Modeling the deagglomeration of micronized benzodiazepines from powder mixtures added to dissolution media.
Modeling the deagglomeration of micronized benzodiazepines from powder mixtures added to dissolution media.
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模拟添加到溶解介质中的粉末混合物中微粉化苯二氮卓类药物的解聚。
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发表时间：
2004
期刊：
影响因子：
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通讯作者：
P. Stewart
中科院分区：
文献类型：
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作者：
F. Zhao;P. Stewart
本研究的目的是模拟苯二氮卓类药物的解聚曲线的百分比团聚与时间时，含有微粉化苯二氮卓类药物的相互作用的混合物被添加到水中。将微粉化地西泮、硝西泮、奥沙西泮和微粉化十二烷基硫酸钠（对于三元混合物）与乳糖-聚维酮颗粒（250-355 μ m）混合。乳糖颗粒快速溶解后，通过激光衍射粒度测定法测定的苯二氮卓类药物的双峰粒度分布代表分散和团聚分布。团聚颗粒的浓度随时间的推移而降低，并趋于恒定值。解团聚配置文件确定和最好的三参数单指数衰减方程建模。使用非线性最小二乘法估计可分散性团聚体（C（0））和不可分散性团聚体（C（0a））的浓度以及解聚速率常数（K（a））。增加乳糖-聚维酮混合物中苯二氮卓类和十二烷基硫酸钠的浓度，可分散和不可分散团聚体的浓度均增加。解聚速率相对较快，半衰期约为15 min。C（0a）和K（a）的估计参数可为优化水溶性差的微粉化药物制剂的设计以最大限度地提高其分散性提供有用的信息。
The objective of this research was to model benzodiazepine deagglomeration profiles of percent agglomerated versus time when interactive mixtures containing micronized benzodiazepines were added to water. Micronized diazepam, nitrazepam, oxazepam, and, for ternary mixtures, micronized sodium lauryl sulfate were mixed with lactose-povidone granules (250-355 microm). After rapid dissolution of the lactose granules, bimodal particle size distributions of benzodiazepines, determined by laser diffraction particle sizing, represented dispersed and agglomerated distributions. The concentrations of agglomerated particle decreased with time and approached constant values. Deagglomeration profiles were determined and best modeled by a three-parameter single-exponential decay equation. A nonlinear least-squares approach was used to estimate the concentration of dispersible (C(0)) and nondispersible agglomerates (C(0a)) and the deagglomeration rate constant (K(a)). Increasing benzodiazepine and sodium lauryl sulphate concentrations in the lactose-povidone mixtures increased both dispersible and nondispersible agglomerate concentrations. Deagglomeration rate was relatively fast with half-lives around 15 min. The estimated parameters of C(0a) and K(a) may provide useful information in optimizing the design of formulations of poorly water soluble, micronized drugs to maximize their dispersion.