Tackiness of acrylic and cellulosic polymer films used in the coating of solid dosage forms.

The objective was to determine the tackiness of acrylic and cellulosic polymer films in order to make predictions on the tackiness (agglomeration) of coated dosage forms during coating and curing. Force-displacement curves of the detachment process of two polymeric films were used as a measure of tackiness. Various polymers (cellulosic (Aquacoat and acrylics (Eudragit RS 30D, L 30D, NE 30D)), plasticizers (triacetin, triethyl citrate, tributyl citrate, acetyltributyl citrate) and anti-tacking agents (talc and glyceryl monostearate) were investigated. The order of tackiness for films prepared from the different aqueous polymer dispersions was in order of Eudragit NE 30D > RS 30D > RL 30D > Aquacoat. The tackiness increased with increasing plasticizer concentration due to the softening of the polymer. A correlation between the minimum film formation temperature and the tackiness was observed, however, no correlation between the tackiness and the lipophilicity of the plasticizer was seen. Talc and glyceryl monostearate (GMS) reduced the tackiness of the films significantly, with GMS being effective at much lower concentrations. Curing of Eudragit RS 30D-coated theophylline beads at temperatures higher than 40 degrees C in an irreversible agglomeration of the beads and damage of the coating upon separation of the beads. This resulted in a faster release than with uncured beads. Blending the beads with talc just prior to the curing step eliminated the agglomeration and therefore film damage, even at a curing temperature of 60 degrees C.     

Dry polymer powder coating and comparison with conventional liquid-based coatings for Eudragit) RS, ethylcellulose and shellac.

Drug-layered pellets were coated with micronized polymer powders (Eudragit) RS, ethylcellulose, and shellac) by a dry powder coating technique as an alternative to organic- and aqueous-based coatings (Eudragit) RS 30D, Aquacoat) ECD) were investigated. High plasticizer concentrations (40%) and a thermal after-treatment (curing) were necessary for the coalescence of the polymer particles and good film formation. Ethylcellulose required a higher curing temperature and time than Eudragit) RS because of its higher glass transition temperature (133 versus 58 degrees C). A smaller polymer particle size also promoted film formation. In general, pellets coated with polymer powders required higher coating levels to obtain similar drug release patterns as pellets coated with organic polymer solutions and aqueous polymer dispersions.     

渗透型丙烯酸树脂包衣控释膜中增塑剂的优选

目的　筛选适合渗透型丙烯酸树脂 Eudragit RS100 膜控释包衣的增塑剂。方法　通过测定膜玻璃化转变温度(Tg)、膜水化前后两种状态的力学性能,研究不同增塑剂的增塑效率;用溶出度和水平扩散池法考察增塑剂从介质中溶出;用加速试验考察贮存时增塑剂的损失。结果　Tg显示EudragitRS10 0具较强增塑剂相容性,水溶性增塑剂三醋酸甘油酯(TR)和水不溶性增塑剂邻苯二甲酸二丁酯(DBP)等均有较高增塑效率;膜水化前后力学性能变化显著,水溶性增塑剂遇介质从膜中快速溶出使湿膜脆碎,而水不溶性增塑剂则相对稳定;于(40±1)℃、相对湿度(RH)75%下贮存40d ,膜TR损失达6.46% ,而DBP仅损失0.29%。结论　DBP等水不溶性增塑剂是较理想的 Eudragit RS100 膜控释包衣膜增塑剂品种     

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.     

Influence of plasticizers on the mechanical properties of pellets containing Eudragit® RS 30 D

The influence of plasticizers on the mechanical properties of single pellets containing the acrylic polymeric dispersion, Eudragit® RS 30 D, as a granulating binder was investigated. Microcrystalline cellulose and anhydrous lactose were used as the substrate powders for pellets prepared by the wet massing and extrusion/spheronization technique. The effects of hydrophilic and hydrophobic plasticizers on the mechanical properties of the pellets and thermal properties of free films were investigated. The mechanical properties, including tensile strength and Young's modulus, of individual pellets were determined by a diametral compression method with a Chatillon® tension/compression apparatus. The results demonstrated that both the tensile strength and Young's modulus of the pellets decreased as the plasticizer content increased in the pellet formulation, with the exception at low plasticizer levels. The influence of plasticization on the granulating polymer was reflected in the mechanical properties of pellets, indicating that the pellets underwent a cohesive fracture. The unexpected increase in the tensile strength and Young's modulus of the pellets containing low levels of plasticizers was ascribed to the antiplasticization of the polymer due to the immobilization of the polymer molecules by hydrogen bonding, van der Waal's forces and steric hindrance from the plasticizer molecules. Pellets containing low levels of plasticizers exhibited a brittle fracture behavior under compression while a ductile property was observed at higher plasticizer concentrations. The transition of the fracture behavior from a brittle to a ductile pattern was found to take place when plasticizer levels in the acrylic polymer were between 10 and 20% based on the weight of dry polymer. The transition was due to the shift of the polymeric binder from a glassy to a rubbery state, which was verified by the glass transition temperature values of the free films.     

Characterisation of the mechanical properties of polymer films formed from aqueous polymer dispersions by creep testing

The mechanical properties of films formed from an aqueous dispersion of polymethlymethacrylate (Eudragit NE30D) and as mixture with an aqueous dispersion of ethylcellulose (Aquacoat ECD30), have been assessed by applying creep tests at different temperatures, using a dynamic mechanical analyser. In the region of linear creep, the film prepared from 100% Eudragit was far less elastic than when 60% Aquacoat was present. In this region, when the applied stress was doubled, the strain response was doubled. In the non-linear region of behaviour, there is clear evidence that the mixed film is more elastic than the film containing only Eudragit.     

Influence of film additives on stabilizing drug release rates from pellets coated with acrylic polymers.

The objective of this study was to investigate the influence of talc and triethyl citrate (TEC) on stabilizing the drug release rates following curing and storage at elevated temperature of pellets coated with an aqueous acrylic polymeric dispersion. Core pellets containing anhydrous theophylline (20%), microcrystalline cellulose, and polyvinylpyrrolidone were prepared by extrusion-spheronization. The aqueous dispersions were prepared by adding up to 30% TEC as a plasticizer and talc up to 200% as an antiadherent to a mixture of Eudragit RS 30D/RL 30D (95:5). The theophylline pellets were coated in a fluidized-bed coating unit and then cured at elevated temperatures. Theophylline pellets were successfully coated with the Eudragit dispersions that contained up to 200% talc, based on the dry polymer weight, and the coating efficiency was greater than 93%. Our results demonstrated that the polymer, which was plasticized by TEC, was able to function as a film-forming agent for dispersions containing high levels of talc. No sticking of the coated pellets was observed during the coating process or during the curing or equilibrating phase, even with high levels of TEC in the film. The dissolution rate of theophylline from the coated pellets was delayed when the film coating dispersion contained high levels of talc. Additionally, the stability of the drug release profiles from the coated pellets after storage was significantly improved. Furthermore, a modified dissolution testing used to simulate mechanical stresses that may be encountered in vivo showed the film coated pellets would have sufficient strength. The results of this study demonstrated that high levels of film additives in the acrylic dispersion contributed to the stabilization of the drug release rates as well as the reproducibility of the coating process.     

Modified release of coated sugar spheres using drug-containing polymeric dispersions

A drug-containing polymeric dispersion was applied onto nonpareil sugar spheres (18/20 mesh) using a fluid-bed spray coater. Eudragit RS30D was selected as the polymeric coating material. Melatonin secreted by the pineal gland in a circadian rhythm was used as a model drug. The release behaviors of the coated sugar spheres were investigated in gastric fluid (pH 1.4) for 2 h, and then continuously in intestinal fluid (pH 7.4) for 14 h. The release rate of the coated sugar spheres decreased with increasing coating levels. The solvent (ethanol) in the coating dispersions significantly decreased the release of the drug due to the good dispersion of the low solubility melatonin in the polymeric films. The polymer (polyvinylpyrrolidone, PVP) and drug contents in the coating dispersions did not affect the release rate. Most of all, the release profiles were drastically changed according to the type and concentration of plasticizers used. The current coating methods that use drug-containing polymeric dispersions could be useful for simultaneous drug loadings and their modified release. The solubilization and controlled release of poorly water-soluble drugs can be achieved as both the solubilizers and drugs are present in the drug-containing polymeric dispersions.     

Effect of plasticizer on the dynamic surface tension and the free volume of Eudragit systems

The purpose of the present study was to determine the changes of dynamic surface tension of aqueous Eudragit dispersions quantitatively and compare these data with the free volume of the free films formed from several dispersions of different dibutyl sebacate (DBS) concentrations. Eudragit L 30D and Eudragit RL 30D aqueous colloidal polymer dispersions and their cast free films were examined. The concentration of DBS varied in the dispersions from 0 to 20%. The dynamic surface tension of the dispersions were measured by the Du Nouy ring method while the free volume of cast films were determined by positron annihilation spectroscopy. The obtained results show that dynamic surface tension measurements indicate the white point (WP) of Eudragit dispersions by a significant standard deviation increase. This may suggest the applicability of dynamic surface tension measurements for the determination of the WP of polymeric dispersions. A decrease in the WP temperature of Eudragit dispersions with an increasing plasticizer concentration was observed up to the DBS concentration of 10% w/w. Above this concentration neither the WP of the polymer dispersion nor the free volume of the free films of the polymer were changed remarkably.     

Spontaneous formation of drug-containing acrylic nanoparticles.

Nanoparticles containing ibuprofen, indomethacin or propranolol were formed spontaneously after the addition of solutions of the drugs and acrylic polymers (Eudragit RS or RL 100) in the water-miscible solvents, acetone or ethanol, to water without sonication or microfluidization. The colloidal dispersions were stabilized by quaternary ammonium groups and did not require the addition of surfactants or polymeric stabilizers. The nanoparticles were compared to nanoparticles prepared either by a microfluidization-solvent evaporation method with a water-immiscible organic solvent, methylene chloride, or by a melt method with respect to particle size and redispersibility of freeze- or spray-dried samples. Nanoparticles prepared by microfluidization or the melt method were easily redispersed while Eudragit RS nanoparticles prepared by spontaneous emulsification were not redispersible. Flexible films were formed from the nanosuspensions after the addition of 15 per cent triethyl citrate, a water-soluble plasticizer. The release of propranolol from the films increased with increasing proportion of RL, but was independent of the order of mixing of the two polymers or nanosuspensions during film preparation. The drug release from indomethacin films was increased by adding water-soluble polymers to the nanosuspension.     

Statistical optimisation of diclofenac sustained release pellets coated with polymethacrylic films

The objective of the present study was to evaluate three formulation parameters for the application of polymethacrylic films from aqueous dispersions in order to obtain multiparticulate sustained release of diclofenac sodium. Film coating of pellet cores was performed in a laboratory fluid bed apparatus. The chosen independent variables, i.e. the concentration of plasticizer (triethyl citrate), methacrylate polymers ratio (Eudragit RS:Eudragit RL) and the quantity of coating dispersion were optimised with a three-factor, three-level Box-Behnken design. The chosen dependent variables were cumulative percentage values of diclofenac dissolved in 3, 4 and 6 h. Based on the experimental design, different diclofenac release profiles were obtained. Response surface plots were used to relate the dependent and the independent variables. The optimisation procedure generated an optimum of 40% release in 3 h. The levels of plasticizer concentration, quantity of coating dispersion and polymer to polymer ratio (Eudragit RS:Eudragit RL) were 25% w/w, 400 g and 3/1, respectively. The optimised formulation prepared according to computer-determined levels provided a release profile, which was close to the predicted values. We also studied thermal and surface characteristics of the polymethacrylic films to understand the influence of plasticizer concentration on the drug release from the pellets.     

Influence of relative humidity on the mechanical and drug release properties of theophylline pellets coated with an acrylic polymer containing methylparaben as a non-traditional plasticizer.

The purpose of this study was to investigate the influence of relative humidity (RH) on the mechanical and dissolution properties of theophylline pellets coated with Eudragit((R)) RS 30 D/RL 30 D containing methylparaben (MP) as a non-traditional plasticizer. The coated beads were stored at 23 degrees C and at different relative humidities (0, 29, 51, 75 and 84% RH). The effect of storage conditions on the rate of drug release from coated beads was determined in pH 7.4 phosphate buffer solution. The mechanical properties, including tensile strength and Young's modulus, of individual beads were determined by a diametral compression method with a Chatillon((R)) tension/compression apparatus. The morphology of the intact and fractured beads was investigated using scanning electron microscopy (SEM). The moisture content of the polymeric films was determined using a Karl Fischer coulometric moisture analyzer. The results from the mechanical studies demonstrated that an increase in the relative humidity resulted in a decrease in the tensile strength and Young's modulus of the coated beads. SEM photographs showed that coated beads stored at 0% RH exhibited brittle fracture failure. The coated beads stored at 84% RH showed ductile behavior, which was attributed to the hydroplasticization effect on the acrylic polymer due to the uptake of moisture. The moisture content in the films was also shown to influence the rate of drug release from Eudragit((R)) RS 30 D/RL 30 D coated beads containing MP as the plasticizer. The change in release profiles could be minimized when the relative humidity was reduced to zero. The dissolution rate of theophylline from the coated beads decreased when stored at high relative humidities. This trend was reversed when the coated beads that were stored at 84% RH for 5 weeks, were then equilibrated at 0% RH.     

Dynamic mechanical thermal analysis studies of polymer films prepared from aqueous dispersion

Dynamic Mechanical Thermal Analysis of cast and sprayed films of an aqueous dispersion of polymethyl methacrylate (Eudragit NE30D) and mixtures with an aqueous dispersion of ethylcellulose (Aquacoat ECD-30) has been undertaken. Such analysis allows the identification of glass transition temperatures and the degree of miscibility of the polymers. It was found that the two polymers formed as cast or sprayed films were not miscible but had an optimal composition of 30% of the ethylcellulose dispersion in the polymethyl methacrylate dispersion.     

Comparison of physicomechanical properties of films prepared from organic solutions and aqueous dispersion of Eudragit RL

BACKGROUND AND THE PURPOSE OF THE STUDY: Mechanical properties of films prepared from aqueous dispersion and organic solutions of Eudragit RL were assessed and the effects of plasticizer type, concentration and curing were examined. METHODS: Films were prepared from aqueous dispersion and solutions of Eudragit RL (isopropy alcohol-water 9:1) containing 0, 10 or 20% (based on polymer weight) of PEG 400 or Triethyl Citrate (TEC) as plasticizer using casting method. Samples of films were stored in oven at 60°C for 24 hrs (Cured). The stress-strain curve was obtained for each film using material testing machine and tensile strength, elastic modulus, %elongation and work of failure were calculated. RESULTS AND MAJOR CONCLUSION: The films with no plasticizer showed different mechanical properties depending on the vehicle used. Addition of 10% or 20% of plasticizer decreased the tensile strength and elastic modulus and increased %elongation and work of failure for all films. The effect of PEG 400 on mechanical properties of Eudragit RL films was more pronounced. The differences in mechanical properties of the films due to vehicle decreased with addition of plasticizer and increase in its concentration. Curing process weakened the mechanical properties of the films with no plasticizer and for films with 10% plasticizer no considerable difference in mechanical properties was observed before and after curing. For those with 20% plasticizer only films prepared from aqueous dispersion showed remarkable difference in mechanical properties before and after curing. Results of this study suggest that the mechanical properties of the Eudragit RL films were affected by the vehicle, type of plasticizer and its concentration in the coating liquid.     

Non-traditional plasticization of polymeric films

The objective of this study was to investigate the influence of methylparaben, ibuprofen, chlorpheniramine maleate and theophylline on the thermal and mechanical properties of polymeric films of Eudragit RS 30 D. The effects of methylparaben and ibuprofen in the film coating on the rate of drug release from Eudragit RS 30 D coated beads were also studied. The physical and mechanical properties of the cast films and coated beads were investigated using thermal analysis, tensile testing, X-ray diffraction analysis and dissolution testing. The results demonstrated that the glass transition temperature of the Eudragit RS 30 D decreased with increasing levels of methylparaben, ibuprofen and chlorpheniramine maleate in the film. Theophylline exerted no influence on the thermal properties of the polymer. The higher levels of the ibuprofen and methylparaben incorporated into the film resulted in a decrease in the tensile strength of the film. The decrease in Young's modulus of Eudragit RS 30 D coated beads was attributed to an increase in the flexibility of the polymeric films when the level of methylparaben or ibuprofen in the polymeric dispersion was increased. The dissolution data demonstrated that the rate of release of the ibuprofen from coated beads was decreased by increasing the amount of ibuprofen and methylparaben in the polymeric film coating.     

Organic solvent-free polymeric microspheres prepared from aqueous colloidal polymer dispersions by a w/o-emulsion technique

Polymeric microspheres were prepared from water-insoluble polymers by a novel technique without the use of organic solvents. Aqueous colloidal polymer dispersions (latexes or pseudolatexes) were emulsified into a heated external oil phase to form a w/o emulsion. The colloidal polymer particles fused (coalesced) into homogeneous polymeric microspheres at temperatures above the minimum film formation temperature upon removal of water. The formation of the microspheres was affected by the glass transition temperature of the polymer, the type of oil and surfactant, the heating temperature and time, and the addition of plasticizers. Plasticizers had to be added to colloidal dispersions with high minimum film formation temperatures. The resulting microspheres were spherical with a smooth surface and non-agglomerated. The particle size could be varied between 5 and 250 μm. Water-soluble compounds such as propranolol HC1 could be entrapped with drug loadings up to 40% within the microspheres by dissolving the drug in the aqueous polymer dispersion prior to the emulsification step. The drug release was sustained over a 6-h period with microspheres prepared with the acrylic pseudolatex, Eudragit RS 30D.     

An Investigation into the Mechanical and Transport Properties of Aqueous Latex Films: A New Hypothesis for the Film-Forming Mechanism of Aqueous Dispersion System

The effects of plasticizer, physical aging, and film-forming temperature on the mechanical and transport properties of films formed from aqueous dispersions of ethylcellulose latex were investigated. The water vapor permeability of latex films was found to decrease with diethyl phthalate to a minimum value and then to increase with diethyl phthalate at higher concentrations. Because of the decrease in free volume and the further coalescence of particles of latex polymer films in the physical aging range, the creep compliance of latex films decreased with physical aging time. Within 60 to 100°C, the film-forming temperature was found to have no effect on the mechanical and transport properties of Aquacoat films. However, since many pinholes formed in the latex films when the film-forming temperature was above 100°C, the water vapor permeability of latex films was higher than that of latex films formed between 60 and 100°C. The formation of films from aqueous latex dispersions is suggested to proceed gradually from the top to the bottom of the latex dispersion in this study.     

酒石酸美托洛尔缓释微丸的制备及处方因素考察

目的：选用Eudragit RS 30 D与Eudragil RL30D两种包衣材料，制备日服2次的酒石酸美托洛尔缓释徽丸，并对其处方因素进行考察。方法：采用Glatt流化床底喷溶液上药法制备载药微丸，考察缓释聚合物Eudragit RS 30D与Eudragit RL 30D的不同质量配比（2：3，7：3和9：1）、聚合物包衣增重（10％，20％和30％）以及增塑利嗣量（10％，20％和40％）和放置时间对药物释放的影响。结果：当Eudragit RS 30D与Eudragit RL 30D的质量比为9：1，聚合物包衣增重为20％，增塑剂用量为20％时，药物的释放行为符合中国药典对缓释制剂释放度的相关规定。结论：通过调整Eudragit RS 30D与Eudragit RL 30D之间的比例，或提高聚合物包衣增重等手段，能使酒石酸美托洛尔载药徽丸具备较理想的缓释效果。     

Effect of pectinolytic enzymes on the theophylline release from pellets coated with water insoluble polymers containing pectin HM or calcium pectinate

Theophylline pellets were coated with cellulosic (Aquacoat ECD 30, Surelease clear) or acrylic (Eudragit NE30D, RS30D) polymer aqueous dispersions, containing 10% (related to the insoluble polymer content) of pectin HM or calcium pectinate, using a Uni-Glatt fluidized-bed coating apparatus. When commercial pectinolytic enzymes were added to the dissolution media (0.05 M acetate - phosphate buffer, pH 6.0), the release of theophylline from the coated pellets was generally slower than that observed in the media without enzymes. The enzymatic slowing down of the drug release, depending on the type of the aqueous polymer dispersion used, is more important with mixed Eudragit NE/calcium pectinate coated pellets. The results obtained have been examined with regard to the validity of the approach based on the combination of pectins and the insoluble polymer aqueous dispersions intended for specific-delivery of drugs to the colon. The mechanism of the hydrophilic drug release from pellets coated with insoluble polymer aqueous dispersions containing an aqueous gel-forming polymer has been also discussed.     

Characterization of the interactions between polymethacrylate-based aqueous polymeric dispersions and aluminum lakes.

Instability in film coating formulations can arise from interactions between aluminum lake pigments and aqueous polymeric dispersions. The purpose of this study was to characterize the interactions between three polymethacrylate-based aqueous polymeric dispersions (Eudragit RS 30 D, Eudragit L 30 D-55, and Eudragit NE 30 D) and aluminum lakes. Particle size measurements, pH stability profiles, zeta potential measurements, and microscopy were used to study mixed dispersions of the polymeric latices and the lakes. Interactions leading to dispersion instability were related to the surface charge of the components in the formulation. Interactions between the ionic polymers and the lakes arose from instability of the lakes outside a certain pH range resulting in the release of electrolytes, which led to aggregation of the polymeric particles. Interactions between the nonionic polymer and the lakes were related to the polymer modifying the surface charge of the lakes, resulting in aggregation of the pigment particles.