Preparation and evaluation of modified release ibuprofen microspheres with acrylic polymers (Eudragit) by quasi-emulsion solvent diffusion method: effect of variables

The aim of this study was to prepare and evaluate microspheres containing ibuprofen. Microspheres were prepared by modified quasi-emulsion solvent diffusion method. The influence of formulation factors (drug-polymer ratio, volumes of solvent, polyvinyl alcohol concentration and type of polymer) on the morphology, particle size distribution, drug loading capacity, micromeritical properties and the in vitro release characteristics of the microspheres were investigated. Physical characterizations of ibuprofen microspheres were also carried out using scanning electron microscopy, X-ray diffractometry and IR spectrophotometry. It was found that the yield of preparation was dependent on the initial temperature gradient between the emulsion phases. When there was an initial difference of temperature between the aqueous phase and dispersed emulsion phases, yield of preparation was increased distinctly. The drug loading capacities were very high for all formulations of the microspheres which were obtained. Mean particle size changed by changing the drug-polymer ratio, volumes of solvent or polyvinyl alcohol concentration. The flow properties were much improved over those of the original crystals. In vitro dissolution results showed that the release rate of ibuprofen was modified in all formulations. Although ibuprofen release rates from Eudragit RS microspheres were very slow, they were fast from Eudragit RL microspheres. These results observed that if Eudragit RS and Eudragit RL are used in combination, optimum release profiles may be obtained.     

Effect of formulation variables on in vitro drug release and micromeritic properties of modified release ibuprofen microspheres

Modified release microspheres of the non-steroidal anti-inflammatory drug, ibuprofen, were formulated and prepared using the emulsion solvent diffusion technique. The contribution of various dispersed phase and continuous phase formulation factors on in vitro drug release and micromeritic characteristics of microspheres was examined. The results demonstrated that the use of Eudragit RS 100 and Eudragit RL 100 as embedding polymers modified the drug release properties as a function of polymer type and concentration. Eudragit RS 100 retarded ibuprofen release from the microspheres to a greater extent than Eudragit RL 100. The drug/polymer concentration of the dispersed phase influenced the particle size and drug release properties of the formed microspheres. It was found that the presence of emulsifier was essential for microsphere formation. Increasing the concentration of emulsifier, sucrose fatty acid ester F-70, decreased the particle size which contributed to increased drug release properties. Scanning electron microscopy revealed profound distortion in both the shape and surface morphology of the microspheres with the use of magnesium stearate as added emulsifier. The application of an additional Eudragit RS 100 coat onto formed microspheres using fluid bed technology was successful and modulated the drug release properties of the coated microspheres.     

Effect of formulation variables on in vitro drug release and micromeritic properties of modified release ibuprofen microspheres.

Modified release microspheres of the non-steroidal anti-inflammatory drug, ibuprofen, were formulated and prepared using the emulsion solvent diffusion technique. The contribution of various dispersed phase and continuous phase formulation factors on in vitro drug release and micromeritic characteristics of microspheres was examined. The results demonstrated that the use of Eudragit RS 100 and Eudragit RL 100 as embedding polymers modified the drug release properties as a function of polymer type and concentration. Eudragit RS 100 retarded ibuprofen release from the microspheres to a greater extent than Eudragit RL 100. The drug/polymer concentration of the dispersed phase influenced the particle size and drug release properties of the formed microspheres. It was found that the presence of emulsifier was essential for microsphere formation. Increasing the concentration of emulsifier, sucrose fatty acid ester F-70, decreased the particle size which contributed to increased drug release properties. Scanning electron microscopy revealed profound distortion in both the shape and surface morphology of the microspheres with the use of magnesium stearate as added emulsifier. The application of an additional Eudragit RS 100 coat onto formed microspheres using fluid bed technology was successful and modulated the drug release properties of the coated microspheres.     

Preparation and characterization of drug-loaded polymethacrylate microspheres by an emulsion solvent evaporation method

Microspheres containing the anti-hypertension drug, felodipine, were prepared by the emulsion solvent evaporation method (o/o) using acrylate methacrylate copolymers, Eudragit RL PO and Eudragit RS PO, as wall materials. In order to increase the encapsulation efficiency, a mixed solvent system comprising 1:1 proportions of acetonitrile and dichloromethane was used as a dispersed phase. The morphology of the microspheres was evaluated using a scanning electron microscope, which showed a spherical shape with smooth surface. The mean sphere diameter was between 9.5-13.2 microm and the microencapsulation efficiencies ranged from 51.4-80.4%. The release profiles and encapsulation efficiencies depended strongly on the structure of the polymers used as wall materials. The release rate of the Eudragit RS PO microspheres was much lower than that of Eudragit RL PO microspheres. Whereas Eudragit RL PO microspheres followed the Higuchi rule, Eudragit RS PO microspheres exhibited a triphasic release profile. It is concluded that drug release rate can be controlled by choice of polymer type.     

乳化-溶剂扩散法制备克拉霉素缓释微球

目的探讨克拉霉素缓释微球的制备工艺。方法以Eudragit RS／RL为囊材,采用乳化一溶剂扩散法制备克拉霉素缓释微球,考察对微球质量、收率、载药量和包封率有影响的处方因素。结果EudragitRS／RL与药物按4：1混合时可得到成形性较好、表面光滑、均匀圆整、分散性好的克拉霉素微球。克拉霉素微球的粒径范围为88～180μm,微球的收率为76．0％,载药量为17．8％,包封收率为67．0％。在pH=5．0的磷酸缓冲液中微球中的克拉霉素缓慢释放。结论乳化-溶剂扩散法适合于克拉霉素缓释微球制备。     

Effects of the permeability characteristics of different polymethacrylates on the pharmaceutical characteristics of verapamil hyhdrochloride-loaded microspheres

Microspheres containing verapamil hydrochloride (VRP) were prepared with various polymethacrylates, with different permeability characteristics (Eudragit RS 100, Eudragit RL 100, Eudragit L 100 and Eudragit L 100-55) and also with mixtures of these polymers in a 1:1 ratio using the solvent evaporation method. The aim was to investigate the effects of the permeability of the polymers on drug release rates and the characteristics of the microspheres. To achieve these aims, yield, incorporation efficiency, particle size and the distribution of microspheres were determined, and the influence of the inner phase viscosities prepared with different polymer and polymer mixtures on particle size and the distribution of microspheres were evaluated. Surface morphologies of microspheres were observed by scanning electron microscope. Drug release rates from microspheres were determined by the half-change method using a flow-through cell. The results indicate that microspheres with different surface morphologies and statistically different yields and incorporation efficiencies could be prepared and their particle size and distribution xariances resulted from the viscosity of the inner phase. Dissolution profiles showed that the drug release rate could be modified depending on the permeability characteristics of polymethacrylates.     

Effects of the permeability characteristics of different polymethacrylates on the pharmaceutical characteristics of verapamil hyhdrochloride-loaded microspheres

Microspheres containing verapamil hydrochloride (VRP) were prepared with various polymethacrylates, with different permeability characteristics (Eudragit RS 100, Eudragit RL 100, Eudragit L 100 and Eudragit L 100-55) and also with mixtures of these polymers in a 1:1 ratio using the solvent evaporation method. The aim was to investigate the effects of the permeability of the polymers on drug release rates and the characteristics of the microspheres. To achieve these aims, yield, incorporation efficiency, particle size and the distribution of microspheres were determined, and the influence of the inner phase viscosities prepared with different polymer and polymer mixtures on particle size and the distribution of microspheres were evaluated. Surface morphologies of microspheres were observed by scanning electron microscope. Drug release rates from microspheres were determined by the half-change method using a flow-through cell. The results indicate that microspheres with different surface morphologies and statistically different yields and incorporation efficiencies could be prepared and their particle size and distribution variances resulted from the viscosity of the inner phase. Dissolution profiles showed that the drug release rate could be modified depending on the permeability characteristics of polymethacrylates.     

The influence of stirring rate on biopharmaceutical properties of Eudragit RS microspheres.

Eudragit RS microspheres containing pipemidic acid, as a model drug, were prepared by the solvent evaporation method using an acetone/liquid paraffin solvent system. The aim of the work was to evaluate the influence of stirring rate on the average particle size, particle morphology, drug content and release kinetics, as well as the influence of particle size on microsphere morphology, drug content and release kinetics. Stirring rate has been found to significantly influence the average diameter of microspheres. The average diameter decreases as the stirring rate increases. This can be explained by production of a finer dispersion of droplets when higher stirring rates are applied and, consequently, by the formation of smaller microspheres. With increasing stirring rate and increasing fraction particle size the drug content also increases. It is assumed that this dependence is a consequence of an uneven diffusion of the drug from the inner to the outer emulsion phase, and an uneven encapsulation of drug particles during the preparation. Drug release follows the Higuchi model. As seen from SEM photographs, larger microspheres are more porous and the microspheres produced at higher stirring rates are more porous than those produced at lower stirring rates. This explains the unexpected finding that the release rate increases as the fraction particle size and the stirring rate increase.     

不同制备条件对硝苯啶缓释微球粒径大小和药物含量的影响

用液中干燥法制备硝苯啶的丙烯酸树脂缓释微球，考察了不同制备条件对微球粒径与药物包封率的影响。     

The influence of stirring rate on biopharmaceutical properties of Eudragit RS microspheres

Eudragit RS microspheres containing pipemidic acid, as a model drug, were prepared by the solvent evaporation method using an acetone/liquid paraffin solvent system. The aim of the work was to evaluate the influence of stirring rate on the average particle size, particle morphology, drug content and release kinetics, as well as the influence of particle size on microsphere morphology, drug content and release kinetics. Stirring rate has been found to significantly influence the average diameter of microspheres. The average diameter decreases as the stirring rate increases. This can be explained by production of a finer dispersion of droplets when higher stirring rates are applied and, consequently, by the formation of smaller microspheres. With increasing stirring rate and increasing fraction particle size the drug content also increases. It is assumed that this dependence is a consequence of an uneven diffusion of the drug from the inner to the outer emulsion phase, and an uneven encapsulation of drug particles during the preparation. Drug release follows the Higuchi model. As seen from SEM photographs, larger microspheres are more porous and the microspheres produced at higher stirring rates are more porous than those produced at lower stirring rates. This explains the unexpected finding that the release rate increases as the fraction particle size and the stirring rate increase.     

Preparation and characterization of ibuprofen microspheres

Ibuprofen was microencapsulated with Eudragit RS using an o/w emulsion solvent evaporation technique. The effects of three formulation variables including the drug:polymer ratio, emulsifier (polyvinyl alcohol) concentration and organic solvent (chloroform) volume on the entrapment efficiency and microspheres size distribution were examined. The drug release rate from prepared microspheres and the release kinetics were also studied. The results demonstrated that microspheres with good range of particle size can be prepared, depending on the formulation components. The drug:polymer ratio had a considerable effect on the entrapment efficiency. However, particle size distribution of microspheres was more dependent on the volume of chloroform and polyvinyl alcohol concentration rather than the drug:polymer ratio. The drug release pattern showed a burst effect for all prepared microspheres due to the presence of uncovered drug crystals on the surface. It was shown that the release profiles of all formulations showed good correlation with the Higuchi model of release.     

Preparation and characterization of ibuprofen microspheres

Ibuprofen was microencapsulated with Eudragit RS using an o/w emulsion solvent evaporation technique. The effects of three formulation variables including the drug:polymer ratio, emulsifier (polyvinyl alcohol) concentration and organic solvent (chloroform) volume on the entrapment efficiency and microspheres size distribution were examined. The drug release rate from prepared microspheres and the release kinetics were also studied. The results demonstrated that microspheres with good range of particle size can be prepared, depending on the formulation components. The drug:polymer ratio had a considerable effect on the entrapment efficiency. However, particle size distribution of microspheres was more dependent on the volume of chloroform and polyvinyl alcohol concentration rather than the drug:polymer ratio. The drug release pattern showed a burst effect for all prepared microspheres due to the presence of uncovered drug crystals on the surface. It was shown that the release profiles of all formulations showed good correlation with the Higuchi model of release.     

Design and evaluation of sustained release microspheres of potassium chloride prepared by Eudragit.

The aim of the present work was to prepare and evaluate the sustained release of potassium chloride formulations. Eudragit RS and/or RL loaded with potassium chloride microspheres were prepared by a solvent evaporation method. The effect of sustained release of Eudragit microspheres was evaluated by an in vitro dissolution test and in vivo oral absorption study, and the results were compared to a commercial product (Slow-K). The results showed that Eudragit microspheres loaded with potassium chloride can be easily prepared and satisfactory results obtained considering the size distribution and shapes of microspheres by incorporating aluminum stearate. The encapsulation efficiency and loading capacity were about 84-90% and 27%, respectively. Moreover, the Eudragit RS (30-45 mesh) and Eudragit RS/RL (20-30 mesh) microspheres showed a similar sustained release effect of commercial product via in vitro dissolution and in vivo oral absorption study.     

Release of diltiazem from Eudragit microparticles prepared by spray-drying

Microparticles containing diltiazem hydrochloride were prepared by the spray-drying technique using acrylatemethacrylate copolymers, Eudragit RS and Eudragit RL, as coating materials. The choice of solvent used during spray-drying determined the structure of the resultant microparticles. Spray-drying using dichloromethane as the solvent resulted in microspheres where the drug was distributed in the coating polymer matrix, whereas using toluene gave microcapsules with the drug coated by the polymer. The particle size distribution for both microspheres and microcapsules was narrow, with mean particle size below 10 μm. DTA-analysis showed that the drug was amorphous in the microspheres but crystalline in the microcapsules. The release pattern of diltiazem hydrochloride was affected by microparticle structure, whether the structure was matrix (microspheres) or reservoir (microcapsules). The results indicate that spray-drying is a method that can be used to prepare microparticles from the Eudragit acrylic resins RL and RS with a narrow particle size distribution. It is concluded that drug release rate can be controlled by choice of polymer type and production conditions during spray-drying.     

Effect of processing temperature on Eudragit RS PO microsphere characteristics in the solvent evaporation process

Eudragit RS PO microspheres containing stavudine as a model drug were prepared by the solvent evaporation method using acetone liquid paraffin system. The influence of processing temperature: 10, 30 and 40 degrees C on various parameters like particle shape, size distribution, drug loading, drug polymer interaction and release kinetic were studied. It was found that at lower temperature (10 degrees C) small particles of irregular size, rough and wrinkled surface were formed, whereas higher temperature gradually increases the particle size as well as improves the shape and smoothness of microspheres. It was found that temperature had no effect on encapsulation efficiency and drug polymer compatibility. Drug release rate from microspheres were found to be a function of mean particle size distribution.     

Preparation and in vitro evaluation of propylthiouracil microspheres made of Eudragit RL 100 and cellulose acetate butyrate polymers using the emulsion-solvent evaporation method

The objectives of this investigation are to evaluate the encapsulation efficiency of the anti-thyroid agent 6-n-propyl-2-thiouracil using two polymers of different characteristics (cellulose acetate butyrate polymer, (CAB-551-0.01) and ammonio methacrylate copolymer (Eudragit RL 100) and to study the effect of this encapsulation on the drug release properties. Polymers were used separately and in combination to prepare different microspheres. Also, the effect of polymer solution phase viscosity was studied for each of the polymers and for their combinations. An Ostwald viscometer was used to evaluate the relative viscosities of polymer solution phases and their combinations. Microspheres with 25% theoretical drug loading of 6-n-propyl-2-thiouracil core material were prepared by the emulsion solvent evaporation method. Microspheres prepared from CAB-551-0.01, which has higher relative polymer phase viscosity than Eudragit RL 100, showed significantly lower drug release rates and a noticeable lag time. Polymer combinations of CAB-551-0.01 and Eudragit RL 100 (1:1) showed an interesting synergistic increase in relative polymer solution viscosities at all concentrations. Unlike microspheres prepared from the two polymers separately which follow Higuchi spherical matrix release kinetics, microspheres prepared using a combination (1:1) of the two polymers showed near zero order with faster rates compared to those prepared using CAB-551-0.01 equivalent polymer concentrations. The results of this study suggest that 6-n-propyl-2-thiouracil was successfully and efficiently encapsulated and release rates of matrix microspheres are related to polymer solution phase viscosity, but when polymer combinations were used other factors such as structural effects must be considered.     

Preparation and in vitro evaluation of slow release ketoprofen microcapsules formulated into tablets and capsules.

Ketoprofen powder was encapsulated with Eudragit RL/RS polymer solutions in isopropanol-acetone 1:1, using a simple and rapid method. Microcapsules were prepared using Eudragit solutions with different RL/RS ratios. The encapsulation process produces free-flowing microcapsules with good drug content and marked decrease in dissolution rate. The retardation in release profile of ketoprofen from microcapsules was a function of the polymer ratio employed in the encapsulation process. In vitro release of ketoprofen from microcapsules either filled in gelatin capsules or compressed into tablets, using calcium sulphate as diluent, confirmed the efficiency of the encapsulation process for preparing prolonged release medication. A capsule formulation with optimum sustained-release profile was suggested.     

Design,in vitro and in vivo evaluation of glipizide Eudragit microparticles

Glipizide microparticles made with Eudragit (RS 100 and RL 100), prepared by emulsion solvent evaporation technique were evaluated for various in-vitro properties viz. encapsulation efficiency, particle size and surface morphology, drug release pattern and in-vivo hypoglycaemic activity. The optimized formulation parameters were used to prepare smooth and spherical microparticles (2–32 µm) with higher entrapment efficiency (67–89%). Drug release patterns of glipizide microparticles of Eudragit RS 100 and Eudragit RL 100 with drug-to-polymer ratio of 1 : 4 (i.e. EGM14 and ELGM14) have shown gradual and extended release for 24 h with cumulative release of glipizide to the extent of 72.3% and 83.9%, respectively. However, EGM14 showed a significant in-vivo hypoglycaemic effect up to 12 h in rabbits while ELGM14 showed for 9 h. Hence, glipizide microparticles of Eudragit RS 100 (glipizide: polymer 1 : 4) is better suited for oral sustained release formulation.     

Eudragit microparticles as a possible tool for ophthalmic administration of acyclovir

This paper describes the production and characterization of polyacrylic polymer (Eudragit RL, RS and NE) microparticles by spray drying method. Microparticles were designed for ophthalmic administration of acyclovir. Microparticle morphology was characterized by optical and electron microscopy. The release kinetics of the drug from microspheres were determined by a dialysis method. The spray drying method described allows the production of microparticles with acceptable encapsulation efficiency and appropriate dimensional characteristics for ophthalmic administration. Release profile data indicate that acyclovir is released from microparticles in a controlled manner. In addition the release pattern of the drug is influenced by the type of Eudragit used for microparticle production. Moreover the plaque reduction efficiency of acyclovir containing microparticles (except for RS/NE microspheres) is comparable to that displayed by the free drug. Finally our results suggest that acyclovir containing microparticles could represent an interesting system for the release of this antiviral drug at the eye site.     

Preparation and in vitro evaluation of slow release ketoprofen microcapsules formulated into tablets and capsules

Abstract

Ketoprofen powder was encapsulated with Eudragit RL/RS polymer solutions in isopropanol-acetone 1:1, using a simple and rapid method. Microcapsules were prepared using Eudragit solutions with different RL/RS ratios. The encapsulation process produces free-flowing microcapsules with good drug content and marked decrease in dissolution rate. The retardation in release profile of ketoprofen from microcapsules was a function of the polymer ratio employed in the encapsulation process. In vitro release of ketoprofen from microcapsules either filled in gelatin capsules or compressed into tablets, using calcium sulphate as diluent, confirmed the efficiency of the encapsulation process for preparing prolonged release medication. A capsule formulation with optimum sustained-release profile was suggested.