The objective of this study is to develop a fixed dose combination orally disintegrating tablet (FDC ODT) containing dexamethasone (DEX) formulation with improved content uniformity and taste masking property and ondansetron HCl (OND) sustained release (SR) granule for once daily dosing. The DEX formulation were established by preparing PEG-based solid dispersion (SD) using hot melting method and then adding taste masking agents. The PEG 6000 was melted at 70℃ and then 4 mg drug was dispersed at different ratios (1:2, 1:3, 1:4, 1:8, 1:12), followed by cooling for 1 hour at a room temperature. The resulting SD powders were the milled and sieved. For further taste masking, SD and Eudragit EPO (1:0.5, 1:1, 1:2) were physically mixed. Then, content uniformity of the drug was determined by HPLC and in vitro taste masking efficiency was measured with an electronic tongue (E-Tongue). OND SR granules were manufactured by melt granulation method using lipophilic melt binders. The melt binder was melted at 80℃ and then 10 mg OND was added at different ratios (1:1, 1:2, 1:3), followed by cooling for 3 min at room temperature. The resulting products were passed through a 20-mesh sieve. In vitro dissolution rate of OND SR granules were investigated in the pH shifting condition for 24 hour. The compatibility study of OND and DEX was conducted at 40ºC/RH 75% for 14 days. After that, ODTs were prepared via direct compression after mixing DEX formulation, OND SR granule, various diluents, disintegrant and magnesium stearate (Mg-st). Changes in dissolution rate between before and after compression were checked by calculating f2 value and investigated in vitro disintegration time. The DEX formulation showed good content uniformity (Mean%: 96.9±1.08%, RSD: 1.11%) and good taste masking efficiency (distance to drug: 378±5.86). When the ratio of OND to Comptirol 888 ATO was 1: 3, OND SR granule was released below 50% for 2 hour in gastric condition and showed sustained release effect for 22 hour in intestinal condition. Compatibility of OND and DEX was good solid state compatibility in physical mixtures. The drug contents and physical appearance were almost unchanged during 14 days. When L-HPC was used as a cushioning agent, the change in drug release before and after compression was the smallest (f2=67.75) and the in vitro disintegration time for all formulations of ODT was between 22.17 and 304.83 s. As a result of Differential scanning calorimetry (DSC) and Powder X-ray diffraction (PXRD) measurements, the preparation process and presence of excipients in both of the two drug formulations did not interfere with the crystallinity of the drugs.
