复方磺胺甲(口恶)唑片均匀性的相关因素分析

目的:分析复方磺胺甲(口恶)唑片批内、批间及厂间均匀性的主要相关因素,为该片均匀性生产过程控制方案的制订提供依据。方法:采用高效液相色谱仪、分析天平、片剂硬度仪和游标卡尺分别测定复方磺胺甲(口恶)唑片4个厂家13批共258片样品的磺胺甲(口恶)唑(SMZ)含量、甲氧苄啶(TMP)含量、片重(TW)和片抗张强度(TRTS),结合近红外光谱、采用方差分析法分析以上相关因素对复方磺胺甲(口恶)唑片批内、批间及厂间均匀性的影响。结果:复方磺胺甲(口恶)唑片批内均匀性的主要相关因素各厂不同,厂A为TW(变异为0.772×10^-5~3.22×10^-5 g²),厂B为SMZ含量[变异为19.3×10^-5~34.4×10^-5(g·g^-1)²]及TMP含量[变异为0.623×10^-5~1.27×10^-5(g·g^-1)²],厂C为TW(变异为6.48×10^-5~24.3×10^-5 g²);批间均匀性的主要相关因素为TW(变异为0.121×10^-5~10.3×10^-5 g²);厂间均匀性的主要相关因素为TW(变异为13.9×10^-5 g²)及SMZ含量[变异为13.2×10^-5(g·g^-1)²]。结论:本研究证明SMZ含量、TMP含量、TW和TRTS均是复方磺胺甲(口恶)唑片均匀性的相关因素。在制订该片均匀性生产过程控制方案时,应控制各厂的主要相关因素以提高批内均匀性:主要控制TW变异以提高批间均匀性,控制TW及SMZ含量的变异以提高厂间均匀性。本研究也为其他片剂的均匀性研究与控制提供了参考。

Objective: To analyze the main factors associating with the uniformities within one batch, between batches and between manufacturers of compound sulfamethoxazole tablets, so as to provide reference for quality control of the manufacturing process.Methods: Sulfamethoxazole(SMZ), trimethoprim(TMP), tablet weights(TW)and tablet radial tensile strengths(TRTS)of 258 samples of compound sulfamethoxazole tablets in 13 batches from 4 manufacturers were determined by high performance liquid chromatograph, analytical balance, tablet hardness tester and caliper, respectively.The effects of above factors on the uniformities within one batch, between batches and between manufacturers of compound sulfamethoxazole tablets were analyzed using variance analysis and near infrared spectra.Results:The main factors associating with the uniformities within one batch differed between each manufacturer as follows: TW(variation 0.772×10^-5-3.22×10^-5 g²)was main factor for the manufacturer A, SMZ content [variation 19.3×10^-5-34.4×10^-5 (g·g^-1)²] and TMP content [variation 0.623×10^-5-1.27×10^-5(g·g^-1)²] for the manufacturer B, and TW(variation 6.48×10^-5 - 24.3×10^-5g²)for the manufacturer C.Main factors for uniformities between batches were TW(variation 0.121×10^-5 - 10.3×10^-5 g²);and factors between manufacturers were TW(variation 13.9×10^-5 g²)and SMZ content [variation 13.2×10^-5 (g·g^-1)²].Conclusion: SMZ content, TMP content, TW and TRTS were all the factors associating with the uniformities of compound sulfamethoxazole tablets.The factors below should be controlled in the manufacturing process:various factors for different manufacturers for the uniformities within one batch, TW for the uniformities between batches, and both of TW and SMZ content for the uniformity between manufacturers.This paper also provided reference for uniformity control of other tablets.