DEVELOPMENT OF A LIQUID ORAL IN-SITU GEL OF VORICONAZOLE FOR SUSTAINED RELEASE AND ENHANCED BIOAVAILABILITY: EQUIVALENCE TESTING USING EARTH MOVER’S DISTANCE

Development of a sustained release liquid oral in-situ gel of Voriconazole with improved bioavailability has been the main aim of this project. Complexation of the drug with hydroxypropyl beta-cyclodextrin was done to improve the solubility and stability of the drug. The mucoadhesive polymer carbopol 934P and release retardant HPMC E50 were used as factors and a two-square factorial design was employed. A simple mixing method was used for the formulation, and evaluation was done. The polymers had a significant effect on gelation time, mucoadhesive strength, and 8 h drug release. Carbopol showed a better- controlled release and mucoadhesive strength than HPMC E50. The experimental values for gelation time, mucoadhesive strength, drug release at 1 h, 8 h, 12 h, and gel strength were found to be 80 sec, 17453 dynes/cm, 21.10%, 62.98%, 90.54%, 55 sec respectively, which were close to the predicted values. Pharmacokinetic studies revealed a 12 h sustained drug release, plasma drug concentrations above 0.5µg/ml (MIC) and 6.76-fold increase in bioavailability. Thermal and photostability studies revealed a shelf life of 2 years. Equivalence testing proved that the prepared formulation was better than the reference as the ϴtest (0.6835) < ϴstd (0.7963). An elegant, needle-free liquid oral in-situ gel of Voriconazole could thus be successfully developed by statistical optimization techniques using mucoadhesive polymers to sustain the drug release up to 12 h, improve bioavailability and patient compliance.