盐酸普萘洛尔药物树脂复合物的制备及其体外释药动力学

Preparation and drug release kinetics in vitro of propranolol hydrochloride-resin complexes

目的:制备盐酸普萘洛尔(propranolol hydrochloride,PH)药物树脂复合物,并考察其体外释药动力学。方法:采用热力学和交换动力学分析方法,研究PH与树脂AMBERLITTIRP69的交换反应热力学和动力学,以及药物树脂复合物在去离子水,0.15,0.6,1 mo.lL-1的NaCl和0.15 mo.lL-1的盐酸以及0.15 mol.L-1的KCl溶液中的释药动力学。结果:交换动力学和热力学结果表明,PH与AMBERLITTIRP69树脂的交换反应属吸热反应,随温度升高,化学反应平衡常数Ke与速率常数k均增大,反应的活化能为14.59 kJ.mol-1,ΔGo为49.55 J.mol-1,ΔHmo为38.2337 kJ.mol-1。体外释药动力学研究表明:PH药物树脂复合物在去离子水中不释放药物,释药速率随介质中离子强度的增加而增加;其释药动力学过程可用Viswanathan方程来描述,并且PH在上述介质中的释放属粒扩散过程控制,粒扩散系数Dr随释放介质中离子强度的增加而增加。结论:PH可制备成药物树脂给药系统。

Objective： To develop a new preparation of propranolol hydrochloride-resin complexes. Methods： The kinetics of the exchange reaction of propranolol hydrochloride（PH） with the pharmaceutical grade resin AMBERLITT IRP69, and the release properties of PH from the drug-resin complexes in deionic water, 0.15, 0.6, 1 mol· L^-1 NaCl, 0.15 mol·L^-1 HCl and 0. 15 mol· L^-1 KCl solutions, were investigated by exchange kinetics and thermodynamics. Results： The exchange reaction of PH with AMBERLITT IRP69 was enthermal. The values of both exchange reactive equilibrium constants Ke and the exchange rate constants k were positively proportional to changes of temperature. The exchange activation energy was about 14. 59 kJ·mol^-1, △G^0 = 49.55 J· mol^ -1, △H^0m = 38. 233 7 kJ· mol^ -1 The study of the drug release kinetics in vitro showed that no PH was released from the drug-resin complexes in deionic water media. The more ionic strength the media environment exists, the higher release rate was. The release kinetics of the PH-resin complex obeyed the Viswanathan＇s equation, featuring a particle diffusion process. The diffusion coefficient Dr was increased with the enhancement of the ionic strength of the releasing media. Conclusion： The propranolol-resin delivery system was achievable.