目的: 建立具有区分力的红霉素原料药的固有溶出速率测定方法。方法: 取4批不同工艺的红霉素原料药,每批3份,每份500 mg,15 MPa压片5 min,转速50 r · min-1,分别在500 mL的pH 6.8与6.0磷酸盐缓冲液中于5、10、15、20、30、45、60 min时测定累积溶出量,选取初始线性部分计算固有溶出速率,通过单因素ANOVA分析评估其差异程度,确立具有区分力的红霉素固有溶出速率测定方法。结果: 在pH 6.8磷酸盐缓冲液中,固有溶出速率测定结果的RSD均<10%,显著性P=0.460,单因素ANOVA分析显示组间显著性P=0.634,4批红霉素原料药固有溶出速率无显著性差异。在pH 6.0磷酸盐缓冲液中,除1批原料药外固有溶出速率测定结果RSD均<10%,考虑为稳定性对测定结果的影响所致,显著性P=0.212,组间显著性P=0.002,存在显著性差异,4批红霉素原料药的固有溶出速率可分为2组,分组结果与工艺分组结果一致。结论: 该方法可较好地测定红霉素固有溶出速率,并具有一定区分力。
Objective: To establish a method for determining the intrinsic dissolution rate of erythromycin API with discriminatory power. Methods: Four batches of erythromycin active pharmaceutical ingredient (API) produced by different manufacturing processes were selected for analysis. For each batch, three samples (500 mg each) were compressed into compacts at 15 MPa for 5 min. The intrinsic dissolution rate (IDR) was determined using a rotating disk apparatus at a rotation speed of 50 r · min-1. Cumulative dissolution amounts were measured at 5, 10, 15, 20, 30, 45, and 60 min in 500 mL of phosphate buffer solutions at pH 6.8 and pH 6.0, respectively. The linear portion of the initial dissolution curve was used to calculate the IDR. One-way analysis of variance (ANOVA) was performed to assess the differences among batches. This study aimed to establish a discriminatory IDR testing method for erythromycin API. Results: In pH 6.8 phosphate buffer, the RSDs of the intrinsic dissolution rate measurements were all below 10%, with a P-value of 0.460. One-way ANOVA showed an inter-group P-value of 0.634, indicating no significant difference in intrinsic dissolution rates among the four batches of erythromycin API. In pH 6.0 phosphate buffer, the RSDs were below 10% for all batches except one, which was considered to be affected by stability issues. The P-value was 0.212, and the inter-group P-value was 0.002, indicating a significant difference. The four batches of erythromycin API could be divided into two groups based on their intrinsic dissolution rates, consistant with the grouping based on manufacturing process. Conclusion: The method enables reliable determination of the intrinsic dissolution rate of erythromycin and possesses discriminatory capability.
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