FORMULATION AND PRODUCTION OF RAPIDLY DISINTEGRATING TABLETS BY LYOPHILIZATION USING HYDROCHLOROTHIAZIDE AS A MODEL-DRUG

The influence of different formulation and process parameters on the c haracteristics of lyophilized oral dosage forms was investigated. Malt odextrins, gelatins, xanthan gum and hydroxyethylcellulose were evalua ted as excipients in the formulation of freeze-dried tablets. The resu lting tablets were analysed for mechanical strength, porosity, disinte gration time and residual moisture. Scanning electron micrographs of t he fracture plane of the tablets were taken. Additionally dissolution tests were performed on lyophilized tablets containing hydrochlorothia zide 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 stron ger tablets. The concentration of the maltodextrins had also an influe nce on the pore size of the freeze-dried product. There was no influen ce of the DE value of the maltodextrin on the characteristics of the t ablets. The disintegration time of the tablets was also affected by th e maltodextrin concentration. The strength of the tablets depended on the xanthan gum concentration and the tablet dimensions. Compared to t he formulations using xanthan gum as a binder in the same concentratio n, the disintegration time of the tablets containing hydroxyethylcellu lose (HEC) was much shorter: 55 s for the xanthan gum formulations and 7 s for the HEC formulations. The in vivo disintegration time was sig nificantly 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(R) LB as a binder was below 23 s for the in vivo test s. Unlike the xanthan gum formulations, no gel-like structure was form ed upon contact with the saliva. The strength of the tablets was enhan ced 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 64.5 5 +/- 2.87% and 77.84 +/- 8.94% for the reference tablets and the lyop hilized tablet formulation, respectively. The addition of PEG 6000 (1% w/v) resulted in an increase of drug release as 93.3% was released fr om the lyophilized tablets within 10 min. However, the incorporation o f PEG 6000 in the formulation resulted in a decrease in the strength o f the tablets. (C) 1997 Elsevier Science B.V.