Belete, Anteneh(PhD)Feleke, Fitsum(PhD)Gadisa, Wondesen2018-06-142023-11-062018-06-142023-11-062015-05http://etd.aau.edu.et/handle/123456789/1027Epilepsy is a serious neurological disorder characterized by spontaneous seizures. Despite the development of successive generations of antiepileptic drugs, phenobarbitone has retained a unique position in the therapeutic armamentarium and is still the most widely prescribed drug for treatment of epilepsy throughout the world. However, the pharmaceutical industry supplies oral solid dosage forms that are generally inadequate for pediatric, geriatrics and patients experiencing difficulty in swallowing needs. Therefore, the present study aims at formulation and optimization of taste-masked orally disintegrating tablets of phenobarbitone using direct compression technique for use in specific population such as pediatrics, geriatrics and dysphagia patients. Thus, the study begins with the determination of the bitterness threshold of phenobarbitone in vivo. Then, taste-masked microspheres of phenobarbitone were prepared by oil in water emulsion solvent evaporation technique using Eudragit®E100 as a polymeric material. The effect of formulation variable i.e., polymer: drug ratio at four different levels (1:1, 2:1, 3:1 and 4:1) and process variable, i.e., stirring rate (500, 650 and 800 rpm) were examined. The prepared formulations were characterized for flow properties, particle size distribution, entrapment efficiency and percentage yield. The study revealed that the mean particle size ranged from 386.01 ± 3.88 to 456.72 ± 3.53 μm, the drug encapsulation efficiency varied from 88.50 ± 2.14 to 97.00 ± 1.26% of the theoretical amount incorporated. The taste-masking efficiency was determined by spectrophotometric analysis based on the amount of drug released from tastemasked microspheres in pH 6.8 phosphate buffer after 5 min. Taste evaluation studies confirmed that microspheres of phenobarbitone having a polymer: drug ratio of 1:1 are tasteless. FT-IR spectra of phenobarbitone and the physical mixture of drug and Eudragit®E100 1:1 suggested no interaction between the drug and polymer. x The effect of various formulation and process variable on phenobarbitone orally disintegrating tablets was investigated. The results of the experiments revealed that the major factors that affect the tablet characteristics are compression force, level of superdisintegrant and MCC/mannitol. Besides, since it has significant effect on drug release, the effect of polymer to drug ratio within the microsphere on the various tablet characteristics was also investigated. Thus, four factors, two level (2 4-1) fractional factorial experimental design was selected to investigate the effects of the selected independent variables on the various responses such as disintegration time, wetting time, hardness, drug release in 5 min and drug release in 15 min of taste-masked orally disintegrating tablets (ODTs). Accordingly, the various models describing the relationship of the selected variables were obtained using Design- Expert 8.0.7.1 software and the models were analyzed. The corresponding surface response and contour plots were also obtained and the optimum area was determined and, finally, the optimum was validated. Simultaneous optimization of the responses gave the most desirable representative optimum formulation, within the common optimum region, with a disintegration time of 31.95 sec., wetting time of 46.41 sec., hardness of 52.13 N, drug release within 5 min 62.21%,and drug release within 15 min of 90.03% at compression force 11.29 KN, SSG of 4.6%, MCC/ mannitol ratio of 1.6 :1 and polymer to drug ratio of 1.26:1. The validity of obtained optimal point was confirmed by the low magnitude of percent prediction error. Key words: phenobarbitone, Orally disintegrating tablets, Eudragit®E100, Tastemasking, direct compression, Fractional factorial designenPhenobarbitone; Orally disintegrating tablets; Eudragit®E100; Tastemasking; Direct compression; Fractional factorial designThesis