Influence Of Talc As Anti-tacking Agents On Eudragit®NE 30D Coatings

The use of controlled release dosage forms has increased significantly in recent years as they result in increased patient compliance and higher therapeutic efficiency. Polymeric materials have been used to coat pharmaceutical solid dosage forms to achieve a prolonged therapeutic effect by slow and continuous release of active ingredients over extended period of time. Insoluble excipients are often included in polymeric film coating formulations to prevent or reduce agglomeration of the solids during the coating process. Talc, a hydrophobic, water-insoluble compound, is one of the most commonly used anti-adherents employed in film coating formulations. The inclusion of these insoluble additives in coating formulations may affect processing parameters, the physical appearance of the final product, the mechanical strength of the film, polymer adhesion, the permeability of the film, and even the dissolution characteristics of the coated solid. This article will address the various polymer properties that may be influenced by the addition of insoluble powder particles to the coating formulation and will discuss how the characteristics of the additive can be used to predict the behavior in the final film coating. In this paper, metoprolol tartrate(MT) was chosen as the model drug, and MT sustained release pellets(SRP) were prepared successfully based on the osmotic pumping and diffusion mechanism, meanwhile the in vitro/vivo release of the MT-SRP were also studied.1. Influence of insoluble excipients on film coating systemsThe resultsof pellet swelling behavior, water vapor transmission test, drug permeability studies, water uptake and weight loss test and scanning electron microscopy showed that marked changes occur in the appearance and the permeability of film when the concentration of an insoluble powder in film coating formulations is no less then50% w/w of the dry polymer which has exceededthe CVC. And the results of free film water uptake and weight loss test showed that talc didn’t affect the swelling of polymer. The mechanicalproperties of the films were determined both in dry and wet state and the results showed that the addition of talc to polymer reduced the tensile strength and elongationand increased the elastic modulus of free films. The results of single pellet dissolution showed that the addition of talc to polymer reduced uniform of film. Talc promoted to form stable film.2. Thedesignsof MT-SRPThe precise and reliable methods to analysis in vitro of MT-SRP wereestablished using UV and HPLC respectively which provided a basis for thefurther studies of pharmaceutics. Effects of layering formulation on the smooth surface and loading efficiency of drug-layered cores were investigated using singlefactor test. On the base of single factor testing, the optimum formulation is as follows: 100% w/v drug solution in ethanol-water(2:1 v/v) containing 20% w/v talc. Effects of coating formulation on in vitro release were invested using single factortest. The optimum formulation is as follows:15% w/v Eudragit®NE30D(based on dry polymer) with 75% w/w talc(based on dry polymer) in water and 15% coating level. t25%, t50% and t75% of MT-SRP is 0.89, 2.68 and 7.94 h, respectively. The drug release behavior in vitro was independent of p H and agitation.Biopharmaceutical study of this optimized formulation was studied in beagle dogs. A close correlation(R2 = 0.98) was established between the in vitro release and the in vivo absorption of drug.Stability data of stress testingand accelerated testing revealed that pellets were stable. Drug release from 15% Eudragit®NE30D-coated pellets with 75% w/w talc(based on dry polymer) in the coating layer followed a first-order release kinetics rather other the traditional sigmoid release pattern.Drug release is likely to be controlled by osmotic pressure inside film and diffusion through the water-filled pores.