| Osmotic pressure difference was used as the driving force,and a constant release rate was the delivering characteristic of the osmotic pump tablet.The release rate of oral osmotic pump tablet was pH-independent and agitation-independent which leaded to comparable in vitro/in vivo correlation.Fluctuant plasma drug concentration of conventional preparations could also be reduced with the osmotic pump tablet. Although monolithic and micro-porous osmotic pump tablet could be prepared simply, they were usually applicable for soluble drugs.In this study,the solvency enhancement of ibuprofen and hesperetin were studied using acid-alkali reaction and inclusion technology,respectively.Then the monolithic osmotic pump tablet and the micro-porous osmotic pump tablet of ibuprofen were successfully prepared.Sodium carbonate was used as solvency enhancer,sodium chloride as osmotic agent,polyethylene oxide(PEO,Mw,5×105) as retardant agent,cellulose acetate(CA) as semi-permeable membrane.The amount of sodium chloride,the amount of PEO (Mw,5×105),the level of PEG-400 in CA(v/w) and the thickness of membrane were selected as four factors of orthogonal design.The optimal formulation was obtained as follows:ibuprofen,150.0 mg;sodium carbonate,38.5 mg;sodium chloride,20.0 mg;PEO(Mw,5×105),5.0 mg;pregelatinized starch,86.5 mg;level of PEG-400 in CA,5.0%(v/w);thickness of membrane,0.171 mm.The monolithic osmotic pump tablet of ibuprofen could deliver drug at a rate of approximate zero-order up to 24 h,independent on release media and agitation rate. The approach of solvency modulation by acid-alkali reaction might be used for the solubilization and preparation of monolithic osmotic pump tablet of other poorly soluble drugs with the ability to react with an acid or an alkali. Micro-porous osmotic pump tablet of ibuprofen was prepared using formulation of core tablet of optimal monolithic osmotic pump tablet of ibuprofen.CA was employed as semi-permeable membrane,PEG/PEO as micro-pore former.Influences of molecular weight of micro-pore former,level of micro-pore former,level of plasticizer and thickness of membrane on drug release profile were investigated.The optimal formulation was obtained as follows:ibuprofen,150.0 mg;sodium carbonate, 38.5 mg;sodium chloride,20.0 mg;PEO(Mw,5×105),5.0 mg;pregelatinized starch, 86.5 mg;level of PEG-400 in CA,5.0%(w/w);level of PEG-6000 in CA,5.0% (w/w);thickness of membrane,0.210 mm.The micro-porous osmotic pump tablet of ibuprofen could deliver drug at a rate of approximate zero-order up to 24 h,independent on release media and agitation rate. The approach of solvency modulation by acid-alkali reaction might be used for the preparation of micro-pore osmotic pump tablet of other poorly soluble drugs with the ability to react with an acid or an alkali.Hesperetin was selected as the model drug.The solubilities of hesperetin in methanol,ethanol,1-butanol,acetone and water were determined.The phase solubilities of hesperetin withβCD,HPβCD and(SBE)7mβCD were investigated. Inclusion complexes were prepared,and dissolution tests were investigated compared with that of hesperetin and physical mixtures.The solubility and dissolution rate of hesperetin could be markedly enhanced by all selected cyclodextrins,and a better solubilization effect was achieved with HPβCD and(SBE)7mβCD.The best solubilization effect was achieved with(SBE)7mβCD.
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