Optimization of a lyophilized fast-disintegrating tablet (LFDT) formulation containing naratriptan hydrochloride, an antimigraine drug, was the foremost objective of the study, aiming in achieving fast headache pain relief. The Design-Expert® v10 software was used to generate formulations using D-optimal mixture design with four components: gelatin (X1), hydrolyzed gelatin (X2), glycine (X3), and mannitol (X4) of total solid material (TSM) w/w. The effect of the relative proportion of each component was determined on friability (Y1), hardness (Y2), and in vitro disintegration time (Y3), which was then applied for formulation optimization. In addition, their effect on tablet porosity was determined via scanning electron microscopy (SEM). Drug-excipient interaction was evaluated using differential scanning calorimetry (DSC). A comparative dissolution study against the conventional tablets was studied. Accelerated stability study was carried out in (Al/Al) and (Al/PVC) blister packs. An in vivo pharmacokinetic study was carried out to compare the optimized formulation and the conventional tablets. The optimized formulation's responses were 0.30%, 3.4 kg, and 6.12 s for Y1, Y2, and Y3, respectively. No drug-excipient interaction was specified via DSC. The optimized formulation exhibited porous structure as determined via SEM. Dissolution study demonstrated complete dissolution within 1.5 min. Study indicated stability for 78 months in (Al/Al) blister packs. In vivo pharmacokinetic study demonstrated that Cmax, AUClast, and AUCinf were significantly higher for the developed formulation. As well, the Tmax was 1 h earlier than that of convenient tablet. An LFDT would achieve a faster onset of action for naratriptan compared to other formulations.
Keywords: fast-disintegrating tablet; lyophilized tablet; migraine; mixture design; naratriptan.