Characterization of Eudragit types and Kollidon SR inter-polymer complexes and their effects on the drug release

A novel of polymer combination promotes an increase of the ability for controlling the drug release. The objectiveof this research was to characterize the inter-polymer complexes (IPCs) of Eudragit (Eud) types (Eud RS, Eud L, orEud E) and Kollidon SR (KSR), and elucidate their effects on the drug release kinetics and mechanism. Differentpreparation techniques were proposed using spray drying and ultrasonic-assisted anti-solvent techniques. The thermalactivity, e.g., glass transition temperature (Tg) and Fourier transform infrared spectroscopy were used to characterizethe molecular interaction of these IPCs. Theophylline (THP) was selected as a drug model. The effect on the drugrelease kinetics and mechanism was the main concern of this study. Depending on the results, the hydrogen bondingformation between polymers was observed by a shifting of OH and carbonyl group vibrations. In addition, the van derWaals interaction was identified by an alteration in the vibrational band around the 1,000–1,500 cm−1. Meanwhile, thechange of physicochemical characteristic was identified by the Tg of IPCs. Eud E-KSR and Eud E-Eud L IPC wereunable to control the THP release. Meanwhile, Eud L-KSR IPC and Eud RS-KSR IPC were success to control theTHP release, but it was pH dependent and independent, respectively. This study concluded that the IPCs allowed theTHP release in a controlled manner based on the IPC characteristics and their interactions. Either positive or negativeinteractions on the drug release were observed due to native characteristics of polymers.

Use of hydrophilic and hydrophobic polymers for the development of controlled release tizanidine matrix tablets

The aim of the present study was to develop tizanidine controlled release matrix. Formulations were designed using central composite method with the help of design expert version 7.0 software. Avicel pH 101 in the range of 14-50% was used as a filler, while HPMC K4M and K100M in the range of 25-55%, Ethylcellulose 10 ST and 10FP in the range of 15 - 45% and Kollidon SR in the range of 25-60% were used as controlled release agents in designing different formulations. Various physical parameters including powder flow for blends and weight variation, thickness, hardness, friability, disintegration time and in-vitro release were tested for tablets. Assay of tablets were also performed as specified in USP 35 NF 32. Physical parameters of both powder blend and compressed tablets such as compressibility index, angle of repose, weight variation, thickness, hardness, friability, disintegration time and assay were evaluated and found to be satisfactory for formulations K4M2, K4M3, K4M9, K100M2, K100M3, K100M9, E10FP2, E10FP9, KSR2, KSR3 & KSR9. In vitro dissolution study was conducted in 900 ml of 0.1N HCl, phosphate buffer pH 4.5 and 6.8 medium using USP Apparatus II. In vitro release profiles indicated that formulations prepared with Ethocel 10 standard were unable to control the release of drug while formulations K4M2, K100M9, E10FP2 & KSR2 having polymer content ranging from 40-55% showed a controlled drug release pattern in the above mentioned medium. Zero-order drug release kinetics was observed for formulations K4M2, K100M9, E10FP2 & KSR2. Similarity test (f 2) results for K4M2, E10FP2 & KSR2 were found to be comparable with reference formulation K100M9. Response Surface plots were also prepared for evaluating the effect of independent variable on the responses. Stability study was performed as per ICH guidelines and the calculated shelf life was 24-30 months for formulation K4M2, K100M9 and E10FP2.

O objetivo do presente estudo foi desenvolver matriz de de tizanidina de liberação controlada. As formulações foram projetadas usando o método do componente, central com a ajuda de software Design expert(r), versão 7.0. Utilizou-se Avicel pH 101, no intervalo de 14-50%, como material de preenchimento, enquanto HPMC K4M e K100M, no intervalo de 25-55%, Etilcelulose 10 ST e 10FP, no intervalo de 15-45% e Kollidon SR, na faixa de 25-60% foram utilizados como agentes de liberação controlada, no planejamento de formulações diferentes. Vários parâmetros físicos, incluindo o fluxo de pó para as misturas e variação de peso, espessura, dureza, friabilidade, tempo de desintegração e liberação in vitro, foram testados para comprimidos. Ensaios dos comprimidos foram, também, realizados, tal como especificado em USP 35 NF 32. Avaliaram-se os parâmetros físicos de ambos, mistura em pó e comprimidos, como índice de compressibilidade, ângulo de repouso, variação de peso, espessura, dureza, friabilidade, tempo de desintegração e de ensaio, considerando-os satisfatórios para as formulações K4M2, K4M3, K4M9, K100M2, K100M3, K100M9, E10FP2, E10FP9, KSR2, KSR3 e KSR9. O estudo de dissolução in vitro foi realizado em 900 mL de HCl 0,1 N, tampão de fosfato pH 4,5 e meio 6,8, usando aparelho USP II. Os perfis de liberação in vitro indicaram que as formulações preparadas com Ethocel 10 padrão não foram capazes de controlar a liberação do fármaco, enquanto as formulações K4M2, K100M9, E10FP2e KSR2, com teor de polímero variando entre 40 e 55% apresentaram padrão de liberação controlada de fármaco no meio anteriormente mencionado. Observou-se cinética de liberação de fármaco de ordem zero para as formulações K4M2 , K100M9, E10FP2 e KSR2. Resultados do teste de similaridade (f 2) para K4M2, E10FP2 e KSR2 foram comparáveis com a formulação de referência K100M9. Gráficos de superfície de resposta também avaliaram o efeito da variável independente sobre as respostas. Estudo de estabilidade foi realizado conforme as diretrizes do ICH e a vida de prateleira calculada foi de 24-30 meses para as formulações K4M2, K100M9 e E10FP2.

Formulation development of directly compressed Naproxen SR tablet using Kollidon SR and Avicel PH 102 polymer.

Naproxen is a well-known non-steroidal anti-inflammatory drug (NSAID). This work has been done for developing a formulation of 280 mg sustained release (SR) tablet where 150 mg active pharmaceutical ingredient (Naproxen) were used along with other excipients like Kollidon SR, Avicel PH 102, Lactose MH, Povidone K 30 and Mg-Stearate. Naproxen SR tablet was prepared by direct compression method aiming to enhance its dissolution properties. The physical parameters (hardness, thickness, diameter, average weight and friability) and drug release profile of this tablet were evaluated. The hardness of tablets from F1 and F2 formulation were highest and rest of them was also satisfactory. F2 formulation did not meet the friability test. But rests of the formulations were acceptable which indicate that others formulations can handle pressure during storage, transportation and packaging. All the formulations released 90% of drug within 120 minutes except F4 formulation. Among the six formulations, release was prompt in F1 formulation because of usage of higher concentration of polymer Kollidon SR. The outcome of this study indicates that the rate of dissolution of Naproxen SR tablet can be considerably improved with Kollidon SR.

Formulation development of directly compressed Naproxen SR tablet using Kollidon SR and Avicel PH 102 polymer.

Naproxen is a well-known non-steroidal anti-inflammatory drug (NSAID). This work has been done for developing a formulation of 280 mg sustained release (SR) tablet where 150 mg active pharmaceutical ingredient (Naproxen) were used along with other excipients like Kollidon SR, Avicel PH 102, Lactose MH, Povidone K 30 and Mg-Stearate. Naproxen SR tablet was prepared by direct compression method aiming to enhance its dissolution properties. The physical parameters (hardness, thickness, diameter, average weight and friability) and drug release profile of this tablet were evaluated. The hardness of tablets from F1 and F2 formulation were highest and rest of them was also satisfactory. F2 formulation did not meet the friability test. But rests of the formulations were acceptable which indicate that others formulations can handle pressure during storage, transportation and packaging. All the formulations released 90% of drug within 120 minutes except F4 formulation. Among the six formulations, release was prompt in F1 formulation because of usage of higher concentration of polymer Kollidon SR. The outcome of this study indicates that the rate of dissolution of Naproxen SR tablet can be considerably improved with Kollidon SR.

In Vitro Evaluation of Oral Extended Release Drug Delivery System for Metoprolol Succinate Using Kollidon SR.

The objective of this study was to develop a sustained release matrix tablet Metoprolol Succinate by cost saving and production efficient process. Among various tablet manufacturing process, direct compression is the simplest and cost saving process. Different trials were formulated and evaluated using different concentrations of directly compressible grade Kollidon SR as release retardant. The formulated tablets were evaluated for physical and dissolution study using buffer medium. The most outstanding aspect of this study is to monitor the influence of different percentage of Kollidon SR on release rate from the matrix tablet. In this study, influence of different ratio of polymer concentration on drug release was evaluated. The release pattern of different batches were evaluated for Zero order, Higuchi, First order, Krosmeyer-Peppas and Hixson-Crowell kinetics and showed that all the batches followed best the Higuchi kinetics. The drug release kinetics was found to be governed by the amount of the polymer in the matrix system. The higher polymeric content in the matrix decrease the release rate of the drug. The nature of the drug release from the matrix tablets was dependent on drug diffusion and polymer relaxation and therefore followed non-Fickian or anomales release. The studies indicated that the drug release can be modulated by varying the concentration of the polymer. Among the four formulations, formulation 1 is the best formulation as it controls the release best and best linearity for zero order plots.

Development and evaluation of sustained release losartan potassium matrix tablet using kollidon SR as release retardant

The present study was undertaken to develop sustained release (SR) matrix tablets of losartan potassium, an angiotensin-II antagonist for the treatment of hypertension. The tablets were prepared by direct compression method, along with Kollidon SR as release retardant polymer. The amount of losartan potassium remains fixed (100 mg) for all the three formulations whereas the amounts of Kollidon SR were 250 mg, 225 mg, and 200 mg for F-1, F-2, and F-3 respectively. The evaluation involves three stages: the micromeritic properties evaluation of granules, physical property studies of tablets, and in-vitro release kinetics studies. The USP apparatus type II was selected to perform the dissolution test, and the dissolution medium was 900 mL phosphate buffer pH 6.8. The test was carried out at 75 rpm, and the temperature was maintained at 37 ºC ± 0.5 ºC. The release kinetics was analyzed using several kinetics models. Higher polymeric content in the matrix decreased the release rate of drug. At lower polymeric level, the rate and extent of drug release were enhanced. All the formulations followed Higuchi release kinetics where the Regression co-efficient (R²) values are 0.958, 0.944, and 0.920 for F-1, F-2, and F-3 respectively, and they exhibited diffusion dominated drug release. Statistically significant (P<0.05) differences were found among the drug release profile from different level of polymeric matrices. The release mechanism changed from non-fickian (n=0.489 for F-1) to fickian (n=0.439 and 0.429 for F-2, and F-3 respectively) as a function of decreasing the polymer concentration. The Mean Dissolution Time (MDT) values were increased with the increase in polymer concentration.

O presente estudo foi realizado para desenvolver (SR) matriz de comprimidos de liberação sustentada de losartana, um antagonista da angiotensina II, para o tratamento da hipertensão arterial. Os comprimidos foram preparados pelo método de compressão direta com Kollidon SR como polímero de liberação lenta. A quantidade de losartana potássica permanece fixa (100 mg) para todas as três formulações enquanto que as quantidades de Kollidon SR foram de 250 mg, 225 mg e 200 mg para F-1, F-2 e F-3, respectivamente. A avaliação envolve três etapas- propriedades micromeríticas dos grânulos, estudo das propriedades físicas dos comprimidos e estudos de cinética de liberação in vitro.. Selecionoou-se o aparelho USP tipo II para realizar o teste de dissolução em meio com 900 mL de tampão fosfato pH 6,8 . O teste foi realizado em 75 rpm e a temperatura foi mantida a 37 ºC ± 0.5 ºC. Analisou-se a cinética de liberação utilizando-se vários modelos cinéticos. Conteúdo mais alto de polímero na matriz reduziu a taxa de liberação do fármaco. Em níveis mais baixos de polímero, a taxa e a extensão de liberação do fármaco foram aumentados. Todas as formulações seguiram a cinética de liberação de Higuchi, em que os valores do coeficiente de regressão (R2) foram 0,958 , 0,944 e 0,920 para F-1, F-2 e F-3, respectivamente, e elas apresentaram liberação do fármaco dominada pela difusão. Encontraram-se diferenças estatisticamente significativas (P<0,05) entre os perfis de liberação do fármaco com diferentes níveis de matrizes poliméricas. O mecanismo de liberação mudou de não-fickiano(n=0,489 para F-1) para fickiano(n=0,439 e 0,429 para F-2 e F-3, respectivamente) em função da diminuição da concentração de polímero. Os valores do Tempo de Dissolução Média (TDM) aumentaram com o aumento da concentração polímero.

Evaluation of Kollidon SR based Ketorolac Tromethamine Loaded Transdermal Film.

The present study concerns the development of polymeric films of Ketorolac tromethamine by solvent casting method to explore the possibilities of using kollidon SR as a transdermal drug delivery system. Ketorolac tromethamine was used as a model drug & incorporated in low doses. The films were prepared by using various amounts of Kollidon SR to prolong the drug release with localized action. Some films were also prepared containing certain percent of PEG-6000 along with the drug & polymer. The prepared polymeric films were evaluated for various parameters like weight uniformity, flatness, % elongation, surface pH, uniformity of drug content, in-vitro dissolution studies. The drug-polymer ratio was found to influence the drug release. The rate of drug release decreased with increased polymer concentration. About 10% increased in polymer concentration causes 50% decreased drug release. All the formulation followed Higuchian kinetics & the mechanism of release was diffusion mediated. When PEG-6000 was used as a channeling agent in this formulation drug release was increased accordingly but higher concentration of PEG-6000 results in decreasing release rate of drug because of increasing viscosity of the matrix channels.

Formulation and comparison of in vitro release profile of hydrophilic and hydrophobic polymer based Naproxen matrix tablets.

The study was aimed to investigate the effect of polymer on the release profile of Naproxen from different percentages of HPMC 5cps and Kollidon SR based matrix systems. Different amount of HPMC and Kollidon SR were used to develop matrix builder in the four proposed formulations (F1-F4) for the study of release rate retardant effect at 25% and 35% of total weight of tablet matrix respectively. The tablets were prepared by direct compression method. The granules and tablets were evaluated for their physical properties and they did not show any significant variations and were found to have good physical integrity. The dissolution study of those proposed formulations were carried out in the simulated intestinal medium (pH 7.4) for 8 hours using USP paddle method with 50 rpm at 37±0.5⁰C. HPMC is hydrophilic and Kollidon SR is hydrophobic in nature. Statistically significant difference were found among the drug release profile from different percent of polymer and the release mechanisms were explored and explained with zero order, Higuchi and Korsmeyer equations. The release of Naproxen from F-1 and F-2 very closely followed Korsmeyer release kinetics where F-3 and F-4 best fitted with Higuchi model. The cumulative percent release of Naproxen was highest in F-2 containing 35% of HPMC. On the basis of results, it was found that the profile of F-1 formulation was the best among the four formulations. Between these two polymers, HPMC showed better percentage of release and Kollidon SR showed better release retardant effect.

Development of pH-independent matrix type sustained release drug delivery system of propranolol hydrochloride.

The characteristics of a new Polyvinylacetate/Povidone based excipient, Kollidon® SR were evaluated for application in extended release matrix tablets. The effects of the following formulation and process variables on tablet properties and drug release were tested: Kollidon® SR concentration in the tablet, addition of external binder for wet granulation, presence of an enteric polymer in the matrix, method of manufacturing and compression force. The similarities in release profiles were evaluated by applying the model independent f2 similarity factor. It was found that Kollidon® SR is suitable for pH-independent extended release matrix tablets. A minimum concentration of 30% polymer was necessary to achieve a coherent matrix, able to extend the release of the incorporated drugs. Increasing the Kollidon® SR concentration in the tablet led to a slower drug release. Drug release followed square root of time dependent kinetics, thus indicating a diffusion-controlled release mechanism. The drug release was influenced by the aqueous solubility of the drug. The drug release rate was faster for wet granulation than direct compression, thus making direct compression the method of choice for manufacturing Kollidon® SR extended release systems. It was found that Kollidon® SR was the main release controlling agent in the presence of an external binder or enteric polymer in the matrix. A significant reduction in the dissolution rates associated with an increase in tablet hardness was observed during the stability test under accelerated conditions. The developed propranolol matrix tablets formulation was compared to the reference listed product (Inderal® LA capsules). It was concluded that Kollidon® SR is a potentially useful excipient for the production of pH-independent extended release matrix tablets.