Factorial design, formulation, in vitro and in vivo evaluation of rapid orally disintegrating tablets prepared by sublimation technique using captopril as a model drug

A factorial design (23) was applied to the formulation of rapid orally disintegrating tablets, in order to investigate the feasibility of using superdisintegrant and sublimation technique on the onset of antihypertensive action of captopril. The three independent factors, superdisintegrant (Ac-di-sol) concentration (2.5% or 5%), subliming agent type (menthol or camphor) and its concentration (5% or 10%), were studied for their main effects on three dependent responses, tablet hardness, disintegration time and in vitro drug release. Statistical analysis of obtained data and optimization of formulation variables were carried out using Design-Expert® software, which selected formulation (F10), prepared with 5% Ac-di-sol and 10% camphor, that displayed suitable in range hardness (3.425 ± 0.12 Kilopond), least disintegration time (17.48 ± 1.36 Seconds) and highest in vitro drug release (99.51 ± 0.24% after 8 min), as the optimum formulation with the highest desirability (0.937). F10 was then chosen for drug-excipients interaction studies (DSC and FTIR), accelerated stability study at 40 °C and 75% RH for 3 months and in vivo evaluation against conventional captopril tablets, in hypertensive rats, using tail-cuff method. F10 showed no interaction between drug and excipients, chemical and physical stability and 15 min faster normalization of mean arterial pressure, of hypertensive rats, than conventional captopril tablets.