Triglyceride-Based Microemulsion for Intravenous Administration of Sparingly Soluble Substances

Abstract

A pharmaceutically acceptable microemulsion system composed of a medium-chain triglyceride (MCT), soybean phosphatidylcholine and poly(ethylene glycol)(660)-12-hydroxystearate (12-HSA-EO15) as amphiphiles, and poly(ethylene glycol) 400 (PEG 400) and ethanol as cosolvents is presented and characterized in terms of phase behavior, microstructure, solubilization capacity and in vivo effects after intravenous administration to conscious rats. At a total concentration of 11.9 wt % of soybean phosphatidylcholine and 12-HSA-EO15, a microemulsion region was formed over a wide range of alpha, where alpha is the weight fraction of MCT/(MCT + water + PEG 400 + ethanol). The microstructure of the microemulsion was of a bicontinuous nature even at high oil concentrations. The mean droplet diameter of the oil-in-water emulsion formed after dilution of microemulsions prepared at different alpha within the one-phase region was between 60 and 200 nm. It was concluded that it is possible to administer up to 0.5 mL/kg of the microemulsion (alpha = 0.5) without producing any significant effect on acid-base balance, blood gases, plasma electrolytes, mean arterial blood pressure (MAP), heart rate (HR), and PQ time (the time between depolarization of atrium and chamber). At a dose of 1.5 mL/kg, a temporary increase in MAP, a decrease in HR, and a prolongation of the PQ time were observed.

Nanoemulsion Components Screening and Selection: a Technical Note

“…Recently, there has been a surge in the exploration of nanoemulsions for transdermal delivery (6)(7)(8). They are also being investigated ardently for potential applications in ocular (9,10), pulmonary (11), nasal (12,13), vaginal (14,15), and parenteral drug delivery (16)(17)(18).…”

A Recent Review on Nasal Microemulsion for Treatment of CNS Disorder

“…Post drug administration into the nasal cavity, a solute can be deposited at one or more of anatomically distinct regions, the vestibular, respiratory and olfactory regions. The human nasal cavity has a total volume of about 16 to 19 ml, and a total surface area of about 150 cm 2 23 and is divided into two nasal cavities via the septum. The volume of each cavity is approximately 7.5 ml, having a surface area around 75 cm 2 .…”

“…The main problem in a microemulsion application is a high concentration and a narrow range of physiologically acceptable surfactants and co-surfactants [23,24]. Large surfactant concentration (10-40%) determines their stability [25].…”

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“…The main problem in a microemulsion application is a high concentration and a narrow range of physiologically acceptable surfactants and co-surfactants 55,56 . Large surfactant concentration (10-40%) determines their stability 57 .…”