Abstract The objective of the study was to evaluate the pharmacokinetic parameters and relative bioavailability of freeze-dried rapidly disintegrating tablets (formulation A) and lyophilized emulsion tablets (formulation B) containing 25 mg hydrochlorothiazide as a model drug. The tablets were produced by freeze-drying an o/w emulsion containing Miglyol 812, maltodextrin and Methocel A15LV or a suspension containing maltodextrin, PEG6000 and xanthan gum in blisters. Dissolution tests were performed on the tablets using a USP XXII paddle method. A content uniformity test was done on the tablets using an HPLC method. Eight healthy volunteers participated in the bioavailability study. Each volunteer received in a randomized cross-over design, 25 mg HCT on three occasions. Serum samples were analysed on HCT concentration using a validated HPLC method. The C max and T max values were determined from the individual serum concentration–time profiles, while the AUC 0–24h and T 1/2 were calculated using a software package. Both the lyophilized dry emulsion tablet and the conventional tablet showed similar release profiles, while the formulation of a freeze-dried rapidly disintegrating tablet containing 6 mg PEG 6000 resulted in an increase in HCT in vitro release rate. The calculated AUC 0–24h values were significantly different between the three formulations: the freeze-dried rapidly disintegrating tablet containing 6 mg PEG 6000 showed a significantly higher AUC 0–24h in comparison with the other formulations. The C max value of the formulation A was higher compared to the other, although not significantly. The T max values for the freeze-dried formulations were lower compared to the conventional tablet, although not significantly. The serum half life ( T 1/2( β)) ranged from 2.1 to 10.5 h for the three formulations. From these results it can be concluded that freeze-dried tablets containing maltodextrin, xanthan gum and PEG 6000 yielded a higher hydrochlorothiazide bioavailability compared to a conventional tablet.