Development of fixed dose combination tablets containing zidovudine and lamivudine for paediatric applications

In view of the lack of suitable paediatric antiretroviral formulations on the market, a novel fixed dose combination (FDC) tablet containing 300 mg zidovudine (AZT) and 160 mg lamivudine (3TC) was developed to improve dosing accuracy and allow flexible drug dosing in function of the body weight of paediatric HIV patients as recommended by WHO.Rectangular tablets with multiple fraction bars were designed and each tablet can be broken into 8 subunits, each subunit containing a drug dose corresponding to a body weight of 5 kg. These fast-disintegrating subunits can easily be administered to children after dispersion in a liquid or mixing with food. In vitro quality control of the FDC tablets was determined and a crossover bioavailability study using 18 adult volunteers was performed after oral administration of the novel FDC tablet and a Duovir tablet.The results of the study showed that the novel tablets as well as its subunits disintegrated fast (<20 s). After 30 min dissolution, AZT and 3TC released from Duovir® and the novel tablets was above 95%, the similarity factors f2 were above 50 for both AZT and 3TC. A tablet breakability test showed low weight variability (125.1 ± 5 mg, R.S.D. = 4.4%), with limited weight loss (0.3%). There was no significant difference in pharmacokinetic parameters (Cmax, tmax and AUC0–12 h values) between Duovir and the novel tablets formulated for paediatric applications.