应用亲水性聚合物制备含盐酸溴己新和富马酸比索洛尔的长效缓释微型片剂

IF 4.9 3区医学 Q1 PHARMACOLOGY & PHARMACY

Pharmaceutics Pub Date : 2024-08-30 DOI:10.3390/pharmaceutics16091153

Agata Grzejdziak, Witold Brniak, Olaf Lengier, Justyna Anna Żarek, Dziyana Hliabovich, Aleksander Mendyk

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引用次数: 0

摘要

迷你片作为一种方便的儿科用药形式，近年来得到了广泛的研究，因为即使是非常年幼的儿童也能成功用药。它们的优点包括：通过单个单位的倍增可以方便地调整剂量，以及可以通过包衣或形成基质系统来改变药物的释放。本研究的目的是证明为儿科患者配制含盐酸溴己新（BHX）和富马酸比索洛尔（BFM）的缓释小药片的可能性。我们使用不同等级的羟丙基甲基纤维素（HPMC）、甲基纤维素、海藻酸钠或聚乙烯醇（PVA）作为缓释聚合物，通过直接压片法制备了直径为 3 毫米、质量为 15 毫克的小药片，每片含有 1 毫克活性物质。对不同数量的聚合物和不同的压缩力进行了评估。迷你片的分析包括其均匀性、硬度和溶解试验。使用专用软件对药物释放动力学进行了分析。所制备的迷你片在质量和含量的均匀性方面均符合药典要求。BFM 的可压缩性明显优于 BHX，但所有小药片都具有良好的机械性能。溶出研究表明，聚合物的类型及其在片剂质量中的含量与溶出率之间有着密切的关系。当使用粘度为 4000 cP 的 HPMC（含量为 30% 至 80%）时，可实现长达 8 小时的缓释。50% 的海藻酸钠也能有效延长溶解时间，但 PVA 的效果要差得多。对释放动力学的研究表明，BHX 缓释小药片的溶出与 Hopfenberg 或 Hixson-Crowell 模型最为吻合，而 BFM 则与 Hopfenberg 或 Korsmeyer-Peppas 模型最为吻合。

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Application of Hydrophilic Polymers to the Preparation of Prolonged-Release Minitablets with Bromhexine Hydrochloride and Bisoprolol Fumarate

Minitablets have been extensively studied in recent years as a convenient pediatric form because they allow successful administration even in very young children. Their advantages include easy dose adjustment by multiplication of single units as well as the possibility of drug release modification by coating or forming matrix systems. The aim of this study was to demonstrate the possibility of the formulation of prolonged-release minitablets with bromhexine hydrochloride (BHX) and bisoprolol fumarate (BFM) dedicated to pediatric patients. Minitablets with 3 mm diameter and 15 mg mass, containing 1 mg of active substance in 1 unit, were prepared by direct compression with hydroxypropyl methylcellulose (HPMC) of different grades, methylcellulose, sodium alginate, or polyvinyl alcohol (PVA) as a sustained-release polymer. Different amounts of polymers and different compression forces were evaluated. Analysis of minitablets included their uniformity, hardness, and dissolution tests. The kinetics of drug substance release were analyzed with dedicated software. The prepared minitablets met the pharmacopeial requirements with respect to the uniformity of mass and content. The compressibility of BFM was significantly better than that of BHX, yet all minitablets had good mechanical properties. Dissolution studies showed a strong relationship between the type of polymer and its amount in the mass of a tablet and the dissolution rate. Prolonged release of up to 8 h was achieved when HPMC of 4000 cP viscosity was used in the amount of 30% to 80%. Sodium alginate in the amount of 50% was also effective in prolonging dissolution, but PVA was much less effective. Studies on the release kinetics showed that dissolution from prolonged-release minitablets with BHX fit the best to Hopfenberg or Hixson–Crowell models, while in the case of BFM, the best fit was found for Hopfenberg or Korsmeyer–Peppas models.

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来源期刊

Pharmaceutics Pharmacology, 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.