Development and Evaluation of Thymol Microparticles Using Cellulose Derivatives as Controlled Release Dosage form

Thymol, an important and advantageous component of many essential oils, has been applied as an antimicrobial agent in animals. To increase the duration of action of this compound in ruminants, it was decided here to prepare a controlled release carrier for thymol. Hydroxy propyl methyl cellulose (HPMC) and ethyl cellulose (EC) were used as the matrix polymer here. Mixtures of thymol with eight different ratios of these polymers were then prepared using emulsion solvent evaporation method (F(1) to F(8)). The prepared microparticles were evaluated for production yield, entrapment efficiency, drug content, particle size, drug release behavior, release kinetics (zero order, first order and Fickian matrix diffusion for spheres) and characterized by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). Mean particle size of microparticles was 1.03 ± 0.02 mm. SEM study revealed that the microparticles were slightly irregular, rough and porous. The formulation with HPMC: EC ratio of 5:1 (F6) showed the highest drug loading (38.8%) and entrapment efficiency (61.2%). This formulation also showed optimum in-vitro drug release. The best fit of release kinetics was achieved with Fickian matrix diffusion for spheres (linear amount released vs t(0.43)). The FTIR spectroscopic and DSC studies show possible interaction between drug and polymers. In this study, thymol was successfully loaded in microparticles prepared from HPMC and EC. These microparticles can be used in further trials to evaluate the effect of slow release thymol on rumen fermentation parameters in ruminants.