Drug distribution in wet granulation: foam versus spray
Drug distribution in wet granulation: foam versus spray
复制标题
湿法制粒中的药物分布：泡沫与喷雾
DOI：
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发表时间：
2013
影响因子：
3.4
通讯作者：
K. Hapgood
中科院分区：
文献类型：
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作者：
M. Tan;Thanh;K. Hapgood
泡沫制粒技术是一种新型的湿法制粒技术。本研究评价了泡沫和喷雾制粒在使用模型制剂实现均匀药物分布方面的性能。为了观察润湿和成核，在静态粉末床上进行单滴/泡沫渗透实验，所述静态粉末床分别由亲水性/疏水性玻璃球和亲水性乳糖/疏水性水杨酸的不同组合物组成。使用亲水性乳糖和疏水性水杨酸的不同组合物在5L混合器中进行高剪切制粒实验。4%羟丙基甲基纤维素（HPMC）溶液以90 g/min作为泡沫（92%FQ）或雾化喷雾递送，同时记录叶轮功耗。干燥后，测量颗粒尺寸分布，并使用在甲醇中的重量过滤估计颗粒组成。与液滴渗透相比，泡沫渗透较少依赖于粉末疏水性。对于玻璃球粉末混合物，泡沫诱导成核产生具有相对均匀的结构和尺寸的核，而不管粉末的疏水性。对于水杨酸和乳糖的混合物，增加水杨酸的比例降低了泡沫和滴粘合剂添加的核颗粒尺寸。粘合剂的加入方式对颗粒剂的药物分布无明显影响。加工条件，包括液体粘合剂量、叶轮速度、湿成团和制剂的润湿性是递送均匀颗粒的主要因素。研究表明，泡沫造粒和喷雾造粒涉及不同的成核机制-喷雾往往会导致早期的液体渗透，而泡沫造粒在机械分散中运行良好。
Foam granulation technology is a new wet granulation approach for pharmaceutical formulations. This study evaluates the performance of foam and spray granulation in achieving uniform drug distribution using a model formulation. To observe wetting and nuclei formation, single drop/foam penetration experiments were performed on a static powder bed comprised of varying compositions of hydrophilic/hydrophobic glass ballotini, and hydrophilic lactose/hydrophobic salicylic acid respectively. High shear granulation experiments were performed in a 5L mixer using varying compositions of hydrophilic lactose and hydrophobic salicylic acid. Four percent hydroxylpropyl methylcellulose (HPMC) solution was delivered at 90 g/min as either a foam (92% FQ) or an atomized spray whilst recording impeller power consumption. After drying, the granule size distribution was measured and the granule composition was estimated using gravimetric filtration in methanol. Foam penetration was less dependent on the powder hydrophobicity compared to drop penetration. For glass ballotini powder mixtures, foam induced nucleation created nuclei with relatively uniform structure and size regardless of the powder hydrophobicity. For salicylic acid and lactose mixtures, increasing the proportion of salicylic acid reduced the nuclei granule size for both foam and drop binder addition. The granule drug distribution was not significantly affected by the binder addition method. Processing conditions, including liquid binder amount, impeller speed, wet massing, and the wettability properties of the formulation were the dominant factors for delivering homogeneous granules. The study reveals that foam and spray granulation involve different nucleation mechanisms – spray tends to incur early liquid penetration whereas foam granulation operates well in mechanical dispersion.