratio), 10% superdisintegrant, and a spheronization speed of 7000 rpm. It exhibited a pellet size of 0.78 ± 0.02 mm, t₈₅ of 15 ± 3.25 min, and disintegration time of 0.83 ± 0.04 min. The pellets showed excellent flowability (angle of repose: 12.04°; Hausner ratio: 1.01), friability (0.12 ± 0.004%), and acceptable hardness (0.55 ± 0.25 g/cm²). In vitro release studies demonstrated > 85% drug release within 15 min in 0.1 N HCl and negligible release in simulated salivary fluid, confirming effective taste masking. Release kinetics followed the Korsmeyer-Peppas model (R² = 0.9862), indicating diffusion-controlled release.

Conclusion

The developed immediate-release pellets of DHC offer improved solubility, rapid gastric release, and effective taste masking, making them a promising pediatric dosage form for abdominal pain management. The optimized formulation (DHP6) demonstrated robust physicochemical and performance characteristics, supporting its potential for pediatric use.

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来源期刊

Journal of Pharmaceutical Innovation PHARMACOLOGY & PHARMACY-

CiteScore

3.70

自引率

3.80%

发文量

审稿时长

>12 weeks

期刊介绍： The Journal of Pharmaceutical Innovation (JPI), is an international, multidisciplinary peer-reviewed scientific journal dedicated to publishing high quality papers emphasizing innovative research and applied technologies within the pharmaceutical and biotechnology industries. JPI''s goal is to be the premier communication vehicle for the critical body of knowledge that is needed for scientific evolution and technical innovation, from R&D to market. Topics will fall under the following categories: Materials science, Product design, Process design, optimization, automation and control, Facilities; Information management, Regulatory policy and strategy, Supply chain developments , Education and professional development, Journal of Pharmaceutical Innovation publishes four issues a year.