By Jiangsu Lefan Capsule Co., Ltd.
Abstract: Objective: To study the influence of Levecaps’ capsules on in vitro dissolution of Ranitidine Hydrochloride Capsules preparation.
Method: In this experiment, the reference Ranitidine Hydrochloride Capsules powder is filled in Levecaps’ vacant capsules, and the rotating basket method is used, to study the dissolution situation of Levecaps’ samples and reference capsules in different media.
Conclusion: Levecaps’ samples have dissolution curves basically same with those of reference capsules in 4 dissolution media: water, pH1.2 hydrochloric acid solution, pH4.5 phosphate buffer, and pH6.0 phosphate buffer, and Levecaps’ samples have better intra-batch homogeneity in water medium.
Keywords: Ranitidine Hydrochloride Capsules; dissolution curve; homogeneity
The evaluation of the in vitro dissolution similarities between generic preparations and reference capsules is of great significance to guaranteeing the in vivo bioequivalence of pharmaceutical preparations. Lefan, from the perspective of capsule manufacturer, examined the dissolution process of Levecaps’ samples and reference capsule preparation in different dissolution media, conducted analysis through f2 factor method, and also examined the intra-batch homogeneity of Levecaps’ samples and reference capsule preparation.
1. Instrument and Reagent
ZRS-8GD Intelligent Dissolution Tester, Tianjin Tianda Tianfa Technology Co., Ltd.; HPLC, U.S. Waters 2695, Waters 2487 UV/Visible Detector; chromatographic column, U.S. Agilent ZORBAX SB-C18, 4.6×150mm, 5μm; KH-500DV Ultrasonic Cleaner, Kunshan Hechuang Ultrasonic Instruments Co., Ltd.;
Reference capsules (150mg): Ranitidine Hydrochloride Capsules purchased from Sanofi (Hangzhou) Pharmaceuticals Co., Ltd., batch No.: 6HG0249; Levecaps’ samples (150mg): vacant gelatin capsules from Jiangsu Lefan Capsule Co., Ltd. (DMF filing No.: 030301), batch No.: G117032N100, with drug powder from the Ranitidine Hydrochloride Capsules of Sanofi (Hangzhou) Pharmaceuticals Co., Ltd., batch No.: 6HG0249; the ranitidine hydrochloride reference listed product purchased from the National Institute for the Control of Pharmaceutical and Biological Products of China, batch No.: 100163-201607;
2. Method and Results
2.1. Dissolution curve measurement
The rotating basket method is used: separately take 6 reference capsules and Levecaps’ samples, use 900ml water, pH1.2 hydrochloric acid solution, pH4.5 phosphate buffer, and pH6.0 phosphate buffer as the dissolution media (not added with surfactant), and separately absorb 2ml solution at 5min, 10min, 15min, 20min, and 30min when the speed is 100r/min; filter them through 0.45um microporous membrane, and take the filtrate and measure the accumulative dissolution quantity in each time point at 230nm wavelength. See Fig. 1, Fig. 2, Fig. 3, and Fig. 4 for the results.
Fig. 1 pH1.2 medium dissolution curve / Fig. 2 pH4.5 medium dissolution curve
Fig. 3 pH6.0 medium dissolution curve / Fig. 4 Water medium dissolution curve
Analyzed from Fig. 1, Fig. 2, Fig. 3, and Fig. 4, and calculated the similarity factor, both the f2 factor of dissolution curves of Levecaps’ samples and reference capsules is larger than 50, and both the dissolution quantity of the them reaches above 85% within 15min, showing that the dissolution curves of both are basically consistent.
2.2. Examination of dissolution homogeneity
The rotating basket method is used: separately take 6 reference capsules and Levecaps’ samples, use 900ml water as the dissolution media, and test when the speed is 100r/min; calculate the intra-batch homogeneity by separately taking the precision of dissolution quantity of samples at 5min, 10min, 15min, 20min, and 30min as the indicator. The RSD of dissolution quantity in time point 1 is required to be less than 20%, and RSD of dissolution quantity of other sampling points is required to be less than 10%. See the following Table 1 and Table 2 for the results.
Table 1 Results of Dissolution Homogeneity of Reference Capsules (%, n=6, batch No.: 6HG0249)
Time/min | 1 | 2 | 3 | 4 | 5 | 6 | Mean | RSD |
5 | 36.49 | 75.31 | 65.16 | 64.77 | 81.96 | 42.01 | 60.95 | 29.69 |
10 | 99.96 | 100.83 | 97.39 | 101.27 | 99.74 | 98.87 | 99.68 | 1.41 |
15 | 103.32 | 100.14 | 101.42 | 104.91 | 106.66 | 102.08 | 103.09 | 2.32 |
20 | 104.04 | 105.93 | 103.05 | 105.51 | 104.51 | 101.68 | 104.12 | 1.52 |
30 | 104.78 | 106.69 | 103.67 | 105.91 | 105.60 | 103.91 | 105.10 | 1.1 |
Table 2 Results of Dissolution Homogeneity of Levecaps’ Capsules (%, n=6, batch No.: G117032N100)
Time/min | 1 | 2 | 3 | 4 | 5 | 6 | Mean | RSD |
5 | 52.61 | 50.44 | 48.82 | 53.27 | 53.90 | 56.61 | 52.61 | 5.18 |
10 | 103.83 | 95.25 | 98.50 | 98.39 | 99.58 | 106.95 | 100.42 | 4.21 |
15 | 106.18 | 99.54 | 99.55 | 101.07 | 100.04 | 104.91 | 101.88 | 2.87 |
20 | 104.25 | 98.90 | 99.75 | 103.33 | 102.38 | 106.35 | 102.49 | 2.73 |
30 | 106.29 | 101.08 | 100.88 | 100.93 | 101.04 | 108.65 | 103.15 | 3.33 |
From Table 1 and Table 2, Levecaps’ samples have good homogeneity in water medium. The RSD of dissolution quantity of Levecaps’ samples in the 1st time point: 5min is within 20%, while that of the reference capsules exceeds 20%, and the RSD of dissolution quantity of both in other sampling times is within 10%.
3. Conclusion
The above research shows that Levecaps’ samples have dissolution curves basically same with those of reference capsules in 4 dissolution media: water, pH1.2 hydrochloric acid solution, pH4.5 phosphate buffer, and pH6.0 phosphate buffer, and Levecaps’ samples have better intra-batch homogeneity in water medium, not affecting the dissolution.
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