Dual coated microparticles for intestinal delivery of nimesulide

Although the underlying mechanisms are still in the realm of speculation, accumulating evidence indicates that NSAIDs can lower the incidence of colorectal carcinomas. However, long-term uses of non-selective NSAIDs can lead to gastrointestinal toxicity from sustained inhibition COX-1. But one can overcome such problem by formulating them as colon specific delivery. In the light of this information, the present study was carried out to develop oral colon targeted drug delivery system for Nimesulide utilizing recently designed and patented system called CODESTM, which consisted of a lactulose containing core over coated with both Eudragit E and Eudragit L designed to rapidly disintegrate in the colon, in order to give a new life for an existing banned drug. CODESTM tablets were prepared by tabletting the granulation of Nimesulide and lactulose, followed with film coating. The prepared tablets were evaluated on the basis of various pharmacopoeial characteristics. The onset of Nimesulide release was found to dependent on the coating level of Eudragit E, and at Eudragit E coating level of 8% (coating weight gain), the onset of in vitro drug release was found to be optimum. It is concluded that Nimesulide can be targeted to hindgut by Novel approach of CODESTM in a simple and economic way. Keywords:Nimesulide; NSAIDs, Colorectal Cancer; Colon Specific Delivery; Polymethacrylate polymers.

LATIN AMERICAN JOURNAL OF PHARMACY

The synthetic polymers and their combinations were employed to retard the release of nimesulide from microcapsules. Microcapsules were prepared in different ratios of Eudragit RL 100 and hydroxy propyl methyl cellulose (HPMC) separately and in combination. All formulations of microcapsules were compressed to tablets. Dissolution of microcapsules and their tablets was performed by USP-apparatus-II in 900 mL borate buffer of pH 8.4 at 37.0 ± 0.5 ºC, at 50 rpm. In vitro kinetics was determined by various models including Zero order, First Order, Higuchi, Korsmeyer-Peppas and Hixson-Crowell. Eudragit showed higher retarding effect over extended period of time on release of drug than HPMC alone or its combination with Eudragit.

Latin Am. J. …, 2010

SUMMARY. The aim of this study was to formulate ethyl cellulose (EC) microparticles for sustained release of nimesulide and study the effect of processing variables, drug to polymer ratio and also study the drug polymer compatibility. The microparticles were ...

Macromolecular Bioscience, 2008

Asian Journal of Pharmaceutics, 2012

T he aim of this research work was to formulate and systematically evaluate in vitro performance of gastroretentive microcapsules of nifedipine for biliary colic. Cross-linked reinforced alginate-chitosan microcapsules were prepared by ionotropic gelation method using calcium chloride (CaCl 2) as a cross-linking agent. The microcapsules were evaluated for physical characteristics such as particle size, particle shape and surface morphology by scanning electron microscopy, drug entrapment efficiency, in vitro drug release and in vitro bioadhesion studies. Results of preliminary trials indicated that the polymer concentration, cross-linking agent and chitosan had a noticeable effect on size and surface morphology. A Box-Behnken design was employed to study the effect of independent variables, polymer concentration (X 1), CaCl 2 concentration (X 2), chitosan (X 3) and pH of encapsulation medium (X 4) on dependent variables, drug entrapment efficiency and percentage drug release respectively. The entrapment efficiency varied from 6.14 to 79.21% depending upon the independent variables. The release can be sustained for more than 7 hours for all batches. It was observed that polymer and cross-linker concentration had a more significant effect on the dependent variables.Validation of optimization study, performed using 6 confirmatory runs, indicated very high degree of prognostic ability of response surface methodology, with mean percentage error (± SD) as-0.85 ± 4.39% and 2.83 ± 2.91% for drug entrapment and drug release. Optimization was done on the basis of maximum entrapment (82.26%) which was predicted using 6% alginate, 8.11% CaCl 2 , 2% chitosan at a pH of 3.55 of encapsulation medium. The optimized formulation depicted a release of 57.17% at 7 hours. Point prediction tool of design expert software shows 101.91% and 96.82% validity of the predicted model for drug entrapment and percent drug release. The release follow Higuchi kinetics followed by non-fickian diffusion process. In vitro wash off test showed 71% bioadhesion after 1 hour.

This work aimed at studying factors affecting preparations of chitosan microcapsules for colonic drug delivery. Chitosan microcores (CS, 45kDa, 87% degree of deacetylation) containing diclofenac sodium (DS) coated with Eudragit®S100 (ED) were prepared by a desolvation technique. Sodium sulfate was used as a desolvating agent and the drying process was freeze-drying. Factors affecting morphology, particle size and zeta potential of microcapsules were evaluated, i.e. weight ratio of DS:CS:ED, surfactant (polysorbate 80), anti-adherent (silicon dioxide), and the use of sonication or homogenization in preparation processes. The weight ratio of DS:CS:ED at 1:2:6 provided the smallest microcapsules of about 82.37±1.61 micrometer in diameter and they were in aggregated forms. Zeta potential of the microcapsules was around -25.74 +4.78 mV which indicated that the core particles of CS and DS with zeta potential of 42.14±1.74 mV were encapsulated by ED. Increasing the amount of CS and ED, the...

Science and Engineering of Composite Materials, 2013

Xanthan-gum-facilitated aspirin-loaded ethyl cellulose microparticles were prepared by multiple-emulsion solvent evaporation technology and the impact on variation in process parameters was investigated systematically. Scanning electron microscopy was performed to determine the surface morphology of the microparticles before and after dissolution study. X-ray diffraction (XRD), differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) analysis were performed, and yield value, swelling study, encapsulation efficiency, flow properties and dissolution profiles of the prepared formulations were evaluated. The size of microparticles varied between 247 and 410 μm, and 58.34% drug entrapment efficiency was achieved depending on the variation in process parameters. The drug release in acid solutions was slower than in alkaline solution. The microparticles provided extended drug release in alkaline dissolution medium, and the drug release was found to be controlled by Fickia...

European Journal of Pharmaceutics and Biopharmaceutics, 2008

Using a novel one-step spray-drying process uncoated and Eudragit Ò S 100 coated chitosan-Ca-alginate microparticles efficiently loaded with budesonide (BDS), with bioadhesive and controlled release properties in GIT, were prepared. Microparticles were spherical with mean particle size of 4.05-5.36 lm, narrow unimodal distribution and positive surface charge. A greater extent of calcium chloride limited the swelling ratio of beads, while swelling behaviour of coated beads was mainly determined by properties of enteric coating. Comparing the release profiles of formulations, under different pH conditions, influence of polymer properties and concentration of cross-linker on the rate and extent of drug release was evident. Coating has successfully sustained release of BDS in buffers at pH 2.0 and 6.8, while providing potential for efficient release of BDS at pH 7.4. Release data kinetics indicated influence of erosion and biodegradation of polymer matrix on drug release from microparticles. Prepared formulations were stable for 12 months period at controlled ambient conditions.

Chitosan, a polymer derived from crustacean chitin, has a number of properties that make it potentially valuable as a pharmaceutical excipient. In the studies described, microcrystalline chitosan (MCCh), a highly crystalline grade of chitosan base, was evaluated for the first time as an excipient. The first objective was to determine its properties in vitro as a gel-forming and drug release rate controlling excipient in granules, and as a mucoadhesive polymer. The properties of MCCh were compared with those of conventional chitosan, which is predominantly amorphous. Attention was also given to the effects of the molecular weight (M w ) and degree of deacetylation (DD) of MCCh on its properties. The ultimate objective was to evaluate, in studies on human volunteers, whether MCCh granules could be useful as slow-release systems for gastro-retentive drug delivery.