RESUMO
BACKGROUND: Oral suspensions are heterogeneous disperse systems, and the particle size distribution, crystalline form of the dispersed solid, and composition of the formulation can be listed as parameters that control the drug dissolution rate and its bioavailability. OBJECTIVE: The aim of this work was to develop a discriminative dissolution test, which, in association with in silico methodologies, can make it possible to safely anticipate bioavailability problems. METHODS: Nimesulide and ibuprofen (BCS class II) and cephalexin (BCS class I) oral suspensions were studied. Previously, solid-state structure and particle size in active pharmaceutical ingredients were characterized and the impact of differences on solubility was evaluated for the choice of discriminative medium. Afterwards, particle size distribution (0.1 to 360 µm), dissolution profile, and in vitro permeability in Caco-2 cell of commercial suspensions, were determined. These parameters were used as input for the establishment of the in vitro-in vivo correlation (IVIVC) for the suspensions using the GastroPlus™ with Wagner-Nelson and Loo- Riegelmann deconvolution approach. RESULTS: The predicted/observed pharmacokinetic model showed good correlation coefficients (r) of 0.960, 0.950, and 0.901, respectively. The IVIVC was established for one nimesulide and two ibuprofen suspensions with r between 0.956 and 0.932, and the percent prediction error (%PE) did not exceed 15%. CONCLUSION: In this work, we have performed a complete study combining in vitro/in silico approaches with the aim of anticipating the safety and efficacy of oral pharmaceutical suspensions in order to provide a regulatory tool for this category of products in a faster and more economical way.
Assuntos
Ibuprofeno , Sulfonamidas , Humanos , Disponibilidade Biológica , Ibuprofeno/química , Ibuprofeno/farmacocinética , Células CACO-2 , Solubilidade , SuspensõesRESUMO
Dissolution is used to determine the rate and extent of drug release from the dosage form into a dissolution medium, which allow to assess the batch-to-batch variability. Considering that the dissolution test is used to predict the vivo performance of the drug as well, it is important to guarantee the quality and reliability of dissolution test results. The aim of this work was to evaluate the measurement uncertainty arising from sampling and analytical steps of dissolution test of prednisone tablets. Dissolution test was performed using 900 mL of purified water as dissolution medium and a dissolution apparatus equipped with paddles rotating at 50 rpm for 30 min. Quantification was performed by UV spectrophotometer. Uncertainty arising from sampling was estimated using the duplicate method (empirical approach), using 17-sampling target, two samples for each sampling target, and three replicas for each sample, totalizing 102 analyses. Uncertainty arising from analytical steps considered the uncertainty from dissolution step (estimated using Monte Carlo method and regression equation obtained using DoE) and uncertainty from quantification step. Overall uncertainty value was found to be 2.2%, which is below the target uncertainty value (ut =2.5%). The contributions of uncertainty sources in this study were as follows: 24% from sampling uncertainty, 29% from the dissolution step uncertainty, and 47% from the quantification step uncertainty. The results of dissolution test should be compared to the specification limits (Q). According to the pharmacopeia requirements, the batch of the medicine should be declared compliant if the dissolved amount of prednisone for six tablets are above the specification limits + 5% (Q+5%=85%). Since the measured values for all six tablets (96.5%, 94.0%, 96,4%, 95.3%, 96.0%, and 96.9%) were above the multivariate acceptance limit (90.2%, calculate as the standard uncertainty multiplied by multivariate coverage factor), the batch of the prednisone tablets was declared complaint, with a reduced total risk of false decision (total risk value below 5%).
Assuntos
Prednisona , Incerteza , Solubilidade , Reprodutibilidade dos Testes , ComprimidosRESUMO
Abstract The aim of this study was to compare the dissolution properties of ibuprofen solid oral dosage forms commercially available in Bosnia and Herzegovina and to estimate the influence of dissolution medium composition on the drug release. Eight products (A-H) were subjected to in vitro dissolution test using experimental conditions described in USP42-NF37. Dissolution properties of one selected product were examined in the presence of alcohol (22.2% v/v) and fruit juice (22.2% v/v). Products marked B-H complied with the pharmacopeial criteria. Dissolution profile of product B was similar with dissolution profiles of products D, E, F and G and similarity was also found between products A-D, C-G, D-G and E-F. Drug release from most of the examined preparations fitted best to the Weibull kinetic model. In the presence of alcohol in the medium, higher amount of ibuprofen was dissolved. Contrary, ibuprofen dissolved in the presence of fruit juice was significantly lower. Differences in the dissolution profiles of investigated preparations suggest that their interchangeability should be additionally considered and demonstrated with in vivo bioequivalence studies. Presence of different substances in the medium can affect dissolution properties of ibuprofen, emphasizing the importance of the patient's compliance.
Assuntos
Ibuprofeno/análise , Intercambialidade de Medicamentos , Dissolução , Comprimidos , Técnicas In Vitro/métodos , Preparações Farmacêuticas/análise , Liberação Controlada de Fármacos/efeitos dos fármacosRESUMO
The purpose of this work was to elaborate a diagnosis of the dissolution test in Africa in comparison with Brazil, evaluating the dissolution profile of low solubility drugs such as albendazole, ibuprofen, furosemide, glibenclamide, hydrochlorothiazide and carvedilol to ascertain their quality. The dissolution profiles were evaluated by utilizing the United States Pharmacopeia (USP). The glibenclamide medicine was evaluated according to the Food and Drug Administration (FDA), while a dissolution method was developed for the carvedilol medicine. A filter selection test for all the drugs showed that cannula is suitable for all, except for carvedilol, which is centrifuged. The various brands of Nigerian and Brazilian medicines tested showed some statistical differences. The suitable conditions that allowed the dissolution of carvedilol to be determined were the USP type II apparatus at 75 rpm containing 900 mL of acetate buffer, pH 4.5. The results of the dissolution test showed that out of the 17 different brands of Brazilian medicines and 17 different products from Nigeria, 94.12% and 58.82% passed respectively
O objetivo deste trabalho foi elaborar um diagnóstico do teste de dissolução na África em comparação ao Brasil, avaliando o perfil de dissolução de medicamentos de baixa solubilidade como albendazol, ibuprofeno, furosemida, glibenclamida, hidroclorotiazida e carvedilol para verificar sua qualidade.Os perfis de dissolução foram avaliados utilizando a Farmacopeia dos Estados Unidos (USP). O medicamento glibenclamida foi avaliado de acordo com a Food and Drug Administration (FDA), enquanto um método de dissolução foi desenvolvido para o medicamento carvedilol.Um teste de seleção de filtro para todos os medicamentos mostrou que a cânula é adequada para todos, exceto para o carvedilol, que é centrifugado. As diversas marcas de medicamentos Nigerianos e Brasileiros testadas apresentaram algumas diferenças estatísticas. As condições adequadas que permitiram a determinação da dissolução do carvedilol foram o aparelho USP tipo II a 75 rpm contendo 900 mL de tampão acetato, pH 4,5. Os resultados do teste de dissolução mostraram que das 17 diferentes marcas de medicamentos brasileiros e 17 diferentes produtos da Nigéria, 94,12% e 58,82% foram aprovados, respectivamente
Assuntos
Solubilidade , Brasil/etnologia , Preparações Farmacêuticas/análise , África/etnologia , Dissolução , United States Food and Drug Administration , Albendazol/farmacologia , Ibuprofeno , Carvedilol/farmacologia , Furosemida/farmacologia , Métodos , Acetatos/efeitos adversosRESUMO
Metronidazole (MT) is an important drug available for Helicobacter pylori infection treatment. However, in the past few years, this drug has presented effective reduction for infection control, one of the most important reasons is attributed to the reduction of retention time in the stomach environment. Mucoadhesive nanostructured polyelectrolyte complexes (nano PECs) based on chitosan (CS) and hypromellose phthalate (HP) were rationally developed using a full factorial design (21 × 21 × 31), for the incorporation of MT based on the enhancement of the antimicrobial potential against active Helicobacter pylori, in the stomach. Different mass ratios of CS:HP (w/w) were tested, reaching the most promising ratios of 1:0.1, 1:0.5, and 1:1, and two methods of polymers addition (pouring-I and drip-II) were also evaluated. From method I, the obtained particles presented a diameter in the range of 811-1293 nm (Z-average) and a polydispersity index (PDI) between 0.47 and 0.88. By method II, there was a significant reduction in diameter and PDI to 553-739 nm and 0.23 at 0.34, respectively. The drug incorporation also resulted in a reduction in the diameter and PDI of the nano PECs. All samples showed positive zeta potential, about 20 mV, and a high percentage of MT incorporation (±95%). The method factor presented a greater influence on the nano PECs characteristics. Interactions in the system constituents were indicated by the FTIR data. Nano PECs mucoadhesiveness was observed and the composition and charge density were responsible for this phenomenon. MT dissolution evaluation showed the similarity of the dissolution profiles of free and loaded MT, in which almost 100% of the drug was in the simulated gastric medium in 120 min of testing. The in vitro antimicrobial potential against H. pylori of loaded nano PECs were measured and the minimum inhibitory concentration observed for free MT was >2000 µg/mL, while for the incorporated MT lower values were observed, showing an increase in the encapsulated MT activity.
RESUMO
BACKGROUND: Lactose intolerance is characterized by the absence of the enzyme lactase (beta-galactosidase) and affects two thirds of the world adult population. Our aim was to evaluate a lactase gastro-resistant formulation to ensure increased activity in the action site of the enzyme (lumen of the small intestine). Simultaneously, we also evaluated the commercial product stability and enzyme activity, because the product containing beta-galactosidase is classified as food supplement according to the Food and Drug Administration (FDA), so it is free to pass quality testing, efficacy and stability. So, it is possible that contain some irregularities as to the content and enzymatic activity. METHODS: The dissolution assay was performed using a dissolution test system and commercial product and the gastro-resistant formulation were evaluated according to a method adapted to the conditions recommended by United States Pharmacopeia (US Pharmacopeia) for gastro-resistant formulations. For the assessment of enzymatic activity throughout the dissolution test was employed the official method of lactase assay described in US Pharmacopoeia. This method is based on a colorimetric reaction which the substrate reacts with the enzyme generate a colored product further analyzed by UVVisible spectrophotometry. RESULTS: When carrying out dissolution test in commercial product it is noted that the existing formulation is not able to protect the enzyme from degrading action of gastric environment (a loss of 86.0 ± 0.8% of lactase activity was observed). Our proposed gastro-resistant pharmaceutical form there was no loss of activity during the acid step and the end of the dissolution test the found activity was 95 ± 1.3%. CONCLUSION: The formulations proposed in this work using hypromellose capsules ensure the enzymatic activity of lactase, preventing its contact with the acid medium. For the other side, the results of commercial tablets for lactase release indicate a significant loss of enzyme activity due to the immediate release of the enzyme in the simulated gastric fluids.
Assuntos
Lactase/química , Cápsulas/química , Química Farmacêutica/métodos , Solubilidade , Comprimidos/química , Estados Unidos , United States Food and Drug AdministrationRESUMO
Secnidazole, a 5-nitroimidazole, is a drug used in the treatment against protozoa, and several bacterial infections. This study purpose was to develop and validate a UV spectrophotometric method to determine secnidazole in pharmaceutical tablet dosage forms once there is no method reported in the pharmacopoeia yet. The quantification was performed using methanol as solvent at 325 nm (maximum wavelength) and three kinds of products marketed in Brazil (reference, generic and similar tablets) containing 1g of secnidazole. The method obeyed Beer's law in the concentration range of 4 - 20 µgmL-1 respectively. The method was validated according to the International Conference on Harmonization (ICH) and Brazil National Health Surveillance Agency (ANVISA) guidelines, showing accuracy, precision, selectivity, robustness and linearity. Tests such as weight range, friability, disintegration, hardness and dissolution were carried out to check tablets' quality and all the trials showed to be in accordance with the general test guidelines of the Brazilian Pharmacopoeia. The dissolution test was carried out and the developed method was applied. The method developed is suitable for the estimation of secnidazole in tablets without any interference from the excipients and can be used for routine in quality control. Still, it's a simple, fast and low cost method.
Secnidazol, um nitroimidazólico, é um fármaco utilizado no tratamento para protozoários, e várias infecções bacterianas. Este trabalho propôs o desenvolvimento e validação de um método espectrofotométrico na região do ultravioleta para a determinação de Secnidazol na forma farmacêutica de comprimidos, uma vez que não há nenhum método relatado nas farmacopeias. A quantificação foi realizada utilizando metanol como solvente a 325 nm (máximo de comprimento de onda) e usando três tipos de produtos comercializados no Brasil (de referência, genéricos e comprimidos similares) contendo 1g de Secnidazol. O método obedeceu a lei de Beer no intervalo de concentração de 4 - 20 µgmL-1, respectivamente. O método foi validado de acordo com a Conferência Internacional de Harmonização (ICH) e diretrizes da Agência Nacional de Vigilância Sanitária do Brasil (ANVISA), apresentando exatidão, precisão, seletividade, robustez e linearidade. Testes como variação de peso, friabilidade, desintegração, dureza e dissolução foram realizados para verificar a qualidade de comprimidos e mostrou-se de acordo com os testes gerais da Farmacopeia Brasileira. O teste de dissolução realizado e o método desenvolvido pode ser aplicado. O método desenvolvido é adequado para a estimativa de secnidazole em comprimidos sem qualquer interferência dos excipientes e pode ser usado para a rotina de controlo de qualidade. Ainda, é um método simples, rápido e de baixo custo.
Assuntos
Controle de Qualidade , Infecções Bacterianas , Anti-Infecciosos , Antibacterianos , NitroimidazóisRESUMO
The aim of this study was to develop and validate a discriminating in vitro release test to evaluate rivastigmine transdermal patches. The Exelon® Patch was chosen as a model transdermal product. The studies of in vitro release were designed to determine the impact of the official apparatus chosen (USP apparatus 5 and USP apparatus 6), the rotation speed, and the dissolution medium characteristics on the rivastigmine release profile from transdermal patches. Patches with different drug release profiles were tested in order to evaluate the discriminating power of the in vitro release test developed and validated. Variables such as the apparatus type, the dissolution medium, and the rotation speed have a significant influence on the drug release characteristics from a transdermal patch. The in vitro release methodologies using the USP apparatus 5 at 50 rpm and USP apparatus 6 at 25 rpm using the medium phosphate-buffered saline pH 7.4 were considered discriminative and adequate to characterize the rivastigmine (RV) release from a commercial transdermal patch, Exelon® Patch.
Assuntos
Liberação Controlada de Fármacos , Rivastigmina/administração & dosagem , Adesivo Transdérmico , Farmacopeias como Assunto , Rivastigmina/química , SolubilidadeRESUMO
ABSTRACT Analytical results are widely used to assess batch-by-batch conformity, pharmaceutical equivalence, as well as in the development of drug products. Despite this, few papers describing the measurement uncertainty estimation associated with these results were found in the literature. Here, we described a simple procedure used for estimating measurement uncertainty associated with the dissolution test of acetaminophen tablets. A fractionate factorial design was used to define a mathematical model that explains the amount of acetaminophen dissolved (%) as a function of time of dissolution (from 20 to 40 minutes), volume of dissolution media (from 800 to 1000 mL), pH of dissolution media (from 2.0 to 6.8), and rotation speed (from 40 to 60 rpm). Using Monte Carlo simulations, we estimated measurement uncertainty for dissolution test of acetaminophen tablets (95.2 ± 1.0%), with a 95% confidence level. Rotation speed was the most important source of uncertainty, contributing about 96.2% of overall uncertainty. Finally, it is important to note that the uncertainty calculated in this paper reflects the expected uncertainty to the dissolution test, and does not consider variations in the content of acetaminophen.
Assuntos
Comprimidos/análise , Método de Monte Carlo , Acetaminofen/análise , Dissolução/métodosRESUMO
Lutein is a carotenoid with antioxidant activity that is present in various dosage forms. The bioavailability of carotenoid from oral dosage formulations depends on their release, dissolution and its permeability through the gastrointestinal tract. Here, a dissolution test was developed for evaluating formulations and the bioavailability was assessed. The test utilized a USP-apparatus II with rotations of 50, 75 and 100rpm in water with P80 at 1, 2 and 5% (w/v). A non-everted rat intestinal sac model was used in conjunction to assess the intestinal permeability. The most discriminative conditions were 100rpm in water with 2% polysorbate 80, which showed profile differences between two formulations. The intestinal permeation studies showed a lag-time and apparent permeability coefficient that were characteristic of highly permeable drugs. We suggest that a dissolution test can be an essential quality control tool for formulations containing compounds as lutein, although not mandatory by the regulation agencies.
Assuntos
Mucosa Intestinal/metabolismo , Animais , Disponibilidade Biológica , Química Farmacêutica , Luteína/farmacologia , Masculino , Permeabilidade/efeitos dos fármacos , Ratos , Solubilidade , ComprimidosRESUMO
A dissolution method for benzoyl metronidazole (BMZ) oral suspensions was developed and validated using a high-performance liquid chromatography (HPLC) method. After determination of sink conditions, dissolution profiles were evaluated using different dissolution media and agitation speeds. The sample insertion mode in dissolution media was also evaluated. The best conditions were obtained using a paddle, 50 rpm stirring speed, simulated gastric fluid (without pepsin) as the dissolution medium, and sample insertion by a syringe. These conditions were suitable for providing sink conditions and discriminatory power between different formulations. Through the tested conditions, the results can be considered specific, linear, precise, accurate, and robust. The dissolution profiles of five samples were compared using the similarity factor (f 2) and dissolution efficiency. The dissolution kinetics were evaluated and described by the Weibull model. Whereas there is no monograph for this pharmaceutical formulation, the dissolution method proposed can be considered suitable for quality control and dissolution profile comparison of different commercial formulations.
Assuntos
Química Farmacêutica/métodos , Metronidazol/análogos & derivados , Administração Oral , Metronidazol/química , Metronidazol/farmacocinética , Tamanho da Partícula , SolubilidadeRESUMO
Gellan gum microspheres were obtained by ionotropic gelation technique, using the trivalent ion Al(3+). The percentage of entrapment efficiency ranged from 48.76 to 87.52% and 2(2) randomized full factorial design demonstrated that both the increase of polymer concentration and the decrease of crosslinker concentration presented a positive effect in the amount of encapsulated drug. Microspheres size and circularity ranged from 700.17 to 938.32 µm and from 0.641 to 0.796 µm, respectively. The increase of polymer concentration (1-2%) and crosslinker concentration (3-5%) led to the enlargement of particle size and circularity. However, the association of increased crosslinker concentration and reduced polymer content made the particles more irregular. In vitro and ex vivo tests evidenced the high mucoadhesiveness of microspheres. The high liquid uptake ability of the microspheres was demonstrated and the pH variation did not affect this parameter. Drug release was pH dependent, with low release rates in acid pH (42.40% and 44.93%) and a burst effect in phosphate buffer pH (7.4). The Weibull model had the best correlation with the drug release data, demonstrating that the release process was driven by a complex mechanism involving the erosion and swelling of the matrix or by non-Fickian diffusion.
Assuntos
Íons/química , Polímeros/química , Polissacarídeos Bacterianos/química , Animais , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Concentração de Íons de Hidrogênio , Mucosa Intestinal/metabolismo , Microesferas , Tamanho da Partícula , SuínosRESUMO
Gemifloxacin mesylate (GFM) is a synthetic, broad-spectrum, fluoroquinolone antibacterial agent. It is different from other class members because it achieves adequate plasma concentrations to inhibit both topoisomerase IV and gyrase. The aim of this study was to develop and validate a dissolution test for GFM in coated tablets, using a simulated absorption profile based on in vivo data obtained from the literature. The fraction and percentage of the dose absorbed were calculated using model-dependent Loo-Riegelman approach for two compartments. The best in vitro dissolution profile was obtained using 900 mL of pH 6.0 phosphate buffer as a dissolution medium at 37 °C ± 0.5 °C and paddles at 50 rpm. The in vitro dissolution samples were analyzed using a liquid chromatography method, and the validation was performed according to USP 34 (2011). The method showed specificity, precision, accuracy, robustness and linearity. Under these conditions, a level-A in vitro-in vivo correlation was suggested (r = 0.9926). The prediction errors were calculated to determine the validity and accuracy of the suggested correlation. The dissolution test can be used to evaluate the dissolution profile of GFM-coated tablets and minimize the number of bioavailability studies as part of new formulation development.
Assuntos
Antibacterianos/química , Indústria Farmacêutica/métodos , Fluoroquinolonas/química , Absorção Intestinal , Modelos Biológicos , Naftiridinas/química , Inibidores da Topoisomerase/química , Animais , Antibacterianos/análise , Antibacterianos/sangue , Antibacterianos/farmacocinética , Disponibilidade Biológica , Brasil , Cromatografia Líquida de Alta Pressão , Simulação por Computador , Indústria Farmacêutica/instrumentação , Liberação Controlada de Fármacos , Fluoroquinolonas/análise , Fluoroquinolonas/sangue , Fluoroquinolonas/farmacocinética , Gemifloxacina , Humanos , Concentração de Íons de Hidrogênio , Modelos Lineares , Naftiridinas/análise , Naftiridinas/sangue , Naftiridinas/farmacocinética , Reprodutibilidade dos Testes , Espectrofotometria Ultravioleta , Comprimidos com Revestimento Entérico , Inibidores da Topoisomerase/análise , Inibidores da Topoisomerase/sangue , Inibidores da Topoisomerase/farmacocinéticaRESUMO
A dissolution test for fesoterodine low dose extended-release tablets using liquid chromatographic (LC) method equipped with a C18 monolithic column was developed and validated. LC system was operated isocratically at controlled temperature (40 °C) using a mobile phase of acetonitrile:methanol:0.03 M ammonium acetate (pH 3.8) (30:15:55, v/v/v), run at a flow rate of 1.5 mL/min and detected at 208 nm. The best dissolution conditions for this formulation were achieved using a USP apparatus 2 (paddle) at 100 rpm and 900 mL of phosphate buffer at pH 6.8 as the dissolution medium. Validation parameters such as the specificity, linearity, accuracy, precision, and robustness were evaluated according to international guidelines, giving results within the acceptable range. The kinetic parameters of drug release were also investigated using model-dependent methods and the dissolution profiles were best described by the Higuchi model. The validated dissolution test can be applied for quality control of this formulation.
RESUMO
Ranitidine is an antisecretory drug with H2 antagonist action useful in treating gastric and duodenal disorders. The dissolution test is used to obtain and compare dissolution profiles and establish similarities of pharmaceutical forms. The aim of this study was to compare the dissolution profiles of 150-mg coated ranitidine tablets of a reference drug (product A) and a generic (product B) and a similar (product C) drug marketed in Bahia, Brazil using a simple, fast and inexpensive ultraviolet method. Dissolution was determined using a USP type 2 apparatus at 50 rpm with 900 mL of distilled water at 37.0 ± 0.5 oC for 1h. The dissolution test was performed in compliance with the American Pharmacopoeia (USP-32). Dissolution efficiency and difference (f1) and similarity (f2) factors were calculated and evaluated. The proposed quantification methodology for drug dissolution test was validated, presenting accuracy, linearity and precision within the acceptance criteria. Products A, B and C showed dissolution efficiency values of 59.29, 73.59 and 66.67%, respectively. Factors f1 and f2 were calculated and showed that the profiles of products A, B and C were dissimilar. However, all the products released ranitidine satisfactorily, with at least 80% of the drug dissolved within 30 min.
A ranitidina é um fármaco antissecretor, antagonista H2, usado no tratamento de desordens gástricas e duodenais. O teste de dissolução é utilizado para obter e comparar perfis de dissolução, estabelecendo semelhança de formas farmacêuticas. Este estudo tem por objetivo comparar perfis de dissolução de comprimidos revestidos contendo 150 mg de ranitidina, em medicamentos de referência (produto A), genérico (produto B) e similar (produto C) comercializados na Bahia-Brasil, usando um método ultravioleta simples, rápido e de baixo custo. As condições que permitiram a determinação da dissolução foram: aparelho USP tipo 2 a 50 rpm, contendo 900 mL de água destilada mantida a 37,0 ± 0,5 °C, durante 1 h. O teste de dissolução foi realizado em conformidade com a Farmacopeia Americana (USP-32). Cálculo da eficiência de dissolução e fatores de diferença (f1) e semelhança (f2) foram avaliados. A metodologia proposta para a quantificação do fármaco no ensaio de dissolução foi validada apresentando precisão, linearidade e exatidão dentro dos critérios de aceitação. Os produtos A, B e C mostraram eficiência de dissolução de 59,29, 73,59 e 66,67%, respectivamente. Calcularam-se os fatores f1 e f2 e mostrou-se que os perfis não foram semelhantes para os comprimidos de produtos A, B e C. No entanto, todos os produtos liberaram o fármaco satisfatoriamente, pois, pelo menos, 80% de ranitidina foram dissolvidos em 30 min.
Assuntos
Ranitidina/farmacocinética , Comprimidos com Revestimento Entérico/farmacocinética , Espectrofotometria Ultravioleta/métodos , Comprimidos/farmacocinética , Brasil , Dissolução/análiseRESUMO
The dissolution process is considered an important in vitro tool to evaluate product quality and drug release behavior. Single dissolution methods for the analysis of combined dosage forms are preferred to simplify quality control testing. The objective of the present work was to develop and validate a single dissolution test for a telmisartan (TEL) and amlodipine besylate (AML) combined tablet dosage form. The sink conditions, stability and specificity of both drugs in different dissolution media were tested to choose a discriminatory dissolution method, which uses an USP type-II apparatus with a paddle rotating at 75 rpm, with 900 mL of simulated gastric fluid (SGF without enzymes) as the dissolution medium. This dissolution methodology provided good dissolution profiles for both TEL and AML and was able to discriminate changes in the composition and manufacturing process. To quantify both drugs simultaneously, a synchronous first derivative spectrofluorimetric method was developed and validated. Drug release was analyzed by a fluorimetric method at 458 nm and 675 nm for AML and TEL, respectively. The dissolution method was validated as per ICH guidance.
O processo de dissolução é considerado como uma importante ferramenta in vitro para avaliar a qualidade do produto e o comportamento de liberação do fármaco. Prefere-se um ensaio único de dissolução para formas farmacêuticas contendo associação de fármacos pela simplificação dos testes de controle de qualidade. O objetivo do presente trabalho foi desenvolver e validar um teste de dissolução único para forma farmacêutica comprimidos contendo telmisartana (TEL) e besilato de anlodipino (AML) associados. Condições "sink", estabilidade e especificidade de ambos os fármacos nos diferentes meios de dissolução foram avaliadas para selecionar um método de dissolução discriminatório, que utiliza um aparato do tipo II da USP, com pás girando a 75 rpm e 900 mL de fluido gástrico simulado (SGF sem enzima) como o meio de dissolução. Estas condições proporcionaram bons perfis de dissolução para ambos, TEL e AML, sendo capaz de discriminar as mudanças na composição e processo de fabricação. Para quantificar os dois fármacos simultaneamente, um método de fluorescência derivada sincronizado foi desenvolvido e validado. A quantidade de fármaco liberado foi analisada pelo método fluorimétrico em 458 e 675 nm para a AML e TEL, respectivamente. O método de dissolução foi validado de acordo com a orientação da ICH.
Assuntos
Espectrometria de Fluorescência/métodos , Anti-Hipertensivos , Controle de Qualidade , Formas de Dosagem , Dissolução/classificaçãoRESUMO
Introducción: el ensayo de disolución es una técnica analítica de empleo común en un laboratorio farmacéutico. Un proceso tecnológico para la elaboración de tabletas fue desarrollado. El ingrediente farmacéutico activo usado fue Tilo ® extracto seco. Objetivo: el objetivo de este trabajo fue desarrollar y validar un ensayo de disolución para evaluar la estabilidad y la calidad de dicho producto. Método: se utilizaron muestras de un lote experimental, un lote placebo y lotes pilotos de tabletas de Tilo ® de 100 mg. Se evaluaron como medios de disolución agua destilada y solución de ácido clorhídrico 0,1 mol/L, realizándose perfiles de disolución a 50, 75 y 100 rpm, empleándose los dos tipos de aparatos establecidos en la literatura para este ensayo (cesta y paleta). El contenido de cumarina fue analizado por HPLC. El ensayo fue validado según la USP. Resultados: los resultados mostraron que el agua destilada fue un medio de disolución adecuado, alcanzándose porcientos de disolución de la droga por encima del 85 por ciento a los 30 minutos, no existiendo diferencias significativas entre los tipos de aparatos recomendados por la USP. Mientras que, los perfiles de disolución a diferentes tiempos y velocidades de agitación mostraron una liberación gradual del principio activo en el tiempo, donde a medida que se incrementa la velocidad de agitación, se incrementa el porcentaje de disolución de la droga en el medio. La validación del ensayo demostró que el mismo era específico y preciso. Conclusiones: se estableció como ensayo de disolución las siguientes condiciones de trabajo: Aparato: paleta, 100 rpm; medio: agua destilada, 500 mL; tiempo: 60 minutos y Temperatura: 37 ± 0,5 ºC(AU)
Introduction: dissolution testing is one of the most common analytical techniques performed in a pharmaceutical analytical laboratory. A technological process for the production of tablets was developed. The active pharmaceutical ingredient used was Tilo ® dry extract. Objective: to develop and to validate the dissolution assay aimed at evaluating the stability study and the quality of this product. Methods: some samples from the experimental batch, the placebo batch and the pilot batches were used in this study. Distilled water and 0,1 mol/L chlorhidric acid were evaluated as dissolution media. The dissolution profiles at 50, 75 and 100 rpm and two types of dissolution devices (basket and paddle) recommended for the USP were evaluated. Coumarin content was analyzed by HPLC method. The dissolution assay was validated according to the United States Pharmacopeia. Results: the results showed that the distilled water was an appropriate dissolution medium, where percentages of released drug higher to 85 percent in 30 minutes were obtained; there were no significant differences among the types of dissolution devices recommended by the USP. The dissolution profiles at different shaking times and speeds showed gradual release of the active principle. As the shaking speed increases, the percentage of the drug dissolution increases in the medium. The assay was considered specific and precise. Conclusions: a type II (paddle) dissolution device, 500 ml of distilled water at 37 ± 0,5 ºC and 100 rpm, were established as parameters of the dissolution assay(AU)
Assuntos
Tilia , Métodos de Análise Laboratorial e de Campo , Avaliação de Medicamentos , DissoluçãoRESUMO
Introducción: el ensayo de disolución es una técnica analítica de empleo común en un laboratorio farmacéutico. Un proceso tecnológico para la elaboración de tabletas fue desarrollado. El ingrediente farmacéutico activo usado fue Tilo ® extracto seco. Objetivo: el objetivo de este trabajo fue desarrollar y validar un ensayo de disolución para evaluar la estabilidad y la calidad de dicho producto. Método: se utilizaron muestras de un lote experimental, un lote placebo y lotes pilotos de tabletas de Tilo ® de 100 mg. Se evaluaron como medios de disolución agua destilada y solución de ácido clorhídrico 0,1 mol/L, realizándose perfiles de disolución a 50, 75 y 100 rpm, empleándose los dos tipos de aparatos establecidos en la literatura para este ensayo (cesta y paleta). El contenido de cumarina fue analizado por HPLC. El ensayo fue validado según la USP. Resultados: los resultados mostraron que el agua destilada fue un medio de disolución adecuado, alcanzándose porcientos de disolución de la droga por encima del 85 por ciento a los 30 minutos, no existiendo diferencias significativas entre los tipos de aparatos recomendados por la USP. Mientras que, los perfiles de disolución a diferentes tiempos y velocidades de agitación mostraron una liberación gradual del principio activo en el tiempo, donde a medida que se incrementa la velocidad de agitación, se incrementa el porcentaje de disolución de la droga en el medio. La validación del ensayo demostró que el mismo era específico y preciso. Conclusiones: se estableció como ensayo de disolución las siguientes condiciones de trabajo: Aparato: paleta, 100 rpm; medio: agua destilada, 500 mL; tiempo: 60 minutos y Temperatura: 37 ± 0,5 ºC
Introduction: dissolution testing is one of the most common analytical techniques performed in a pharmaceutical analytical laboratory. A technological process for the production of tablets was developed. The active pharmaceutical ingredient used was Tilo ® dry extract. Objective: to develop and to validate the dissolution assay aimed at evaluating the stability study and the quality of this product. Methods: some samples from the experimental batch, the placebo batch and the pilot batches were used in this study. Distilled water and 0,1 mol/L chlorhidric acid were evaluated as dissolution media. The dissolution profiles at 50, 75 and 100 rpm and two types of dissolution devices (basket and paddle) recommended for the USP were evaluated. Coumarin content was analyzed by HPLC method. The dissolution assay was validated according to the United States Pharmacopeia. Results: the results showed that the distilled water was an appropriate dissolution medium, where percentages of released drug higher to 85 percent in 30 minutes were obtained; there were no significant differences among the types of dissolution devices recommended by the USP. The dissolution profiles at different shaking times and speeds showed gradual release of the active principle. As the shaking speed increases, the percentage of the drug dissolution increases in the medium. The assay was considered specific and precise. Conclusions: a type II (paddle) dissolution device, 500 ml of distilled water at 37 ± 0,5 ºC and 100 rpm, were established as parameters of the dissolution assay
Assuntos
Dissolução , Avaliação de Medicamentos , Tilia , Métodos de Análise Laboratorial e de CampoRESUMO
The association of meloxicam and pridinol is indicated for treating muscular contractures and low back pain. A dissolution test for the meloxicam-pridinol combined tablet formulation was developed and validated, using a suitable HPLC method for simultaneously quantitating both dissolved drugs. The optimized conditions include the use of USP apparatus 2 at a paddle rotation rate of 75 rpm and 900 ml of 50 mM phosphate buffer (pH= 7.5) as dissolution medium, at 37.0±0.5°. The test, which demonstrated to be robust against small changes in bath temperature, paddle rotation speed and pH of the dissolution medium, was applied to two different brands of tablets; the corresponding dissolution profiles were constructed and both brands showed to dissolve at least 75% of the drugs at the 45 min time point.
RESUMO
A dissolution test for tablets containing 100 mg of lamotrigine was developed and validated. The dissolution test was applied to compare the dissolution profile of Neural® with the reference product Lamictal®. The analysis procedure was carried out using a simple ultraviolet method at 267 nm. After the determination of solubility and sink conditions, the parameters selected were paddles at 50 rpm, 900 mL of 0.01 M hydrochloric acid, and 30 minutes duration (single point). This method was validated for specificity, linearity, accuracy, precision and robustness. Lamotrigine stability was also evaluated in dissolution medium.
A finalidade deste estudo foi desenvolver e validar um método de dissolução para o fármaco lamotrigina na forma farmacêutica comprimido. Este método também foi utilizado para comparar o perfil de dissolução entre o Neural® e o produto de referência Lamictal®. O procedimento analítico foi realizado utilizando-se espectrofotometria de absorção no ultravioleta (267 nm) como forma de quantificação do fármaco. Após a determinação da solubilidade e das condições sink, os parâmetros selecionados foram: pás (50 rpm), 900 mL de ácido clorídrico 0.01 M e o tempo de 30 minutos (único ponto). Este método foi validado através da especificidade, linearidade, exatidão, precisão e robustez. A estabilidade da lamotrigina também foi avaliada no meio de dissolução.