Test of dissolution and comparison of in vitro dissolution profiles of coated ranitidine tablets marketed in Bahia, Brazil

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.

[Does ranitidine alter the pharmacokinetic of metformin?]

As Metformin is prescribed for a long-term therapy, it may be coadministered with a lot of other medicines. Ranitidine is a cationic drug and theoretically could decrease the excretion of metformin by competing for renal tubular transport. Increased metformin levels may increase the risk of lactic acidosis, in type II diabetic patients. The main goal of study the pharmacokinetics of Metformin is to help physicians to determine the accurate dose of Metformin, that enable them to have good glycemic control in patient with type II diabetes mellitus. Many medicines alter the pharmacokinetics of Metformin use and that make modifying of the dose necessary. An overview of metformin in the treatment of type II diabetes mellitus was studied by Davidson and Peters [1997]. Marked hypoglycemia was seen in patients on Glibenclamide when treated with Ranitidine [Lee et al; 1987], and another report briefly describes hypoglycemia in two patients given Cimetidine, and two other given Ranitidine, while taking un-named sulfonylureas [Girardin et al. 1992]. Another study reported that the hypoglycemic effect was reduced by Cimetidine and Ranitidine [Guthrie 1996]. In general view of the potential interactions, which may ultimately be hazardous due to long-term therapy of metformin with H2 receptor antagonists, the present study is focused on drug interactions of metformin with the commonly prescribed H2 receptor antagonist Ranitidine at human body temperature. This research aims to study the interaction between Metformin and one of another medicines which are commonly used together. We choose to study the interaction between the Ranitidine and Metformin, in patients with type II diabetes mellitus. Especially when different studies, about the coadministration of metformin and antacids, was contradictories, and was realized in lab. conditions not in humans. Fifteen male volunteers [25-40 years] received oral Metformin [500 mg every 12 hours] for 4 days, Ranitidine [150 mg every 12 hours] in combination of oral Metformin [500 mg every 12 hours] for 4 days. Plasma samples were collected on day 4 of each regimen. The result showed that coadministration of Metformin and Ranitidine had no significant effects on the steady state pharmacokinetics [AUC: 0-12 h, Cmax, Tmax or Tl/2] of Metformin in patient with type II diabetes mellitus

Influence of certain retardants on the release of ranitidine hydrochloride

Solid dispersions of ranitidine hydrochloride with different polymers of methacrylic resins were prepared using different drug-retardants ratios and adopting the coprecipitation technique. The influence of these retardants on the dissolution rate of the drug was studied. It was found that the type of retardants as well as their concentrations affected to a great extent the release of ranitidine hydrochloride from the prepared solid dispersions. The solid dispersion consisted of the drug with a mixture of Eudragit RS 100 and a chewing gum base in a ratio of 1: 2 in both cases. Analysis of the dissolution data by the linear regression method revealed that the release of the drug from its solid dispersions followed the first order kinetics with Eudragits as well as a mixture consisting of Eudragit RS 100 and chewing gum base. It was found that solid dispersions made with drug and Gelucires as well as Rhodopases followed the diffusion model. Infrared spectroscopy revealed that ranitidine hydrochloride formed insoluble complexes with Eudragit RS 100

Ranitidina, inhibidor de la permeabilidad vascular en la rata / Inhibitory effects of ranitidine on the vascular permeability in rat

La alta afinidad de la ranitidina hacia el receptor histaminérgico H2 y la sospecha de su participación en cambios de permeabilidad vascular, nos motivo a investigar si la ranitidina tiene efectos inhibitorios sobre los cambios en la permeabilidad provocados por la histamina. Para lograr este objetivo, se utilizaron 3 lotes de ratas variedad Wistar: Lote control, lote histamina y lote ranitidina + histamina. Se determinaron las concentraciones de proteínas totales, albúmina, sodio y cloro como indicadores de cambios en la permeabilidad vascular. Nuestros resultados demuestran parcialmente, que la ranitidina inhibe los incrementos de permeabilidad provocados por la histamina. Aunque clásicamente se ha atribuido al receptor H1, la regulación de la permeabilidad inducida por histamina, es probable que el receptor H2 también este involucrado tal como se demostró en este trabajo al bloquear su activación con ranitidina

Modelos isotermicos cinéticos de disolución de clorhidrato de ranitidina en tabletas / Kinetic isotermic models of dissolution of ranitidin hydrocloride tablets

Mediante un diseño experimental de bloques completamente aleatorizados, se determinó la cinética de disolución del clorhidrato de ranitidina en tabletas en dos medios de disolución. En medio acuoso, todos los productos investigados siguen una cinética de disolución de orden uno con un error de 1 por ciento y del 5 por ciento. En medio ácido, con error del 1 por ciento y del 5 por ciento el producto A sigue una cinética de disolución de orden uno, mientras que el producto B y C siguen la cinética de disolución de la raíz cúbica. en general las tabletas de clorhidrato de ranitidina se disuelven más rápidamente en medio acuoso

Pharmacokinetics of oral ranitidine in Mexicans

The pharmacokinetics of oral ranitidine were studied in 24 Mexican male healthy volunteers. Subjects received a tablet containing 150 mg of ranitidine (Azantac TM, Glaxo de Mexico, Mexico, City) after an overnight fast and blood samples were drawn at several times for a period of 24 h. Ranitidine concentration in plasma was measured by high performance liquid chromatography and pharmacokinetic parameters were determined by non-compartmental analysis. Ranitide plasma concentration increased with time, reaching a maximum of (mean ñ SEM) 484 ñ 34 ng/ml in 2.7 ñ 0.2 h. Plasma levels then decayed with a terminal half-life of 4.8 ñ 0.3 h. The area under the plasma concentration against time curve was 2440 ñ 126 ngh/ml. Oral ranitidine pharmacokinetic parameters in mexicans appeared to be similar to those previously reported for caucasians

Farmacocinetica da nitrendipina em pacientes com hipertensao arterial: estudo de interacao / Pharmacokinetics of nitrendipine in patients with arterial hypertension: a drug interaction study

Em estudo randomizado cruzado administrou-se nitrendipina, sob forma de comprimidos, 20mg/dia p.o. e placedo, ou dose identica de nitrendipina associada a 300 mg de ranitidina, 150 mg duas vezes ao dia a 12 pacientes com hipertensao essencial sistemica. Um deles foi excluido do estudo apos desenvolvimento de falha renal. Os niveis plasmaticos da nitrendipina no intervalo de dose foram significativamente aumentados, p < 0,001, quando a ranitidina foi associada. O clearance da antipirina foi reduzido em 15%, p < 0,001, pela ranitidina numa extensao inferior aquela provocada pela cimetidina. A depuracao plasmatica foi reduzida de 2008 mais ou menos 246ml/min para 1284 mais ou menos 182 ml/min, p < 0,002, ranitidina; consequentemente o parametro AUC 0-24 foi aumentado, p < igual 0,01, quando a ranitidina foi coadministrada. Os parametros cineticos da nitrendipina estimados nao foram significativamente alterados pela ranitidina, relativamente as constantes de velocidade e respectivas meias-vidas das fases de absorcao, distribuicao e eliminacao. Nao ha evidencia de acumulo da nitrendipina pela ranitidina, apesar da interacao farmacocinetica obtida em pacientes hipertensivos