Multiple unit gastroretentive drug delivery systems: a new preparation method for low density microparticles.
Multiple unit gastroretentive drug delivery systems: a new preparation method for low density microparticles.
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DOI：
10.1080/0265204021000058384
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发表时间：
2003
影响因子：
3.9
通讯作者：
A. Streubel;J. Siepmann;R. Bodmeier
中科院分区：
文献类型：
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作者：
A. Streubel;J. Siepmann;R. Bodmeier
本研究的目的是开发一种新的低密度泡沫基漂浮微粒的制备方法，并证明该系统的体外性能。新的制备技术的主要优点包括：（i）加工时间短，（ii）成分不暴露于高温，（iii）避免有毒有机溶剂的可能性，以及（iv）接近100%的高封装效率。通过用药物和聚合物的有机溶液浸泡微孔泡沫载体并随后干燥，制备由聚丙烯泡沫粉末、模型药物[马来酸氯苯那敏（CPM）、盐酸地尔硫卓、茶碱或盐酸维拉帕米]和聚合物[Eudragit RS或聚甲基丙烯酸甲酯（PMMA）]组成的漂浮微粒。研究了各种制剂和加工参数对所得的体外漂浮行为、内部和外部颗粒形态、载药量、体外药物释放和掺入药物的物理状态的影响。在大多数情况下观察到良好的体外漂浮行为，并且通过改变药物负载和聚合物类型可以实现多种药物释放模式。有趣的是，PMMA为基础的微粒显示不完全的药物释放维拉帕米盐酸盐。这种限制可以通过在微粒制备之前形成药物的游离碱来克服。与盐相反，游离碱充当PMMA的增塑剂，导致足够高的扩散系数，因此完全释放药物。将低密度微粒压缩成快速崩解的片剂，以提供可口服给药的剂型。
The aim of this study was to develop a new preparation method for low density foam-based, floating microparticles and to demonstrate the systems' performance in vitro. Major advantages of the novel preparation technique include: (i) short processing times, (ii) no exposure of the ingredients to high temperatures, (iii) the possibility to avoid toxic organic solvents, and (iv) high encapsulation efficiencies close to 100%. Floating microparticles consisting of polypropylene foam powder, model drug [chlorpheniramine maleate (CPM), diltiazem HCl, theophylline or verapamil HCl] and polymer [Eudragit RS or polymethyl methacrylate (PMMA)] were prepared by soaking the microporous foam carrier with an organic solution of drug and polymer and subsequent drying. The effects of various formulation and processing parameters on the resulting in vitro floating behaviour, internal and external particle morphology, drug loading, in vitro drug release and physical state of the incorporated drug were studied. Good in vitro floating behaviour was observed in most cases and a broad variety of drug release patterns could be achieved by varying the drug loading and type of polymer. Interestingly, PMMA-based microparticles showed incomplete drug release with verapamil HCl. This restriction could be overcome by forming the free base of the drug prior to microparticle preparation. In contrast to the salt, the free base acted as a plasticizer for PMMA, resulting in sufficiently high diffusion coefficients and, consequently, complete drug release. The low density microparticles were compressed into rapidly disintegrating tablets in order to provide an administrable oral dosage form.