Microparticle size control and glimepiride microencapsulation using spray congealing technology.

Drug-free microparticles were prepared using a spray congealing process with the intention of studying the influence of processing parameters. By varying the atomizing pressure and liquid feed rate, microparticles with median sizes (d((0.5))) from 58 to 278 microm were produced, with total process yields ranging from 81% to 96%. An increased liquid feed rate was found to increase microparticle size, and higher atomizing pressures were found to decrease microparticle size. Greater change in microparticle size was achieved by varying atomizing pressure, which can be considered a dominant process parameter regarding microparticle size. In addition, microparticles with glimepiride, a model poorly water-soluble drug, were prepared by spray congealing using three different hydrophilic meltable carriers: Gelucire 50/13, poloxamer 188, and PEG 6000. Spherical microparticles with relatively smooth surfaces were obtained, with no drug crystals evident on the surfaces of drug-loaded microparticles. XRPD showed no change in crystallinity of the drug due to the technological process of microparticle production. All glimepiride-loaded microparticles showed enhanced solubility compared to pure drug; however, Gelucire 50/13 as a carrier represents the most promising approach to the dissolution rate enhancement of glimepiride. The influence of storage (30 degrees C/65% RH for 30 days) on the morphology of glimepiride/Gelucire 50/13 microparticles was studied, and the formation of leaf-like structures was observed (a "blooming" effect).

Comparison of different intestinal epithelia as models for absorption enhancement studies.

In this study we compared the effect of two surfactants (laureth-6 and sodium docusate) on the permeability of a model hydrophilic drug across three different epithelia (Caco-2 cells, stripped porcine jejunum and rat ileo-jejunum). Among the tested epithelia Caco-2 cells are the tightest with the trans-epithelial electrical resistance of 372+/-4 Omega cm2 followed by porcine jejunum (124+/-8 Omega cm2) and rat ileo-jejunum (33+/-2 Omega cm2). Both surfactants decreased the trans-epithelial electrical resistance and increased the permeability of a model drug across Caco-2 cells at concentrations as low as 0.02 mg/ml, with more pronounced effect observed for laureth-6. On the other hand, ten times higher concentrations (0.2 mg/ml) did not affect the permeability of the model drug across the porcine jejunum. Similarly, laureth-6 at this high concentration had no effect on the trans-epithelial electrical resistance of the rat ileo-jejunum and did not increase the permeability of the model drug across this tissue. On the basis of these results we concluded that Caco-2 cells are much more sensitive to the investigated surfactants, that act as permeation enhancers, than the native intestinal tissues. Therefore, the results obtained in the experiments with Caco-2 cells might exaggerate the effects of the surfactants on the permeability compared to in vivo situation.

Micronization of drugs using supercritical carbon dioxide.

Particles from gas saturated solutions, a novel method for high pressure material processing, has been used for micronization of practically insoluble calcium-channel blockers nifedipine and felodipine and the hypolipidemic agent fenofibrate with the aim of increasing their dissolution rate and hence their bioavailability. Dependent on the pre-expansion conditions, a mean particle size of between 15 and 30 microm was achieved for micronized nifedipine and 42 microm for micronized felodipine. The particle size of processed fenofibrate, on the other hand, increased due to agglomeration. The highest dissolution rate was achieved by preparation of drug coprecipitates with PEG 4000.

Alternative solvent-free preparation methods for felodipine surface solid dispersions.

Surface solid dispersions were prepared via physical mixture and were either heated in a vacuum dryer or in a microwave oven for different periods of time. The physical state of felodipine in solid dispersions was studied using differential scanning calorimetry and x-ray powder diffractometry. USP paddle method was used for felodipine dissolution studies. The use of vacuum or microwave energy led to a significant improvement of felodipine dissolution which was caused partly by the amorphous state of felodipine and a large surface area of amorphous silicon dioxide.

Compatibility study between acetylcysteine and some commonly used tablet excipients.

Differential scanning calorimetry (DSC), Fourier transform infra-red spectroscopy (FT-IR), HPLC and TLC were used to investigate the interactions between the mucolytic drug acetylcysteine and a number of commonly used tablet and capsule excipients. Acetylcysteine was found to be compatible with microcrystalline cellulose (Avicel PH 101), sodium carboxymethylcellulose, amorphous silicon dioxide (Aerosil), PVP, cross-linked PVP (Polyplasdone XL), corn starch, saccharose and magnesium stearate. Acetylcysteine thermal stability (onset degradation temperature) was decreased in mixtures with corn starch, magnesium stearate, saccharose and lactose. Interactions of acetylcysteine with lactose, PEG 4000 and 6000, glycine, adipic acid and saccharin sodium were found using DSC and studied in detail with FT-IR, HPLC and TLC. The results suggest that acetylcysteine in mixtures with PEG 4000, glycine or saccharin sodium is degraded during storage at conditions of high temperature and humidity.