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 both, lipophilic and hydrophilic drugs, in poly(epsilon-caprolactone) (PCL) microparticles 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 were characterized in terms of morphology, size, encapsulation efficiency and drug release. The physical state of the drugs and the polymer was determined by scanning electron microscopy (SEM), X-ray powder diffractometry, and differential scanning calorimetry (DSC). Nifedipine (calcium antagonist) and propranolol HCl (beta-blocker), used for the treatment of hypertension, were chosen as lipophilic and hydrophilic drugs. The microparticles were spherical with diameters in the range of 191-351 microm by the o/w-method, and in the range of 302-477 microm by the w/o/w-method. The encapsulation efficiency (EE) was 91% for nifedipine and 37% for propranolol HCl with the o/w-method, and 83% for nifedipine and 57% for propranolol HCl with the w/o/w-method. DSC and X-ray diffraction studies showed that PCL maintained its semi-crystalline structure, while the drugs were either dispersed or dissolved in the polymer. In vitro release studies revealed a controlled release of nifedipine and propranolol HCl from microparticles prepared by the o/w-method; a burst release of propranolol HCl was observed from microparticles prepared by the w/o/w-method. In conclusion, microparticles containing both a hydrophilic and a lipophilic drug were successfully prepared.

Preparation and characterization of ethylcellulose microspheres containing 5-fluorouracil.

Ethylcellulose microspheres containing 5-fluorouracil (5-FU) were prepared by a solvent evaporation technique using light mineral oil as the continuous phase. The drug was suspended in the acetone solution of the polymer. Three drug/polymer ratios (1/1, 1/2 and 1/3) were utilized. The microspheres were studied with respect to size, drug content and surface characteristics; the higher the polymer content, the smoother the microspheres. The drug was suspended in the polymer and the drug loading was important (more than 90%) with the three types of microspheres. In vitro dissolution studies in phosphate buffer showed that the 5-FU release was dependent on the drug/polymer ratio for the 400-500 microns granulometric fraction.