Análisis comparativo de la cinética de liberación de diclofenaco sódico a partir de matrices hidrofílicas en medios de disolución convencionales y biorrelevantes / A comparative analysis of the release kinetics of sodium diclofenac from hydrophilic matrices in conventional dissolution media and biorelevant media is carried out

Se utilizaron dos polímeros hidrofílicos comúnmente empleados en la formulación de matrices de liberación extendida, hidroxipropil-metil-celulosa (HPMC, hipromelosa) y óxido de polietileno (PEO), junto con celulosa microcristalina y lactosa, con el objetivo de estudiar la cinética de liberación del diclofenaco sódico en los aparatos II y III de la USP, en un medio de disolución compendial y en medios biorrelevantes. La cinética de liberación predominante en el aparato II fue uno y en el aparato III, cero. El valor de las constantes n y k aplicando la ley del exponente, indicaron tanto para el aparato II como para el III, que no se presenta el efecto "burst" y que el mecanismo predominante en la liberación del fármaco, es la relajación y la erosión del polímero. Los resultados sugieren que la metodología de disolución en un medio biorrelevante es apropiada para discriminar entre formulaciones y para predecir el desempeño in vivo de tabletas de liberación extendida de diclofenaco sódico.

Two hydrophilic polymers commonly employed on the development of extended release products, hydroxypropyl-methyl-cellulose (HPMC, hypromellose) and polyethylene oxide (PEO) were formulated with microcrystalline cellulose or lactose in order to investigate the release kinetics of sodium diclofenac on USP apparatus II and III using a compendial or biorelevant media, respectively. The dominant release kinetic on apparatus II was first order and zero on apparatus III. The values of the kinetic constant (k) and the release exponent (n) from the Power Law Model indicated that there was no burst effect in none of the studied formulations, relaxation and polymer erosion was the dominant mechanism of drug release in both methods. The results suggest that biorelevant dissolution methodology is appropriate for the discrimination of formulations and prediction of in vivo performance of MR diclofenac sodium matrices.

Development and Evaluation of Sustained Release Matrix Tablets of Indapamide using Methocel K15M CR.

In the present study an attempt has been taken to develop Indapamide sustained release matrix tablet using Methocel K15M CR by direct compression method. Various amount of polymer was used in the five proposed formulations (F-1to F-5) for the study of release rate retardant effect at 26.47%, 29.41%, 32.35%, 35.29% and 38.24% of total weight of tablet matrix respectively. Then the tablets were evaluated in terms of their physical parameters (weight variation, hardness, friability and thickness), drug content and in vitro release studies. All the formulations showed compliance with pharmacopoeial standards. The in vitro dissolution study were conducted using USP 30 dissolution apparatus type I (Basket method) in 900 ml phosphate buffer (pH 6.8) at 100 rpm for a total period of 24 hours. The release mechanisms were explored and explained by Zero order, Higuchi, First order and Korsmeyer-Peppas equations. Based on the dissolution data comparison with innovator brand formulation F-3 (32.35% Methocel K15M CR w/w) was found as the best formulation. The drug release profile of this formulation was well controlled and uniform throughout the dissolution studies. The drug release of formulation F-3 followed First Order kinetic model (r2 = 0.99) and the mechanism was found to be non- Fickian/anomalous according to Korsmeyer-Peppas equation.

Formulation and characterization of gastroretentive drug delivery system of losartan potassium.

Floating matrix tablets of losartan potassium were developed with an aim to prolong its gastric residence time and increase the bioavailability of drug. Rapid gastrointestinal transit could result in incomplete drug release from the drug delivery system above the absorption zone leading to diminished efficacy of the administered dose. The tablets were prepared by wet granulation technique, using polymers Methocel K15 and Methocel K100 in combination with other standard excipients. Sodium bicarbonate was incorporated as gas generating agent. The effects of sodium bicarbonate and polymers on drug release profile and floating properties were investigated. It was found that viscosity of Methocel K15 and Methocel K100 along with sodium bicarbonate had significant impact on the release and floating properties of the delivery system. The decrease in the release rate was observed with an increase in the viscosity of the polymeric system. Polymer with high viscosity Methocel K100 was shown to be beneficial than low viscosity polymer Methocel K15 in improving the floating properties of gastric floating drug delivery system (GFDDS). The observed difference in the drug release and floating properties of GFDDS could be attributed to the difference in the basic properties of two polymers, Methocel K15 and Methocel K100 due to their water uptake potential and functional group substitution. The release mechanism were explored and described with zero-order, first-order and Korsmeyer-Peppas equations. The drug release profiles and buoyancy of the floating tablets were stable when stored at 40°C/75% RH for 6 months.

Formulation and characterization of gastroretentive drug delivery system of losartan potassium.

Floating matrix tablets of losartan potassium were developed with an aim to prolong its gastric residence time and increase the bioavailability of drug. Rapid gastrointestinal transit could result in incomplete drug release from the drug delivery system above the absorption zone leading to diminished efficacy of the administered dose. The tablets were prepared by wet granulation technique, using polymers Methocel K15 and Methocel K100 in combination with other standard excipients. Sodium bicarbonate was incorporated as gas generating agent. The effects of sodium bicarbonate and polymers on drug release profile and floating properties were investigated. It was found that viscosity of Methocel K15 and Methocel K100 along with sodium bicarbonate had significant impact on the release and floating properties of the delivery system. The decrease in the release rate was observed with an increase in the viscosity of the polymeric system. Polymer with high viscosity Methocel K100 was shown to be beneficial than low viscosity polymer Methocel K15 in improving the floating properties of gastric floating drug delivery system (GFDDS). The observed difference in the drug release and floating properties of GFDDS could be attributed to the difference in the basic properties of two polymers, Methocel K15 and Methocel K100 due to their water uptake potential and functional group substitution. The release mechanism were explored and described with zero-order, first-order and Korsmeyer-Peppas equations. The drug release profiles and buoyancy of the floating tablets were stable when stored at 40°C/75% RH for 6 months.

Enhancement of dissolution rate of rapidly dissolving oral film of meclizine hydrochloride by complexation of Meclizine hydrochloride with ß-cyclodextrine.

Motion sickness is a very common disturbance of the inner ear that is caused by repeated motion such as from the swell of the sea, the movement of a car, the motion of a plane in turbulent air, etc. Most medications for motion sickness need to be taken at least 30 minutes prior exposure to the activity that can cause the problem. This project is based on the hypothesis that Mouth Dissolving Films (MDF) are rapidly dissolving dosage forms which when placed in the mouth release the drug immediately. These dosage forms would be preferred by pediatric and geriatric patients since these are not associated with fear of choking. The fast dissolving films prepared by solvent casting method with suitable appearance, mechanical strength, peelability and disintegration time were obtained using Methocel E-5 as a primary film former. Meclizine HCl, a poorly water soluble and bitter drug could be successfully incorporated in the fast dissolving films with the help of solubilizers such as β-Cyclodextrine and PEG-400.

Development of Sustain Release Matrix Tablet of Ranolazine Based on Methocel K4M CR: In Vitro Drug Release and Kinetic Approach.

In this study an attempt was made to design and evaluate oral sustained release matrix tablets of ranolazine using Methocel K4M CR as the retardant polymer. Tablets were prepared by conventional wet granulation technique. Tablets were evaluated for parameters such as weight variation, hardness, friability and drug content. All the formulations showed compliance with pharmacopieal standards. In vitro release studies were performed using USP type II apparatus (paddle method) in 900 mL of 0.1N HCl at 50 rpm for 8 hours. The release kinetics was analyzed using the zero-order, first order, Higuchi, Hixson-Crowell and Korsmeyer-Peppas equations to explore and explain the mechanism of drug release from the matrix tablets. In vitro release studies revealed that percent drug release decreased with increase of polymer loading. Based on the dissolution data comparison with innovator brand F-5 formulation (16% Methocel K4M CR w/w of drug) was elected as the best formulation. The drug release profile of the best formulation was well controlled and uniform throughout the dissolution studies. The drug release of optimized formulation follows the Higuchi kinetic model (R2 = 0.99) and the mechanism is found to be non-Fickian/anomalous according to Korsmeyer–Peppas equation. All the formulations were checked for stability as per ICH guidelines and formulations were found stable during the study.

Effect of stearic acid on the properties of metronidazole/methocel K4M floating matrices / Efeito do ácido esteárico nas propriedades de metronidazol / Methocel K4M matrizes flutuante

The properties of metronidazole/Methocel K4M sustained release floating tablets have been studied varying the proportion of the lubricant, stearic acid, on formulations with and without sodium bicarbonate. The variables studied include technological properties of the tablets such as tablet hardness and ejection pressure, the drug release profile, the hydration kinetics and the floating behaviour. The presence of stearic acid and sodium bicarbonate improves the floating behaviour for more than 8 hours. The hydration volume, the tablet hardness and the ejection pressure decrease as the stearic acid content increases and the polymer content decreases. Drug dissolution increases with increasing proportions of stearic acid and decreasing proportions of the polymer in the tablets. The presence of sodium bicarbonate extends the differences in dissolution produced by stearic acid. These results are attributed to decreasing matrices coherence with an increasing quantity of stearic acid and a reducing polymer proportion. The carbon dioxide bubbles produced by sodium bicarbonate expand the matrices facilitating the dissolution, although their presence obstructs also the diffusion path through the hydrated gel layer.

Estudaram-se as propriedades de comprimidos flutuantes de metronidazol/Methocel K4M de liberação controlada, variando-se a proporção do lubrificante, ácido esteárico, nas formulações com e sem bicarbonato de sódio. As variáveis estudadas incluem propriedades tecnológicas dos comprimidos, tais como dureza, pressão de ejeção, perfil de liberação do fármaco, cinética de hidratação e comportamento de flutuação. A presença de ácido esteárico e do bicarbonato de sódio melhora o comportamento de flutuação para mais de 8 horas. O volume de hidratação, a dureza e a pressão de ejeção do comprimido decrescem à medida que o conteúdo de ácido esteárico e de polímero diminui. A dissolução do fármaco aumenta com o aumento das proporções de ácido esteárico e a diminuição das proporções de polímero nos comprimidos. A presença de bicarbonato de sódio amplia as diferenças na dissolução produzidas pelo ácido esteárico. Estes resultados são atribuídos à coesão decrescente das matrizes, com o aumento da quantidade de ácido esteárico e a redução da proporção de polímero. Bolhas de dióxido de carbono produzidas pelo bicarbonato de sódio expandem as matrizes, facilitando a dissolução, embora a presença delas obstrua, também, a difusão através da camada de gel hidratado.