Consistency Evaluation on the Dissolution Behavior and Related Indicators between Generic and Original Pre- parations of Oxcarbazepine Scored Tablets / 中国药房

OBJECTIVE：To evaluate the dissolution behavior consistency between the generic drugs and original drugs of Oxcarbazepine scored tablets ，and to compare the appearance ，the friability of the split portions ，loss of mass of the split portions as well as crystal form and morphology of raw material from different enterprises. METHODS ：HPLC method was adopted. The paddle method （rotation speed of 60 r/min，the temperature of 37.0℃）was adopted to determine accumulative dissolution rate of generic and original drugs in 4 mediums [ 0.6％ SDS hydrochloric acid solution （pH＝1.2），0.6％ SDS acetate buffer solution （pH＝4.5），0.6％ SDS phosphate buffer solution （pH＝6.8）and 0.6％ SDS water solution]. The similarity factor method was used to evaluate the similarity of dissolution curves as well as intra-batch uniformity of the split portions and whole tablets. The friability tester and electronic balance were used to determine the friability and the loss of mass of the split portions. X-ray diffractometer and scanning electron microscope were used to observe the crystal form and crystal morpho logy of the raw materials of different enterprises. RESULTS ：The linear range of oxcarbazepine was LOD was 0.04 μg/mL；RSDs of precision ，stability，reprodu- cibility and durability tests were lower than 2.0％；the reco- veries were 99.80％-101.63％（RSD＝0.37％-0.91％，n＝3）. The average cumulati ve dissolution rate of generic drug A ， generic drug B and original drug in 4 different dissolution media at 90 min were 92％，87％，90％ [0.6％ SDS hydrochloric acid solution（pH＝1.2）]；94％，94％，90％ [0.6％ SDS acetate buffer solution （pH＝4.5）]；95％，95％，91％ [0.6％ SDS phosphate buffer solution （pH 6.8）]；97％，98％，95％（0.6％ SDS water solution ）. The similarity factors of generic drug A ，generic drug B and original drug in 4 kinds of different dissolution media were 66 and 81，71 and 69，71 and 61，59 and 39. In the first 15 min，the difference of dissolution rate of split portions and whole tablets were －3％-13％，－2％-24％ and －3％-7％ for generic drug A ， generic drug B and original drug ，respectively. RSDs of accumulative dissolution rate of split portions and whole tablets were 6％-14％ and 2％-9％ for generic drug A （n＝12），4％-10％ and 1％-8％ for generic drug B （n＝12）and 2％-7％ and 2％-8％ for original drug. The appearance of the original drug was fusiform ，and the notch was deep ；the shape of the generic drug was different from each other ，and the notch of the generic drug was significantly shallower than that of original drug. The friability ， the loss of mass of the split portions for generic drug A and generic drug B ，original drug were 0.62％and 0.67％，0.12％ and 0.11％，0.08％ and 0.05％. The domestic raw materials possessed irregular lumps and debris ，while the raw materials produced by original drug enterprises possessed regular flat cuboids and regular strips with little debris ；but X-ray diffraction peaks of them were basically the same. CONCLUSIONS ：The dissolution behavior of generic drug A in 4 medium is consistent with that of the original drug；dissolution behavior of generic drug B in water containing 0.6％SDS is different from that of the original drug ；there is no significant change in the homogeneity of the original drug before and after splitting ，but the homogeneity of the generic drug A and B after splitting is lower than that of the whole tablet ；the fragility of generic drugs and loss of mass of split portions are higher than those of the original drugs ；two kinds of raw material have the same crystal form but different crystal morphology.

Evaluation of Dosage form Characteristics of Fuzi Lizhongwan Based on Dissolution Behavior / 中国实验方剂学杂志

Objective:Based on the previous studies, to investigate the dissolution behavior of Fuzi Lizhongwan by simultaneously determining the dissolution of benzoylmesaconine, benzoylaconine and benzoylhypaconine in Aconiti Lateralis Radix Praeparata. Method:The simultaneous determination of benzoylmesaconine, benzoylaconine and benzoylhypaconine in Fuzi Lizhongwan was established by HPLC-QQQ-MS. The dissolution amounts of three compositions in 15 batches of Fuzi Lizhongwan from 5 manufacturers at different time points, the cumulative dissolution was calculated and the dissolution curve was drawn. The f2 similarity factor method was adopted to evaluate similarity of dissolution curves of index components in different batches of samples from the same manufacturer, and to evaluate similarity of dissolution curves of samples from different manufacturers based on the same index component. The dissolution model of Fuzi Lizhongwan was concluded by fitting with the dissolution data. Result:When hydrochloric acid solution with pH of 1.2 was used as the dissolution medium, the three alkaloids had the best dissolution effect. The dissolution behavior of three monoester alkaloids in Fuzi Lizhongwan was basically synchronous and the dissolution lasted for 24 h. Three batches of samples from the same manufacturer (manufacturer 1, 3, 4 and 5) appeared to be similar on dissolution behavior, indicating that the dissolution behavior of the majority of samples from different manufacturers was similar. The dissolution behavior of batch 1 sample was different from batch 2 and 3 samples in manufacturer 2, suggesting that the quality of different batches of samples in manufacturer 2 might be different. The fitting results of dissolution data of index components in samples from different manufacturers were consistent, and the Weibull model was the best. Conclusion:Index components in fifteen batches of samples from 5 manufacturers are continuously dissolved within 24 h, indicating that the samples have the characteristics of slow dissolution. The dissolution curves of samples from the same manufacturer are similar to each other, indicating that the quality of different batches of products from most manufacturers is stable. The dissolution behavior of benzoylmesaconine, benzoylaconine and benzoylhypaconine in samples form different manufacturers has some differences, which may be caused by the source of medicinal materials and preparation technology parameters.

Dissolution behavior of Fuzi Lizhong pill based on simultaneous determination of two components in Glycyrrhizae Radix et Rhizoma / 中国中药杂志

To preliminarily investigate the dissolution behavior of Fuzi Lizhong pill, provide the basis for its quality control and lay foundation for dissolution behavior by determining the dissolution rate of liquiritin and glycyrrhizic acid. High-performance liquid chromatography (HPLC) method for simultaneous content determination of the two active ingredients of liquiritin and glycyrrhizic acid in Fuzi Lizhong pill was established; The dissolution amount of these two active ingredients in fifteen batches of Fuzi Lizhong pill from five manufacturers was obtained at different time points, and then the cumulative dissolution rate was calculated and cumulative dissolution curve was drawn. The similarity of cumulative dissolution curve of different batches was evaluated based on the same factory, and the similarity of cumulative dissolution curve of different factories was evaluated based on the same active ingredients. The dissolution model of Fuzi Lizhong pill based on two kinds of active ingredients was established by fitting with the dissolution data. The best dissolution medium was 0.25% sodium lauryl sulfate. The dissolution behavior of liquiritin and glycyrrhizic acid in Fuzi Lizhong pill was basically the same and sustained release in 48 h. Three batches of the factories (factory 2, factory 3, factory 4 and factory 5) appeared to be similar in dissolution behavior, indicating similarity in dissolution behavior in most factories. Two of the three batches from factory 1 appeared to be not similar in dissolution behavior of liquiritin and glycyrrhizic acid. The dissolution data of the effective ingredients from different factories were same in fitting, and Weibull model was the best model in these batches. Fuzi Lizhong pill in 15 batches from 5 factories showed sustained release in 48 h, proving obviously slow releasing characteristics "pill is lenitive and keeps a long-time efficacy". The generally good dissolution behavior also suggested that quality of different batches from most factories was stable. The dissolution behavior of liquiritin and glycyrrhizic acid in different factories was different, suggesting that the source of medicinal materials and preparation technology parameters in five factories were different.

Preparation and in vitro Dissolution Behavior Investigation of Frovatriptan Succinate Film-coated Tablet / 中国药房

OBJECTIVE:To prepare Frovatriptan succinate film-coated tablet,and investigate its in vitro dissolution behavior. METHODS:Using lactose monohydrate,microcrystalline cellulose,dioxide,silica,sodium carboxymethyl starch and magnesium stearate as accessories,Frovatriptan succinate tablet was prepared. Using opadry premix spray-coating liquid,Frovatriptan succinate film-coated tablet was prepared. Single factor test was used,using moisture,angle of repose,rigidity,friability,disintegration time and dissolution rate as indexes,to screen the formulation;using dissolution degree as index,coating material dosage was screened. The dissolution curves in vitro of self-made tablets and imported tablets in water,0.1 mol/L HCL,pH of 5.5,6.8 phos-phate buffer solutions were compared. RESULTS:The optimal formulation of Frovatriptan succinate uncoated tablet was as follow as frovatriptan succinate 3.91 mg,lactose monohydrate 99.18 mg,microcrystalline cellulose 33.06 mg,magnesium stearate 1.40 mg,sodium carboxymethyl starch 1.05 mg,silica 1.40 mg;optimal coating weighed quality was 2.0%-4.0%. In the 4 mediums, the dissolution behavior of self-made tablets and imported tablets were similar. CONCLUSIONS:Frovatriptan succinate film-coated tablet is prepared successfully,and its in vitro dissolution behavior is similar to the imported preparations.

Absorption Study of Genistein Using Solid Lipid Microparticles and Nanoparticles: Control of Oral Bioavailability by Particle Sizes

In this study, the effect of particle size of genistein-loaded solid lipid particulate systems on drug dissolution behavior and oral bioavailability was investigated. Genistein-loaded solid lipid microparticles and nanoparticles were prepared with glyceryl palmitostearate. Except for the particle size, other properties of genistein-loaded solid lipid microparticles and nanoparticles such as particle composition and drug loading efficiency and amount were similarly controlled to mainly evaluate the effect of different particle sizes of the solid lipid particulate systems on drug dissolution behavior and oral bioavailability. The results showed that genistein-loaded solid lipid microparticles and nanoparticles exhibited a considerably increased drug dissolution rate compared to that of genistein bulk powder and suspension. The microparticles gradually released genistein as a function of time while the nanoparticles exhibited a biphasic drug release pattern, showing an initial burst drug release, followed by a sustained release. The oral bioavailability of genistein loaded in solid lipid microparticles and nanoparticles in rats was also significantly enhanced compared to that in bulk powders and the suspension. However, the bioavailability from the microparticles increased more than that from the nanoparticles mainly because the rapid drug dissolution rate and rapid absorption of genistein because of the large surface area of the genistein-solid lipid nanoparticles cleared the drug to a greater extent than the genistein-solid lipid microparticles did. Therefore, the findings of this study suggest that controlling the particle size of solid-lipid particulate systems at a micro-scale would be a promising strategy to increase the oral bioavailability of genistein.

Influência do processo de secagem e condição de armazenamento de extratos secos de Bauhinia forficata e Passiflora alata sobre seu perfil de dissolução / Influence of the drying process and storage condition on the dissolution behavior of dried extracts of Bauhinia forficata and Passiflora alata

No Brasil, os produtos fitoterápicos são considerados medicamentos, sendo necessário o estabelecimento de estudos que assegurem a manutenção dos requisitos de qualidade durante o processamento e o armazenamento. Testes de dissolução podem ser empregados para se estimar a biodisponibilidade de um fármaco, sendo uma análise rotineira no desenvolvimento e controle de qualidade de medicamentos alopáticos. A determinação do perfil de dissolução de fitoterápicos também pode ser um importante critério para avaliação da sua qualidade lote-a-lote, bem como para os estudos de desenvolvimento e de estabilidade. O objetivo deste trabalho foi investigar a influência dos métodos de secagem e da condição de armazenagem sobre os perfis de dissolução dos flavonoides totais de extratos secos de duas plantas medicinais bastante difundidas no Brasil, a Bauhinia forficata e a Passiflora alata. Os extratos secos foram produzidos pelo processo de secagem em leito de jorro e em spray drying, sendo submetidos a condições de armazenagem aceleradas (temperatura de 40 ± 2ºC e umidade relativa de 75 ± 5%, por um período de 90 dias). Os perfis de dissolução foram obtidos para amostras de extratos secos antes e após o período de armazenamento. O teor de flavonoides totais foi quantificado por espectrofotometria. Os extratos secos de B. forficata e P. alata apresentaram adequada liberação de flavonoides nos ensaios de dissolução. Os extratos secos de Passiflora alata apresentaram completa dissolução dos flavonoides, 92% e 98% dos teores originais após 60 minutos de ensaio, respectivamente para o extrato seco em leito de jorro e em spray drying.

In Brazil, most of the herbal medicinal products are considered as medicine. Therefore, it is necessary the establishment of tests to guarantee the maintenance of quality requirements during their processing and storage. The dissolution test is used to estimate the bioavailability of drugs and is routinely used in the development and the quality control of allopathic medicines. The determination of the dissolution profile of herbal products can also be an important criterion for assessing the batch-to-batch quality as well as for studies of product development and stability. This work aimed to investigate the dissolution profiles of dried extracts of two medicinal plants widely used in Brazil, the Bauhinia forficata and Passiflora alata, by assessing the effect of the drying methods and storage condition on the release of the total flavonoid contents. Spouted bed and spray drying were the processes used for the production of the dried extracts. The products were subjected to accelerated storage conditions (temperature of 40 ± 2ºC and relative humidity of 75 ± 5%, for 90 days). The dissolution profiles of the dried extracts, before and after storage, were determined. The concentration of total flavonoids was quantified by spectrophotometry. Adequate dissolution profiles of flavonoids from B. forficata and P. alata were obtained for all the dried extracts produced. The dried extracts of Passiflora alata showed the complete dissolution of flavonoids in the dissolution media investigated, respectively 92% and 98% of flavonoids present in the dried extracts in spouted bed and spray drying after 60 minutes of the dissolution testing.

Study on characteristics and dissolution behavior in decoction for boiling powders of Chinese materia medica / 中草药

Objective: To study the powder characteristics and dissolution behavior of the composition in decoction for boiling powders of Chinese materia medica, and to provide scientific evidence for particle size control and its application. Methods: Four kinds of herbal pieces such as Scutellariae Radix, Coptidis Rhizoma, Puerariae Radix, and Glycyrrhizae Preparata Radix were prepared in powders. Powder characteristics including particles distribution and mobility, and dispersion properties of particles in the water decoction were investigated. Additionally, dissolution behaviors of the composition in decoction made from powders and pieces were compared. Results: Well-distributed particles and high mobility were observed in Scutellariae Radix, Coptidis Rhizoma, and Glycyrrhizae Radix Preparata powders, rather than in Puerariae Radix powder. The suspended particles in the decoction in both powders and pieces were submicron. However, optical and electrical properties showed that the suspended particles in the decoction made from powders were more, bigger, and easier to settle as heterogeneous liquid was. Dissolution velocity and amount of the active ingredients in the decoction made from powders were significantly higher than those of pieces. Conclusion: As a new type of herbal decoction which could increase the dissolution of active ingredients, it could shorten decocting duration and improve the availability of herbs. The boiling powders are worth being studied and promoted.

Study on dissolution test of Xinkeshu capsule / 中国生化药物杂志

Objective To establish a method of the dissolution test of Xinkeshu capsule and study the dissolution behavior of sodium Danshensu, protocatechuic aldehyde, salvianolic acid B and puerarin in Xinkeshu capsule.Methods Using the dissolution determination first law of Chinese Pharmacopoeia 2010 II edition, according to the dissolution test conditions in Japan′s“quality of medical drugs information set”, different Xinkeshu capsule were inspected in pH 1.2 solution,pH 4.0 acetate buffer, pH 6.8 phosphate buffer and water.The HPLC gradient elution method was adopted to determine the dissolution of sodium Danshensu,protocatechuic aldehyde,salvianolic acid B and puerarin in Xinkeshu capsule.ResuIts Dissolution of sodium Danshensu, protocatechuic aldehyde, puerarin and salvianolic acid B of Xinkeshu capsule sample from each manufacturer were in good condition, 45min dissolution were 80% and dissolution uniformity.ConcIusion The method is simple, accurate and reproducible for the dissolution determination of this capsule .