The Compression of Spheres Coated with an Aqueous Ethylcellulose Dispersion

Tablets were compressed from commercial samples of Sugar Spheres NF, Sucrose NF, Corn Starch NF, as well as ground spheres and a physical mixture of ground sucrose plus cornstarch. Additional tablets were compressed from spheres that had been coated with a water-soluble cellulosic polymer solution followed by an aqueous ethylcellulose dispersion. Tableting parameters measured “in-die” included work of compression, peak offset time, tablet density, and Young's modulus. Following ejection, tensile strength was determined under diametrical loading. Dissolution of a marker contained in the water-soluble layer was determined for both compressed and uncompressed spheres. Porosities at peak pressure and peak offset times or tensile strength as functions of peak pressure did not differ between tablets compressed from pristine spheres or from ground spheres. Tablets compressed from spheres had higher values for porosity, tensile strength, and peak offset time than those compressed from sucrose or the sucrose:starch mixture. Values for work of compression were higher for tablets compressed from pristine spheres or from starch. This was attributed to the work required for particle deformation and for breaking of the spheres. The greatest elastic recovery during decompression was observed for tablets compressed from pristine spheres or starch. More brittle behavior was observed for tablets compressed from sucrose or the sucrose:starch mixture. Tablets compressed from ground spheres were more brittle than those compressed from the pristine spheres, indicating an effect due to grinding. Most mechanical properties of tablets compressed from the coated spheres were comparable to those of tablets compressed from uncoated spheres. An exception was diametric strain for tablets compressed from spheres coated with the aqueous ethylcellulose dispersion. These values increased since the plasticized ethylcellulose allowed greater distortion of the tablet before failure occurred. The dye marker was released more rapidly from tablets compressed from spheres coated with the aqueous ethylcellulose dispersion than from comparable uncompressed spheres. At both the 5% and 10% coating levels, spheres coated with the aqueous ethylcellulose dispersion fused into nondisintegrating matrices during compression. Little difference in release rates was seen between the two tablets.     

Controlled-Release Matrix of Acetaminophen-Ethylcellulose Solid Dispersion

In this study ethylcellulose was evaluated as a carrier for preparation of prolonged release acetaminophen tablets. Solid dispersions containing three levels of ethylcellulose and acetaminophen (1:3; 1:1; 3:1) were prepared by the solvent method. Also physical mixtures at the same level of ethylcellulose and acetaminophen were prepared. Systems composed of solid dispersion or physical mixture containing the equivalent weight of 50 mg acetaminophen, Lactose fast-flo as diluent and 1% magnesium stearate as lubricant were compressed into tablets and tested for dissolution. The dissolution data showed that the drug release decreased as the level of ethylcellulose increased in the solid dispersion formulations. The drug release from tablets prepared with solid dispersion followed the diffusion controlled model for inert porous matrix, while the drug release from tablets prepared with physical mixture followed the first-order kinetic model.     

Controlled-Release Matrix of Acetaminophen-Ethylcellulose Solid Dispersion

Abstract

In this study ethylcellulose was evaluated as a carrier for preparation of prolonged release acetaminophen tablets. Solid dispersions containing three levels of ethylcellulose and acetaminophen (1:3; 1:1; 3:1) were prepared by the solvent method. Also physical mixtures at the same level of ethylcellulose and acetaminophen were prepared. Systems composed of solid dispersion or physical mixture containing the equivalent weight of 50 mg acetaminophen, Lactose fast-flo as diluent and 1% magnesium stearate as lubricant were compressed into tablets and tested for dissolution. The dissolution data showed that the drug release decreased as the level of ethylcellulose increased in the solid dispersion formulations. The drug release from tablets prepared with solid dispersion followed the diffusion controlled model for inert porous matrix, while the drug release from tablets prepared with physical mixture followed the first-order kinetic model.     

Fine-Particle Ethylcellulose as a Tablet Binder in Direct Compression,Immediate-Release Tablets

Ethylcellulose has traditionally been used in tablets as a binder in an alcohol solution form. In the present study, fine-particle ethylcellulose (FPEC) was used as a binder to manufacture immediate-release tablets by the direct compression technique. The binding potential of FPEC is compared to that of commercially available coarse-particle ethylcellulose at the same viscosity grade and to that of hydrophilic binders. The compression force setting was kept constant for all batches. The concentration of the binder was varied from 5% to 25%. Acetaminophen was used as a model drug because capping is a problem frequently observed during high-speed compaction and further processing of acetaminophen tablets. In this study, there would be an increase in the contact area with FPEC and hence greater bond formation. This greater bond formation should be able to reduce the problem of capping in tablets containing highly elastic materials such as acetaminophen. Tablets were evaluated based on the following tests: weight variation, extent of capping, hardness, friability, disintegration, and dissolution. Based on the results of these tests, FPEC proved to be an effective binder for directly compressed acetaminophen tablets. The 10% and 15% formulations of FPEC passed all the tests and also produced the hardest tablets.     

Some Factors Affecting the Release of Drug from Membrane Coated Slow Release Tablets

Tablets containing sodium salicylate were prepared by direct compression and coated with ethylcellulose and polyethylene glycol 3350. The effect of drug loading, direct compression carrier type, polymer ratio in the coating solution, pH of the dissolution medium, and agitation speed on the drug release were investigated using the USP XXI paddle method. It was observed that direct compression carriers, ratio of ethyl cellulose to polyethylene glycol, the amount of drug present in the tablet, and agitation speed used did not have any influence on the drug release from coated tablets, while the pH of the dissolution medium (gastric vs. intestinal fluids) was found to affect the drug release.     

Fine-Particle Ethylcellulose as a Tablet Binder in Direct Compression, Immediate-Release Tablets

Ethylcellulose has traditionally been used in tablets as a binder in an alcohol solution form. In the present study, fine-particle ethylcellulose (FPEC) was used as a binder to manufacture immediate-release tablets by the direct compression technique. The binding potential of FPEC is compared to that of commercially available coarse-particle ethylcellulose at the same viscosity grade and to that of hydrophilic binders. The compression force setting was kept constant for all batches. The concentration of the binder was varied from 5% to 25%. Acetaminophen was used as a model drug because capping is a problem frequently observed during high-speed compaction and further processing of acetaminophen tablets. In this study, there would be an increase in the contact area with FPEC and hence greater bond formation. This greater bond formation should be able to reduce the problem of capping in tablets containing highly elastic materials such as acetaminophen. Tablets were evaluated based on the following tests: weight variation, extent of capping, hardness, friability, disintegration, and dissolution. Based on the results of these tests, FPEC proved to be an effective binder for directly compressed acetaminophen tablets. The 10% and 15% formulations of FPEC passed all the tests and also produced the hardest tablets.     

Investigation of Ethylcellulose as a Matrix Former and a New Method to Regard and Evaluate the Compaction Data

Abstract

Three types of ethylcellulose—having different molecular weights, i.e., different viscosity grades (7, 22, 50 cP)-were used for our polymer compression tests for the production of matrix tablets. The production methods used were direct compression and wet granulation. We tested the compactability, the compressibility, and the energy involved in compaction by the use of F-D curves and the controlled drug release from the ethylcellulose matrix tablets using the above-mentioned methods. A lower viscosity grade in ethylcellulose is more compressible than the higher grade. Wet-granulated ethylcellulose also shows a better compactibility than directly compressed ethylcellulose. Our investigation indicates also that the dissolution rates are indirectly proportional to the hardness of the tablets. Furthermore, wet-granulated tablets produce a more rapid drug release than those which are directly compressed.     

Factors Influencing the Release of Aminophylline from Tableted Ethylcellulose Microcapsules

Microcapsules containing aminophylline cores in ethylcellulose walls have been prepared and tableted. The mechanical properties and the release characteristics of tablets obtained by direct compression at six different pressures (ranging from 265 to 1060 Kg.cm^-2) were studied. The release rate of the drug from tableted microcapsules increased with the increase of compression force and was higher than from uncompressed microcapsules, indicating that some damage of the polymeric wall occurred during the compression process. Among the various excipients tested as binding and protective agents, paraffined starch (a mixed system appositely set up) gave the best results, producing the slowest drug release rate. No important effect on drug release rate was found by changing the size of the microcapsules.     

Investigation of Ethylcellulose as a Matrix Former and a New Method to Regard and Evaluate the Compaction Data

Three types of ethylcellulose—having different molecular weights, i.e., different viscosity grades (7, 22, 50 cP)-were used for our polymer compression tests for the production of matrix tablets. The production methods used were direct compression and wet granulation. We tested the compactability, the compressibility, and the energy involved in compaction by the use of F-D curves and the controlled drug release from the ethylcellulose matrix tablets using the above-mentioned methods. A lower viscosity grade in ethylcellulose is more compressible than the higher grade. Wet-granulated ethylcellulose also shows a better compactibility than directly compressed ethylcellulose. Our investigation indicates also that the dissolution rates are indirectly proportional to the hardness of the tablets. Furthermore, wet-granulated tablets produce a more rapid drug release than those which are directly compressed.     

Factors Influencing the Release of Aminophylline from Tableted Ethylcellulose Microcapsules

Abstract

Microcapsules containing aminophylline cores in ethylcellulose walls have been prepared and tableted. The mechanical properties and the release characteristics of tablets obtained by direct compression at six different pressures (ranging from 265 to 1060 Kg.cm^?2) were studied. The release rate of the drug from tableted microcapsules increased with the increase of compression force and was higher than from uncompressed microcapsules, indicating that some damage of the polymeric wall occurred during the compression process. Among the various excipients tested as binding and protective agents, paraffined starch (a mixed system appositely set up) gave the best results, producing the slowest drug release rate. No important effect on drug release rate was found by changing the size of the microcapsules.     

Comparative Evaluations of Aqueous Film Coated Tablet Formulations by High Humidity Aging

Compressed tablets of ticlopidine hydrochloride were coated with three aqueous film coating formulations and aged under 95% relative humidity at 23° and 37°. The in vitro dissolution of the drug from tablets coated with the formulation containing polymethacrylic acid esters before aging was slower than the tablets coated with the formulations containing hydroxypropyl methylcellulose or ethylcellulose dispersion. On aging, the in vitro drug dissolution of the coated and uncoated tablets decreased and the decrease depended on the film forming excipient in the coating formulation and the temperature of aging. The tablets coated with the formulation containing polymethacrylic acid esters dissolved very slowly after aging. Higher moisture contents of the tablets after aging under 95% relative humidity at 23° compared to 37° resulted in a consistently lower tablet crushing strength. The tablets coated with the formulation containing 10% hydroxypropy1 methylcellulose showed a smaller decrease in the tablet crushing strength on aging compared to the other two formulations.     

Evaluation of Ethylcellulose as a Matrix for Prolonged Release Formulations. II. Sparingly Water-Soluble Drugs: Ibuprofen and Indomethacin

The main purpose of this investigation was to evaluate ethylcellulose as a carrier for the preparation of prolonged release solid dispersions of sparingly water-soluble drugs, ibuprofen and indomethacin. Solid dispersions containing various concentrations of ethylcellulose of different viscosity grades were prepared by the solvent method. Tablets were directly compressed from solid dispersions (40/100 mesh) with 0.5% Primojel as a disintegrant and 0.5% magnesium stearate as a lubricant. In vitro release studies employed a rotating bottle system with Sorenson's buffer solution (pH 7.4). It was found that prolongation of drug release was primarily associated with an increase in amount of ethylcellulose rather than the viscosity grade. Nonetheless, the higher the viscosity grade of ethylcellulose, the slower the release of drug from granular and compressed solid dispersions. The release rate of ibuprofen was faster than that of indomethacin from different solid dispersion formulations.     

Moisture-Activated dry Granulation in a high Shear Mixer

The applicability of a 25 litre high shear mixer for moisture-activated dry granulation was examined. Microcrystalline cellulose, potato starch or a mixture of 50% m/m of each was used as moisture absorbing material. The effects of water content, wet massing time, moisture absorbing material and dry mixing time on the size distribution, and the compressibility of the granulations were investigated. Tablets were compressed on a single punch press from all the granulations and on a rotary press from a few of the granulations.

It was shown that the physical properties of the tablets were primarily affected by the water content, the moisture absorbing material, and the compression force. Tablets with low mass variation, high crushing strength, low friability, and short disintegration time were achieved with both tablet presses by using a mixture of microcrystalline cellulose and potato starch as moisture absorbing material.     

Comparative Evaluations of Aqueous Film Coated Tablet Formulations by High Humidity Aging

Compressed tablets of ticlopidine hydrochloride were coated with three aqueous film coating formulations and aged under 95% relative humidity at 23° and 37°. The in vitro dissolution of the drug from tablets coated with the formulation containing polymethacrylic acid esters before aging was slower than the tablets coated with the formulations containing hydroxypropyl methylcellulose or ethylcellulose dispersion. On aging, the in vitro drug dissolution of the coated and uncoated tablets decreased and the decrease depended on the film forming excipient in the coating formulation and the temperature of aging. The tablets coated with the formulation containing polymethacrylic acid esters dissolved very slowly after aging. Higher moisture contents of the tablets after aging under 95% relative humidity at 23° compared to 37° resulted in a consistently lower tablet crushing strength. The tablets coated with the formulation containing 10% hydroxypropy1 methylcellulose showed a smaller decrease in the tablet crushing strength on aging compared to the other two formulations.     

Evaluation of Ethylcellulose as a Matrix for Prolonged Release Formulations. II. Sparingly Water-Soluble Drugs: Ibuprofen and Indomethacin

Abstract

The main purpose of this investigation was to evaluate ethylcellulose as a carrier for the preparation of prolonged release solid dispersions of sparingly water-soluble drugs, ibuprofen and indomethacin. Solid dispersions containing various concentrations of ethylcellulose of different viscosity grades were prepared by the solvent method. Tablets were directly compressed from solid dispersions (40/100 mesh) with 0.5% Primojel as a disintegrant and 0.5% magnesium stearate as a lubricant. In vitro release studies employed a rotating bottle system with Sorenson's buffer solution (pH 7.4). It was found that prolongation of drug release was primarily associated with an increase in amount of ethylcellulose rather than the viscosity grade. Nonetheless, the higher the viscosity grade of ethylcellulose, the slower the release of drug from granular and compressed solid dispersions. The release rate of ibuprofen was faster than that of indomethacin from different solid dispersion formulations.     

Formulation of Controlled Release Matrices by Granulation with a Polymer Dispersion

The objective of this work was to incorporate an ethylcellulose-based controlled-release coating suspension (Surelease, Colorcon) within a tablet matrix to provide a release controlling mechanism. Anhydrous theophylline, chlorpheniramine maleate, and acetaminophen were selected as model drug entities. Surelease dispersion was incorporated as the granulating agent either to the drug entity alone or to a blended mixture of drug and filler. Control batches included simple aqueous granulations and direct compression mixtures. Tablets were prepared on a single stroke tablet press. Dissolution was performed by the USP Method I (rotating basket) in purified water for the granulations and the resulting tablets. The uncompressed granulations did not exhibit prolonged release. In general, tablets prepared with the polymer suspension as the granulating agent were non-disintegrating, and exhibited slower dissolution than the control tablets. Release profiles were affected by drug concentration and excipient levels. By the dissolution method selected, complete drug release for the various formulations ranged from less than 1 hour to greater than 12 hours. The use of the polymer dispersion appears to enhance the processing characteristics of some materials, and to provide the formulator with control over drug release.     

Direct Compression Controlled Release Tablets Using Ethylcellulose Matrices

Controlled release erodible matrix tablets were manufactured by a simple, direct compression process using ethylcellulose alone as the matrix former. Each of four different viscosity grades of ethylcellulose (10, 20, 45 and 100 cp) was dry mixed with either indomethacin or theophylline and a small amount of lubricant, then directly compressed into tablets. In initial trials, compression force was held constant, resulting in tablets of varying hardness. In a second study, the compression force was varied to produce tablets of equal hardness. Lower viscosity grades of ethylcellulose were more compressible than higher viscosity grades, allowing production of harder tablets for a given drug. Harder tablets resulted in controlled release of the drug over a longer time period. Dissolution studies indicated that tablet hardness is more important in determining dissolution rate than is the polymer viscosity grade. A mathematical model combining diffusion and erosion mechanisms was developed to describe drug release. Improved r² values over pure diffusion, erosion and diffusion/relaxation models were obtained. Examination of residuals indicated that the derived composite model was more appropriate for the data     

Improvement of the low-temperature stability of an aqueous colloidal ethylcellulose dispersion,Aquacoat ECD,and preparation/characterization of a redispersible Aquacoat ECD powder

Aquacoat ECD, an aqueous ethylcellulose dispersion, is susceptible to low-temperature storage, resulting in irreversible coagulation as indicated by a strong increase in viscosity and particle size. This destabilization of the ethylcellulose dispersion is caused by the anionic surfactant sodium dodecyl sulfate, which precipitates at low temperatures because of its low Krafft point. This problem could be solved by using the more hydrophilic, ethoxylated, sodium dodecyl ether sulfate, which was an effective stabilizer at low temperatures. A redispersible ethylcellulose powder was prepared by freeze- or spray-drying of the original polymer dispersion (Aquacoat ECD). The pH of the dispersion medium had a strong influence on the redispersibility of the dried ethylcellulose particles because of the dissociation behavior. At a pH > 7, polymer dispersions in the colloidal size range were obtained. At lower pH values, the dried ethylcellulose agglomerates could not be redispersed. Drug release studies from pellets coated with the redispersed and the original dispersion showed a comparable release pattern when using alkalized aqueous dispersion systems. Higher plasticizer concentration and curing of the coated pellets improved the film formation of the redispersed polymer particles.     

Tablets containing drug-loaded polymeric nanocapsules: an innovative platform

The aim of the present work was to evaluate the feasibility to convert drug-loaded nanocapsule suspensions in a solid dosage form (tablets). Dexamethasone was used as a model drug due to its low aqueous solubility and fast drug release from conventional tablets. Granules containing dexamethasone-loaded nanocapsules were obtained by a wet granulation process using a dispersion of polyvinylpirrolidone/nanocapsules as a binder system. Granules were compressed in an eccentric compression machine (D-NC-T). A control formulation (tablets without nanocapsules) was also prepared (D-T). Tablets were characterized by means of mean weight, hardness, friability, diameter, thickness, disintegration time, drug content, morphological analysis by scanning electron microscopy (SEM), and in vitro drug release studies. D-NC-T showed adequate physicochemical characteristics according to the pharmacopeial requirements in terms of mean weight, hardness, friability, disintegration time and drug content. Intact nanocapsules in tablets were observed by SEM. In vitro drug release studies showed a slower release of dexamethasone from these tablets (D-NC-T) compared to the control formulation (D-T). Results showed that these tablets represent an interesting platform to the development of oral drug delivery systems containing polymeric nanocapsules.     

Evaluation of Ceolus™ microcrystalline cellulose grades for the direct compression of enteric-coated pellets

The preparation of multiparticulate tablets by direct compression of functionally coated pellets is technologically challenging. The objective was to investigate the influence of different grades of microcrystalline cellulose (Ceolus? UF-711, PH-102, PH-200 and KG-802) as fillers on the properties of blends and tablets containing enteric pellets. Celphere? spheres were drug-layered and then functionally coated with Eudragit(?) L 30 D-55/FS 30D dispersion. Tablets loaded with 50% pellets were prepared using pure or binary blends of microcrystalline cellulose fillers. The influence of the filler on the blend flow, segregation tendency, tablet hardness and enteric release properties were studied using a mixture design, and the optimum filler composition was determined. Rapidly disintegrating tablets, which yielded a drug release of less than 10% after 2 hours in acidic medium, could be successfully prepared. The blend composition had a significant effect on the flowability, but less on the tablet hardness which was influenced by the selection of lubricant. Blends containing celluloses with low bulk densities exhibited a reduced tendency to segregate. Pellet distribution uniformity was further improved when using Ceolus? UF-711 blended with a high-density grade. As a conclusion, multiparticulate tablets containing enteric pellets with preserved delayed-release properties were successfully prepared using Ceolus? microcrystalline celluloses as tableting excipients. The optimized filler blend for the direct compression of 50% enteric pellets into tablets contained Ceolus? UF-711 as main component in combination with Ceolus? PH-200.