Eudragit L30D-55 Research Articles

Influence of Tablet Hardness and Hydrophobicity on the Adhesive Properties of an Acrylic Resin Copolymer

The adhesive properties--including the force of adhesion, elongation at adhesive failure, the modulus of adhesion, and the adhesive toughness--of an acrylic resin copolymer were determined using the butt adhesion technique. Flat-faced tablets containing up to 30% hydrogenated castor oil were coated with an aqueous dispersion of Eudragit L30D-55. Using data obtained from a Chatillon digital force gauge attached to a motorized test stand, force-deflection profiles, similar to stress-strain curves generated in the tensile testing of free films, were constructed. The surface characteristics of the tablets significantly influenced polymer-substrate interaction. The force of adhesion, the elongation at adhesive failure, and the adhesive toughness decreased as the surface of the tablet became more hydrophobic through the addition of wax to the tablet formulation. Lower adhesive properties were found with increasing tablet hardness, due to a decrease in the effective area of contact between the film coating and the tablet surface. Increased polymer loading resulted in stronger adhesion, indicating a relationship between the mechanical and adhesive properties of the polymer. The present study demonstrated that the area under the force-deflection profile in conjunction with the force of adhesion was more representative of the adhesive properties of the polymer.

Variables That Affect the Mechanism of Drug Release from Osmotic Pumps Coated with AcrylatefMethacrylate Copolymer Latexes

The feasibility of using modified Eudragit acrylic latexes as microporous coatings for osmotic devices was investigated. Potassium chloride tablets were coated with mixtures of Eudragit RS30D and RL30D acrylic latexes that also contained a plasticizer (triethyl citrate or acetyl tributyl citrate) and a pore‐forming agent (urea). A 25‐1fractional factorial experimental design was employed to determine the effect of five formulation variables (RS30D:RL30D polymer ratio plasticizer type, plasticizer level, urea level, and cure) on the in vitro release rate of KCl in deionized water (di water), lag time, and coat burst strength. The RS30D:RL30D polymer ratio had the greatest effect on the release rate, and both lag time and burst strength were most affected by the urea level. Statistical optimization was performed, and a coat formulation with predicted desirable in vitro performance was prepared and tested. The in vitro release rate (di water), lag time, and coat burst strength agreed well with the prediction. Dissolutions were also performed in phosphate buffered saline (PBS; pH 7.4); several formulations released markedly slower in PBS than in di water. This discrepancy was dependent on the type of plasticizer and the amount of pore former. Only those coat formulations containing acetyl tributyl citrate as the plasticizer and a 100% urea [(g urea/g polymer solids) × 100] level exhibited similar release rates in di water and PBS. The mechanism of release from these devices was primarily osmotic, whereas the release from devices coated with a formulation containing triethyl citrate and 50% urea was not dependent on the osmotic pressure difference. Devices with an osmotic release mechanism behaved similarly in vivo and in vitro. Devices that were not osmotic released KCl at rates that were substantially slower in PBS and in vivo than release rates in di water.

Measurement of Adhesive Force between Particles of Organic Substances and Polymer Substrates by the Centrifugal Separation Method: Effect of Electrostatic Charge.

Effects of electrostatic force on adhesion between pharmaceutical powder particles (phenacetin and sulfadimethoxine) and various polymer substrates (polyethylene (PE), polyvinylchloride (PVC), Eudragit E100, polyvinylacetal diethylamino acetate (AEA), Eudragit L30D-55) were investigated using the centrifugal separation technique. Two methods were used to attach powder particles to a substrate, the free falling method and the fluidization method. Average adhesive force, f 50 , and electric potential, V, in the fluidized method were found to be greater than those in the free falling method for all the pharmaceutical powder/polymer substrate systems examined. Average adhesive force, f 50 , increased with a decrease in surface polarity, P 0 , of polymer substrate for each powder

Evaluation of Thermal and Film Forming Properties of Acrylic Aqueous Polymer Dispersion Blends: Application to the Formulation of Sustained-Release Film Coated Theophylline Pellets

Aqueous acrylic polymer dispersions were blended in order to improve processing and film formation from acrylic polymers with poor film forming properties and/or to obtain sustained-release film coated pellets with optimal barrier properties according to the physico-chemical and pharmacokinetic requirements of the active substance. Heterogeneous film structures are generally obtained from blends containing an association of hard acrylic polymers (Eudragit RS30D, S100) with the soft Eudragit NE30D when the drying temperature is lower than the minimum film forming temperature (MFT) of the hard acrylic polymers. The Tg and MFT values of the hard acrylic polymers are not modified in the presence of the soft polymer as shown by the thermograms of these blends which are generally characterized by two individual glassy transitions. On the other hand, a wide range of drug dissolution profiles can be obtained from film coated pellets either by using, in different proportions, the insoluble but readily permeable Eudragit RL30D in association with the less permeable Eudragit RS30D in order to obtain pH-independent permeability membrane, or by mixing the anionic methacrylic acid copolymers (L30D, S100) with the neutral NE30D in order to obtain pH-dependent permeability film coated pellets showing higher dissolution release rates at intestinal pH values.

Morphine Polymeric Coprecipitates for Controlled Release: Elaboration and Characterization

Coprecipitates of morphine were prepared by using EudragitR L30D as a carrier in order to obtain controlled release dosage systems. Differential Scanning Calorimetry and IR, 1H- and 13C-NMR spectroscopies were applied in order to explain the mechanism of this interaction. The results obtained indicated that there was an intermolecular association between the polymer and the drug consisting in two different hydrogen bonds interactions. The proposed reaction involves coprecipitates having morphine contents greater than 50%.

Evaluation of Aqueous Enteric Coated Granules Prepared by Moisture Control Method in Tumbling Fluidized Bed Process.

Based on the moisture control system developed previously, we have already reported that the operational moisture content during aqueous polymeric coating by a type of fluidized bed should be controlled for a better coating efficiency.In this paper, effects of operational moisture content and agitator rotational speed on the properties of granules prepared by the aqueous polymeric coating were investigated experimentally, and optimization of this process was conducted. Core granules (mean diameter 600 μM) containing a model drug, pigment Blue No. 1, were coated with the aqueous dispersion of enteric polymer (Eudragit L30D) by the tumbling fluidized bed with controlling the operational moisture content. The coated granules were evaluated by dissolution tests in JP 1st (pH 1.2) and 2nd fluid (pH 6.8) and by agglomeration tendency. Film thickness and specific surface area of the granules were examined to discuss the film forming process. Based on the evaluation, effects of the operational variables on the drug release rate and agglomeration tendency were investigated. It was found that the drug release rate was suppressed with increase in moisture content at any rotational speed in the JP 1st and 2nd fluid, and the agglomeration tendency was prevented with increase in moisture content and agitator rotational speed. It was concluded from the results that the aqueous coating with the enteric polymer by the tumbling fluidized bed process should be carried out under a condition of moisture content between 12 and 14% with agitation below 5 rps.

Development and Application of Moisture Control System with IR Moisture Sensor to Aqueous Polymeric Coating Process.

A new practical method of controlling the moisture content of particles in an aqueous polymeric coating by a tumbling fluidized bed is described. The method was based on the on-line measurement and feedback control of moisture content by use of an IR (infrared) moisture sensor. Spherical core particles made of crystalline cellulose were coated in the tumbling fluidized bed by atomizing the suspension of enteric acrylic copolymer (Eudragit L30D-55). The influence of moisture control, conducted with different methods (PID (proportional-integral-derivative) control and on-off control), on the drug release rate and on the agglomeration tendency of coated particles was investigated. It was found that moisture control by the PID control method was useful for producing the desired coated particles which exhibited excellent properties in delayed release with a low agglomeration tendency.

Passive protective effect of chicken egg yolk immunoglobulins against experimental enterotoxigenic Escherichia coli infection in neonatal piglets.

Passive protection of neonatal piglets against fatal enteric colibacillosis was achieved with powder preparations of specific antibodies against K88, K99, and 987P fimbrial adhesins of enterotoxigenic Escherichia coli. The antibody powders were obtained by spray drying the water-soluble protein fraction of egg yolks from immunized hens after the lipid components were precipitated with an aqueous dispersion of acrylic resins (Eudragit L30D-55; Rohm pharma). The anti-K88, -K99, and -987P antibody preparations reacted specifically against the corresponding fimbrial antigens in an enzyme-linked immunosorbent assay. The orally administered antibodies protected in a dose-dependent fashion against infection with each of the three homologous strains of E. coli in passive immunization trials with a colostrum-deprived piglet model of enterotoxigenic E. coli diarrhea. Scanning electron microscopy revealed adherence of enterotoxigenic E. coli in intestinal epithelial surfaces of control piglets, whereas in treated piglets treated with high-titer antibodies, a resistance to bacterial adhesion was observed. An enzyme immunoassay with avidin-biotin complex demonstrated specific local antibody activity in target areas of the small intestines. In vitro, E. coli K88+, K99+, and 987P+ strains adhered equally to porcine duodenal and ileal epithelial cells but failed to do so in the presence of homologous anti-fimbrial antibodies. Absorption of egg yolk antibodies with fimbrial immunosorbent removed the anti-fimbrial antibody fraction and reduced significantly the protective nature of the antibody preparation in a passive immunization experiment, suggesting that anti-fimbrial antibodies were the active components.

Leaching of water-soluble plasticizers from polymeric films prepared from aqueous colloidal polymer dispersions

AbstractThe leaching of water-soluble plasticizers from polymeric films prepared by casting and drying of plasticized colloidal polymer dispersions was investigated with respect to the type and concentration of plasticizer (triethyl citrate or triacetin), film thickness, type of colloidal polymer dispersions (acrylic: Eudragit RS30D, RL30D, or L30D; cellulosic: Aquacoat), Eudragit RS30D/RL30D ratio, and method of film preparation (solvent- or pseudolatex-casting). The leaching increased with increasing level of plasticizer as indicated by an increase in the release rate constant while the release rate constant was independent of the film thickness. The leaching was more rapid from Aquacoat films than from Eudragit RS30D films at all plasticizer concentrations. Increasing the amount of the more hydrophilic polymer dispersion, Eudragit RL30D, in mixed Eudragit RS/RL films increased the rate of leaching. The incorporation of propranolol HCl into the polymeric films significantly increased the leaching rate c...

Development of extended-release solid dispersions of nonsteroidal antiinflammatory drugs with aqueous polymeric dispersions: optimization of drug release via a curve-fitting technique.

Extended-release solid dispersions of nonsteroidal antiinflammatory drugs were prepared by using aqueous polymeric dispersions of Eudragit RS30D and Eudragit RL30D as the inert carriers. The effects of different polymer ratios of Eudragit RS30D and Eudragit RL30D, different particle sizes, and different combination of various formulations of solid dispersions on the in vitro release kinetics of drugs from the dosage forms were investigated. A computer curve-fitting process was developed to choose the optimum formulation of the solid dispersion with the desired drug release profile. This process might offer the advantages of efficiency and simplicity in the formulation development of extended-release solid dispersions.

Effectiveness of an oral enteric coated vibrio vaccine for use in salmonid fish.

An oral enteric-coated Vibrio anguillarum vaccine was developed by initially coating lyophilized bacteria onto 0.9 mm diameter dextrose sugar beads followed by an Eudragit L-30D coat to serve as enteric protection. Vaccine efficacy was determined by both an in vivo challenge with live pathogen and measurements of serum and mucus antibody levels by ELISA. Survival rates after challenge were 80.3%, 83.3% and 70.3% among the vaccine group, positive and negative controls respectively. Serum and mucus antibody levels were found to be significantly greater in the vaccine group (p less than 0.01). In cases where equivalent survival among tested groups is observed, determination of antibody titer by ELISA may be a preferable indicator of vaccine efficacy.

Propranolol HCl release from acrylic films prepared from aqueous latexes

Polymeric films containing propranolol HCl were prepared by dissolving the drug in the aqueous colloidal polymer dispersion, Eudragit RS 30D, before casting and drying. The release of propranolol HCl was studied as a function of drug content, Eudragit RS 30D/RL 30D ratio, plasticizer content, method of film preparation and storage humidity. The addition of the more hydrophilic Eudragit RL 30D increased the permeability of the films. The amount of water-soluble plasticizer, triethyl citrate, added had a pronounced effect on drug release. The release was rapid at low and high plasticizer concentrations because of incomplete coalescence of the latex and leaching of the plasticizer. The drug release from latex-cast films was faster when compared to that from solvent-cast films.

Controlled Release Theophylline Tablet with Acrylic Polymers Prepared by Spray-Drying Technique in Aqueous System

Sustained release and enteric theophylline tablets were prepared by directly compressing spray-dried microsphers with Eudragits L30D, L100-55 and E30D. The spray-drying process was free from using organic solvent. Drug dissolution of the enteric tablet in an acidic solution (pH 1.2) was highly dependent on the polymer content of the microsphere. Completely enteric function was observed with drug-to-polymer ratio of 1:3 using Eudragit L30D or L100-55. Tablet with Eudragit E30D formulated at the 2–40% level showed good sustained drug release which was throughly independent of the pH of dissolution media. The dissolution pattern was similar to that of Theo-dur and gave a straight line in Higuchi plot. In each tablet, the controlled drug release was attributed to continuous and well-dispersed polymer matrix formed by spray-drying and subsequent compressing process

Coating of pharmaceutical powders by fluidized bed process. II. Microcapsules produced by layering of fine powder on coarse particles and subsequent aqueous enteric coating.

The Wurster process (Glatt GPCG-1) could produce particles whose outer layer consisted of fine phenacetin particles (70% under 20μm) adhering to or fixed on lactose particles (90μm), when a mixture of both powders was fluidized and sprayed with a binder solution. The enteric coating of layered particles was performed with an aqueous methacrylic acid-ethylacrylate (MA-EA) copolymer suspension (Eudragit L30D-55).The simple MA-EA microcapsules of coarse lactose crystals (120μm) exhibited a delayed release characterized by a lag time in the JP XI disintegration 1st fluid (pH 1.2), as previously reported. The layered phenacetin and hydroxypropylcellulose used as the binder in this study had no significant effect on the delayed relase of lactose. However, phenacetin was released according to biphasic zero-order kinetics, different from the case of directly coated coarse crystals (128μm). The apparent dissolution rate increased after the first slow release. The formation of a fine phenacetin suspension within microcapsules after the dissolution of lactose accounted for such an enhanced release.When polvinylpyrrolidone (PVP) was used as the binder, the lag times of the release of phenacetin and lactose were remarkably prolonged. The release rate of phenacetin after the lag time increased. The water intake into the microcapsules enhanced by PVP, which induced an extremely large expansion of the particles, and the reduction of viscosity accounted for these phenomena.The results showed that when PVP was used as the binder, the enteric coating through the layering process was sufficiently protective against the release of both phenacetin and lactose at the 50% coating level.

Coating of pharmaceutical powders by fluidized bed process. IV. Softening temperature of acrylic copolymers and its relation to film-formation in aqueous coating.

The softening temperature (Ts) of films of commercially available and newly developed acrylic copolymers for aqueous coating was measured by thermomechanical analysis. The results are discussed in relation to the film-formation of their latices in the Wurster process.Methacrylic acid (MA)-ethyl acrylate (EA)(1: 1) copolymer dispersion (Eudragit L30D-55) containing 10% triacetin exhibited excellent film-forming ability in coating at a temperature (31°C) far lower than its Ts (91°C). The product exhibited no stickiness during drying at 60°C. The dissolution properties were little changed by heating at 60°C.On the other hand, the copolymer dispersion consisting of hydrophobic acrylic esters and minor quaternary ammonium esters (Eudragit RS30D, Ts=83°C) did not form a film under the same coating conditions in spite of its Ts being lowered to 49°C by the addition of 10% triacetin. The product was sticky during drying at 60°C. The copolymer consisting of only hydrophobic esters (Eudragit E3OD) had a good film-forming ability due to its low Ts (18°C), but the product was too sticky to be discrete particles even at room temperature.These results suggested that hydrophilic residues such as carboxyl and hydroxyl contribute to film-formation of the latices.

A new enteric tablet of acetylsalicylic acid. I. Technological aspects

The aim of this study was to develop a multiple-units enteric tablet of acetylsalicylic acid (ASA). ASA crystals were coated with acrylic latex (Eudragit L30D) and then compressed into tablets. Depending on both structure and concentration of plasticizer used, we obtained tablets with good gastric resistance properties. Propyleneglycol (PROP) at a 30% level (w/w compared to the polymer) could be recommended as plasticizer. The analysis of Heckel's plots recorded during compression of ASA crystals was in agreement with the results of the gastric resistance tests.

<i>In vitro</i> Release Kinetics Study of Ambroxol Hydrochloride Pellets Developed by Extrusion Spheronization Technique Followed by Acrylic Polymer Coating

The aim of the present study was to investigate the effect of Ammonio Methacrylate Copolymer Dispersion Type A (Eudragit RL 30 D) and Ammonio Methacrylate Copolymer Dispersion Type B (Eudragit RS 30 D) combination in different weight ratios on the release kinetics of Ambroxol Hydrochloride from coated pellets. Microcrystalline cellulose, lactose, maize starch, hydroxypropyl methylcellulose and the drug was incorporated in the nuclei prepared by Extrusion-Spheronization technique which was coated with Eudragit RL 30D and Eudragit RS 30D in 1:1,1:1.5,1:2,1:2.5 and 1:3 ratios. The in vitro dissolution studies were carried out in 0.1N HCl for 1 hour followed by phosphate buffer (pH 6.8) for 11 h with USP dissolution apparatus Type-II. Drug release decreased with increasing amount of Eudragit RS 30 D in all cases. The drug release followed first order and Higuchi release kinetics. The Korsmeyer plot revealed n=0.50-0.61 or non-Fickian transport mechanism for drug release. From one way ANOVA it was found that the ratio of binary polymer mixer had significant (p < 0.05) effect on drug release. Key words: Aqueous coating, Eudragit, release kinetics, pellet, extrusion-spheronization  DOI = 10.3329/dujps.v7i1.1222 Dhaka Univ. J. Pharm. Sci. 7(1): 75-81, 2008 (June)