Miyazaki Yasunori, Takayama Kozo, Uchino Tomonobu, Kagawa Yoshiyuki
Department of Clinical Pharmaceutics, School of Pharmaceutical Sciences, University of Shizuoka.
Chem Pharm Bull (Tokyo). 2016;64(12):1698-1706. doi: 10.1248/cpb.c16-00546.
Scientific approaches for dispensation are important for the quality and efficacy of drug treatments. Therefore, for the dispensation of powdered medicines, we have developed a powder blending method using a planetary centrifugal mixer (PCM) to replace the empirical manual method involving a mortar and pestle. The aim of this study was to optimize the formulation of pharmaceutical diluents for dispensing powdered medicines, using PCM. The diluents, composed of powdered lactose, crystalline lactose, and corn starch were assigned to a {3,2}-Simplex Lattice design. Then, the designed diluents were blended with model powders, such as carbazochrome sodium sulfonate powder, rifampicin capsule contents, and crushed sulfasarazine tablets, at ratios of 1 : 4, 1 : 1, and 4 : 1 using PCM at 800 rpm for 60 s at a 20% filling rate. The mixtures were examined for content uniformity relative standard deviation (RSD) and flowability angle of repose (AOR). Response surface methodology was applied to optimize the formulation with the smallest RSD and AOR, and then the design space of desired diluents was estimated. On the basis of the design space, crystalline lactose, the mixture of lactose powder and crystalline lactose at a ratio of 1 : 4, and the mixture of corn starch and crystalline lactose at a ratio of 1 : 4, were suitable diluents for the powdered formulation, the content of the capsules, and the crushed tablets, respectively. The selected diluents were successfully applied to other model medicines showing a sufficient RSD and AOR. This technique could contribute to the development of scientific approaches for dispensation.
配药的科学方法对于药物治疗的质量和疗效至关重要。因此，对于散剂配药，我们开发了一种使用行星式离心混合机（PCM）的粉末混合方法，以取代涉及研钵和杵的经验性手工方法。本研究的目的是使用PCM优化用于调配散剂的药物稀释剂配方。由乳糖粉、结晶乳糖和玉米淀粉组成的稀释剂被分配到一个{3,2}-单纯形格子设计中。然后，将设计好的稀释剂与模型粉末，如卡巴唑磺酸钠粉、利福平胶囊内容物和碾碎的柳氮磺吡啶片，以1:4、1:1和4:1的比例在800转/分钟的条件下使用PCM以20%的填充率混合60秒。对混合物进行含量均匀度相对标准偏差（RSD）和流动安息角（AOR）的检测。应用响应面方法优化具有最小RSD和AOR的配方，然后估计所需稀释剂的设计空间。基于该设计空间，结晶乳糖、乳糖粉与结晶乳糖比例为1:4的混合物以及玉米淀粉与结晶乳糖比例为1:4的混合物，分别是散剂配方、胶囊内容物和碾碎片剂的合适稀释剂。所选稀释剂已成功应用于其他模型药物，显示出足够的RSD和AOR。该技术有助于配药科学方法的发展。
