Spontaneous Emulsification of Nifedipine-Loaded Self-Nanoemulsifying Drug Delivery System

Abstract

ABSTRACT. Self-nanoemulsifying drug delivery system (SNEDDS) can be used to improve dissolution of poorly water-soluble drugs. The objective of this study was to prepare SNEDDS by using ternary phase diagram and investigate their spontaneous emulsifying property, dissolution of nifedipine (NDP), as well as the pharmacokinetic profile of selected SNEDDS formulation. The results showed that the composition of the SNEDDS was a great importance for the spontaneous emulsification. Based on ternary phase diagram, the region giving the SNEDDS with emulsion droplet size of less than 300 nm after diluting in aqueous medium was selected for further formulation. The small-angle X-ray scattering curves showed no sharp peak after dilution at different percentages of water, suggesting non-ordered structure. The system was found to be robust in different dilution volumes; the droplet size was in nanometer range. In vitro dissolution study showed remarkable increase in dissolution of NDP from SNEDDS formulations compared with NDP powders. The pharmacokinetic study of selected SNEDDS formulation in male Wistar rats revealed the improved maximum concentration and area under the curve. Our results proposed that the developed SNEDDS formations could be promising to improve the dissolution and oral bioavailability of NDP.

Cytochromes P450 Inhibitory Excipient-Based Self-Microemulsions for the Improved Bioavailability of Protopanaxatriol and Protopanaxadiol: Preparation and Evaluation

“…Previously, an SME of PPD resulted in an increase of bioavailability by 3-fold [16]. The underlying mechanisms were attributable to the facilitation of lymphatic transport and the improvement in intestinal absorption, as documented previously [16,[26][27][28]. In the present study, both SME-1 and SME-2 could increase the bioavailability of PPT and PPD, but SME-1 resulted in significantly higher increases than SME-2.…”

A Liposomal Formulation for Improving Solubility and Oral Bioavailability of Nifedipine

“…Although oral administration is the best convenient route and has better patient compliance, bioavailability of nifedipine has been limited by poor solubility, photo-instability, or short plasma half-life [1]. Nifedipine is a BCS class II agent with a solubility of 5-6 µg/mL in the pH range from 4 to 13 [2], resulting in low bioavailability [3]. Improving solubility and membrane permeability could lead to enhance of oral bioavailability [4].…”

Simultaneous LC‐MS/MS bioanalysis of etoposide and paclitaxel in mouse tissues and plasma after oral administration of self‐microemulsifying drug‐delivery systems

“…The results showed that ETP/PTX-loaded SMEDDS significantly enhanced the bioavailability compared with suspension formulation. In addition to P-gp and CYP3A inhibition, the other possible reasons for increased bioavailability may include: (a) SMEDDS maintained the drug in a solubilized state in the gastrointestinal tract and thus improved the oral bioavailability of poorly water-soluble drugs (Wu, Wang, et al, 2006); (b) the increased surface area of small droplets contributed to a significant increase in drug absorption (Shahnaz, Hartl, et al, 2011;Zhao, Huang, et al, 2013); and (c) droplets with a diameter size of <50 nm in SMEDDS dispersed rapidly in blood and lymph (Amri, Le Clanche, et al, 2014), and lymphatic transport can bypass the first-pass effect (Weerapo, Limmatvapira, et al, 2015). The tissue distribution results of ETP and PTX are presented in Figure 3.…”