| This study was done to enhance the compatibility between an acidic and basic drug when used in combination within the same dosage form by encapsulating the drugs within an ethyl cellulose microsphere. The drugs encapsulated include acidic (acetaminophen and aspirin) and basic (theophylline, and hydroxyzine) drugs. Microspheres were prepared by the solvent evaporation technique using methylene chloride and acetone as the dispersed phase and light mineral oil with span 80 as the continuous phase. Various drug to polymer ratios (1:1, 1:2, and 1:3) were chosen and evaluated to determine which microspheres resulted in the highest drug entrapment efficiency. The microspheres with highest drug entrapment were characterized by performing particle size analysis, differential scanning calorimetry (DSC), scanning electron microscopy (SEM), fourier transform infrared spectroscopy (FTIR), and in vitro drug release. Stability studies were performed with a (1:1) mixture of an encapsulated acidic and basic drug at 40 °C for three months.;The 1:1 ratio had the highest entrapment for the drugs aspirin (32%) and hydroxyzine (41%), while the 1:3 ratio had the highest entrapment for acetaminophen (65%) and theophylline (52%). Spherical, uniform microspheres were collected and the average particle size was found for acetaminophen (91.17 microm), aspirin (193.36 microm), hydroxyzine (93.89 microm) and theophylline (264.56 microm). DSC thermograms for the drug loaded microspheres determined that the drug present exists in an amorphous phase in the polymeric matrix indicating no interaction between the drug and the polymer. The in vitro drug release studies showed that acetaminophen and hydroxyzine released in 15-30 minutes and aspirin and theophylline released in 180-240 minutes. The drug release data was fitted to various kinetic models which resulted in acetaminophen following first order release (R2 value of 0.9693), aspirin following zero order release (R2 value of 0.9925), hydroxyzine following first order release (R2 value of 0.9744) and theophylline following Korsemeyer-Peppas release (R 2 value of 0.9296). FTIR results, over three months, showed inconclusive results, so further analysis is required. After evaluation of the microspheres, the data collected indicates the microspheres, when used in combination, need to be further analyzed using HPLC to determine if any interactions are occurring between the acidic and basic drugs. |
