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

Abstract

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.

Formulation of Self-Nanoemulsifying Drug Delivery System of Cephalexin: Physiochemical Characterization and Antibacterial Evaluation

“…This could be due to surfactant and co-surfactant accessibility at the oil/water interface, which helped to reduce interfacial tension and contribute to system stability [16,18]. Similar findings have already been reported in literature [22,23]. The surfactant and co-surfactant together showed opposite effect, with globule size decreasing as the concentration increased.…”

“…The equilibrium solubility method was used to select the oil, surfactant, and cosurfactant [22]. The solubility of CEP in each components was evaluated in order to select the oil, surfactant, and co-surfactant.…”

“…The aqueous titration method was used for preparation of CEP-SNEDDS [22]. A total of seventeen formulations were developed as per the composition given in Table 2.…”

“…Self-emulsification time is the time required for the sample to become self-emulsified with distilled water. The self-emulsification process was visually evaluated for the emulsification property [22]. The study was performed with a USP paddle-type apparatus (Sotex AG, Aesch, Switzerland) to determine the emulsification time.…”

Reduced the Food Effect and Enhanced the Oral Bioavailability of Ivacaftor by Self-Nanoemulsifying Drug Delivery System (SNEDDS) Using a New Oil Phase

“…Selection of excipients such as oil, surfactant, and co-surfactant were conducted by saturation solubility and % transmittance study. 38 , 39 Saturation solubility studies were developed separately by adding 0.5 g IVA in 1.0 g various excipients, such as IPM, DHML, erucic acid, soybean oil, ethyl oleate, Capmul MCM, Capmul GMO (oil), Tween 80, Span 80, Labrasol and Kolliphor EL (surfactant), and PEG 400, glycerol, Transcutol HP (co-surfactants) in a glass vial and placed on a rotary shaker for mixing at 25 rpm for 24 h, at 37 ± 0.5℃. The samples were then taken out and centrifuged at 5000 rpm (RFC = 3435 g) for 10 min at room temperature.…”