Microencapsulation of terbutaline sulphate by the solvent evaporation technique.

Terbutaline sulphate microcapsules were prepared by coacervation-phase separation (solvent evaporation) technique using ethyl cellulose as a coating material. Acetone, ethyl alcohol and isopropyl alcohol were employed as solvents for coating material. Microcapsules were evaluated for their drug content, particle size distribution (microscopic method), flow properties, bulk density, in vitro dissolution, drug release kinetics and surface characteristics (scanning electron microscopy).     

Microencapsulation of propranolol hydrochloride by the solvent evaporation technique.

Propranolol hydrochloride microcapsules were prepared by the coacervation-phase separation induced by solvent evaporation technique. The cellulose acetate phthalate was employed as coating material alone and in combination with ethyl cellulose. The prepared microcapsules were evaluated for their drug content, particle size distribution (microscopic method), flow properties, bulk density, in vitro dissolution and drug release kinetics.     

Preparation of microspheres by the solvent evaporation technique

The microencapsulation process in which the removal of the hydrophobic polymer solvent is achieved by evaporation has been widely reported in recent years for the preparation of microspheres and microcapsules based on biodegradable polymers and copolymers of hydroxy acids. The properties of biodegradable microspheres of poly(lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA) have been extensively investigated. The encapsulation of highly water soluble compounds including proteins and peptides presents formidable challenges to the researcher. The successful encapsulation of such entities requires high drug loading in the microspheres, prevention of protein degradation by the encapsulation method, and predictable release of the drug compound from the microspheres. To achieve these goals, multiple emulsion techniques and other innovative modifications have been made to the conventional solvent evaporation process.     

Microencapsulation by solvent evaporation: state of the art for process engineering approaches

Microencapsulation by solvent evaporation technique is widely used in pharmaceutical industries. It facilitates a controlled release of a drug, which has many clinical benefits. Water insoluble polymers are used as encapsulation matrix using this technique. Biodegradable polymer PLGA (poly(lactic-co-glycolic acid)) is frequently used as encapsulation material. Different kinds of drugs have been successfully encapsulation: for example hydrophobic drugs such as cisplatin, lidocaine, naltrexone and progesterone; and hydrophilic drugs such as insulin, proteins, peptide and vaccine. The choice of encapsulation materials and the testing of the release of drug have been intensively investigated. However process-engineering aspects of this technique remain poorly reported. To succeed in the controlled manufacturing of microspheres, it is important to investigate the latter. This article reviews the current state of the art concerning this technique by focusing on the influence of the physical properties of materials and operating conditions on the microspheres obtained. Based on the existing results and authors' reflection, it gives rise to reasoning and suggested choices of materials and process conditions. A part of this paper is also dedicated to numerical models on the solvent evaporation and the solidification of microspheres. This review reveals also the surprising lack of knowledge on certain aspects, such as the mechanism of formation of pores in the microspheres and the experimental study on the solidification of microspheres.     

Microencapsulation of allopurinol by solvent evaporation and controlled release investigation of drugs

Abstract

The microencapsulation of drugs is gaining importance in many research activities. A common technique for preparing microcapsules is the solvent evaporation method which is simple but has a large number of reaction control parameters. This study reports the microcapsulation of allopurinol by the solvent evaporation method and the release of the drug from the microcapsules. The effect of concentration of poly(vinyl alcohol) (as a surfactant), molecular weight of ethyl cellulose and stirrer speed in the preparative method were studied. The effect of molecular weight of ethyl cellulose and particle size on drug release were also investigated. It has been found that the drug release is decreased with increasing molecalar weight of polymer and increasing particle size.     

Microencapsulation of superoxide dismutase into poly(epsilon-caprolactone) microparticles by reverse micelle solvent evaporation

The aim of this work was to encapsulate superoxide dismutase (SOD) in poly(epsilon-caprolactone) (PCL) microparticles by reverse micelle solvent evaporation. The concentration of PCL, the hydrophile-lipophile balance (HLB), and concentration of the sucrose ester used as surfactant in the organic phase were investigated as formulation variables. Relatively higher encapsulation efficiency (approximately 48%) and retained enzymatic activity (>90%) were obtained with microparticle formulation made from the 20% (w/v) PCL and 0.05% (w/v) sucrose ester of HLB = 6. This formulation allowed the in vitro release of SOD for at least 72 hr. These results showed that reverse micelle solvent evaporation can be used to efficiently encapsulate SOD in PCL microparticles. Such formulations may improve the bioavailability of SOD.     

Polylactic acid microspheres containing quinidine base and quinidine sulphate prepared by the solvent evaporation technique. I. Methods and morphology

D,1-polylactic acid (PLA) microspheres containing the antiarrhythmic drug, quinidine, were prepared by the solvent evaporation method. The drug was present as either the base or as the sulphate salt. A slight modification in the process resulted in high yields of free-flowing, non-aggregated microspheres. The successful entrapment of drug within the microspheres was highly dependent on drug solubility in the aqueous phase. Diffusion and drug loss to the aqueous phase was minimized by adjusting the pH of the aqueous phase to minimal drug solubility. Saturation of the aqueous phase with drug further improved the payload of the microspheres. The appearance of the microsphere surface depended on the pH of the aqueous phase, the electrolyte concentration, and the type and amount of drug present. Structural changes and erosion of the polymer were observed at high pH-values.     

Polylactic acid microspheres containing quinidine base and quinidine sulphate prepared by the solvent evaporation technique. I. Methods and morphology

Abstract

D, 1-polylactic acid (PLA) microspheres containing the antiarrythmic drug, quinidine, were prepared by the solvent evaporation method. The drug was present as either the base or as the sulphate salt. A slight modification in the process resulted in high yields of free-flowing, non-aggregated microspheres. The successful entrapment of drug within the microspheres was highly dependent on drug solubility in the aqueous phase. Diffusion and drug loss to the aqueous phase was minimized by adjusting the pH of the aqueous phase to minimal drug solubility. Saturation of the aqueous phase with drug further improved the payload of the microspheres. The appearance of the microsphere surface depended on the pH of the aqueous phase, the electrolyte concentration, and the type and amount of drug present. Structural changes and erosion of the polymer were observed at high pH-values.     

Microencapsulation using emulsification/solvent evaporation: an overview of techniques and applications

This review describes the microencapsulation of pharmaceuticals using the technique of emulsification-solvent evaporation. Guidelines are given for development of encapsulation processes for drugs with either high or low aqueous solubilities. Methods for microsphere characterization and assessment are detailed. The properties of a range of encapsulating polymers are described with examples of drugs encapsulated. The article concludes by speculating the clinical potential of microsphere-based drug delivery systems.     

pH梯度法结合逆向蒸发法制备硫酸多黏菌素E脂质体

目的制备硫酸多黏菌素E脂质体,并对其处方工艺进行研究。方法采用pH梯度法和pH梯度法结合逆向蒸发法制备硫酸多黏菌素E脂质体,用超滤法分离游离药物与脂质体,用HPLC法测定包封率,考察各处方及工艺因素对包封率的影响。结果硫酸多黏菌素E脂质体最佳处方和工艺:磷脂和胆固醇质量比为3∶1,药物与磷脂质量比为1∶20,pH值梯度范围为3.0~5.8,50℃孵育20 min,包封率达70%以上。结论采用pH梯度法结合逆向蒸发法制备的硫酸多黏菌素E脂质体具有较高的包封率。     

Preparation and evaluation of abietic acid microcapsules by a solvent evaporation technique.

Abietic acid was isolated from rosin N Grade (ISI) by a simple process and the product was further standardized. Sulphadiazine microcapsules were prepared by the solvent evaporation technique, using abietic acid as a wall-forming material. Discrete, spherical and free-flowing microcapsules were obtained by phase separation induced by solvent evaporation using bentonite as a solid emulsifier. The prepared microcapsules were evaluated for drug content, wall thickness, flow properties, size distribution, density and in vitro dissolution studies in gastric fluid. The effect of various process variables such as agitation speed, coat-core ratio, etc., on the micromeritic and release characteristics has been described.     

Microencapsulation of ovalbumin in poly(lactide-co-glycolide) by an oil-in-oil (o/o) solvent evaporation method

Abstract

The objective of this study was to produce biodegradable poly(lactide-co-glycolide) (PLGA; 50/50) microspheres by an oil-in-oil (o/o) solvent evaporation method to prolong the in vitro release of ovalbumin (OVA) as a model protein. The effects, on loading efficiency, microsphere yield, morphology and drug release, of two dispersing agents, aluminum tristearate and Span 80, in mineral oil were examined. PLGA 50/50 microspheres containing OVA powder (sieved through a 53 μm mesh) were prepared using an o/o solvent evaporation method. When aluminum tristearate was employed as a dispersing agent, the loading efficiency and yield of OVA had maximum values of 89 and 72% at 0·15% (w/v) aluminum tristearate, respectively. Morphology studies suggested that the obtained microspheres were spherical, and had a smooth surface. The diameters of the microspheres ranged between 100 and 200 μm. The loading efficiency, or yield, for microspheres decreased significantly above or below 0·15% (w/v) aluminum tristearate, and microspheres wkh irregular shapes were observed. The minimum sedimentation volume ratio (F) was obtained at a dispersity of carbon black particles in ethanol containing 0·15% (w/v) aluminum tristearate by a sedimentation study, and the cloudy supernatant suggested a defiocculated suspension. However, on the contrary, when Span 80 was added into the mineral oil as a dispersing agent, the concentration of Span 80 had little or no effect on the characteristics of the prepared microspheres. Drug loadings (60–70%) were obtained within the Span 80 concentrations employed in the present study (0·05–1·0% (w/v)). The yields were also in the same levels. The microspheres prepared in mineral oil containing Span 80 had an average diameter less than 50 μm in all cases. Sustained-release characteristics were demonstrated for PLGA microspheres prepared in mineral oil containing aluminum tristearate as a dispersing agent, even though a burst release at the initial phase was observed. This initial burst release from PLGA microspheres was reduced to some extent by micronization of the OVA powder using a planetary-type ball mill. However, PLGA microspheres prepared in mineral oil containing Span 80 as a dispersing agent, exhibited a large initial burst release. This burst release seems to be due to the smaller size of microspheres and the OVA powder adhering to the surface of PLGA microspheres (confirmed by scanning electron microscope (SEM) study).     

Prolonged release terbutaline sulphate microcapsules.

Terbutaline sulphate microcapsules were prepared by coacervation-phase separation induced by solvent evaporation technique. The cellulose acetate phthalate was employed as coating material alone and in combination with ethyl cellulose. The prepared microcapsules were evaluated for their drug content, particle size distribution (microscopic method), flow properties, bulk density and in vitro dissolution.     

Study of a microencapsulation process of a virucide agent by a solvent evaporation technique

Abstract

A highly water-soluble virucide agent was microencapsulated by a water/oil/water emulsification-solvent evaporation method. An aqueous drug solution was emulsified into a solution of polymer in methylene chloride, followed by emulsification of the primary emulsion in an external aqueous phase. Microcapsules were formed after solvent evaporation, the solidification of the microcapsule walls was followed by an optical method. The influence of stirring speed was analysed to find the optimal hydrodynamic conditions with respect to the process yield, corresponding to the weight of obtained microcapsules per litre of water/oil/water emulsion, the initial virucide agent content and the drug release kinetics. The optimal conditions were obtained for the complete suspension speed. The improvement of the microencapsulation process was attempted by increasing the concentration of the primary emulsion and by the reuse of the external aqueous phase after removal of the microcapsules.     

Release kinetics of drugs from rosin-glycerol ester microcapsules prepared by solvent evaporation technique.

Rosin-glycerol ester microcapsules containing sulphadiazine were prepared by solvent evaporation technique. The goodness of fit of the release data was tested with first order, Higuchi matrix model and Hixon-Crowell cube root law. All these models were sufficiently linear. Application of the differential rate treatment showed that release from most of the microcapsules followed first order equation. Whereas up to 40-50 per cent of release, a zero order, membrane controlled kinetics was observed, the release is apparently first order under nonsteady, state conditions.     

Effect of solvents on the characteristics of rosin walled microcapsules prepared by a solvent evaporation technique

Rosin microcapsules were prepared by a solvent evaporation technique using solvents with different rates of evaporation. Sulphadiazine was used as a model drug. The microcapsules were studied for their size, drug content, wall thickness, surface characteristics and in vitro release. The mean diameter increased and the drug content decreased as the rate of evaporation of the solvent increased. Fast evaporating solvents produced thick walled microcapsules with innumerable surface pores/cracks compared with slow evaporating solvents.     

硫酸特布他林干粉吸入剂制备工艺的优化研究

目的:优化硫酸特布他林干粉吸入剂的制备工艺。方法:采用喷雾干燥技术制备硫酸特布他林干粉吸入剂,采用双层液体碰撞器测定其体外肺沉积率,扫描电镜观察干粉的表观形貌,热重分析仪测定干粉的水分含量,激光粒度测定仪测定粒径大小,以产品收率、水分含量、粉末的空气动力学粒径及体外肺沉积率为考察指标,通过正交设计结合多指标综合评价法优化最佳制备工艺。结果:通过正交试验-多指标综合评价,最佳制备工艺为:喷雾压力190 kPa,干燥风速0.7 m3.min-1,供液速度7.0 mL.min-1,入口温度120℃。结论:按最佳制备工艺制得的干粉收率为50.54%,水分含量为0.467%,空气动力学粒径为1.80μm,体外肺沉积率为55.19%。正交试验结合多指标综合评价法用于硫酸特布他林干粉吸入剂制备工艺的优化有效可用。     

Polylactic acid microspheres containing quinidine base and quinidine sulphate prepared by the solvent evaporation technique. II. Some process parameters influencing the preparation and properties of microspheres

D,L-polylactic acid (PLA) microspheres containing quinidine base and quinidine sulphate were prepared by the solvent evaporation method. The present study was carried out to examine how various process parameters in the aqueous phase influenced the preparation and properties of PLA-microspheres. The amount of drug that could be incorporated into the microspheres depended primarily on the solubility of the drug in the aqueous phase and the precipitation of PLA at the droplet surface. The drug content was found to be influenced by the organic solvent: aqueous phase ratio, the temperature of the aqueous phase, and the amount of emulsifying agent. Time-dependent pH-change studies in the aqueous phase showed that polymer precipitation at the outer surface of the microspheres, and drug loss due to partitioning, occurred rapidly. A partition method for increasing the payload of drug in the microspheres was developed by incorporating drug in both the aqueous and the organic phases. Using this method, drug could be loaded into the microspheres independent of the pH of the aqueous media. The partition method circumvented the surface degradation observed with PLA microspheres prepared at high pH values of the aqueous phase. This method may prove useful for the entrapment of water-soluble drugs.     

Stereoselective sulphate conjugation of racemic terbutaline by human liver cytosol.

1. The enantioselectivity of the sulphation of racemic terbutaline by phenolsulphotransferases was examined in vitro using cytosol from human livers (n = 3) and [35S]-3'-phosphoadenosine-5'-phosphosulphate (PAP35S) as the sulphate donor. 2. The radioactive sulphate conjugate formed was isolated by h.p.l.c. and its enantiomers were separated intact by h.p.l.c. after chiral derivatization. 3. Sulphation of racemic terbutaline occurred with the same apparent Km value for both enantiomers (270 microM). The extent of sulphation of the (+)-enantiomer was double that of the (-)-enantiomer, solely due to a difference in their apparent Vmax values. 4. Sulphation of racemic prenalterol, a structural analogue of terbutaline, also showed a two-fold preference for the (+)-enantiomer. 5. These findings suggest that enantioselective sulphate conjugation of chiral phenolic sympathomimetic amine drugs may lead to enantioselective pharmacokinetics that should be considered in the clinical use of these drugs.