粉末稀釋劑的選擇與磨粉分包藥品的品質

Selection of Powder Diluents and the Quality of Powder Packets

現今仍有兒童臨床需求沒有市售品，必須進行磨粉分包以得適用劑量，文獻建議添加適量稀釋劑。以增加粉末體積，減少分包劑量誤差。目前最常使用的粉末稀釋劑為乳糖，因製作方式不同，粉末流動性會有很大的差異。本研究之目的在探討以不同型態的乳糖做為稀釋劑，對磨粉分包藥品的影響，藉由模擬實際作業，將每錠含有warfarin sodium 5 mg的錠劑磨粉，分別與兩種乳糖混合後進行分包，量設定為每包總重200 mg，內含0.625 mg warfarin sodium。每組試驗進行三重複，每批次抽樣10包藥品測量粉末淨重及含量後，計算平均重量／含量、重量／含量相對標準差，做為觀察單位劑量均一度的指標，研究結果顯示，以研磨方式加工的乳糖做為稀釋劑時，平均重量分別為179.073±9.14 mg。I91.713±1096mg與201.30±15.42 mg，重量相對標準差為5.10%-5.72%與7.66%若以噴霧乾燥方式進行加工乳進行分包平均重量較接近目標重量（193.55±575 mg，194.13±2.68 mg與193.493±1.98 mg），且重量相對標準差較小（2.97%。1.38%與1.02%）。以Student's t test檢定比較兩組的重量相對標準差，顯示兩者有顯著差異（p＝0.0126）。以研磨方式加工的乳糖做為稀釋劑的分包藥品平均含量各批次間基較大，分別為標誌含量的73 42%、86.69%及90.24%；以噴霧乾燥方式進行加工的乳糖作為稀釋劑的分包藥品，三批次前平均含量則為標誌含量的70.68%、71.01%及71.51%。且含量相對標準差的結果與重量標準差的結果有相同的趨勢可互相呼應。本研究結果顯示，以噴霧乾燥方式製造、流動性佳的乳糖做為稀釋劑進行分包，可調製單位劑量較圴一的分包藥品、且可利用重量檢測，計算重量相對標準差的方法，作為簡易評估魔粉包藥品的品質指標。

Abstract: Nowadays commercial drug products still cannot fulfill all the clinical needs of children. Pharmacists may need to pulverize the tablets or open the capsules, and divided the powders to prepare the dosage forms with appropriate dose. Addition of powder diluent to expand the total volume to minimize dosage deviation is recommended by literatures. Lactose is the most frequently used diluent, and the flowability of lactose manufactured by different methods are different. The purpose of this study is to explore the influence of the different types of lactose on the quality of the powder packets. Warfarin 5 mg tablets were triturated and mixed with lactose according to clinical practice, and the target weight of each pack was 200 mg containing 0.625 mg warfarin sodium. Each test group had 3 repeats. Ten packs per batch were sampled. The net weight and content of active ingredient per pack were measured. Then the standard deviation (S.D.) and relative S.D.(R.S.D.) were calculated as the indicator of uniformity. The results showed that in the group with lactose manufactured by milling, the average weight of the 3 batches were 179.07 ± 9.14mg, 191.71 ± 10.96 mg and 201.30 ± 15.42 mg, and the R.S.D. were 5.10%, 5.72% and 7.66%ˤIn the group with lactose manufactured by spray-drying, the average weights were closer to the target weight (193.55 ± 5.75 mg, 194.13 ± 2.68 mg and 193.49 ± 1.98 mg), and the R.S.D. were smaller (2.97%, 1.38% and 1.02%). Student’s t test indicated that the weight deviation between the 2 groups were significantly different (p烌0.0126). In the group with lactose manufactured by milling, the average content of the 3 batches were 73.42%, 86.69% and 90.24%, and in the group with lactose manufactured by spray-drying, the average content were 70.68% , 71.01% and 71.51%. And the results of R.S.D of content were correlated to the results of R.S.D of weight. Accordingly, lactose manufactured by spray-drying has better flowability, and is recommended as the diluent for powder packets to ensure better uniformity. And the R.S.D. of weight could be an indicator for evaluating quality of powder packets.