Phosphate Phenylpropanoid Piperazine Morpholine Drugs - Resin Sustained Release Suspensions

Ion-exchange resins as new kinds of drug carrier were being widely applied.In this paper,the several basic properties of the resins were determined using the styrene strongly acidic cation-exchange resin of gel type(OO1 X 7) as a model. The bulk density, specific surface, static exchange amount, active exchange amount and inflation rate of resin were determined as O.577⁴).773 mg/mi, 2.83X iO m2/g, 4.8$?.88 mmol/g, 5.Ol---5.lO mmol]g and 51.O?9.9% respectively.Based on the shell-core model theoty, the exchange mechanism between drug and resin was discussed using benproperine phosphate as a model drug .The factors that influence the exchange process were described. It wad found that the controlled-rate stage of the exchange reaction was the diffusing process of drug in the capillary in the resin particle. The exchange reaction rate was enhanced with the decrease of the resin size and the increase of the reaction temperature. By fitting the exchange kinetics profiles, it was indicated that the exchange reaction between drug and resin accorded with first order reaction. The related thermodynamic parameters such as H(48.77 kJ/mol), 憕 G(-7.047 kJ/mol ) and kinetics constants such as exchange reaction equilibrium constant (17.16), exchang reaction velocity constant (0.0378 -4 .6300min1), exchang reaction energy (51 .30--55.82 kJ/mol) were obtained. The release reaction of drug from3Abstractdrug-resin complex was also consistent with first order reaction. The release rate was affected by the resin size, reaction temperature and release media concentration.The exchange and release process were reversible processe.By in-liquid drying, sustained-release pellets were prepared taking Eurdragit RL100 as coating material and drug-resin complex as core. The facters affecting drug release were investigated.In order to find the optimum coating formulas and process, orthogonal experiment was carried out.After studying the properties of the sustained-release pellets and all kinds of suspension media, drug-resin sustained-release suspensions was prepared. Then, the release mechanism was studied and it was indicated that the drug release profiles were consistant with Higuchi equation.The result of stability test showed that the suspensions were stable when exposed to light, high temperature and low temperature.The pharmacokinetics of the sustained-release suspensions in human was carried out by IIPLC.Its Tm^6.OOh,ti^{l 8.14h}and Cmax(441 .7ng/ml) were bigger than commercial tablets . Its relative bioavailability was 112.8% . Obvious correlation existed between absorption percentage in vivo and release rate in vitro.