Effect of hexacosanol on the characteristics of novel sustained-release allopurinol solid lipospheres (SLS): factorial design application and product evaluation

This investigation involved the evaluation of the effect of hexacosanol (HC, ceryl alcohol), a new hydrophobic wax modifier (WM) in comparison with conventional modifiers, on the development of sustained-release allopurinol (AP) solid lipospheres (SLS) intended for use in a suspension formulation and other oral dosage forms. Various beeswax (BW)WM blends (composition ratio 1: 1) were thus used to prepare SLS by a modified oil-in-water emulsion meltable disperse-phase (MDP) encapsulation method without using organic solvents and the influence of these blends on the drug encapsulation efficiency (EE), size distribution and the time for 50% of the drug to be released (t(50%)) was investigated. Results indicated that incorporation of HC in wall matrix of SLS provided the means to enhance the EE of AP and to modulate the rate of drug release into dissolution media (simulated gastric fluid (S.G.F.: pH 1.2) and simulated intestinal fluid (S.I.F.: pH 7.4). The effects of the process variables;, HC concentration, dispersant (pluronic F-68: PF-68) concentration and drug:wax ratio were also studied on the properties of AP-loaded SLS by a 23 factorial design. The EE values were in the range of 80.8-92.67%. The only significant parameter affecting (P < 0.01) the size and size distribution of the SLS formulations was the amount of the PF-68, whereas the factor with the biggest influence (P < 0.05) on the drug EE was the initial loading of AP (in terms of the drug:wax ratio). The amount of HC blended with wax and the initial drug loading significantly (P < 0.01) affected the t(50%) values of all of the formulations. The release of AP was more extended (t(50%) values (S.I.F.; pH 7.4) = 9.91-25.36 h, depending on the drug:wax ratio) and surface morphology of SLS was improved with higher HC content (15%, w/w) formulations. The release patterns fitted the Baker-Lonsdale dissolution kinetics for spherical matrices. A significant decrease of plasma uric acid levels (P < 0.05) and hepatic impairment in male rats was observed after oral administration of a SLS (mean size: 120 mu m) suspensions of the optimum formulation, compared to suspensions of pure AP. (c) 2005 Elsevier B.V. All rights reserved.