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To explore the quality consistency evaluation method for multi-component traditional Chinese medicine and establish a dissolution evaluation method suitable for the characteristics of multi-component Chinese patent medicine, this study discussed the characteristics and advantages of the flow-through cell method in the dissolution evaluation of Chinese patent medicine by comparing the impact of the small cup method and the flow-through cell method on the dissolution behavior of water-soluble and lipid-soluble major active components of Danshen Tablets. Dissolution tests were performed using the small cup method as described in the 2020 edition of the Chinese Pharmacopoeia and the newly introduced flow-through cell method(closed-loop method) with water solution containing 0.5% SDS as dissolution medium. Cumulative dissolution curves of the water-soluble component salvianolic acid B and the lipid-soluble component tanshinone Ⅱ_A in Danshen Tablets were plotted, and fitting and similarity analysis of the dissolution models was conducted to identify the characteristics and advantages of the flow-through cell method. For the small cup method, 150 mL of water containing 0.5% SDS was used as the dissolution medium, with a rotation speed of 75 r·min~(-1) and a temperature of(37±0.5) ℃, and 3 mL of samples were taken at 15, 30 min, 1, 2, and 4 h, with fresh dissolution medium added at the same temperature and volume. For the flow-through cell method, a closed-loop system was used. Danshen Tablets were placed in the flow-through cell with approximately 6.7 g of glass beads, and 150 mL of water containing 0.5% SDS was used as the dissolution medium. The flow rate was set at 20 mL·min~(-1), and the temperature and sampling were the same as the small cup method. The results showed that compared with the small cup method, the flow-through cell method had stronger discriminative power and higher sensitivity in distinguishing the dissolution behavior of the two components, and could better reflect the differences in formulation quality, especially for water-insoluble lipid-soluble components. Given that there were no essential differences in the in vitro release kinetics between the two methods, the flow-through cell method could not only replace the traditional small cup method but also better guide the formulation development and identify quality issues of formulations.
Subject(s)
Salvia miltiorrhiza , Medicine, Chinese Traditional , Tablets , Water , Lipids , SolubilityABSTRACT
Objective: This study was proposed to evaluate and compare the in vitro dissolution profiles of six Metformin Hydrochloride (MH) market products. Methods: Different dissolution apparatuses (USP apparatus II, IV and beaker method) were used to evaluate the dissolution profiles (in phosphate buffer, pH 6.8) of two immediate release (IR) generic products of Metformin Hydrochloride (MH): Cidophage® 1000 mg (G1, Egyptian market) and Metformin arrow® 1000 mg (G2, French market) with respect to the reference products named Glucophage® 850 mg (R1, Egyptian market and R2, French market). In addition to a generic controlled-release (CR) product; Cidophage Retard® 850 mg (G3) versus the reference product; Glucophage XR® 1000 mg (R3) (both from Egyptian market). Dissolution efficiency (D. E.) and the similarity factor (f2) were calculated. Weight uniformity, hardness, tablet dimensions and MH content were measured. Results: Results of the three apparatuses showed that MH IR products studied (reference and generics) did not meet the 75% USP 30 specifications for MH dissolved at 30 min. For MH CR products, Glucophage XR® did not fulfill the USP release criteria, while Cidophage Retard® did. USP apparatus IV revealed the highest sensitivity and discriminative capability. Conclusion: Generally, MH IR generics (G1 and G2) might be interchangeable with the innovator product (Glucophage®). However, Cidophage Retard® might not be interchangeable with Glucophage XR®.
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A new method of dissolution test was established to better simulate the in vivo dissolution behavior of drugs from preparations and to distinguish the quality difference between drug preparations. With flow-through cell being chosen to be the dissolution apparatus and nimodipine tablet to be the model drugs,this study developed,on the basis of IVIVC theory,a new dissolution method which was subsequently used to evaluate the dissolution con-sistency of domestically produced nimodipine tablet as test preparation and its reference preparation. Meanwhile, conventional four-dissolution-curves method based on paddle apparatus was selected for comparison to evaluate the efficiency of the new dissolution method. The results indicated that the new dissolution method not only had a good correlation with the in vivo process of drugs,but also could reveal the internal quality differences between pharmaceutical preparations effectively. This research will provide further theoretical support for the application of flow-through cell apparatus in IVIVC study.
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This study explored the effect of nano-crystalline cellulose (NCC) on Meloxicam (MX) solid dispersion (SD) prepared by co-grinding technique compared to micro-crystalline cellulose (MCC) in presence of lactose. MX-tablets were prepared by direct compression of different co-ground SDs or physical mixtures. The solubility, dissolution, SEM and DSC of different preparations were studied. Flow-through cell apparatus (FTC) was used to study the dissolution of MX from tablets at pH 7.4. Generally, the results revealed that increasing NCC loadings showed a direct increase in both the solubility and dissolution of MX. MCC did not improve either the solubility or the dissolution of MX in the physical mixture, while, co-grinding dramatically decreased the dissolution rate of MX. It was interesting to find that grinding of MX-powder alone or in a mixture with lactose highly increased MX solubility and dissolution. SEM as well as DSC were found to be very good tools, without a single exception, to describe the observed solubility and dissolution of MX in these proposed preparations. SEM-images showed the particle size reduction upon grinding or co-grinding techniques. While DSC-data proved that the crystalline structure of MX has been changed to an amorphous state.
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OBJECTIVE: To indroduce the research progress and application of an innovative dissolution test method-flow-through cell method (FTC).
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OBJECTIVE: To develop a unified and discriminative method for the characterization of different diclofenac sodium extended release tablets. METHODS The flow-through cell method was employed to investigate the dissolution characteristics of all the samples at different flow rates and in different dissolution media. The dissolution data under the finally selected dissolution condition was also used to analyze the similarity of dissolution curves and statistical significance of Weibull parameters. RESULTS: The dissolution behaviors of the samples were not significantly influenced by flow rates in the selected range. The dissolution at a flow rate of 4 mL · min-1 and in hydrochloric acid (0.1 mol · L-1) for one hour followed by water for another seven hours was satisfactory to discriminate the samples, which was demonstrated by f2 and Weibull parameters analysis. CONCLUSION: This method can be used for dissolution tests of diclofenac sodium extended release tablet samples from the manufacturers in this study with meanings in guiding both comprehensive investigation on the dissolution of diclofenac sodium extended release tablets and quality improvement of generic drugs.