Premix Membrane Emulsification: Preparation and Stability of Medium-Chain Triglyceride Emulsions with Droplet Sizes below 100 nm.

Lara El-Hawari,Heike Bunjes

doi:10.3390/molecules26196029

Abstract

Premix membrane emulsification is a promising method for the production of colloidal oil-in-water emulsions as drug carrier systems for intravenous administration. The present study investigated the possibility of preparing medium-chain triglyceride emulsions with a mean particle size below 100 nm and a narrow particle size distribution using sucrose laurate as an emulsifier. To manufacture the emulsions, a coarse pre-emulsion was repeatedly extruded through alumina membranes (Anodisc™) of 200 nm, 100 nm and 20 nm nominal pore size. When Anodisc™ membranes with 20 nm pore size were employed, nanoemulsions with z-average diameters of about 50 nm to 90 nm and polydispersity indices smaller than 0.08 could be obtained. Particle growth due to Ostwald ripening was observed over 18 weeks of storage. The Ostwald ripening rate linearly depended on the emulsifier concentration and the concentration of free emulsifier, indicating that micelles in the aqueous phase accelerated the Ostwald ripening process. Long-term stability of the nanoemulsions could be achieved by using a minimised emulsifier concentration or by osmotic stabilisation with soybean oil added in a mass ratio of 1:1 to the lipid phase.

Highlights

Many newly developed drugs have a poor water solubility and need special formulations to be administered to patients
The present study addresses the question whether it is possible with premix membrane emulsification (PME) to obtain nanoemulsions with mean particle sizes smaller than 100 nm and narrow particle size distributions (polydispersity index (PDI) smaller than 0.1) with the perspective of parenteral use
The achievable particle size range for 200 nm, 100 nm and 20 nm pore size AnodiscTM membranes could be determined according to earlier approaches of our group [29]

Summary

Introduction

Many newly developed drugs have a poor water solubility and need special formulations to be administered to patients. Lipid nanoemulsions for parenteral use are commonly manufactured by high-pressure homogenisation. Premix membrane emulsification (PME) has been established as a promising alternative to produce these systems. In this procedure, a coarse preemulsion is repeatedly extruded through a nanoporous membrane, resulting in droplets with sizes in the nanometre range. Nanoemulsions can be produced at very small scales (e.g., 0.5 mL) with PME, which is a benefit in the development process of new formulations with highly potent or expensive drugs. High-pressure homogenisation may lead to particle sizes in the lower nanometre range but often yields rather broad particle size distributions [5,6]. Very narrow particle size distributions can be achieved with PME [7,8]

Methods

Results

Conclusion