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
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 30 min (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 30 mg of CH, 50 mg of CAP, 149.75 mg of TW 20, 55 mg of TRP and 260.75 mg of Neusilin US2. It showed an average Q30 of 97.6%, ET of 23.3 min, GS of 89.5 nm 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.
KEY WORDSfactor mode effect analysis Taguchi screening design Box-Behnken design pharmacokinetic study bioavailability enhancement
The authors are thankful to Matrix Pharma India for providing the gift sample of Cinacalcet hydrochloride. M/s Gattefosse Pvt. Ltd. India, M/s BASF GmbH, Minden, Germany, Abitec Pvt. Ltd. USA and Gangwal Chemicals Pvt. Ltd. India are gratefully acknowledged for providing the essential excipients for the research work. The authors are grateful to Stat-Ease, Minneapolis, MN for the design expert ver. 11.1.01 software. The authors would also like to acknowledge BIT, Mesra, India for providing the facility of XRD and SEM. The authors are thankful to the Institute of Life Science, Bhubaneswar, India for the facility of Zetasizer.
Compliance with Ethical Standards
Declaration of Interest
The authors declare that they have no conflict of interest.
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