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 delivery of poorly water soluble drugs using a lyophilization technique. The influence of formulation parameters on the characteristics of the lyophilized dry emulsion (LDE) tablets was investigated. Oil-in-water emulsions were made using a medium chain triglyceride as the oil phase and a maltodextrin solution (5-20% w/v) as the water phase. In addition different emulsifier-tablet binder combinations were evaluated. The emulsions 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 micrographs (SEM) of the fracture plane of the tablets were taken. Dissolution tests were performed on lyophilized tablets containing hydrochlorothiazide (HCT) as a model drug. A significant influence of the maltodextrin type on the tablet disintegration time was seen. Maltodextrin formulations with a high dextrose equivalent (DE) value (DE38) resulted in a faster disintegration time compared to DE12 and DE24 maltodextrin formulations (p < 0.05). There was a significant influence of maltodextrin concentration on tablet strength, disintegration time and porosity. Tablet strength increased significantly with increasing maltodextrin concentration (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 showed an increase in pore diameter with a decreasing maltodextrin concentration. No significant influence of Miglyol 812 concentration on tablet 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 tests 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 the HCT release was observed. It can be concluded that maltodextrins and methylcellulose are useful excipients in the formulation of LDE tablets. The concentration of maltodextrin, the medium chain triglyceride and methylcellulose influenced the tablet characteristics. (C) 1998 Elsevier Science B.V. All rights reserved.