Encapsulation of indomethacin using coaxial ultrasonic atomization followed by solvent evaporation.

We have encapsulated indomethacin into poly (lactide-co-glycolide) (PLGA) using coaxial ultrasonic atomization technique. The specific aims of this study were to evaluate the effect of drug loading and a change in relative concentration of polymer in the inner and outer layers of coflowing spray liquids on the physicochemical characteristics of the particles. Indomethacin, a non steroidal anti-inflammatory drug, was selected as a model compound. The micro/nanocapsules prepared using a drug free PLGA solution as an outer layer showed higher encapsulation efficiency. Thermal analysis of the formulations indicated that indomethacin was dissolved within the PLGA matrix. The formulations prepared with 25 mg indomethacin showed relatively smaller particle size compared with the formulations prepared with 50 mg indomethacin. The particles, in general, showed bi- and tri-modal distribution. Irrespective of the compositions of the liquids 1 and 2, all the particles were smooth and spherical. A cross-section view of the particles revealed the presence of three different internal morphologies. These formulations were a mixture of hollow or solid spheres, and single or multiple spheres encapsulated into a larger sphere. To the best of our knowledge, this is the first study revealing the cross-sectional view of particles prepared with coaxial ultrasonic atomization technique.

Preparation of polylactide-co-glycolide and chitosan hybrid microcapsules of amifostine using coaxial ultrasonic atomizer with solvent evaporation.

The objective of this study was to evaluate the effect of various processing and formulation factors on the characteristics of amifostine hybrid microcapsules. Amifostine-loaded hybrid microcapsules were prepared using PLGA and chitosan. In short, amifostine powder was dissolved in de-aerated water with or without chitosan. The amifostine solution was later emulsified into PLGA solution in dichloromethane containing phosphatidylcholine. The resultant emulsion was fed through the inner capillary of a coaxial ultrasonic atomizer. The liquid fed through the coaxial outer capillary was either water or chitosan solution. The atomized droplets were collected into PVA solution and the droplets formed microcapsules immediately. The hybrid microcapsules prepared with chitosan solution only as an outer layer liquid showed the maximum efficiency of encapsulation (30%). The median sizes of all three formulations were 33-44 microm. These formulations with chitosan showed positive zeta-potential and sustained drug release with 13-45% amifostine released in 24 h. When chitosan was incorporated into inner as well as outer liquid layers, the drug release increased significantly, 45% (compared with other formulations) released in 24 h and almost 100% released in 11 days. Hybrid microcapsules of amifostine showed moderately high efficiency of encapsulation. The cationic charge (due to the presence of chitosan) of these particles is expected to favour oral absorption and thus overall bioavailability of orally administered amifostine.

Effect of co-solvents on the characteristics of enkephalin microcapsules.

The objective of this project was to study the effect of the presence of co-solvents with dichloromethane on the properties of leu-enkephalin microcapsules. Six co-solvents, including ethyl acetate, methanol, ethanol, acetone, isopropanol and acetonitrile, at three concentrations of 5%, 10% and 20% (v/v), respectively, of dichloromethane were selected for this study. The resulting microcapsules were evaluated for morphology and particle size, surface area, thermal characteristics and efficiency of encapsulation. The analysis of particle size distribution showed bi- and tri-modal distribution of the microcapsules. The median particle size of the microcapsules was between 17 microm and 57 microm. All microcapsules were smaller than 90 microm. Approximately 10% of the microcapsules were smaller than 500 nm. In general, the microcapsules prepared with co-solvents showed relatively smaller median size. The microcapsules were spherical in shape. DSC analysis of the microcapsules showed that there were no significant differences in the glass transition temperatures. There were significant changes in the efficiency of encapsulation due to the addition of co-solvents. Substitution with 20% methanol resulted in 40% increase in the efficiency of encapsulation (12% vs. 17%). Furthermore, substitution with 20% ethyl acetate, isopropanol, or acetonitrile, reduced the efficiency of encapsulation to as low as 6%.

Effect of surfactant on the characteristics of biodegradable microcapsules.

The objective of this project was to evaluate the effect of several lipophilic surfactants on the characteristics of PLGA microcapsules. BSA was used as a model peptide. Seven different lipophilic surfactants were used and each of the surfactants was used at three different concentrations, 0.1, 0.5 and 1% (w/w), respectively. The microcapsules were prepared using the double emulsion solvent evaporation technique. The microcapsules were all spherical in shape with a smooth surface. The median size of the microcapsules varied between 4 and 49 microm. The zeta potential of the microcapsules varied between -26 and -43 mV. The efficiency of encapsulation varied between 8 and 45%. Efficiency of encapsulation appears to be dependant on both the type and concentration of the surfactant. Cumulative percent of BSA released up to 35 days varied from 18 to 78%. In conclusion, the physical characteristics of the microcapsules do not appear to be greatly affected by the type of surfactant. All of the samples appear to show polydispersity in their particle sizes. Particle charge depended on both the type and concentration of the surfactant. The overall dissolution of these microcapsules was very slow.

Effect of different ratios of high and low molecular weight PLGA blend on the characteristics of pentamidine microcapsules.

Two different PLGA samples (Resomer 502 and Resomer 506), either alone or in combinations, were used to prepare microcapsules. Microcapsules were prepared using a double emulsion solvent evaporation technique. The efficiency of encapsulation increased significantly when a mixture of 1 part Resomer 506 and 7 parts Resomer 502 was used to prepare the microcapsules. The efficiency of encapsulation of this batch was 23.7%, whereas the efficiency of encapsulations was only 13.9 and 9.8%, respectively, when the microcapsules were prepared with 100% Resomer 502 or 100% Resomer 506. In contrast, irrespective of the relative ratio of Resomer 502/Resomer 506, the median particle size of the microcapsules showed similar distribution pattern with the median size lies between 49 and 83microm. The glass transition temperature (T(g)) decreased significantly (44.6-25.5 degrees C) as the amount of Resomer 502 was increased in the formulation. The presence of Resomer 502 at lower concentration, along with Resomer 506, initially reduced the "burst effect." However, incorporation of a higher amount of Resomer 502 increased the "burst effect." Drug release from these microcapsules continued over 80 days. In conclusion, efficiency of encapsulation increased significantly when Resomer 506 was mixed with Resomer 502 at a ratio of 1:7. Blending of Resomer 502 with Resomer 506 reduced the glass transition temperature, which resulted in higher amount of drug release throughout the dissolution study.