Enhanced microemulsion formation in lipid-based drug delivery systems by combining mono-esters of medium-chain fatty acids with di- or tri-esters

  • Abu T. M. Serajuddin Professor

Abstract

To develop strategies for selecting appropriate lipids from mono-, di- and tri-esters of medium-chain fatty acids for the development of lipid-based drug delivery systems, ternary phase diagrams of propylene glycol (PG) monocaprylate (Capryol 90; HLB~7), PG dicaprylocaprate (Labrafac PG; HLB~2) and glycerol tricaprylocaprate (Labrafac Lipophile WL1349; HLB~2) were determined using a common surfactant, PEG-35 castor oil (Cremophor EL; HLB~13), and water. Particle size and viscosity in different regions of phase diagrams were measured, solubility of a model drug, danazol, in different lipid-surfactant mixtures was determined, and dispersion testing by diluting selected preconcentrates with 0.01NHCl was performed. Further, phase diagrams were constructed using binary mixtures of lipids (mono ester with diester, or monoester with triester) in place of single lipids. Phase diagrams of PG dicaprylocaprate and glycerol tricaprylocaprate were similar, while it was distinctly different for PG monocaprylate, indicating that the polarity of lipids rather than degree of esterification was the determining factor for structures of phase diagrams. The microemulsion regions in phase diagrams were rather limited for individual lipids. Additionally, di- and tri- esters showed pronounced gel regions in phase diagrams, which can influence drug release from preconcentrates. The mixing of PG monocaprylate (monoester) with PG dicaprylocaprate (diester) or glycerol tricaprylocaprate (triester) had dramatic effects on the performance of lipids as evident from greatly reduced gel phases, much bigger microemulsion regions, faster dispersion of preconcentrates in an aqueous medium, and lower particle size of microemulsions formed.

Author Biography

Abu T. M. Serajuddin, Professor
Abu Serajuddin, Ph.D., is a Professor of Industrial Pharmacy at St. Johns University, Queens, New York, USA. At St. Johns, he is building active research programs and centers of excellence in drug delivery sciences and pharmaceutical processing technologies. One focus of his research is identification and characterization of polymeric and lipidic carriers for developing bioavailable oral dosage forms of poorly water-soluble drugs. Prior to joining academia in September 2008, he worked in the pharmaceutical industry for three decades with increasing scientific and managerial responsibilities at Sanofi-Aventis (through mergers), Bristol-Myers Squibb and Novartis. In his latest positions in the industry, Dr. Serajuddin served as Executive Director and the US Head of Drug Product Development (1999-2003) and the Global Head of Science and Technology Development (2003-2008) for Novartis Pharmaceuticals Corp. In recognition of his extraordinary scientific achievements, he was named a Novartis Leading Scientist in 2005. He contributed extensively to basic pharmaceutics and drug delivery systems. He authored over 75 research papers and book chapters and made 80 invited presentations in major scientific conferences (US, France and China). He is a co-inventor in 14 patents, the majority of the patents being on drug delivery technology platforms. Among his professional recognitions, he attained Fellow status in American Association of Pharmaceutical Scientists (AAPS), American Pharmacists Association (APhA), International Union of Pure and Applied Chemistry (IUPAC), and American Association of Indian Pharmaceutical Scientists (AAiPS). He serves in the Editorial Advisory Board s of Journal of Pharmaceutical Sciences and Journal of Excipients and Food Chemicals. Among his many professional contributions, he chaired AAPS Pharmaceutics and Drug Delivery Section (2001) and AAPS Preformulation Focus Group (1994-1996). A graduate in pharmacy from Dhaka University, Bangladesh, Serajuddin received his Ph.D. in Industrial Pharmacy from St. John's University, New York, M.S. in Pharmaceutics from Columbia University, New York, and Advanced Training in Industrial Pharmacy from the University of Pisa, Italy.
Published
2012-06-20
How to Cite
SERAJUDDIN, Abu T. M.. Enhanced microemulsion formation in lipid-based drug delivery systems by combining mono-esters of medium-chain fatty acids with di- or tri-esters. Journal of Excipients and Food Chemicals, [S.l.], v. 3, n. 2, p. 29-44, june 2012. ISSN 21502668. Available at: <https://ojs.abo.fi/ojs/index.php/jefc/article/view/138>. Date accessed: 28 oct. 2021.
Section
Original Research Articles

Keywords

Lipid-based drug delivery; medium chain lipid; propylene glycol ester; triglyceride; phase diagram; drug solubility; dispersion test