Oral yolla veriliş için kandesartan sileksetil içeren proniozomların hazırlanması: Formülasyon parametreleri ve etkin madde salımının değerlendirilmesi
Özet
In our study, candesartan cilexetil which is practically insoluble in water and has low bioavailability, loaded proniosomes were prepared with various surfactants [sorbitan esters (Span), polyoxyethylene ethers of sorbitan esters (Tween) and polyoxyethylene stearyl ethers (Brij)] and various ratios; formulation parameters and drug release properties were evaluated.The physicochemical properties of active agent and its interaction with other ingredients were determined using differential scanning calorimetry (DSC) and X-ray powder diffractometry. The spectrophotometric method used for quantitative assay of the active agent was validated. The proniosome preparation methods (spray method and slurry method) were evaluated and the optimum method was chosen. Preformulation studies were carried out without using the active agent and various formulation parameters (quantity of the organic solvent to be used, particle size range of the carrier material to be used, moiety ratio of surfactant mixture to the carrier material) were optimized. In experiments, the effects of vortex process and hydration temperature while preparing niosomal dispersions from proniosomal powder were evaluated. The dose of candesartan cilexetil was chosen as 8 mg in the formulations. Prepared proniosomes from formulations were visualized by optical microscope and additionally, yields (%) and entrapment efficiencies (%) were calculated. For drug release analysis, first the method to be used was chosen. Particle size analysis and zeta potential analysis were carried out for F2 coded final formulation. Drug release properties of the final formulation were assessed at different dissolution mediums with different pH values; and these findings were compared with the results obtained from the commercial drug containing 8mg candesartan cilexetil. The results of DSC and X-ray powder diffractometry analysis showed that the active agent is in the state of form I and it is in amorph form in proniosomes. The slurry method was chosen for proniosomes preparation. When preparing niosomes from proniosomes it was shown that niosomes can be obtained without using any vortex process, and besides this niosomes could be formed from by hydratation of proniosomes with liquids in room and body temperature.Yields (%) in formulations were between % 97.19 and % 98.83; entrapment efficiencies (%) of niosomes were between 69.60 % -99.16 %. The percentages of drug release from F2 coded formulation in the dissolution mediums containing 0.2 % w/v Tween 80 (pH 1.2, pH 4.5, and pH 6.8) were 42.3 %, 71.39 % and 99.38 % respectively. The percentages of drug release from commercial drug in the dissolution mediums containing %0.2 w/v Tween 80 (pH 1.2, pH 4.5, and pH 6.8) were % 20.54, %25.6 and %70.36 respectively. According to experimental findings, as the particle size of sorbitol used during production of proniosomes decreases, the drug release accelerates; and when the particle size of sorbitol increases the drug release decelerates.In conclusion, the solubility of candesartan cilexetil loaded into proniosomal vesicles, was increased in the pH values of gastrointestinal system. By preparing proniosomal powders which can overcome the physical stability problems of liquid niosomal dispersions, a convenient formulation was obtained for oral administration of candesartan cilexetil.