Particle Size Distribution Of Microspheres Research Articles

Polycaprolactone-blended gelatin microspheres and their morphological study

Polycaprolactone (PCL)-blended gelatin microspheres were prepared in the size ranges of 5–20 μm as well as 70–340 μm and modified through different compositions of PCL to gelatin in the oil-in-water emulsion solvent evaporation method. The formation of the polymer particles and particle morphology, stability, crystallinity, and thermal behavior of the polymer blends were studied. The changes in physiochemical properties of the blends were also studied with the addition of very less amount of polyvinylpyrrolidone (PVP), as it enhances the particle size distribution of microspheres as well as the surface morphology. Differential scanning calorimetry analysis shows the shifting of exothermic peak in the PCL/gelatin blend, and the PCL/gelatin blend stabilized by PVP results in the decrease in crystallinity. PCL-blended gelatin microspheres were smooth with definite shape and fine dispersibility with the increased concentration of gelatin to the polymer while lower concentration of the gelatin caused agglomeration. Optimization of the gelatin and PVP ratio to the polymer matrix results in large-size spherical stable microparticles. The stabilizing ability of microsphere decreases with the increased concentration of PCL during the solvent evaporation method. The addition of PVP to the PCL/gelatin blend enhanced the particle size distribution of microspheres as well as the surface morphology.

Preparation, characterization and pharmacokinetics evaluation of clarithromycin-loaded Eudragit(®) L-100 microspheres.

The aim of this work was to prepare pH-dependent clarithromycin microsphere formulation by emulsion solvent evaporation method, employing Eudragit(®) L-100. Prepared microspheres were evaluated by carrying out in vitro release and in vivo pharmacokinetics studies. Drug-polymer interactions were studied by differential scanning calorimetry, X-ray diffractometry analyses and results showed that clarithromycin was molecularly dispersed in the polymer. The particle size distribution of microspheres was found over the range of 10~50μm. The drug is hardly released in the HCl solution pH 1.2 in the first 2h, but is rapidly released in phosphate buffer pH 7.2, and the cumulated release reached 98.1% at 8h. The pharmacokinetic profiles were conducted open, randomized, two-period crossover design with a 7-day interval between doses in healthy beagle dogs. The results indicated that the extent of absorption of the clarithromycin-load microspheres was the same as pure drug, but different in the rate of drug absorption in vivo.

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.

Determination of microsphere solidification time in the solvent evaporation process

The aim of this work was to define the time of microsphere solidification during the solvent evaporation process. Microspheres were prepared by the solvent evaporation method, using acetone/liquid paraffin solvent system, ketoprofen as a model drug and Eudragit RS as a matrix polymer. Two sets of experiments were performed—in the first one the initial temperature of the emulsion system was 5°C and in the second one 25°C. In each set, two batches of microspheres were compared at constant emulsion stirring rate 250 and 1000 rpm and intermediate batches where the emulsion stirring rate was lowered from 1000 to 250 rpm at pre-defined times after the beginning of the inner phase solvent evaporation. By comparison of the properties of these microspheres, an insight was obtained into the mechanism of microspheres formation. The criterion for determination of microsphere solidification time was the resemblance between the microsphere properties of the batches prepared by stirring rate change and the batch prepared by constant stirring at 1000 rpm. A stirring rate change after the solidification has no influence on microsphere properties, that means that they are the same as of the batch prepared by constant stirring at 1000 rpm. The results of the sieve analysis and particle size distribution of microspheres show that the time of microspheres solidification is in the interval between 15–20 min if the initial temperature is 5°C and between 10–20 min if the initial temperature is 25°C. From the release profiles of ketoprofen, one can infer that the times of solidification for both initial temperatures are a bit lower. The microscopic pictures, which enable one to follow the processes in the system, confirmed the result obtained by the sieve analysis. In spite of its inability to distinguish between single particles and agglomerates, the sieve analysis enabled one to determine the actual time of solidification, while the drug release determination was not sensitive enough to trace small differences in surface area due to particles aggregation.

Effect of Process Variables on Particle Size of Gelatin Microspheres Containing Lactic Acid

Gelatin microspheres containing lactic acid were prepared by a polymerization technique using glutaraldehyde as the cross‐linking agent. Because particle size distribution of microspheres is a vital factor in the characterization of microspheres, the present study was carried out to evaluate the effect of process variables on the microspheres size distribution. It was found that concentration of a gelatin solution is the most important parameter that influences the particle size of microspheres. By using different concentrations of gelatin solution, microspheres with different size ranges were prepared. Both the stirring rate of the system and the volume ratio of aqueous and oil phases exerted a great influence on microsphere‐size distribution, whereas, cross‐linking time and cross‐linker concentration only affected the yield. Lower‐phase volume ratios resulted in small uniform microspheres with smooth surfaces and a narrow size range. The effect of emulsifier concentration (span 80), below 1% (w/w, with respect to the weight of the oil phase), on particle size was appreciable. However, at higher concentrations, little effect was observed.

Preparation of biodegradable microspheres and matrix devices containing naltrexone.

In this study, the use of biodegradable polymers for microencapsulation of naltrexone using solvent evaporation technique is investigated. The use of naltrexone microspheres for the preparation of matrix devices is also studied. For this purpose, poly(L-lactide) (PLA) microspheres containing naltrexone prepared by solvent evaporation technique were compressed at temperatures above the Tg of the polymer. The effect of different process parameters, such as drug/polymer ratio and stirring rate during preparation of microspheres, on the morphology, size distribution, and in vitro drug release of microspheres was studied. As expected, stirring rate influenced particle size distribution of microspheres and hence drug release profiles. By increasing the stirring speed from 400 to 1200 rpm, the mean diameter of microspheres decreased from 251 microm to 104 microm. The drug release rate from smaller microspheres was faster than from larger microspheres. However, drug release from microspheres with low drug content (20% wt/wt) was not affected by the particle size of microspheres. Increasing the drug content of microspheres from 20% to 50% wt/wt led to significantly faster drug release from microspheres. It was also shown that drug release from matrix devices prepared by compression of naltrexone microspheres is much slower than that of microspheres. No burst release was observed with matrix devices. Applying higher compression force, when compressing microspheres to produce tablets, resulted in lower drug release from matrix devices. The results suggest that by regulating different variables, desired release profiles of naltrexone can be achieved using a PLA microparticulate system or matrix devices.

Preparation, characterization and in vitro drug release of isosorbide dinitrate microspheres

Microspheres of isosorbide dinitrate (ISDN) were prepared using the emulsification/solvent evaporation method. The impacts of different factors such as stirring rate, concentration of ethyl cellulose (EC) as matrix polymer, poly vinyl chloride (PVA) as stabiliser and ISDN on the characteristics of the microspheres were investigated. The morphology of microspheres was studied using optical and scanning electron microscopy and it was shown that microspheres had a spherical shape and smooth surface. The particle size distribution of microspheres, analysed by a sieving method, was affected by stirring rate and concentrations of EC, PVA and ISDN. Larger microspheres showed greater drug loading and smaller microspheres showed a faster drug release. The in vitro drug release from microspheres was predictable and reproducible, conforming to the Higuchi model of release kinetics.

Environmentally benign formation of polymeric microspheres by rapid expansion of supercritical carbon dioxide solution with a nonsolvent.

A novel method is reported for forming polymer microparticles, which reduce atmospheric emissions of environmentally harmful volatile organic compounds such as toluene and xylene used as paint solvent in paint industry. The polymer microparticles have formed through rapid expansion from supercritical solution with a nonsolvent (RESS-N). Solubilization of poly(styrene)-b-(poly(methyl methacrylate)-co-poly (glycidyl methacrylate)) copolymer(PS-b-(PMMA-co-PGMA), MW = 5000, PS/PMMA/PGMA = 2/5/3), poly(ethylene glycol) (PEG, M. W = 4000), bisphenol A type epoxy resin (EP, MW = 3000), poly(methyl methacrylate) (PMMA; MW = 15000, 75000, 120000), and poly(oxyalkylene) alkylphenyl ether (MW = 4000) in carbon dioxide (CO2) was achieved with the use of small alcohols as cosolvents. The solubility of the PS-b-(PMMA-co-PGMA) is extremely low in either CO2 or ethanol but becomes 20 wt % in a mixture of the two. Because ethanol is a nonsolvent for the polymer, it can be used as a cosolvent in rapid expansion from supercritical solution to produce 1-3 microm particles that do not agglomerate. Obtained polymer particles by RESS-N were applied as powder coatings. The resulting coatings have a smooth and coherent film. The particle size distribution of microspheres was controlled by changing the polymer concentration, preexpansion pressure, temperature, and injection distance. The feed compositions were more effective than the other factors in controlling the particle size. The polymeric microparticles formed by RESS-N method can be utilized to make the thin coating film without anytoxic organic solvents and/or surfactants.