Studies on Controlled Release Formulations of Pentazocine Hydrochloride

Abstract

This work embodies studies, performed with micropellet type dosage forms of Pentazocine Hydrochloride (Pz-HCl), using single and composite matrices of Eudragit RS100 (RS) and RL100 (RL). The effects of formulation parameters on various dosage form criteria - namely drug loading, particle size distribution, release profiles etc. have been investigated. Results indicate, that the two polymers can be successfully combined to produce different changes in release kinetics, with simple modifications of coating composition and initial drug loads.     

Effect of Various Polymers on Formulation of Controlled Release (CR) Ibuprofen Tablets by Fluid Bed Technique

Abstract

The need for controlled release (CR) formulations of ibuprofen tablet, is well recognized. Some such formulations have been marketed but in general only patented.

The purpose of this study was to develop an air suspension method, using a laboratory scale fluidized bed drier to coat the ibuprofen granules. Different polymers including, Eudragits L100, S100, RL100, RS100, L100+S100 (1:1), RL100+RS100 (1:1), ethyl cellulose (EC) and Eudragit RS100+EC (1:1) were utilized. The drug release medium consisted of buffer pH 1.2 for 1st 2h, buffer pH 4.5 for 2nd 2h and buffer pH 7.5 for remaining period of time in all experiments, but the release behaviour of the drug from some formulations was also studied using distilled water. Of the polymers investigated, Eudragit RS100, EC, Eudragit S100 and Eudragit RS100+EC (1:1) exhibited proper release characteristics when used as coating materials. The release patterns were analyzed from the standpoint of diffusion-controlled processes and as first-order kinetics.     

Effect of Various Polymers on Formulation of Controlled Release (CR) Ibuprofen Tablets by Fluid Bed Technique

The need for controlled release (CR) formulations of ibuprofen tablet, is well recognized. Some such formulations have been marketed but in general only patented.

The purpose of this study was to develop an air suspension method, using a laboratory scale fluidized bed drier to coat the ibuprofen granules. Different polymers including, Eudragits L100, S100, RL100, RS100, L100+S100 (1:1), RL100+RS100 (1:1), ethyl cellulose (EC) and Eudragit RS100+EC (1:1) were utilized. The drug release medium consisted of buffer pH 1.2 for 1st 2h, buffer pH 4.5 for 2nd 2h and buffer pH 7.5 for remaining period of time in all experiments, but the release behaviour of the drug from some formulations was also studied using distilled water. Of the polymers investigated, Eudragit RS100, EC, Eudragit S100 and Eudragit RS100+EC (1:1) exhibited proper release characteristics when used as coating materials. The release patterns were analyzed from the standpoint of diffusion-controlled processes and as first-order kinetics.     

Controlled Release Salbutamol Sulphate Molded Tablets Using Eudragit Retard

Abstract

Permeable acrylic resins were used as efficient retarding materials to prepare controlled release salbutamol sulphate molded tablets. The formulation is simple, efficient, economic and is easily shaped into molded tablets. The effects of two types of acrylic resins, namely: Eudragit RL100 ad Eudragit RS100 in concentrations 1, 2 and 5% w/w on the physical characteristics as well as on the in vitro release patterns of salbutamol sulphate from molded tablets prepared with either polyethylene glycol (PEG) 4000 or 6000 were studied. It was revealed that, as the molecular weight of the PEG increased, the hardness of the tablets increased. Considerable retardation in the drug release was observed by using Eudragit RS100 as compared to Eudragit RL100. The formulation prepared with PEG 6000 and 5% Eudragit RS100 produced much more release time prolongation than the other tested formulations. On the other hand, tablets prepared by the direct compression technique produced a faster release of salbutamol sulphate than those prepared by molding.     

Controlled Release Salbutamol Sulphate Molded Tablets Using Eudragit Retard

Permeable acrylic resins were used as efficient retarding materials to prepare controlled release salbutamol sulphate molded tablets. The formulation is simple, efficient, economic and is easily shaped into molded tablets. The effects of two types of acrylic resins, namely: Eudragit RL100 ad Eudragit RS100 in concentrations 1, 2 and 5% w/w on the physical characteristics as well as on the in vitro release patterns of salbutamol sulphate from molded tablets prepared with either polyethylene glycol (PEG) 4000 or 6000 were studied. It was revealed that, as the molecular weight of the PEG increased, the hardness of the tablets increased. Considerable retardation in the drug release was observed by using Eudragit RS100 as compared to Eudragit RL100. The formulation prepared with PEG 6000 and 5% Eudragit RS100 produced much more release time prolongation than the other tested formulations. On the other hand, tablets prepared by the direct compression technique produced a faster release of salbutamol sulphate than those prepared by molding.     

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.     

Preparation and Evaluation of Sustained release Indomethacin Nonpareil Seeds

A controlled release oral drug delivery system of Indomethacin was developed using nonpareil seeds as a matrix system. These seeds were coated with different concentrations of drug release controlling materials viz Eudragit RL100 and Eudragit RS100, and bees wax. The particle size of the seeds and the concentration as well as the type of the drug release controlling Eudragits has a pronounced effect on the release rate profile of Indomethacin. All types of formulations showed release rate pattern which can be described by both first-order and diffusion controlled mechanism.     

Preparation and Evaluation of Sustained release Indomethacin Nonpareil Seeds

Abstract

A controlled release oral drug delivery system of Indomethacin was developed using nonpareil seeds as a matrix system. These seeds were coated with different concentrations of drug release controlling materials viz Eudragit RL100 and Eudragit RS100, and bees wax. The particle size of the seeds and the concentration as well as the type of the drug release controlling Eudragits has a pronounced effect on the release rate profile of Indomethacin. All types of formulations showed release rate pattern which can be described by both first-order and diffusion controlled mechanism.     

Indices of Tableting Performance for Acrylic Resin Polymers with Plastic and Brittle Drugs

The indices of tableting performance were used to investigate the compaction properties of two methacrylate ester copolymers (Eudragit® RS PM and RL PM) and three methacrylic acid copolymers (Eudragit® S 100, L 100, and L 100-55). These polymers were designed to be incorporated directly into solid dosage forms for controlled-release purposes. The polymers were combined in the dry state with either sodium sulfathiazole (a brittle drug) or theophylline (a plastic drug) at concentrations ranging from 0 to 100% polymer. All powders were blended for 15 minutes and compacts measuring 1 inch square and weighing 5 g each were made using a die that decompressed triaxially and a Carver® press equipped with a strain gauge. Solid fractions were kept constant at 0.81. Two of the tableting indices, the bonding index (BI) and brittle fracture index (BFI), were studied for all mixtures. The BFI of the sulfonamide (0.49) was nearly three times greater than the BFI for theophylline(0.17) The three methacrylic acid copolymers had high BFI values ranging from 0.99 to 1.60, demonstrating the brittle characteristics of these polymers. The BFI decreased with increasing drug content in all cases. Of the five polymers, the BI was greatest for Eudragit® L 100-55 with both drugs, especially at the 20% drug concentration, followed by Eudragits L 100 and S 100. These three resins were prepared by a spray-drying process. The strongest interactions (positive deviations for the BFI; negative deviations for indentation hardness and BI) of either drug with the polymers were always seen with the spray-dried materials. Low bonding indices were obtained for both of the methacrylate ester copolymers. However, all mixtures of both drug with these milled polymers (RL PM and RS PM) formed successful tablets.     

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.     

A New Approach for Controlling the Release Rate of Pheniramine Aminosalicylate Via Solid Dispersion in Different Types of Eudragit

Abstract

Co-precipitates of pheniramine aminosalicylate in different types of Eudragit were prepared. IR spectra indicated the absence of molecular interaction between the drug and Eudragit. The effect of polymer type on the retardation of drug release rate was in the following order: Eudragit S 100> Eudragit L 100> Eudragit RSPM or Eudragit RS 100> Eudragit RLPM or Eudragit RL 100. The concentration of the polymer in the system was a determining factor in controlling the release rate of the drug. As the concentration of the polymer in the system increased, the release rate of the drug decreased.

Co-precipitates of the drug in different ratios of Eudragit blends were also prepared. The release rate of the drug decreased by decreasing the concentration of the permeable Eudragit RLPM or Eudragit RSPM in the system.

The rapid release rate of the drug from the physical mixtures excluded their application in controlling drug release.     

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.     

Indices of Tableting Performance for Acrylic Resin Polymers with Plastic and Brittle Drugs

Abstract

The indices of tableting performance were used to investigate the compaction properties of two methacrylate ester copolymers (Eudragit® RS PM and RL PM) and three methacrylic acid copolymers (Eudragit® S 100, L 100, and L 100–55). These polymers were designed to be incorporated directly into solid dosage forms for controlled-release purposes. The polymers were combined in the dry state with either sodium sulfathiazole (a brittle drug) or theophylline (a plastic drug) at concentrations ranging from 0 to 100% polymer. All powders were blended for 15 minutes and compacts measuring 1 inch square and weighing 5 g each were made using a die that decompressed triaxially and a Carver® press equipped with a strain gauge. Solid fractions were kept constant at 0.81. Two of the tableting indices, the bonding index (BI) and brittle fracture index (BFI), were studied for all mixtures. The BFI of the sulfonamide (0.49) was nearly three times greater than the BFI for theophylline(0.17) The three methacrylic acid copolymers had high BFI values ranging from 0.99 to 1.60, demonstrating the brittle characteristics of these polymers. The BFI decreased with increasing drug content in all cases. Of the five polymers, the BI was greatest for Eudragit® L 100–55 with both drugs, especially at the 20% drug concentration, followed by Eudragits L 100 and S 100. These three resins were prepared by a spray-drying process. The strongest interactions (positive deviations for the BFI; negative deviations for indentation hardness and BI) of either drug with the polymers were always seen with the spray-dried materials. Low bonding indices were obtained for both of the methacrylate ester copolymers. However, all mixtures of both drug with these milled polymers (RL PM and RS PM) formed successful tablets.     

Preparation and characterization of heparin-loaded polymeric microparticles

Microparticles containing heparin were prepared by a water-in-oil-in-water emulsification and evaporation process with pure or blends of biodegradable (poly-epsilon-caprolactone and poly(D,L-lactic-co-glycolic acid)) and of positively-charged non-biodegradable (Eudragit RS and RL) polymers. The influence of polymers and some excipients (gelatin A and B, NaCl) on the particle size, the morphology, the heparin encapsulation rate as well as the in vitro drug release was investigated. The diameter of the microparticles prepared with the various polymers ranged from 80 to 130 microns and was found to increase significantly with the addition of gelatin A into the internal aqueous phase. Microparticles prepared with Eudragit RS and RL exhibited higher drug entrapment efficiency (49 and 80% respectively) but lower drug release within 24 h (17 and 3.5% respectively) than those prepared with PCL and PLAGA. The use of blends of two polymers in the organic phase was found to modify the drug entrapment as well as the heparin release kinetics compared with microparticles prepared with a single polymer. In addition, microparticles prepared with gelatin A showed higher entrapment efficiency, but a significant initial burst effect was observed during the heparin release. The in vitro biological activity of heparin released from the formulations affording a suitable drug release has been tested by measuring the anti-Xa activity by a colorimetric assay with a chromogenic substrate. The results confirmed that heparin remained unaltered after the entrapment process.     

Sustained Release Matrix of Mebeverine Hydrochloride Using Polyacrylate Resin “Eudragit Retard” Kinetic of Drug Release and Evaluation of a Kinetic Model

In this study Eudragit RS PM and RL PM were evaluated as carriers for the preparation of prolonged release solid dispersions of mebeverine hydrochloride by solvent and melting methods. The prepared tablets were examined for dissolution at pH 1.2 and 7.4, Eudragit RS PM and RL PM were found satisfactory as potential slow release carriers. The solid dispersion prepared by the solvent method showed a slow release pattern. Drug release appeared to fit both, first order and Higuchi matrix model kinetics. However, on application of the differential rate treatments, the evidence supported the Higuchi matrix model. Effect of temperatures on dissolution rate was studied for thermodynamic consideration.

The drug release was pH-independent until pH 7.4.As the pH increased, the release was significantly reduced due to solubility problem.     

Preparation of Acetaminophen Microcapsules by Coaservation-Phase Separation Method

In this study, it was aimed to prepare prolonged action microcapsules of acetaminophen with short biological half-life by a non-solvent addition method which is one of the conservation-phase separation techniques.

For this purpose, the three different particle size ranges of acetaminophen (0.088-0.177 mn, 0.250-0.354 mn, 0.420-0.500 mn) were used. The solution of polyisobuthylene in cyclohexane as a non-solvent and Eudragit RS and Eudragit RL as coating polymers were also used. The prepared mi crosapsules were compressed by a hydraulic press using different types of direct tableting agents such as Ludipress, Avicel PH 101 and Lactose EP D 30. Dissolution rates of each tablet containing 160 mg of microencapsulated acetaminophen were examined by continuous flow-through cell method

The results of this study showed that the release rate of drug from microcapsules prepared with Eudragit RS was lower than that of microcapsules prepared with Eudragit RL. However different particle size ranges of drug didn't affect significantly the release rate; but different types of direct tableting agents were effective on the release rate of drug.     

Sustained Release Matrix of Mebeverine Hydrochloride Using Polyacrylate Resin “Eudragit Retard” Kinetic of Drug Release and Evaluation of a Kinetic Model

Abstract

In this study Eudragit RS PM and RL PM were evaluated as carriers for the preparation of prolonged release solid dispersions of mebeverine hydrochloride by solvent and melting methods. The prepared tablets were examined for dissolution at pH 1.2 and 7.4, Eudragit RS PM and RL PM were found satisfactory as potential slow release carriers. The solid dispersion prepared by the solvent method showed a slow release pattern. Drug release appeared to fit both, first order and Higuchi matrix model kinetics. However, on application of the differential rate treatments, the evidence supported the Higuchi matrix model. Effect of temperatures on dissolution rate was studied for thermodynamic consideration.

The drug release was pH-independent until pH 7.4.As the pH increased, the release was significantly reduced due to solubility problem.     

Influence of Formulation and Other Factors on the Release of Chlorpheniramine Mateate from Polymer Coated Beads

Controlled release beads containing chlorpheniramine maleate, coated with Eudragit RL and RS, were prepared using the Wurster process. The effect of membrane thickness, polymer ratio of the coating material, agitation speed and pH of the dissolution medium on drug release were investigated using the USP dissolution basket method. The in vitro release of drug was described adequately by a previously published equation. The release rate constant (K) was dependent on the membrane thickness, the polymer ratio and pH of the dissolution medium. On the other hand, agitation speed used in this study did not have any influence on the release of the drug.     

d-Indobufen Extended-Release Pellets Prepared by Coating with Aqueous Polymer Dispersions

Abstract

A multiple units dosage form has been prepared in order to control the release of d-Indobufen, a carboxylic acid used as an inhibitor of platelet aggregation.

The system consists of cores containing the active substance coated with a diffusive film and represents a classic “reservoir” system.

Extrusion-spheronization was used in order to prepare the active cores. The drug release control was obtained by modifying both the core composition and the film composition characteristics.

Acid and basic compounds were incorporated in the core to influence the inside microenvironment pH. Polymers chosen for the film formulation were: ethylcellulose (Aquacoat) and copolymers of acrylic esters with differing permeability characteristics (Eudragit RL/RS 30D).

Technological and physical characteristics of coated pellets proved the production feasibility of an extended release multiple unit dosage form of d-Indobufen.

Preliminary data of accelerated stability indicated the important role played by the thermal treatment of polymer membrane after the coating process.