Formulation And Optimization Of Taste-masked Phenobarbitone Orally Disintegrating Tablets Prepared By Direct Compression Method

Epilepsy is a serious neurological disorder characterized by spontaneous seizures.rnDespite the development of successive generations of antiepileptic drugs,rnphenobarbitone has retained a unique position in the therapeutic armamentariumrnand is still the most widely prescribed drug for treatment of epilepsy throughout thernworld. However, the pharmaceutical industry supplies oral solid dosage forms thatrnare generally inadequate for pediatric, geriatrics and patients experiencing difficultyrnin swallowing needs. Therefore, the present study aims at formulation andrnoptimization of taste-masked orally disintegrating tablets of phenobarbitone usingrndirect compression technique for use in specific population such as pediatrics,rngeriatrics and dysphagia patients. Thus, the study begins with the determination ofrnthe bitterness threshold of phenobarbitone in vivo. Then, taste-masked microspheresrnof phenobarbitone were prepared by oil in water emulsion solvent evaporationrntechnique using Eudragit®E100 as a polymeric material.rnThe effect of formulation variable i.e., polymer: drug ratio at four different levelsrn(1:1, 2:1, 3:1 and 4:1) and process variable, i.e., stirring rate (500, 650 and 800 rpm)rnwere examined. The prepared formulations were characterized for flow properties,rnparticle size distribution, entrapment efficiency and percentage yield. The studyrnrevealed that the mean particle size ranged from 386.01 ± 3.88 to 456.72 ± 3.53 μm,rnthe drug encapsulation efficiency varied from 88.50 ± 2.14 to 97.00 ± 1.26% of therntheoretical amount incorporated. The taste-masking efficiency was determined byrnspectrophotometric analysis based on the amount of drug released from tastemaskedrnmicrospheres in pH 6.8 phosphate buffer after 5 min. Taste evaluationrnstudies confirmed that microspheres of phenobarbitone having a polymer: drug ratiornof 1:1 are tasteless. FT-IR spectra of phenobarbitone and the physical mixture ofrndrug and Eudragit®E100 1:1 suggested no interaction between the drug andrnpolymer.rnxrnThe effect of various formulation and process variable on phenobarbitone orallyrndisintegrating tablets was investigated. The results of the experiments revealed thatrnthe major factors that affect the tablet characteristics are compression force, level ofrnsuperdisintegrant and MCC/mannitol. Besides, since it has significant effect onrndrug release, the effect of polymer to drug ratio within the microsphere on thernvarious tablet characteristics was also investigated. Thus, four factors, two level (2rn4-1) fractional factorial experimental design was selected to investigate the effects ofrnthe selected independent variables on the various responses such as disintegrationrntime, wetting time, hardness, drug release in 5 min and drug release in 15 min ofrntaste-masked orally disintegrating tablets (ODTs). Accordingly, the various modelsrndescribing the relationship of the selected variables were obtained using Design-rnExpert 8.0.7.1 software and the models were analyzed. The corresponding surfacernresponse and contour plots were also obtained and the optimum area wasrndetermined and, finally, the optimum was validated.rnSimultaneous optimization of the responses gave the most desirable representativernoptimum formulation, within the common optimum region, with a disintegrationrntime of 31.95 sec., wetting time of 46.41 sec., hardness of 52.13 N, drug releasernwithin 5 min 62.21%,and drug release within 15 min of 90.03% at compressionrnforce 11.29 KN, SSG of 4.6%, MCC/ mannitol ratio of 1.6 :1 and polymer to drugrnratio of 1.26:1. The validity of obtained optimal point was confirmed by the lowrnmagnitude of percent prediction error.rnKey words: phenobarbitone, Orally disintegrating tablets, Eudragit®E100, Tastemasking,rndirect compression, Fractional factorial design

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