FORMULATION OF A LYOPHILIZED DRY EMULSION TABLET FOR THE DELIVERY OF POORLY SOLUBLE DRUGS

The objective was to develop a dry emulsion tablet for the flash deliv ery of poorly water soluble drugs using a lyophilization technique. Th e influence of formulation parameters on the characteristics of the ly ophilized dry emulsion (LDE) tablets was investigated. Oil-in-water em ulsions were made using a medium chain triglyceride as the oil phase a nd a maltodextrin solution (5-20% w/v) as the water phase. In addition different emulsifier-tablet binder combinations were evaluated. The e mulsions were filled into PVC blisters and freeze-dried. The resulting tablets were analyzed for strength, disintegration time, porosity and residual moisture. X-ray diffractions and scanning electron micrograp hs (SEM) of the fracture plane of the tablets were taken. Dissolution tests were performed on lyophilized tablets containing hydrochlorothia zide (HCT) as a model drug. A significant influence of the maltodextri n type on the tablet disintegration time was seen. Maltodextrin formul ations with a high dextrose equivalent (DE) value (DE38) resulted in a faster disintegration time compared to DE12 and DE24 maltodextrin for mulations (p < 0.05). There was a significant influence of maltodextri n concentration on tablet strength, disintegration time and porosity. Tablet strength increased significantly with increasing maltodextrin c oncentration (p < 0.05). The porosity of the tablets made with DE38 5% , 10% and 20% (w/v) was 92%, 85% and 81%, respectively. SEM pictures s howed an increase in pore diameter with a decreasing maltodextrin conc entration. No significant influence of Miglyol 812 concentration on ta blet strength was observed. A significant influence of methylcellulose concentration, used as emulsifier-tablet binder (Methocel(R) E15LV), on tablet strength and disintegration time was observed. Dissolution t ests on 25 mg HCT containing tablets resulted in a % HCT release of 35 .1% and 24.1% for the LDE tablet and conventional tablet, respectively . No significant influence of the oil content in the LDE tablets on th e HCT release was observed. It can be concluded that maltodextrins and methylcellulose are useful excipients in the formulation of LDE table ts. The concentration of maltodextrin, the medium chain triglyceride a nd methylcellulose influenced the tablet characteristics. (C) 1998 Els evier Science B.V. All rights reserved.