Formulation and production of rapidly disintegrating tablets by lyophilisation using hydrochlorothiazide as a model drug

The influence of different formulation and process parameters on the characteristics of lyophilized oral dosage forms was investigated. Maltodextrins, gelatins, xanthan gum and hydroxyethylcellulose were evaluated as excipients in the formulation of freeze-dried tablets. The resulting tablets were analysed for mechanical strength, porosity, disintegration time and residual moisture. Scanning electron micrographs of the fracture plane of the tablets were taken. Additionally dissolution tests were performed on lyophilized tablets containing hydrochlorothiazide as a model drug. The concentration of the maltodextrins, used as the matrix forming agent, influenced the integrity and strength of the tablets. Increasing the maltodextrin concentrations resulted in stronger tablets. The concentration of the maltodextrins had also an influence on the pore size of the freeze-dried product. There was no influence of the DE value of the maltodextrin on the characteristics of the tablets. The disintegration time of the tablets was also affected by the maltodextrin concentration. The strength of the tablets depended on the xanthan gum concentration and the tablet dimensions. Compared to the formulations using xanthan gum as a binder in the same concentration, the disintegration time of the tablets containing hydroxyethylcellulose (HEC) was much shorter: 55 s for the xanthan gum formulations and 7 s for the HEC formulations. The in vivo disintegration time was significantly higher at 0.5% (w/v) HEC compared to 0.25% (w/v) (P<0.01). The in vivo disintegration time of the tablets containing hydrolysed gelatin Solugel® LB as a binder was below 23 s for the in vivo tests. Unlike the xanthan gum formulations, no gel-like structure was formed upon contact with the saliva. The strength of the tablets was enhanced by using higher maltodextrin concentrations. The incorporation of hydrochlorothiazide in the formulations induced a decrease in strength of the tablets. The percentage of HCT released within 10 min was 64.55±2.87% and 77.84±8.94% for the reference tablets and the lyophilized tablet formulation, respectively. The addition of PEG 6000 (1% w/v) resulted in an increase of drug release as 93.3% was released from the lyophilized tablets within 10 min. However, the incorporation of PEG 6000 in the formulation resulted in a decrease in the strength of the tablets.