Preparation and Preliminary Evaluation of Eudragit RL and RS Pseudolatices for Controlled Drug Release

Eudragit RL and RS pseudolatices were prepared by the solvent change technique, which consisted of dissolving the polymer in a water miscible organic solvent or in a mixed water miscible organic solvent system, followed by dispersian in deionized water under mild agitation. The organic solvent (s) was removed from the aqueous organic solution to leave a stable Eudragit latex.

Eudragit pseudolatex coated theophylline pellets were prepared in a fluidized-bed coating machine. The effects of polymer type and coating level, plasticizer concentration, and PH of the dissolution medium on drug release were investigated. The higher content of quaternary ammonium groups attached to the polymer backbone make the coatings produced from Eudragit RL too water sensitive; and hence unsuitable for controlling theophylline release. On the other hand, Eudragit RS films retarded theophylline release. On the other hand, Eudragit RS films retarded theophylline release over a wide pH range. Release of the drug was found to be a function of the polymer coating level, plasticizer concentration and dependent on pH of the dissolution medium.     

Controlled Release Kinetics of Captopril From Tableted Microcapsules

Abstract

Different viscosity grades ethylcellulose coated captopril microcapsules were prepared using temperature induced coacervation method from cyclohexane containing 2% Tween 80. Microcapsules were compressed directly into tablets. In vitro dissolution was carried out in 0.1 N HCl at 37°C using the rotating basket method. Release from tablets of all the batches was extensively prolonged in comparison to the respective microcapsules. The longest time for 70% drug release was shown by microcapsules (55min) and tablets (378 min) of the batch E-2. Release rate constants, correlation, determination and regression coefficients were calculated for the first-order, zero-order and Higuchi's equations. The best fit of release kinetics with the highest correlation and determination coefficients was achieved with the first-order followed by Higuchi's plot.     

Eudragit Microcapsules of Nifedipine and Its Dispersions in HPMC-MCC: Physicochemical Characterization and Drug Release Studies

Nifedipine and its solid dispersions in hydroxypropyl methyl cellulose-microcrystalline cellulose (HPMC-MCC) were microencapsulated with Eudragit RL PM by an emulsion solvent evaporation method. The microcapsules are spherical, discrete, free flowing, and covered with a continuous coating of the polymer. XRD and DTA indicated the presence of nifedipine in solution form in the solid dispersions and their microcapsules. No chemical interaction between nifedipine and excipients in the microcapsules was observed. Nifedipine as such and its microcapsules gave very slow release because of its highly crystalline nature and poor solubility. Solid dispersion in HPMC-MCC gave fast and rapid dissolution of nifedipine. When these solid dispersions were microencapsulated a slow, controlled, and complete release over a period of 12 hr was observed from the resulting microcapsules. Drug release depended on the proportion of HPMC-MCC in the solid dispersion used as a core, coat, core ratio, and size of the microcapsules. Release was independent of pH and ionic strength. Drug release was governed by diffusion rate and followed first-order kinetics.     

Eudragit Microcapsules of Nifedipine and Its Dispersions in HPMC-MCC: Physicochemical Characterization and Drug Release Studies

Abstract

Nifedipine and its solid dispersions in hydroxypropyl methyl cellulose-microcrystalline cellulose (HPMC-MCC) were microencapsulated with Eudragit RL PM by an emulsion solvent evaporation method. The microcapsules are spherical, discrete, free flowing, and covered with a continuous coating of the polymer. XRD and DTA indicated the presence of nifedipine in solution form in the solid dispersions and their microcapsules. No chemical interaction between nifedipine and excipients in the microcapsules was observed. Nifedipine as such and its microcapsules gave very slow release because of its highly crystalline nature and poor solubility. Solid dispersion in HPMC-MCC gave fast and rapid dissolution of nifedipine. When these solid dispersions were microencapsulated a slow, controlled, and complete release over a period of 12 hr was observed from the resulting microcapsules. Drug release depended on the proportion of HPMC-MCC in the solid dispersion used as a core, coat, core ratio, and size of the microcapsules. Release was independent of pH and ionic strength. Drug release was governed by diffusion rate and followed first-order kinetics.     

Preparation, Characterization and In-Vitro Release Kinetics of Salbutamol Sulphate Loaded Albumin Microspheres

Salbutamol sulphate loaded Bovine serum albumin microspheres were prepared by heat denaturation method. The effects of such preparation conditions as denaturation temperature, denaturation time, protein concentration and phase volume ratio on the extent of drug loading, size and size distribution and drug release were studied. An increase in protein concentration from 5% w/v to 15% w/v increased the mean particle size from 8.5 μm to 16.6 μm and decreased the drug loading from 46% w/w to 18% w/w. A decrease in the phase volume ratio substantially lowered mean particle size and size distribution. An increase in the severity of denaturaion conditions lowered both the drug incorporated and drug released. The kinetics of drug release from microspheres were compared to the theoretical models of Higuchi diffusional release and first order release. Both the models gave an adequate fit to the data. Scanning electron microscopy revealed that the dummy microspheres are spherical with smooth surfaces. As the drug-protein ratio increased, the microspheres exhibited rough surfaces showing the presence of drug crystals.     

Preparation,Characterization and In-Vitro Release Kinetics of Salbutamol Sulphate Loaded Albumin Microspheres

Abstract

Salbutamol sulphate loaded Bovine serum albumin microspheres were prepared by heat denaturation method. The effects of such preparation conditions as denaturation temperature, denaturation time, protein concentration and phase volume ratio on the extent of drug loading, size and size distribution and drug release were studied. An increase in protein concentration from 5% w/v to 15% w/v increased the mean particle size from 8.5 μm to 16.6 μm and decreased the drug loading from 46% w/w to 18% w/w. A decrease in the phase volume ratio substantially lowered mean particle size and size distribution. An increase in the severity of denaturaion conditions lowered both the drug incorporated and drug released. The kinetics of drug release from microspheres were compared to the theoretical models of Higuchi diffusional release and first order release. Both the models gave an adequate fit to the data. Scanning electron microscopy revealed that the dummy microspheres are spherical with smooth surfaces. As the drug-protein ratio increased, the microspheres exhibited rough surfaces showing the presence of drug crystals.     

In-Vitro Release and Permeation Kinetics of Pentazociwe From Matrix-Dispersion Type Trawsdwul Drug Delivery Systw

A matrix-dispersion type Transdermal Drug Delivery System (TDS) of Pentazocine (PZ) was fabricated, using combinations of rate controlling polymers, namely Eudragits RS100 (RS), RL100 (RL), Ethylcellulose (EC) and Polyvinyl pyrrolidone (PVP), with the objective of examining the effects of formulation variables on drug-permeation profiles. In depth in-vitro drug release and skin-permeation kinetics with three different loads, and also the effects of combination of isopropyl Myristate (IPM), as permeation enhancer, were studied using male albino mice abdominal skin. The release of PZ over a 12 hour period followed Higuchi kinetics, while in-vitro mice-skin permeation of PZ followed an apparent Zero-order kinetics over a period of 24 hours.     

In-Vitro Release and Permeation Kinetics of Pentazociwe From Matrix-Dispersion Type Trawsdwul Drug Delivery Systw

Abstract

A matrix-dispersion type Transdermal Drug Delivery System (TDS) of Pentazocine (PZ) was fabricated, using combinations of rate controlling polymers, namely Eudragits RS100 (RS), RL100 (RL), Ethylcellulose (EC) and Polyvinyl pyrrolidone (PVP), with the objective of examining the effects of formulation variables on drug-permeation profiles. In depth in-vitro drug release and skin-permeation kinetics with three different loads, and also the effects of combination of isopropyl Myristate (IPM), as permeation enhancer, were studied using male albino mice abdominal skin. The release of PZ over a 12 hour period followed Higuchi kinetics, while in-vitro mice-skin permeation of PZ followed an apparent Zero-order kinetics over a period of 24 hours.     

The MiniWiD-Coater. III. Effect of Application Temperature on the Dissolution Profile of Sustained-Release Theophylline Pellets Coated with Eudragit Rs 30 D

Theophylline pellets were coated with Eudragit RS 30 D in a miniature fluid-bed pan coater called MiniWiD developed recently. The dispersions were plasticized with varying amounts of triethyl citrate (TEC), dibutyl phthalate (DBP), and polyethylene glycol 6000 (PEG) and applied at different temperatures ranging from 25 to 45 °C. Theophylline release was tested by dissolution using the USP Apparatus 2 (paddle) in 0.1 N hydrochloric acid under sink conditions over 6 hours.

At a coating level of 4 % (0.7 mg/cm²) sustained-release profiles were obtained from dispersions plasticized with TEC or DBP. By reducing the amount of plasticizer from 20 to 10%, films with higher permeabilities were obtained. This effect was compensated by tempering the pellets at 50 deg;C for 24 hours. The coating temperature had little effect on the dissolution profiles of TEC-plasticized films and no effect on films with DBP.

Coatings plasticized with 20% PEG were applied at temperatures ranging from 25 to 45 °C. These films required a coating level of about 18 % (3.3 mg/cm²) to provide comparable sustained-release properties. In contrast to DBP and TEC, a strong influence of the coating temperature on the release rates was observed in which higher temperatures led to slower release rates. This behavior can be explained by the minimum film-forming temperature (MFT). Since PEG does not lower the MFT of Eudragit RS 30 D, the application of these films below the MFT of 45 °C is associated with a lower degree of film formation.     

The MiniWiD-Coater. III. Effect of Application Temperature on the Dissolution Profile of Sustained-Release Theophylline Pellets Coated with Eudragit Rs 30 D

Abstract

Theophylline pellets were coated with Eudragit RS 30 D in a miniature fluid-bed pan coater called MiniWiD developed recently. The dispersions were plasticized with varying amounts of triethyl citrate (TEC), dibutyl phthalate (DBP), and polyethylene glycol 6000 (PEG) and applied at different temperatures ranging from 25 to 45 °C. Theophylline release was tested by dissolution using the USP Apparatus 2 (paddle) in 0.1 N hydrochloric acid under sink conditions over 6 hours.

At a coating level of 4 % (0.7 mg/cm²) sustained-release profiles were obtained from dispersions plasticized with TEC or DBP. By reducing the amount of plasticizer from 20 to 10%, films with higher permeabilities were obtained. This effect was compensated by tempering the pellets at 50 deg;C for 24 hours. The coating temperature had little effect on the dissolution profiles of TEC-plasticized films and no effect on films with DBP.

Coatings plasticized with 20% PEG were applied at temperatures ranging from 25 to 45 °C. These films required a coating level of about 18 % (3.3 mg/cm²) to provide comparable sustained-release properties. In contrast to DBP and TEC, a strong influence of the coating temperature on the release rates was observed in which higher temperatures led to slower release rates. This behavior can be explained by the minimum film-forming temperature (MFT). Since PEG does not lower the MFT of Eudragit RS 30 D, the application of these films below the MFT of 45 °C is associated with a lower degree of film formation.     

Eudragit RL and RS Pseudolatices: Properties and Performance in Pharmaceutical Coating as a Controlled Release Membrane for Theophylline Pellets

Theophylline Active pellets were coated with Eudragit RL and RS pseudolatices in a fluidized bed. The effects of polymer ratio, additional oven drying, addition of dispersed solids, and addition of water miscible organic solvents on sustained drug release through the lates film were determined by using a modified U.S.P. Paddle dissolution method.

The release rate of theophylline can be varied by changing the polymer ratio. permeability to the drug increases with an increase in the content of Eudragit RL. Additional oven drying at 60°C for 10 hours caused no significant change in the dissolution profiles. The addition of dispersed solids such as talcum and silica resulted in an increase in drug release rate. There is no significant change in dissolution profiles when 50% methanol or acetone was added to the Eudragit RS pseudolatex.     

Kinetics and Mechanism of Drug Release From Calcium Alginate Membrane Coated Tablets

Compressed tablets containing guaifenesin (model drug), calcium acetate (reactant) and pharmaceutical excipients were prepared. The tablets were coated with calcium alginate hydrogel using a novel, self-correcting membrane coating technique. Effects of coating time, the type of alginate polymer and pH of the dissolution medium on the rate of drug release were evaluated. In distilled water, zero order drug release profiles were obtained from the coated tablets. The release rate decreased with an increase in the coating time (increased coat thickness) and molecular weight of alginate polymer. The release rate constants correlated with model for spherical reservoir system and, were used to calculate permeability of guaifenesin in the calcium alginate coatings. Alginate polymer with higher guluronic acid content provided acid stable coating and higher molecular weight polymer produced membrane with lower permeability for guaifenesin.     

Mechanistic Analysis of Drug Release from Theophylline Pellets Coated by Films Containing Pectin,Chitosan and Eudragit® RS

The objective of this study was to obtain detailed information on the mechanism of drug release from mixed-film of pectin-chitosan/Eudragit® RS. Pellets (710–840 μm in diameter) containing 60% theophylline and 40% microcrystalline cellulose were prepared by extrusion-spheronization method. Eudragit® L100-55 enteric coating capsules included film-coated pellets of theophylline in theoretical coating weight gains of 10, 15, and 20%, with pectin-chitosan complex contents of 5, 10, 15, and 20% for each level of weight gain were prepared and subjected to in vitro drug release. Drug release from this system showed a bimodal release profile characteristic with the drug release enhancement, being triggered (burst release) in the colonic medium. The reason for burst drug release may be due to the enzymatic degradation of pectin via pectinolytic enzymes in the simulated colonic medium. The mechanism of drug release from each formulation was evaluated in the terms of zero-order, first-order, Higuchi and Korsmeyer-Peppas models. It was observed that none of the enteric coating capsules showed any drug release in the simulated gastric medium (phase I). The analysis of release profiles showed that zero-order kinetics was found as the better fitting model for all formulations in the simulated small intestine (phase II) and it could be due to the pectin-chitosan swelling and subsequent formation of aqueous channels. In the colonic medium (phase III), due to degradation of pectin and its leaching from the mixed-film, there was a modification in drug release kinetics from swelling-controlled at phase II to anomalous at phase III. It also was found that both zero-order and Higuchi models contributed in colonic drug release from most of the formulations.     

In-Vitro Release of Acetaminophen from Sodium Alginate Controlled Release Pellets

The production of spheres loaded with acetaminophen by the cross linking technique was achieved. The hydrophilic polymer sodium alginate which gels in presence of a cross linking ion was used as a matrix for the spheres production. Two processing variables were studied. The drug load in the formula which varied from 5% w/v to 20% w/v, and the cross linking agents used; calcium chloride, calcium acetate, and aluminum sulfate. Also the effects of the dissolution medium and the rotational speed of the dissolution apparatus on drug release were investigated. Spheres were compacted into 450 mg tablets without the aid of excipients. The drug release from spheres containing 20% w/v drug was 90% after 6 hours, while the drug release from compacts of these spheres was 90% after 12 hours. The mechanism of drug release from spheres and compacts containing 20% w/v drug and prepared with 5% w/v cross linking material     

In-Vitro Release of Acetaminophen from Sodium Alginate Controlled Release Pellets

Abstract

The production of spheres loaded with acetaminophen by the cross linking technique was achieved. The hydrophilic polymer sodium alginate which gels in presence of a cross linking ion was used as a matrix for the spheres production. Two processing variables were studied. The drug load in the formula which varied from 5% w/v to 20% w/v, and the cross linking agents used; calcium chloride, calcium acetate, and aluminum sulfate. Also the effects of the dissolution medium and the rotational speed of the dissolution apparatus on drug release were investigated. Spheres were compacted into 450 mg tablets without the aid of excipients. The drug release from spheres containing 20% w/v drug was 90% after 6 hours, while the drug release from compacts of these spheres was 90% after 12 hours. The mechanism of drug release from spheres and compacts containing 20% w/v drug and prepared with 5% w/v cross linking material     

Pharmacokinetic and In-Vitro Characteristics of Sustained Release Verapamil Products

The in-vitro dissolution and in-vivo pharmacokinetics of two marketed sustained release formulations, Verelan (V) and Isoptin SR (ISR), were compared. The effect of food on V was also examined in a separate study with conventional Isoptin (I) as a reference. Both sustained release preparations had extended dissolution profiles with 50% release times (T50%) of 4 hours for ISR and 8 hours for V. The extended in-vitro profile of V versus ISR was confirmed in-vivo with a Tmax of 7.3 hours compared to 5.0 hours, a Cmax of 114.3 compared to 171.0 and a peak to trough ratio of 3.8 compared to 10.1 for V and ISR respectively. In a second pharmacokinetic study the rate and extent of absorption of verapamil from V was shown to be unaffected by food.     

Novel application of Eudragit RL and cholesteryl oleyl carbonate to thermo-sensitive drug delivery system

The Eudragit RL 100 and propylene glycol (PG) membranes with and without cholesteryl oleyl carbonate (COC) were prepared by the solvent casting method to pioneer a novel application of a thermo-sensitive drug delivery system. After that, the properties of these membranes were investigated by thermal, scanning, and porosity studies. Drug permeation studies through all membranes were carried out using salbuthamol sulphate (SBS) at constant temperatures (25°C and 37°C), respectively. The permeability of SBS through the membranes with COC has been shown to be a discontinuous function of temperature, that is, their permeability increased steeply above the phase transition temperature (37°C) of the COC. The thermo-sensitive permeation mechanism for the membranes might be based on the structure change of the membranes caused by the phase transition, so that the membranes could absorb more water. Considering the high biological safety of Eudragit RL 100 and PG membranes with and without COC might be used to develop a novel thermo-sensitive drug delivery system.     

Pharmacokinetic and In-Vitro Characteristics of Sustained Release Verapamil Products

Abstract

The in-vitro dissolution and in-vivo pharmacokinetics of two marketed sustained release formulations, Verelan (V) and Isoptin SR (ISR), were compared. The effect of food on V was also examined in a separate study with conventional Isoptin (I) as a reference. Both sustained release preparations had extended dissolution profiles with 50% release times (T50%) of 4 hours for ISR and 8 hours for V. The extended in-vitro profile of V versus ISR was confirmed in-vivo with a Tmax of 7.3 hours compared to 5.0 hours, a Cmax of 114.3 compared to 171.0 and a peak to trough ratio of 3.8 compared to 10.1 for V and ISR respectively. In a second pharmacokinetic study the rate and extent of absorption of verapamil from V was shown to be unaffected by food.     

Ketoprofen spray-dried microspheres based on Eudragit RS and RL: study of the manufacturing parameters

The preparation of ketoprofen spray-dried microspheres can be affected by the long drug recrystallization time. Polymer type and drug-polymer ratio as well as manufacturing parameters affect the preparation. The purpose of this work was to evaluate the possibility to obtain ketoprofen spray-dried microspheres using the Eudragit RS and RL; the influence of the spray-drying parameters on morphology, dimension, and physical stability of microspheres was studied. Ketoprofen microspheres based on Eudragit blend can be prepared by spray-drying and the nebulization parameters do not influence significantly particle properties; nevertheless, they can be affected by drying and storage methods. No effect of the container material is found.     

In-Vitro Release and In-Vivo Availability of Chloro-Quine Phosphate Formulated Suppositories

Abstract

Chloroquine phosphate suppositories were formulated using witepsol H15 as a model base. The physicomechanical properties of the prepared suppositories were studied. In-vitro drug release as well as in-vivo availability were determined and compared with those from commercial tablets containing the same dose of the drug (250 mg). In addition, the effect of pH of the different segments of GIT on the partition coefficient of the drug was tested

Results revealed that formulated suppositories exhibit good mechanical properties as well as high release characteristics. Volunteers received suppositories showed urine peak level after 2 hrs while with those administered the tablets the peak was reached after 3 hrs. The total amounts released were 60% and 48% from the administered dose in case of suppositories and tablets respectively. The higher bioavailability of the medicament after rectal therapy is explained on the basis of the partition coefficient data. The obtained values were 0.667, 0.941 and 5.333 at pH 1.2, 6.8 and 7.4 respectively. Volunteers used the formulated suppositories did not suffer from any GI irritation which is accompanying the oral administration of the drug. The proposed formula had no irritating effect on the rectum