Desenvolvimento de metodologia para avaliação do perfil de dissolução de comprimidos de atorvastatina cálcica 20 mg comercializados no Peru, Brasil e Bolívia / Development of a methodology to evaluate the dissolution profile of atorvastatin calcium tablets 20 mg marketed in Peru, Brazil and Bolivia

O presente estudo teve por finalidade desenvolver uma metodologia de dissolução discriminativa para avaliar comprimidos contendo diferentes polimorfos de atorvastatina cálcica (ATR). Este trabalho é conformado por quatro capítulos, no qual o primeiro apresenta uma breve revisão de literatura sobre as características dos polimorfos da ATR, abordando-se informações mais relevantes sobre o ATR em relação ao polimorfismo e sua influência na biodisponibilidade. No segundo capítulo, apresenta-se a importância da caracterização dos polimorfismos e suas implicações para a ATR. As amostras de ATR foram identificadas por difração raio X e análise térmica e, posteriormente, demonstrou-se as diferenças entre quatro amostras comercializadas no mercado brasileiro relacionadas ao hábito cristalino, tamanho de partícula e solubilidade. No terceiro capítulo, demonstra-se o desenvolvimento do método de dissolução discriminativo para comprimidos contendo duas formas polimórficas da ATR. Para tanto, avaliou-se a solubilidade destas pelo método do equilíbrio e determinou-se as condições experimentais mais adequadas para o ensaio de dissolução por intermédio de planejamento fatorial completo do tipo 23, sendo as variáveis independentes o meio de dissolução, a velocidade de agitação e as formas polimórficas (I e VIII). Os resultados obtidos foram tratados estatisticamente através da análise de variância, dos gráficos de Pareto e de superfície de resposta. Concluiu-se que a velocidade de agitação e o meio de dissolução impactam os resultados, afetando a dissolução das formulações com os polimorfos avaliados. Assim, as condições selecionadas foram: 750 mL de meio água a 65 rpm. Após o desenvolvimento do método, este foi comparado com o da Food and Drug Administration (FDA) para comprimidos de atorvastatina cálcica. Ao final dos ensaios, o método desenvolvido mostrou-se adequado para apontar diferenças entre os polimorfos da ATR. No quarto capítulo, o método desenvolvido foi utilizado para avaliar o perfil de dissolução de comprimidos comercializados em três países sul-americanos: Brasil, Peru e Bolívia. As porcentagens de fármaco dissolvidas e a Eficiência de Dissolução foram as variáveis estudadas e, posteriormente, tratadas estatisticamente através da análise de componentes principais, sendo possível comparar o perfil de dissolução de dessete formulações. Dessa forma, foi possível concluir que cinco formulações avaliadas (BR1, BR2 PE6, BR7 e BO3) possuíam a forma polimórfica VIII, enquanto duas formulações (BR5 e PE2) continham a forma polimórfica I. As demais, possivelmente, apresentam misturas ou outras formas polimórficas

This present study was aimed at developing a discriminative dissolution methodology to evaluate tablets containing different calcium atorvastatin (ATR) polymorphs. This paper consists of four chapters. The first chapter presents a brief literature review of the characteristics of ATR polymorphs, and addresses more relevant information about ATR in relation to polymorphism and its influence on bioavailability. The second chapter presents the importance of the characterization of polymorphs and their implications for ATR. The ATR samples were identified by X-ray diffraction and thermal analysis. Subsequently, the differences among the four samples marketed in the Brazilian market with relation to crystalline habit, particle size and solubility were demonstrated. The third chapter demonstrates the development of the discriminative dissolution method for tablets containing two polymorphic forms of ATR. For this, their solubilities were evaluated by the equilibrium method and the most suitable experimental conditions for the dissolution test were determined by means of complete factorial design of type 23, and the independent variables were the dissolution medium, the stirring speed and polymorphic forms (I and VIII). The results obtained were statistically treated through analysis of variance, Pareto and response surface graphs. It was concluded that the stirring speed and the dissolution medium influenced the results, affecting the dissolution of the formulations with the evaluated polymorphs. Thus, the selected condition was 750 mL of water at 65 rpm. Following the development of the method, it was compared with that of the Food and Drug Administration (FDA) for atorvastatin calcium tablets. At the end of the tests, the developed method was adequate to point out differences between the ATR polymorphs. In the fourth chapter, the developed method was used to evaluate the dissolution profile of tablets marketed in three South American countries: Brazil, Peru and Bolivia. Dissolved drug percentages and Dissolution Efficiency were the studied variables and statistically treated by principal component analysis. Through this method, it was possible to compare the dissolution profile of seventeen formulations. Thus, it was possible to conclude that five formulations evaluated (BR1, BR2, PE6, PE7 e BO3) had the polymorphic form VIII, while two formulations (BR5 e PE2) contained the polymorphic form I. The others possibly have mixtures or other forms polymorphic

Research Strategy of Dissolution Test of Soft Capsules / 中国药学杂志

OBJECTIVE: To provide references for effective quality control of soft capsules and discuss the applicability of method for dissolution test of soft capsules. METHODS: Based on analyzing dissolution requirements of soft capsules, we were compared the differences of methods for dissolution test in the pharmacopoeias of several countries with current correlative research from home and abord. RESULTS: The dissolution characteristics of soft capsules are more complex than common oral solid dosage forms, and the requirments are different in the pharmacopoeias of several countries. The formula of contents, hydrophilicity, rupture test and crossliking have impacts on the dissolution characteristics as well as dissolution device and so on. CONCLUSION: In order to develop the method for dissolution test of soft capsules, the dissolution device and medium, rupture test and in vitro-in vivo correlation etc. should be studied.

Preparation of thermo-sensitive diammonium glycyrrhizinate binary liposome gel and the in vitro drug-release behaviors / 中成药

AIM To prepare thermo-sensitive diammonium glycyrrhizinate binary liposome gel and to evaluate the in vitro drug-release behaviors.METHODS Cold dissolution method was adopted in the preparation of gel.With gel transition temperature as an evaluation index,amounts of Poloxamer 407 (P407),Poloxamer 188 (P188) and polysaccharides from Bletillae Rhizoma as influencing factors,central composite design-response surface method was applied to optimizing the formulation.Then the in vitro drug-release behaviors were evaluated by HPLC and Franz vertical diffusion cell method.RESULTS The optimal formulation was determined to be 18％ for P407 amount,4％ for P188 amount,and 0.6％ for polysaccharides' amount,the gel transition temperature was (37.5 ± 0.3) ℃.The accumulative release rate of obtained thermo-sensitive binary liposome gel was (65.52 ± 0.63) ％ within 48 h,which showed more obvious sustained-release effect as compared with liposome and thermosensitive gel.CONCLUSION Thermo-sensitive diammonium glycyrrhizinate binary liposome gel can reduce drug-release rate and increase its retention time in the rectum.

Study on the Feasibility of Evaluating Drug in vitro Sustained Release Performance by Overflow Dissolu-tion Method / 中国药房

OBJECTIVE:To study the feasibility of overflow dissolution method for evaluating the drug in vitro sustained re-lease performance. METHODS:Overflow dissolution method was established by simulating the drugs elimination in vivo. Using Nifedipine sustained-elease tablets(Ⅰ)from 2 different manufacturers as model drug A,B,concentration-time curve,cumulative release rate- time curve,release velocity-time curve of model drugs in release pool at 3 different overflow speed (0,1.50,3.00 mL/min)were investigated. RESULTS:When overflow speed was 0,the cumulative dissolution was consistent with that of the con-ventional dissolution method. As the overflow speed increased,cmax of drug A,B was decreased [A:(8.89±0.20),(5.21±0.04), (3.51±0.03)μg/mL;B:(7.62±0.05),(4.80±0.09),(2.89±0.04)μg/mL];cumulative release rate was increased [A:(85.47± 2.45)%,(94.29 ± 2.44)%,(96.04 ± 2.56)%;B:(73.28 ± 1.13)%,(78.46 ± 1.94)%,(82.50 ± 1.69)%] ;tmax was ahead (A:1.5,1.0,0.5 h;B:2.0,1.0,0.5 h). CONCLUSIONS:Overflow dissolution method has avoided the inhibition of too large drug concentration on drug release,making complete drug release and more accurate evaluation of in vivo sustained release performance of the preparation.

Development and validation of a dissolution method using HPLC for diclofenac potassium in oral suspension

The present study describes the development and validation of an in vitro dissolution method for evaluation to release diclofenac potassium in oral suspension. The dissolution test was developed and validated according to international guidelines. Parameters like linearity, specificity, precision and accuracy were evaluated, as well as the influence of rotation speed and surfactant concentration on the medium. After selecting the best conditions, the method was validated using apparatus 2 (paddle), 50-rpm rotation speed, 900 mL of water with 0.3% sodium lauryl sulfate (SLS) as dissolution medium at 37.0 ± 0.5°C. Samples were analyzed using the HPLC-UV (PDA) method. The results obtained were satisfactory for the parameters evaluated. The method developed may be useful in routine quality control for pharmaceutical industries that produce oral suspensions containing diclofenac potassium.

O presente estudo descreve o desenvolvimento e validação de um método de dissolução in vitro para avaliação da liberação de diclofenaco potássico suspensão oral. O teste de dissolução foi desenvolvido e validado de acordo com as diretrizes internacionais. Parâmetros como linearidade, especificidade, precisão e exatidão foram avaliados, bem como a influência da velocidade de rotação e a concentração de tensoativono meio. Depois de selecionar as melhores condições, o método foi validado usando o aparato 2 (pás), velocidade de rotação de 50 rpm, 900 mL de água com 0,3% de lauril sulfato de sódio (LSS) como meio de dissolução a 37,0 ± 0,5 ºC. As amostras foram analisadas pelo método de CLAE-UV (PDA). Os resultados obtidos foram satisfatórios para os parâmetros avaliados. O método desenvolvido pode ser útil na rotina de controle de qualidade para as indústrias farmacêuticas que produzem suspensões orais contendo diclofenaco potássico.

Comparison Study on Determination of Trace Element Content in Peach Pulp between Wet Digestion Method and Carbonize Acid Dissolution Method / 世界科学技术-中医药现代化

This study was aimed to determine trace elements in Peach pulp . The wet digestion method and car-bonize acid dissolution method were applied to digest the sample, and flame atomic absorption spectroscopy was used to determine the content of trace elements (Fe, Cu, Mn) in Peach pulp . The results showed that the content is not consistent among different pretreatment methods. However, the metalion content among these three methods are in the order of Fe > Mn > Cu, with the average recovery rate between 92.6% and 119.6%. The RSD is less than 2.86%. It was concluded that this method is with high accuracy and stability as well as reliable accurate re-sults. It also proved that Peach pulp . is rich in Fe, Cu and Mn. It provides some useful information for further pharmacological study of Peach pulp .