Viscosity Grades Of Ethyl Cellulose Research Articles

Peculiar effect of polyethylene glycol in comparison with triethyl citrate or diethyl phthalate on properties of ethyl cellulose microcapsules containing propranolol hydrochloride in process of emulsion-solvent evaporation

Plasticizers play a crucial role in various process of microencapsulation. In this study, the effect of incorporation of plasticizer in process of emulsion solvent evaporation was investigated on properties of ethyl cellulose (EC) microcapsules containing propranolol hydrochloride. The effect of plasticizer type and concentration were investigated on characteristics of microcapsules prepared from different viscosity grades of EC. Product yield, encapsulation efficiency, mean particle size, shape, surface characteristics, solid state of drug, and drug release profiles were evaluated. Product yield and encapsulation efficiency were not dependent on plasticizer type and concentration. However, encapsulation efficiency decreased with increase in EC viscosity grade in the most of the cases. The mean particle size was in the range of 724–797 μm and was not dependent on plasticizer type. Microcapsules formed in the presence of PEG had a very smooth surface with few pores. XRD and DSC studies revealed a reduction of drug crystallinity after microencapsulation especially in presence of PEG. The results showed that the presence of TEC and DEP with different concentrations had no marked effect on drug release from microcapsules containing different viscosity grades of EC. This was not the case when PEG was used, and despite its water solubility it reduced the drug release rate noticeably. The reduction in the drug release in the presence of PEG was concentration-dependent. The use of PEG as a plasticizer in process of emulsion solvent evaporation highly improved the EC microcapsule structure and retarded the drug release rate and therefore is recommended.

Effect of Variation in Viscosity Grade of Ethycellulose on Theophylline Microcapsule Properties Prepared by Emulsion Solvent Evaporation.

There are conflicting reports regarding the effect of polymer viscosity grade on microcapsule properties. The aim of the present study was to investigate the effect of just viscosity grade of ethylcellulose (EC) (not polymeric solution) on properties of theophylline microcapsules prepared by emulsion solvent evaporation. The effect of EC viscosity grade and drug:polymer ratio was investigated on microcapsule properties (yield, particle size, morphology, surface characteristics and drug release). Differential scanning calorimetry (DSC) and X-ray powder diffraction (XRD) were implemented to study the interaction and solid state of drug. The microcapsules were compressed in the presence of excipients and drug release was evaluated. The yield of microencapsulation and encapsulation efficiency at 1:1 drug:polymer ratio was dependent on EC viscosity. Microcapsules were spherical with some pores on their surfaces. The number of pores was more and their size was bigger for EC 100 cP microcapsules. Theophylline remained in crystalline form after encapsulation. DSC studies confirmed lack of interaction between drug and polymer. The drug release was rapid at 2:1 drug:polymer whilst it was slowed down at 1:1 drug:polymer ratio. Microcapsules obtained from EC 100 cP showed slightly faster drug release at latter ratio. Marginal changes in release rate were observed after compression of microcapsules. All viscosity grades of EC were able to sustain the release of the drug from microcapsules. Considering the similar release profiles for microcapsules prepared from different viscosities of EC, the use of lower viscosity grade of EC is recommended due to the ease of production and also less processing time.

The importance of the molecular weight of ethyl cellulose on the properties of aqueous-based controlled release coatings

Previous investigations of aqueous based ethyl cellulose (EC) latex dispersions have mainly focused on the commercially available viscosity grade 20cps. In this study, dispersions of EC with varying viscosity grades (which correspond to molecular weights), ranging from 4 to 100 cps, were produced and characterised. The dispersions showed particle sizes around 200nm and highly negative ζ-potentials (approx. −100mV), which indicated stable dispersions as confirmed by sedimentation studies. The different latexes were used to produce free-standing film coatings. We hypothesised that the different viscosity grades of EC would result in different properties of the films. We found that an increase in viscosity grade (and higher molecular weight) resulted in lower coalescence between the particles during film formation and thus to higher water permeability than in film coatings of lower molecular weight. After exposure to water the EC 4cps and 20cps film coatings had a more porous structure in the side facing the air during production and drying after immersion in water. Molecular weight is therefore a factor that should be considered when producing pharmaceutical coatings for controlled release.

Preparation and Characterization of Gastro-retentive Sustained Release Microcapsules of Salbutamol Sulphate

The objective of this study was to prepare gastro-retentive microcapsules using solvent evaporation method containing salbutamol sulphate. The effect of various viscosity grades of ethylcellulose (EC) on In vitro drug release and buoyancy was evaluated. The influence of formulation factors (stirring speed, Drug: EC ratio, various viscosity grades of EC) on particle size, encapsulation efficiency, in-vitro release characteristics was studied. FT-IR and DSC studies revealed no interaction between drug and EC. The yields and the encapsulation efficiencies were high for all microcapsule formulations. Floating lag time was zero for all microcapsules prepared with EC 7 cPs whereas EC N50 based microcapsules did not show buoyancyl. EC 18-22 cPs based microcapsules showed zero floating lag time for formulations with drug to EC ratio of 1:1 and 1:1.5 but 1:2 ratio did not exhibit buoyancy. Stirring speed was inversely related to the size of the microcapsules. In-vitro release studies revealed that the drug release was sustained upto 12 h for microcapsules prepared with EC 18-22 cPs and EC N50 whereas EC 7 cPs based microcapsules could not sustain the release for more than 6 h. Stability studies as per ICH guidelines revealed no significant change in drug entrapment efficiency, in vitro buoyancy and in vitro drug release. Hence incorporation of optimum concentration of EC 18-22 cPs (F5) in the formulation of microcapsules by solvent evaporation method proved to be an effective method in achieving desired release behavior and buoyancy.

Development and evaluation of injection-molded sustained-release tablets containing ethylcellulose and polyethylene oxide

Purpose: 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. Methods: 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 × 106, 1 × 106, and 1 × 105 Mw) on processability and drug release was determined. Results: 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. Conclusion: It was concluded that injection molding can be applied successfully to develop sustained-release PEO/EC matrix tablets.

Development of injection moulded matrix tablets based on mixtures of ethylcellulose and low-substituted hydroxypropylcellulose

The objective of this study was to produce sustained-release matrix tablets by means of injection moulding and to evaluate the influence of matrix composition, process temperature and viscosity grade of ethylcellulose on processability and drug release by means of a statistical design. The matrix tablets were physico-chemically characterized and the drug release mechanism and kinetics were studied. Formulations containing metoprolol tartrate (30%, model drug), ethylcellulose with dibutylsebacate (matrix former and plasticizer) and L-HPC were extruded and subsequently injection moulded into tablets (375 mg, 10 mm diameter, convex-shaped) at different temperatures (110, 120 and 130 °C). Dissolution tests were performed and tablets were characterized by means of DSC, X-ray powder diffraction studies, X-ray tomography, porosity and hardness. Tablets containing 30% metoprolol and 70% ethylcellulose (EC 4cps) showed an incomplete drug release within 24 h (<50%). Formulations containing L-HPC and EC in a ratio of 20/50 and 27.5/42.5 resulted in nearly zero-order drug release, while the drug release rate was not constant when 35% L-HPC was included. Processing of these formulations was possible at all temperatures, but at higher processing temperatures the drug release rate decreased and tablet hardness increased. Higher viscosity grades of EC resulted in a faster drug release and a higher tablet hardness. The statistical design confirmed a significant influence of the EC and L-HPC concentration on drug release, while the processing temperature and EC viscosity grade did not affect drug release. Tablet porosity was low (<5%), independent of the formulation and process conditions. DSC and XRD demonstrated the formation of a solid dispersion. The hydration front in the tablets during dissolution was visualized by dynamic X-ray tomography, this technique also revealed an anisotropic pore structure through the tablet.

Effect of viscosity grades of ethylcellulose on the sustained release properties of indomethacin from its tablets matrix

The objective of the present study was to estimate the influence of ethyl cellulose (EC) with different viscosity grades on in vitro drug release from EC matrix tablets containing Indomethacin. Four viscosity grades of EC (7, 10, 50 and 100 cp) were studied. The 90 - 125/µm particle size fraction was collected by manual dry sieving and the compression force was varied to produce tablets of equal hardness. The drug release from Indomethacin tablets was determined by dissolution testing as described in the United States Pharmacopoeia (USP). The tablets pore characteristics were studied using helium pycnometry and mercury porosimetry. The release rate constant ranged from 1.25 ± 0.98 for the 7cp viscosity grade tablets to 1.49 ± 1.02 for the 100cp viscosity grade tablets whereas porosity ranged from 5.6% ± 0.3 to 6.8 ± 0.1 when based on gaz pycnometry and from 3.9% ± 0.4 to 5.1 ± 0.2 when based on mercury intrusion. These results indicate that the release rates marginally increased with an increase in viscosity grade. The main explanation for the viscosity grade effect on release rates would be differences in tablet porosity. Key words: Matrix, ethylcellulose, viscosity grade, indomethacin, dissolution, porosity paste electrode, pharmaceutical formulations, biological samples, voltammetric techniques.

Evaluation of injection moulding as a pharmaceutical technology to produce matrix tablets

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 °C. Tablets containing 30% metoprolol and 70% ethylcellulose (EC 4 mPa 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.

Ethylcellulose matrix controlled release tablets of a water-soluble drug

Pseudoephedrine hydrochloride was used as a model drug to prepare direct compression sustained release tablets with ethylcellulose (EC). Initially, different viscosity grades of EC were studied. An increase in viscosity grade resulted in a marginal to moderate increase in the release rate. However, lower viscosity grades produced harder tablets. The highly compressible 10 cp grade was used to study the effect of drug loading, particle size, compression force, and magnesium stearate concentration on release properties. The rate of drug release decreased with a decrease in the drug concentration in the matrix. Except for tablets prepared with EC having a particle size fraction 250–420 and 177–250 μm, drug release up to 80% exhibited a square root of time dependency and tablets remained intact during dissolution. Tablets prepared with either the EC 250–420 or 177–250 μm particle size fraction eroded. The square of the release rate is proportional to drug concentration in the matrix, indicating that the release of pseudoephedrine hydrochloride from EC matrices is primarily matrix-controlled.

Microencapsulation of isoprinosine with ethylcellulose

Isoprinosine, an antiviral agent with a bitter taste, has been clinically used up to a maximum of 4 g daily in 4–8 doses. In this investigation, isoprinosine was microencapsulated with ethylcellulose 22 cps, 50 cps and 100 cps by means of polymer deposition from cyclohexane through temperature change. Complete removal of cyclohexane from the microcapsules was necessary, since ethylcellulose-coated microcapsules obtained from cyclohexane medium were heavily solvated with cyclohexane and formed lumps even after drying. The displacement of cyclohexane byn-hexane during isolation of microcapsules (Method III) or the freezing of the final-washed microcapsules before drying (Method II) provided the dried products which were more discrete microcapsules than those which were simply dried in the air overnight (Method I). Method III was especially the most effective procedure in preparing finer and more discrete microcapsules. The drug-release from microcapsules was influenced by the ratio of core to wall, the viscosity grade of ethylcellulose and the overall microcapsule size. The release rate was adequately fitted to both the first-order and the diffusion-controlled processes. It is therefore possible to design the release-controlled microcapsules with ethylcellulose of different viscosity along with various core to wall ratio.

Controlled release captopril microcapsules: Effect of ethyl cellulose viscosity grade on thein vitrodissolution from microcapsules and tableted microcapsules

Captopril microcapsules were prepared using four different viscosity grades of ethyl cellulose (core: wall ratios 1:1, 1:2 and 1:3) by temperature induced coacervation from cyclohexane. In vitro dissolution studies in 0.1 M hydrochloric acid showed that the drug release was dependent on the core to wall ratio, the viscosity grade of the ethyl cellulose and thus the total viscosity of the coacervation system. Viscosity grade of greater than 100 c.p. was unsuitable for microencapsulation by coacervation method at the concentration used. The surface characteristics of a 1:2 core to wall ratio were studied by scanning electron microscopy. The surface of the microcapsules prepared with 10 c.p. viscosity grade was comparatively more porous with larger size pores than 50 c.p. viscosity grade of ethyl cellulose. However, 300 c.p. viscosity grade showed incomplete wall formation. The microcapsules did not fragment during dissolution, alter in shape or size, or show evidence of enlargement of the surface pores. The tensile strength of tablets prepared at constant pressure from each batch of microcapsules (mean diameter 675 microns) increased as both the core to wall ratios and the viscosity of ethyl cellulose increased. The dissolution rate of the drug from tableted microcapsules was significantly delayed. The in vitro release gave best correlation with first order release kinetics when compared to zero-order and square-root-of-time equations.

Controlled release captopril microcapsules: effect of non-ionic surfactants on release from ethyl cellulose microcapsules.

Captopril microcapsules were prepared with different viscosity grades of ethyl cellulose by temperature induced coacervation from cyclohexane. Both non-ionic surfactants or their combinations and 2 per cent absolute alcohol as cosolvent were added to the coacervation system to ensure complete solvation of the ethyl cellulose and efficient microencapsulation of the drug. The in vitro dissolution was studied in 0.1 N hydrochloric acid. Microcapsules prepared using 2 per cent Tween 80 with ethyl cellulose of 41 c.p. viscosity grade exhibited the most prolonged release with a t70 per cent of 55 min in comparison to 7.75 min for control microcapsules prepared without surfactant. Different kinetic models have been used to explain the release. The best fit with the highest correlation coefficients was the first-order kinetics plot with two straight lines having two different slopes. The initial slope presents the faster release rate than the terminal slope. This fast release would be useful for the initial dose of the prolonged release formulation.

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

AbstractThe 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.

In vivo evaluation of ethyl cellulose microcapsules containing ampicillin using rabbits, beagle dogs and humans.

Ampicillin, an orally administered antibiotic, was microencapsulated with different viscosity grades of ethyl cellulose (10, 50 and 100 cps EC) and was orally administered to rabbits, beagle dogs and humans. A significant sustained release pattern was observed in rabbits. While a significant decrease in the area under the plasma concentration curve occurred, and the sustained release pattern was not obtained in beagle dogs. In humans, the extent of the sustained release was intermediate between the pattern observed in beagle dogs and rabbits. The treatment of data by log-log plots yielded a linear relation between half lives of dissolution of ampicillin from microcapsules in vitro (T50) and the ratios of pharmacokinetic parameters of microcapsules to those of powder. In order to explain the difference in the sustained release pattern of rabbits, beagle dogs and humans, a pharmacokinetic model, considering gastric-emptying and intestinal-transit rates of drug formulations, was established and the pharmacokinetic consideration was done on the basis of the model. It seems that success in sustained release of a drug depended on the magnitude of the gastric-emptying and intestinal-transit rate constant (kgi) of microcapsules, in the case of a drug with a small absorption rate constant (ka) as observed with ampicillin. The magnitude of kgi was thought to be in the order of beagle dogs, humans and finally rabbits.

Preparation and biopharmaceutical evaluation of microcapsules of ampicillin.

Microencapsulation of ampicillin, an orally administered antibiotic, with different viscosity grades of ethyl cellulose was studied. The preparation of microcapsules was done as follows; the mixture of ethyl cellulose-CH2Cl2-ampicillin was dispersed in purified water containing 0.5% (w/w) sodium lauryl benzenesulfonate, and then CH2Cl2 was dried out by elevating the temperature. The dissolution curves for the release of ampicillin from microcapsules prepared using the four different viscosity grades of ethyl cellulose were quite different. The release of ampicillin increased with decreasing ethyl cellulose viscosity. The evaluation of prepared microcapsules was made using gastric-emptying-controlled rabbits. The plasma concentration of ampicillin obtained by the administration of microcapsules showed a significant sustained-release pattern. The area under the plasma concentration curve (AUC) of ampicillin obtained after a single oral administration of microcapsules prepared using 10 cps ethyl cellulose was 1.8 times greater than that obtained after double oral administration of powder. This fact will be caused by the delaying of gastric-emptying, intestinal-transit and dissolution of ampicillin there. It was confirmed that a large number of microcapsules still remained in the stomach and each microcapsules still contained ampicillin at 24 h after dosing from the experiment using gastric-emptying-controlled rabbits.