Quality by Design Enabled Development of Oral Self-Nanoemulsifying Drug Delivery System of a Novel Calcimimetic Cinacalcet HCl Using a Porous Carrier: In Vitro and In Vivo Characterisation.

Abstract

In this present research, work quality by design-enabled development of cinacalcet HCl (CH)-loaded solid self-nanoemulsifying drug delivery system (S-SNEDDS) was conducted using a porous carrier in order to achieve immediate drug release and better oral bioavailability. Capmul MCM (CAP), Tween 20 (TW 20) and Transcutol P (TRP) were selected as excipients. Cumulative % drug release at 30min (Q30), emulsification times (ET), mean globule size (GS) and polydispersity index (PDI) were identified as critical quality attributes (CQAs). Factor mode effect analysis (FMEA) and Taguchi screening design were applied for screening of factors. The optimised single dose of S-SNEDDS obtained using Box-Behnken design (BBD) consisted of 30mg of CH, 50mg of CAP, 149.75mg of TW 20, 55mg of TRP and 260.75mg of Neusilin US2. It showed an average Q30 of 97.6%, ET of 23.3min, GS of 89.5nm and PDI of 0.211. DSC, XRD and SEM predict the amorphous form of S-SNEDDS. In vivo pharmacokinetic study revealed better pharmacokinetic parameters of S-SNEDDS. The above study concluded that the optimised S-SNEDDS is effective to achieve the desired objective. Graphical Abstract.