Lecithin-Based Microemulsions for Pharmaceutical use - Phase behavior and Solution Structure

Research output: ThesisDoctoral Thesis (compilation)

Abstract

Microemulsions are thermodynamically stable, transparent solutions of water, oil and amphiphile(s). It is possible to incorporate large amounts of oil in microemulsions, which makes them interesting for use as a drug delivery vehicle for water insoluble drugs. A prerequisite for pharmaceutical use, however, is a low toxicity of the composition. The aim of this thesis has thus been to characterize microemulsion systems based on the pharmaceutically acceptable components lecithin (soybean phosphatidylcholine), medium-chain and long-chain triglycerides and isopropyl myristate (IPM). An analysis was made of the microstructure of these systems and their phase behavior determined. The effect of the addition of hydrophilic amphiphiles (the IPM system) and of two drug compounds, felodipine and BIBP3226 was also analyzed. Felodipine, being practically insoluble in water and slightly soluble in MCT, was found to act as a non-penetrating oil with only a slight influence (decrease) on the curvature of the amphiphilic film. BIBP3226, on the other hand, being practically insoluble in MCT but slightly soluble in the aqueous phase, had an affinity for the lecithin monolayer which significantly increased both the solubility and the spontaneous curvature of the film. At the point of saturation, approximately 60 percent of the drug molecules were located in the film.

A microemulsion system suitable for intravenous administration is presented. It is composed of a medium-chain triglyceride as the oil, soybean phosphatidylcholine and polyethylene glycol(660)-12-hydroxystearate as amphiphiles, and polyethylene glycol 400 and ethanol as cosolvents. The microstructure of this microemulsion was found to be of a bicontinuous nature, even at high oil concentrations. When diluted with water, the microemulsion spontaneously formed an oil-in-water emulsion with a mean droplet diameter between 60 and 200 nm depending on the oil content of the microemulsion. It was possible to administer up to 1.5 ml/kg of the microemulsion intravenously to conscious rats without causing any permanent changes in the hemodynamic parameters studied.

Details

Authors
  • Christian von Corswant
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Food Engineering

Keywords

  • Food and drink technology, felodipine, solubilization, drug delivery, self-diffusion NMR, alkylmaltoside, microstructure, isopropyl myristate, triglyceride, soybean phosphatidylcholine, Microemulsion, lecithin, Livsmedelsteknik
Original languageEnglish
QualificationDoctor
Awarding Institution
Supervisors/Assistant supervisor
  • [unknown], [unknown], Supervisor, External person
Award date1998 Nov 21
Publisher
  • Department of Food Technology, Lund University
Publication statusPublished - 1998
Publication categoryResearch

Bibliographic note

Defence details Date: 1998-11-21 Time: 13:15 Place: Lecture hall A, Center for Chemistry and Chemical Engineering, Lund External reviewer(s) Name: Strey, Reinhard Title: Prof Affiliation: Institut für Physikalische Chemie, Universität zu Köln, Köln, Germany --- Article: 1. Microemulsions Based on Soybean Phosphatidylcholine and Triglycerides. Phase Behavior and MicrostructureChristian von Corswant, Sven Engström and Olle SödermanLangmuir, 1997, 13, 5061-5070 Article: 2. Effect of Adding Isopropyl Myristate to Microemulsions Based on Soybean Phosphatidylcholine and TriglyceridesChristian von Corswant and Olle SödermanLangmuir, 1998, 14, 3506-3511 Article: 3. Microemulsions Based on Soybean Phosphatidylcholine and Isopropyl Myristate- Effect of Addition of Hydrophilic SurfactantsChristian von Corswant, Camilla Olsson and Olle SödermanLangmuir, submitted Article: 4. Solubilization of Sparingly Soluble Active Compounds in Lecithin-Based Microemulsions - Influence on Phase behavior and MicrostructureChristian von Corswant and Per E. G. ThorénLangmuir, submitted Article: 5. Triglyceride-Based Microemulsion for Intravenous Administration of Sparingly Soluble SubstancesChristian von Corswant, Peter Thorén and Sven EngströmJ. Pharm. Sci., 1998, 87, 200-208