ethyl-cellulose and dibutyl-sebacate

It was the aim of the present study to develop sustained-release matrix tablets by means of injection molding of ethylcellulose (EC) and polyethylene oxide (PEO) mixtures and to evaluate the influence of process temperature, matrix composition, and viscosity grade of EC and PEO on processability and drug release.. Formulations consisting of metoprolol tartrate (MPT, concentration: 30%), EC plasticized by dibutyl sebacate, and PEO were extruded and consequently injection molded into tablets. The influence of process temperature (120°C and 140°C), matrix composition, viscosity grade of EC (4, 10, 20, 45, and 100 mPa·s) and PEO (7 × 10(6), 1 × 10(6), and 1 × 10(5) Mw) on processability and drug release was determined.. Formulations consisting of 70% EC and 30% MPT showed incomplete drug release, whereas drug release was too fast for formulations without EC. Higher PEO concentrations increased drug release. Formulations containing 30% metoprolol, EC, and different concentrations of PEO showed first-order release rates with limited burst release. Drug release from direct compressed tablets showed faster drug release rates compared to injection-molded formulations. There was no clear relationship between the molecular weight of EC and drug release. The melting endotherm (113.9°C) of MPT observed in the differential scanning calorimeter thermogram of the tablets indicated that a solid dispersion was formed which was confirmed by X-ray diffractogram. X-ray tomography demonstrated a difference in pore structure between tablets processed at 120°C and 140°C.. It was concluded that injection molding can be applied successfully to develop sustained-release PEO/EC matrix tablets.

Topics: Calorimetry, Differential Scanning; Cellulose; Delayed-Action Preparations; Dicarboxylic Acids; Excipients; Metoprolol; Polyethylene Glycols; Tablets; Temperature; Time Factors; Tomography, X-Ray Computed; Transition Temperature; Viscosity; X-Ray Diffraction

The object of this study was to investigate the influence of static and dynamic forces on mechanical properties of the biocompatible polymer ethyl cellulose. Similar polymeric films containing 40% (w/w) of the plasticizer dibutyl sebacate were subjected to tensile forces at different velocities. The average Young's modulus and the variation of yield strength, strain, and strain energy at different velocities complied with the pre-established theories of dynamic loadings. The ultimate strength and the yield strength and/or strain displayed linearity with the velocity, though the ultimate strain and therefore, the plastic and/or ultimate working energies proved non-linear pseudo-Michaelis-Menten behavior. The speculation was that achieving the maximum displacement would probably be the most important cause of failure. Finally the most suitable velocity at which the data would obtain the most demonstrable stress-strain diagrams was selected: tensile forces at almost low velocities, best illustrated as static forces, proved immature failure of the specimens during or shortly after the yield; so that the specimen resembled as a brittle material. High velocities of loadings were also avoided since the strain would usually approach the plateau and would therefore disrupt the rational correlation between forces and displacements during the end region of the curve.

Topics: Cellulose; Chemistry, Pharmaceutical; Coated Materials, Biocompatible; Delayed-Action Preparations; Dicarboxylic Acids; Materials Testing; Models, Theoretical; Plasticizers; Surface Properties; Tensile Strength

Sustained-release matrix tablets were developed by injection moulding using metoprolol tartrate (MPT) and ethylcellulose (EC) as sustained-release agent. Dibutyl sebacate was selected as plasticiser. The influence of matrix composition, plasticiser concentration, and drug load on drug release was evaluated. The influence of plasticiser addition was assessed on processability and drug release: Dibutyl sebacate was added to a dichloromethane/EC solution and subsequently spray-dried, or was mixed as a liquid with EC powder. Hydrated tablets were evaluated by frequency sweep and creep rheological tests to correlate the results with drug release. Xanthan gum (XG) was added to the formulation because drug release was too slow (<50%, 24 h) from EC/MPT matrices (70%/30%, w/w). Increasing XG concentrations provided faster MPT release rates characterised by zero-order release kinetics, no burst release was observed. Lower plasticiser concentrations and higher drug loads increased drug release substantially. The plasticiser addition method did not affect drug release. Matrix composition, drug load, and plasticiser level affected the rheological properties of the swollen matrix tablets. X-ray diffraction demonstrated the formation of solid dispersions. Formulations composed of XG/EC (ratio 1:1.5) and 30% (w/w) MPT had a low relative bioavailability compared with the commercial product Lopressor®, which significantly improved at higher MPT concentration (50%, w/w).

Topics: Administration, Oral; Adrenergic beta-1 Receptor Antagonists; Animals; Biological Availability; Cellulose; Chemistry, Pharmaceutical; Delayed-Action Preparations; Dicarboxylic Acids; Dogs; Drug Carriers; Drug Compounding; Male; Methylene Chloride; Metoprolol; Plasticizers; Polysaccharides, Bacterial; Rheology; Solubility; Tablets; Technology, Pharmaceutical; Water; X-Ray Diffraction

The aim of this study was to develop sustained-release matrix tablets by means of injection moulding and to evaluate the influence of process temperature, matrix composition (EC and HPMC concentration) and viscosity grade of ethylcellulose (EC) and hydroxypropylmethylcellulose (HPMC) on processability and drug release. The drug release data were analyzed to get insight in the release kinetics and mechanism. Formulations containing metoprolol tartrate (30%, model drug), EC with dibutyl sebacate (matrix former and plasticizer) and hydrophilic polymer HPMC were extruded and subsequently injection moulded into tablets (375 mg, 10 mm diameter, convex-shaped) at temperatures ranging from 110 to 140 degrees C. Tablets containing 30% metoprolol and 70% ethylcellulose (EC 4mPa s) showed an incomplete drug release within 24 h (<50%). Increasing production temperatures resulted in a lower drug release rate. Substituting part of the EC fraction by HPMC (HPMC/EC-ratio: 20/50 and 35/35) resulted in faster and constant drug release rates. Formulations containing 50% HPMC had a complete and first-order drug release profile with drug release controlled via the combination of diffusion and swelling/erosion. Faster drug release rates were observed for higher viscosity grades of EC (Mw>20 mPa s) and HPMC (4000 and 10,000 mPa s). Tablet porosity was low (<4%). Differential scanning calorimetry (DSC) and X-ray powder diffraction studies (X-RD) showed that solid dispersions were formed during processing. Using thermogravimetrical analysis (TGA) and gel-permeation chromatography no degradation of drug and matrix polymer was observed. The surface morphology was investigated with the aid of scanning electron microscopy (SEM) showing an influence of the process temperature. Raman spectroscopy demonstrated that the drug is distributed in the entire matrix, however, some drug clusters were identified.

Topics: Calorimetry, Differential Scanning; Cellulose; Delayed-Action Preparations; Dicarboxylic Acids; Excipients; Hypromellose Derivatives; Methylcellulose; Metoprolol; Plasticizers; Porosity; Spectrum Analysis, Raman; Tablets; Technology, Pharmaceutical; Temperature; Viscosity; X-Ray Diffraction

This research was conducted to investigate the physico-mechanical characteristics of the EC-based coating membranes plasticized with two informal ingredients of vitamin resources, cholecalciferol and alpha-tocopherol, with respect to the commercial plasticizer DBS. Proceeding the experiment, free thin polymer sheetings of the sample formulations, incorporating incremental weight percents of the individual plasticizers were prepared employing a revised casting method of delayed solvent evaporation whereby similar flat specimens of standard dimensions were subjected to tensile loadings and extensions. The data were analyzed through the known equations of membrane theory in spherical subjects considering the complete symmetry of assumingly spherical pellets and/or granules. The relative tensile parameters of the experimental and commercial plasticizers in the resilient region were also estimated to fairly decide on a moderate explanation of a strong, hard, and tough structure among the specimens. The results implied the great compatibility of the oily soluble vitamins in EC networks projecting higher factors of safety and greater ultimate strength, toughness, and young coefficient of the formulations compared to the specimens plasticized with the commercial DBS within a concentration range of 40-50% (w/w) of the polymer solids. alpha-Tocopherol represented supremacy over colecalciferol to result in relatively a 2-fold (and practically a 4-fold with respect to DBS) greater increase in the modulus of resilience. The vitamin compounds and in essential alpha-tocopherol, in consequence, can properly be applied at concentrations of 40-50% (w/w) as efficient plasticizers to provide a greater protection of the structure against sudden fractures of dynamic and continuously increasing environmental and biological stresses.

Topics: alpha-Tocopherol; Cellulose; Chemistry, Pharmaceutical; Cholecalciferol; Dicarboxylic Acids; Plasticizers; Tensile Strength; Vitamins

The mechanical properties of polymer films used in pharmaceutical coatings of pulsatile drug delivery systems were evaluated in the dry and the wet state by a newly developed puncture test, which allowed the time-dependent measurement of the mechanical properties on the same film specimen. Force, puncture strength, energy at break, modulus, and strain were investigated as a function of water exposure time with respect to the type of polymer and the type and concentration of plasticizer and pore former (hydroxypropyl methylcellulose, HPMC). Eudragit RS films were very flexible, had a high strain, and broke upon puncture with only small cracks. In contrast, ethylcellulose films were more brittle with a lower strain and showed complete film rupture. Increased amounts of the hydrophilic pore former, HPMC, resulted in a reduced puncture strength and in an increase in water uptake and weight loss of the films. The puncture strength decreased with increasing plasticizer concentration and was lower with the lipophilic dibutyl sebacate than with the hydrophilic triethyl citrate.

Topics: Acrylic Resins; Cellulose; Citrates; Dicarboxylic Acids; Drug Delivery Systems; Hypromellose Derivatives; Mechanics; Methylcellulose; Pulsatile Flow; Time Factors; Water

The aim of this study was to investigate the ability of n-alkenyl succinic anhydrides (n-ASAs) to improve the film-forming characteristics of a novel coating polymer, potato starch acetate degree of substitution 2.8 (SA). n-ASAs were also applied to improve the otherwise brittle properties of ethyl cellulose (EC) aqueous dispersion (Aquacoat) and EC solvent-based films.. The effectiveness of two n-ASAs, 2-octenyl succinic anhydride (OSA) and 2-dodecen-1-ylsuccinic anhydride were evaluated as plasticizers. Mechanical properties, both water vapor and drug permeabilities, and glass transition temperatures of the cast free films were measured. Triethyl citrate and dibutyl sebacate were used as reference plasticizers.. The long hydrocarbon chain of n-ASA, with its accessible carbonyl groups, enabled a strong plasticization effect on the tested polymers. Due to the excellent mechanical properties (i.e., a tough film structure with considerable flexibility) and low permeability of the plasticized films, n-ASAs, and especially OSA proved to be an ideal plasticizer particularly for EC based coatings. Also, the EC aqueous dispersion plasticized with n-ASAs resulted in a markedly enhanced coalescence of the colloidal polymer particles, even at low drying temperatures.. In applications where a coating with high flexibility is required, n-ASAs can be used as plasticizers at moderately high concentrations (up to 60-70%, w/w) without losing the high tensile strength, excellent toughness and low permeability of EC and SA films.

Topics: Algorithms; Calorimetry, Differential Scanning; Cellulose; Chemical Phenomena; Chemistry, Physical; Citrates; Crystallization; Dicarboxylic Acids; Permeability; Plasticizers; Solvents; Starch; Succinic Anhydrides; Tensile Strength; Water

The development of a loading method of a water-soluble drug using aqueous binding solution to produce microgranules that were then coated with an aqueous ethylcellulose dispersion to sustain drug release is described. The results, in terms of drug used, showed that besides the fluidized bed parameters, the amount of drug dissolved in the binder solution plays an important role in obtaining a satisfying result during the spraying process. Thus, it seems necessary to determine the critical concentration above which the material started to adhere to the interior of the fluidization column, and the possibility of drug layering onto carrier material is aggravated. ANOVA of the time parameter for release of 63.2% of total drug (td) value showed significant influence of ethylcellulose (Aquacoat ECD-30) and dibutyl sebacate concentration on diphenhydramine hydrochloride (DPH) release. The dissolution rate decreased with an increase in polymer concentration. The diffusional exponent n of the Peppas equation indicated that the DPH release kinetic was non-Fickian but approached Fickian diffusion, particularly at higher coating levels.

Topics: Cellulose; Chemistry, Pharmaceutical; Delayed-Action Preparations; Dicarboxylic Acids; Diffusion; Diphenhydramine; Drug Carriers; Kinetics; Microscopy, Electron, Scanning; Plasticizers; Povidone; Solubility; Suspensions; Water

The release of the hydrophilic etofylline and the lipophilic propyphenazone (octanol/water partition coefficient PC = 0.35 and 119, respectively) from diffusion pellets coated with the aqueous ethyl cellulose dispersion Aquacoat ECD-30 and 20% dibutyl sebacate (DBS) as plasticizer is investigated as a function of pH. The relatively slow release is not constant, due to the broad distribution of different release rates within the pellet population and the non-linearity of the release of each diffusion pellet itself. The release proceeds according to a partition mechanism at a pH < 6. The partition mechanism is not influenced by the osmotic pressure difference between the release medium and the saturated solution within the diffusion pellets. The diffusion coefficients of different drugs in the plasticized coating are in the range 1 to 5 x 10(-8) cm2/s. At a of pH > 6 an additional hydrophilic pathway without partition exists if the diffusion pellets did not have any contact with an acidic medium. This is due to the strongly increased water uptake of more than 20% by the coatings as a consequence of the dissociation of carboxyl groups in the ethyl cellulose.

Topics: Cellulose; Dicarboxylic Acids; Diffusion; Drug Implants; Guaifenesin; Hydrogen-Ion Concentration; Osmotic Pressure; Plasticizers; Porosity; Sucrose; Suspensions; Theophylline

The surface free energy parameters of ethylcellulose (EC) films were determined using the Lifshitz-van der Waals/acid-base approach and the influence of plasticizers on their surface energetics was assessed. Films were prepared by dip-coating glass slides in organic solvents containing EC and the advancing angles of drops of pure liquids on the EC films were measured with a contact angle goniometer using the captive drop technique. EC has lower surface free energy than cellulose. The acid-base (AB) term made only a slight contribution to the total surface free energy and the surfaces exhibited predominantly monopolar electron-donicity. The addition of plasticizer (dibutyl sebacate or dibutyl phthalate) resulted in a small decrease in the total surface free energy. The effects of film forming variables, including solvent system, concentration and post-formation treatment (annealing), on the surface free energy parameters of EC films were also investigated. These data were then used to analyze how the surface energetics affect the interaction of the EC films with other surfaces based on interfacial tension, work of adhesion and spreading coefficient calculations. Lifshitz-van der Waals (LW) interactions provided the major contribution to the work of adhesion for EC with all of the solid substrates analyzed. However, the AB interactions contributed significantly to the work of adhesion for EC with 'bipolar' substrates and to the spreading coefficients of EC over substrates. The consideration of work of adhesion and spreading coefficient based on surface free energy parameters may have potential use in evaluating factors affecting film adhesion and, furthermore, in optimizing pharmaceutical film coating processes.

Topics: Cellulose; Dibutyl Phthalate; Dicarboxylic Acids; Mathematics; Methanol; Methylene Chloride; Plasticizers; Solvents; Surface Properties; Surface Tension; Thermodynamics

The influence of curing time and curing temperature for a commercially available ethylcellulose latex coating dispersion (Aquacoat) were evaluated using response surface methodology. Levels for the factor curing time ranged from 30 to 300 minutes while levels for curing temperature ranged from 45 degrees to 75 degrees C. Responses, A, kappa, and gamma, were derived from regression analysis of the dissolution profiles and correspond to the maximum amount of drug released over the 12 hour sampling period, the rate of release, and the inflection point of the dissolution profile, respectively. The nature of the response surface was dramatically influenced by the plasticizer incorporated into the coating formula. When dibutyl sebacate was employed as the plasticizer, faster release resulted (higher A and kappa values, lower gamma values) when samples were exposed to higher curing temperatures or were stored for longer periods of time. Paradoxically, when tributyl citrate was used as the plasticizer, slower release resulted when samples were exposed to more rigorous conditions. Overall, curing temperature had a more dramatic effect than curing time.

Topics: Cellulose; Citrates; Dicarboxylic Acids; Drug Compounding; Latex; Microspheres; Plasticizers; Solubility; Surface Properties; Temperature; Time Factors