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).

The study of drug release from microspheres adhered on pig vesical mucosa.

The object of our work is the preparation of a mucoadhesive drug delivery system intended for intravesical application. In the present work, microspheres with Eudragit RS matrix polymer and different mucoadhesive polymers, i.e. chitosan hydrochloride (Ch), sodium salt of carboxymethyl cellulose (CMC) and polycarbophil (PC) were prepared to evaluate their influence on the mucoadhesive properties of microspheres. Different parameters were determined and their influence on pipemidic acid release from microspheres adhered on intact and damaged pig vesical mucosa was evaluated: swelling of polymers, mucoadhesion strength of polymeric films and drug dissolution according to USP XXIV method. The dissolution rate from microspheres containing different mucoadhesive polymers decreases as follows: PC>Ch>CMC. PC swelled to the largest volume among all polymers and as a result the fastest release of the drug from PC microspheres was obtained. The release rate of pipemidic acid from microspheres adhered on intact mucosa followed the order PC>CMC>Ch. These results show that both drug dissolution and mucoadhesion strength strongly influence drug release from adhered microspheres. The slowest release from Ch microspheres could be interpreted by the largest mucoadhesion strength of Ch polymeric films. The release rate of pipemidic acid from microspheres adhered on damaged mucosa followed the order PC=Ch>CMC. The results obtained on pathologically changed mucosa model support the indication of the role of glycosaminoglycans and polymer charge in the mucoadhesion process on vesical mucosa. Analysis of release data shows that the drug dissolution profiles follow the Higuchi kinetics better than the release profiles from adhered microspheres and different kinetics might be a consequence of different release mechanisms.

Effects of chloropyramine and famotidine on postischaemic and posthypoxic myocardial damage in isolated rat hearts.

In isolated rat hearts effects of chloropyramine (CP), histamine H1 antagonist, and famotidine (FA), H2 antagonist, upon two different myocardial injuries, ischaemia-reperfusion and hypoxia-reoxygenation were studied. In both types of injury the effects of drugs were seen mainly during reperfusion and reoxygenation, respectively. During reperfusion neither CP nor FA influenced amplitude of contractions, but CP lowered heart rate, +dp/dtmax and coronary flow. During reoxygenation CP and FA lowered early posthypoxic contractions, whereas CP decreased and FA increased heart rate. CP and FA did not significantly influence the post-ischaemic and posthypoxic lactate dehydrogenase (LDH) release. Present results indicate the existence of H1 and H2 receptors in rat heart as well as their involvement in both types of studied injuries.