Development of Piperine-Loaded Solid Self-Nanoemulsifying Drug Delivery System: Optimization, In-Vitro, Ex-Vivo, and In-Vivo Evaluation

Hypertension is a cardiovascular disease that needs long-term medication. Oral delivery is the most common route for the administration of drugs. The present research is to develop piperine self-nanoemulsifying drug delivery system (PE-SNEDDS) using glyceryl monolinoleate (GML), poloxamer 188, and transcutol HP as oil, surfactant, and co-surfactant, respectively. The formulation was optimized by three-factor, three-level Box-Behnken design. PE-SNEDDs were characterized for globule size, emulsification time, stability, in-vitro release, and ex-vivo intestinal permeation study.

The optimized PE-SNEDDS (OF3) showed the globule size of 70.34 ± 3.27 nm, percentage transmittance of 99.02 ± 2.02%, and emulsification time of 53 ± 2 s Finally, the formulation OF3 was transformed into solid PE-SNEDDS (S-PE-SNEDDS) using avicel PH-101 as adsorbent. The reconstituted SOF3 showed a globule size of 73.56 ± 3.54 nm, PDI of 0.35 ± 0.03, and zeta potential of −28.12 ± 2.54 mV. SEM image exhibited the PE-SNEDDS completely adsorbed on avicel. Thermal analysis showed the drug was solubilized in oil, surfactant, and co-surfactant. S-PE-SNEDDS formulation showed a more significant (p < 0.05) release (97.87 ± 4.89% in 1 h) than pure PE (27.87 ± 2.65% in 1 h).

It also exhibited better antimicrobial activity against S. aureus and P. aeruginosa and antioxidant activity as compared to PE dispersion. The in vivo activity in rats exhibited better (p < 0.05) antihypertensive activity as well as 4.92-fold higher relative bioavailability than pure PE dispersion. Finally, from the results it can be concluded that S-PE-SNEDDS might be a better approach for the oral delivery to improve the absorption and therapeutic activity.

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Materials: Beijing Mesochem Technology Co. Pvt. Ltd. (Beijing, China) provided the Piperine (98.21% purity). Eucalyptus oil, Almond oil, Sunflower oil, and Ethyl oleate were procured from SD-fine chemicals (Mumbai, India). Labrafac WL, Caprol PGE-860, Capmul MCM, Labrafil M1944 CS, and Transcutol HP were procured from the Gattefosse Mumbai, India. Glyceryl monolinoleate (GML) Cremophor RH 40, Solutol HS 15, and Span 20 were obtained from the BASF India Ltd. (Bandra East, Mumbai, India). Polyethylene glycol-400 (PEG-400), PEG200, propylene glycol (PG), and hydrochloric acid were purchased from Acros organic (Mumbai, India). Poloxamer 188, poloxamer 127, and avicel PH101 were obtained from Sigma Aldrich (St Louis, MO, USA).

Article information: Zafar, A.; Imam, S.S.; Alruwaili, N.K.; Alsaidan, O.A.; Elkomy, M.H.; Ghoneim, M.M.; Alshehri, S.; Ali, A.M.A.; Alharbi, K.S.; Yasir, M.; Noorulla, K.M.; Alzarea, S.I.; Alanazi, A.S. Development of Piperine-Loaded Solid Self-Nanoemulsifying Drug Delivery System: Optimization, In-Vitro, Ex-Vivo, and In-Vivo Evaluation. Nanomaterials 2021, 11, 2920. https://doi.org/10.3390/nano11112920