Ozaki Masakazu, Kobayashi Toshihiko, Fujinaga Aki, Nishioka Mitsuaki, Shikichi Kyoko, Okano Satoshi, Sakai Yasuhito, Fujii Sayumi, Matsui Nobuaki, Takasago Miwako, Okada Naoto, Yamasaki Takahiro, Kitahara Takashi
Pharmacy Department , Yamaguchi University Hospital, 1-1-1, Minami-kogushi, 755-8505, Ube, Yamaguchi, Japan.
Division of Laboratory, Yamaguchi University Hospital, 1-1-1, Minami-kogushi, 755-8505, Ube, Yamaguchi, Japan.
J Pharm Health Care Sci. 2023 Dec 27;9(1):50. doi: 10.1186/s40780-023-00323-9.
Pharmaceutical companies do not sell formulations for all diseases; thus, healthcare workers have to treat some diseases by concocting in-hospital preparations. An example is the high-concentration 2% cyclosporine A (CyA) ophthalmic solution. Utilizing a filter in sterility operations is a general practice for concocting in-hospital preparations, as is the case for preparing a 2% CyA ophthalmic solution. However, whether filtering is appropriate concerning the active ingredient content and bacterial contamination according to the post-preparing quality control of a 2% CyA ophthalmic solution is yet to be verified.
We conducted particle size, preparation concentration, and bacterial contamination studies to clarify aforementioned questions. First, we measured the particle size of CyA through a laser diffraction particle size distribution. Next, we measured the concentration after preparation with or without a 0.45-µm filter operation using an electrochemiluminescence immunoassay. Finally, bacterial contamination tests were conducted using an automated blood culture system to prepare a 2% CyA ophthalmic solution without a 0.45 μm filtering. Regarding the pore size of the filter in this study, it was set to 0.45 μm with reference to the book (the 6th edition) with recipes for the preparation of in-hospital preparations edited by the Japanese Society of Hospital Pharmacists.
CyA had various particle sizes; approximately 30% of the total particles exceeded 0.45 μm. The mean ± standard deviation of filtered and non-filtered CyA concentrations in ophthalmic solutions were 346.51 ± 170.76 and 499.74 ± 76.95ng/mL, respectively (p = 0.011). Regarding bacterial contamination tests, aerobes and anaerobes microorganisms were not detected in 14 days of culture.
Due to the results of this study, the concentration of CyA may be reduced by using a 0.45-µm filter during the preparation of CyA ophthalmic solutions, and furthermore that the use of a 0.45-µm filter may not contribute to sterility when preparing CyA ophthalmic solutions.
制药公司并非销售针对所有疾病的制剂；因此，医护人员不得不通过配制院内制剂来治疗某些疾病。高浓度2%环孢素A（CyA）眼药水就是一个例子。在无菌操作中使用过滤器是配制院内制剂的常规做法，制备2% CyA眼药水时也是如此。然而，根据2% CyA眼药水制备后的质量控制，过滤对于活性成分含量和细菌污染是否合适，仍有待验证。
我们进行了粒度、制剂浓度和细菌污染研究，以阐明上述问题。首先，我们通过激光衍射粒度分布测量CyA的粒度。接下来，我们使用电化学发光免疫分析法测量在有或没有0.45 µm过滤器操作的情况下制备后的浓度。最后，使用自动血培养系统进行细菌污染测试，以制备未经过0.45 µm过滤的2% CyA眼药水。关于本研究中过滤器的孔径，参考日本医院药剂师协会编辑的《院内制剂制备配方》（第6版）设定为0.45 µm。
CyA有各种粒度；总颗粒中约30%超过0.45 µm。眼药水中过滤和未过滤的CyA浓度的平均值±标准差分别为346.51±170.76和499.74±76.95 ng/mL（p = 0.011）。关于细菌污染测试，在14天的培养中未检测到需氧菌和厌氧菌。
根据本研究结果，在制备CyA眼药水时使用0.45 µm过滤器可能会降低CyA的浓度，此外，在制备CyA眼药水时使用0.45 µm过滤器可能无助于无菌操作。
