Laboratory of Pharmaceutical Science and Technology; Hoshi University; 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-0063, Japan, Email:
Hoshi University; Department of Pharmacy.
Pharmazie. 2023 Jul 1;78(6):93-99. doi: 10.1691/ph.2023.3544.
In powder formulations, it is a problem that the required therapeutic dose is not obtained because of loss of the active pharmaceutical ingredient (API). In this study, we investigated three types of lactose diluents, which are widely used as pharmaceutical excipients, for dispensing prednisolone powder. Extra-fine crystalline lactose, commonly used as a diluent in compounding powder formulations, was used as a comparison. The effect of lactose on the API loss rate was examined by analyzing the amount of prednisolone in the powder formulation taken out of a single-dose package after dispensing. The results showed that Dilactose-F had the lowest API loss rate (22%), followed by powder lactose (37.8%), extra-fine crystalline lactose (45.9%), and crystal form lactose (48.6%), indicating that the use of Dilactose-F as a diluent significantly improved API loss when compounding the powder formulation. Because each mixture of commercial prednisolone powder and lactose was within acceptable uniformity and loss rate before packaging, we considered that API loss occurred when the powder was taken out of the single-dose package before patients ingested them. Then, the physical properties of these lactose types affecting the API loss rate were examined. Strong correlation was not found between flowability and the API loss rate, but particle size distribution and bulk density were strongly correlated with the API loss rate. Furthermore, Dilactose-F, which showed the lowest API loss rate, did not show an exothermic peak due to epimerization to anhydrous β -lactose in differential scanning calorimetry and showed a peak specific to β -lactose in powder X-ray diffractometer. These results suggested that in powder compounding where the API content is low, the physical properties of lactose, such as particle size distribution, bulk density, and crystalline form, are intricately related to API loss.
在粉末制剂中，由于活性药物成分（API）的损失，无法获得所需的治疗剂量是一个问题。在这项研究中，我们研究了三种乳糖稀释剂，它们作为药用辅料广泛用于配制泼尼松龙粉末。将常用作赋形剂的超细结晶乳糖作为比较。通过分析从单剂量包装中取出的粉末制剂中泼尼松龙的量，考察了乳糖对 API 损失率的影响。结果表明，Dilactose-F 的 API 损失率最低（22%），其次是粉末乳糖（37.8%）、超细结晶乳糖（45.9%）和晶型乳糖（48.6%），表明在配制粉末制剂时，使用 Dilactose-F 作为稀释剂可显著降低 API 损失。由于在包装前，每种商业泼尼松龙粉末与乳糖的混合物均在可接受的均匀性和损失率范围内，我们认为在患者服用之前，从单剂量包装中取出粉末时会发生 API 损失。然后，考察了这些影响 API 损失率的乳糖类型的物理性质。发现流动性与 API 损失率之间没有很强的相关性，但粒度分布和堆密度与 API 损失率有很强的相关性。此外，显示 API 损失率最低的 Dilactose-F 在差示扫描量热法中没有因差向异构化为无水β-乳糖而出现放热峰，并且在粉末 X 射线衍射仪中显示出β-乳糖的特征峰。这些结果表明，在 API 含量低的粉末混合中，乳糖的物理性质，如粒度分布、堆密度和晶型，与 API 损失密切相关。
