The preparation and evaluation of poly(epsilon-caprolactone) microparticles containing both a lipophilic and a hydrophilic drug

An original dosage form for oral delivery based on the encapsulation of bot h, lipophilic and hydrophilic drugs, in poly(epsilon-caprolactone) (PCL) mi croparticles prepared either by the oil-in-water (o/w) or the water-in-oil- in-water (w/o/w) solvent evaporation method was developed. Microparticles w ere characterized in terms of morphology, size, encapsulation efficiency an d drug release. The physical state of the drugs and the polymer was determi ned by scanning electron microscopy (SEM), X-ray powder diffractometry, and differential scanning calorimetry (DSC). Nifedipine (calcium antagonist) a nd propranolol HCl (beta-blocker), used for the treatment of hypertension, were chosen as lipophilic and hydrophilic drugs. The microparticles were sp herical with diameters in the range of 191-351 mu m by the o/w-method, and in the range of 302-477 mu m by the w/o/w-method. The encapsulation efficie ncy (EE) was 91% for nifedipine and 37% for propranolol HCl with the o/w-me thod, and 83% for nifedipine and 57% for propranolol HCl with the w/o/w-met hod. DSC and X-ray diffraction studies showed that PCL maintained its semi- crystalline structure, while the drugs were either dispersed or dissolved i n the polymer. In vitro release studies revealed a controlled release of ni fedipine and propranolol HCl from microparticles prepared by the o/w-method ; a burst release of propranolol HCl was observed from microparticles prepa red by the w/o/w-method. In conclusion, microparticles containing both a hy drophilic and a lipophilic drug were successfully prepared. (C) 2000 Elsevi er Science B.V. All rights reserved.