Research Of Factors Associating With The Uniformities Of Compound Sulfamethoxazole Tablets

This paper establishes a method to analyze the main factors associating with the uniformities within one batch, between batches and between manufacturers of compound sulfamethoxazole tablets by Fourier transform near infrared spectroscopy (FT-NIRS) and chemometrics. The sulfamethoxazole (SMZ) and trimethoprim (TMP) contents, tablet weight (TW) and tablet radial tensile strength (TRTS) for 258 samples of compound sulfamethoxazole tablets were determined by high performance liquid chromatograph, analytical balance, tablet hardness tester and caliper, respectively. Then the variance values for four factors associating of within one batch, between batches and between manufacturers were calculated, separately. And then the main factors associating with the uniformities within one batch, between batches and between manufacturers of compound sulfamethoxazole tablets were analyzed. This method could offer reference for the uniformities manufacturing process quality control of compound sulfamethoxazole tablets and other tablets.OBJECTIVE:To analyze the main factors associating with the uniformities within one batch, between batches and between manufacturers of compound sulfamethoxazole tablets for the manufacturing process quality control.METHODS:1. Determination the values of factors associating of compound sulfamethoxazole tablets(1) The SMZ content and TMP content for 258 samples of compound sulfamethoxazole tablets were simultaneously were determined by high performance liquid chromatograph, respectively. And external standard method calculated the values.(2) The TW values for 258 samples of compound sulfamethoxazole tablets were respectively measured by one over ten-thousand analytical balance.(3) The values of TRTS by formula (1) after the diameter (D), thickness (T) and force (F) for radial crushing for 258 samples of compound sulfamethoxazole tablets were respectively measured by caliper and tablet hardness tester.2. Establishment the analytical method for factors associating with the uniformities of compound sulfamethoxazole tablets(1) The main factors associating with the uniformities of within one batch were analyzed by the VA and generalized variance results of within one batch of FT-NIRS.(2) The main factors associating with the uniformities of between batches were analyzed by the VA and generalized variance results of between batches of FT-NIRS.(3) The main factors associating with the uniformities of between manufacturers were analyzed by the VA and variance results of between batches.RESULTS:.1. Determination the values of factors associating of compound sulfamethoxazole tablets(1) The values ranges of factors associating of SMZ content and TMP content for 258 samples of compound sulfamethoxazole tablets were 0.6402-0.8059 g·g-1 and 0.1301-0.1658 g·g-1, respectively.(2) The values range of factors associating of TW for 258 samples of compound sulfamethoxazole tablets was 0.4999-0.5897 g.(3) The values range of factors associating of TRTS for 258 samples of compound sulfamethoxazole tablets was 0.4069-2.1960 MPa.2. The main factors associating with the uniformities of compound sulfamethoxazole tablets(1) The main factors associating with the uniformities within one batch of compound sulfamethoxazole tablets changed from manufacturer to manufacturer, TW (variation 0.772×10-5-3.22×10-5 g2) 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 6.48×10-5-24.3×10-5 g2) for the manufacturer C.(2) The main factor associating with the uniformities between batches of compound sulfamethoxazole tablets was TW (variation 0.121×10-5 10.3×10-5g2).(3) The main factors associating with the uniformities between manufacturers of compound sulfamethoxazole tablets were TW (variation 13.9×10-5 g2) and SMZ content (variation 13.2×10-5 (g·g-1)2).CONCLUSION:This study demonstrated that all of SMZ content, TMP content, TW and TRTS were the factors associating with the uniformities of compound sulfamethoxazole tablets. The below factors 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 study also proved the reference for uniformities research and control for other pharmaceutical tablets.