Formulation and pharmacodynamic evaluation of captopril sustained release microparticles.

Cellulose propionate (CP) microparticles containing captopril (CAP) were prepared by solvent evaporation technique. The effects of polymer molecular weight, polymer composition and drug:polymer ratios on the particle size, flow properties, morphology, surface properties and release characteristics of the prepared captopril microparticles were examined. The anti-hypertensive effect of the selected CAP formulation in comparison with aqueous drug solution was also evaluated in vivo using hypertensive rats. The formulation containing drug:polymer blend ratio 1:1.5 (1:1 low:high molecular weight CP), namely F7, was chosen as the selected formulation with regard to the encapsulation efficiency (75.1%), flow properties (theta=24 degrees, Carr index=5%, Hausner ratio=1.1, packing rate=0.535) and release characteristics. Initial burst effect was observed in the release profile of all examined formulations. DSC and SEM results indicated that the initial burst effect could be attributed to dissolution of CAP crystals present on the surface or embedded in the superficial layer of the matrix. The release kinetics of CAP from most microparticle formulations followed diffusion mechanism. After oral administration of the selected microparticle formulation (F7) to hypertensive rats, systolic blood pressure decreased gradually over 24 h compared to reference drug solution. These results may suggest the potential application of cellulose propionate microparticles as a suitable sustained release drug delivery system for captopril.

Disposition of the flavonoid quercetin in rats after single intravenous and oral doses.

The pharmacokinetic and mean time tissue distribution parameters, after a single 50-mg/kg dose of quercetin administered as intravenous bolus, oral solution, and oral suspension, were determined using rat as an animal model. Following intravenous administration, the elimination rate constant and the elimination half-life were found to be 0.0062 min(-1) and 111 min, respectively. Examining the mean time tissue distribution parameters reflected a strong binding affinity of the drug molecules to both plasma and tissue proteins. In addition, the low permeability rate of drug molecules in the peripheral system was demonstrated. Following the oral administration of the drug, the extent of absorption was greater from solution than from suspension. Moreover, the solution showed a shorter Tmax and a higher Cmax than suspension. The absolute bioavailability for the solution was 0.275 and that for suspension was 0.162. The mean residence time (MRT) and the mean absorption time (MAT) were higher for suspension, reflecting the need for dissolving the drug in order to be absorbed. The mean (in-vivo) dissolution time (MDT(in-vivo)) was 34.5 min. Thus, an oral quercetin formulation that can readily form a drug solution in the gastrointestinal tract may enhance the absorption of the drug.