Uhumwangho M U, Okor R S
Department of Pharmaceutics, University of Benin, Benin City, Nigeria.
Pak J Pharm Sci. 2006 Jan;19(1):22-7.
Acetaminophen granules have been formed by a melt granulation process with the objective of retarding drug release for prolonged action formulations. The waxes used were goat wax, carnuba wax and glyceryl monostearate. In the melt granulation procedure, acetaminophen powder was triturated with the melted waxes and passed through a sieve of mesh 10 (aperture size 710 microm). The content of wax in resulting granules ranged from 10 to 40%w/w. Acetaminophen granules were also formed by the convectional method of wet granulation with starch mucilage (20%w/w). The granules were subjected to in-vitro drug release tests. The release data were subjected to analysis by three different well-established mathematical models (release kinetics) namely, - zero order flux, first order, and the Higuchi square root of time relationship. The convectional granules exhibited an initial zero order flux (first 55%) followed by a first order release profile (the remaining 45%). The pattern of drug release from the melt granulations was consistent with the first order kinetic and the Higuchi square root of time relationship, indicating a diffusion-controlled release mechanism. The first order release rate constant of the convectional granules was 1.95 +/- 0.02 h(-1). After melt granulation (wax content, 20%w/w) the rate constants dropped drastically to 0.130+/-0.001 h(-1) (goat wax), 0.120+/-0.003 h(-1) (carnuba wax), and 0.130+/-0.002 h(-1) (glyceryl monosterate) indicating that all three waxes were equivalent in retarding drug release from the melt granulations.
对乙酰氨基酚颗粒已通过熔融制粒工艺制备，目的是为长效制剂延缓药物释放。所使用的蜡为羊蜡、巴西棕榈蜡和单硬脂酸甘油酯。在熔融制粒过程中，对乙酰氨基酚粉末与熔融的蜡研磨混合，并通过10目筛（孔径710微米）。所得颗粒中蜡的含量为10%至40%（w/w）。对乙酰氨基酚颗粒也通过常规的湿法制粒方法，用淀粉糊（20%w/w）制备。对颗粒进行体外药物释放试验。释放数据通过三种不同的成熟数学模型（释放动力学）进行分析，即零级通量、一级和Higuchi时间平方根关系。常规颗粒呈现出初始的零级通量（前55%），随后是一级释放曲线（其余45%）。熔融制粒的药物释放模式符合一级动力学和Higuchi时间平方根关系，表明是扩散控制释放机制。常规颗粒的一级释放速率常数为1.95±0.02 h⁻¹。熔融制粒（蜡含量20%w/w）后，速率常数急剧下降至0.130±0.001 h⁻¹（羊蜡）、0.120±0.003 h⁻¹（巴西棕榈蜡）和0.130±0.002 h⁻¹（单硬脂酸甘油酯），表明所有三种蜡在延缓熔融制粒药物释放方面效果相当。
