A Comparative Evaluation of Mono-, Di- and Triglyceride of Medium Chain Fatty Acids by Lipid/Surfactant/Water Phase Diagram, Solubility Determination and Dispersion Testing for Application in Pharmaceutical Dosage Form Development

Abstract

PurposeTo compare physiochemical properties of mono-, di- and triglycerides of medium chain fatty acids for development of oral pharmaceutical dosage forms of poorly water-soluble drugs using phase diagrams, drug solubility, and drug dispersion experiments.MethodsPhase diagrams were prepared using a monoglyceride (glycerol monocaprylocaprate: Capmul MCM® EP), a diglyceride (glycerol dicaprylate) and two triglycerides (glycerol tricaprylate: Captex 8000®; caprylic/capric triglycerides: Captex 355 EP/NF®) in combination with a common surfactant (PEG-35 castor oil: Cremophor EL®) and water. Psuedoternary phase diagrams using mixtures of monoglyceride with either diglyceride or triglyceride were constructed to determine any potential advantage of using lipid mixtures.ResultThe monoglyceride gave microemulsion (clear or translucent liquid) and emulsion phases, whereas di- and triglycerides exhibited an additional gel phase. Among individual mono-, di- and triglycerides, the oil-in-water microemulsion region was the largest for the diglyceride. Gel phase region within diglyceride and triglyceride phase diagrams could be practically eliminated and microemulsion regions expanded by mixing monoglyceride with di- or tri-glycerides (1:1). Addition of a model drug, danazol, had no effect on particle sizes of microemulsions formed. Dispersion of drug in aqueous media from mixtures of mono- and diglyceride or mono- and triglyceride was superior to individual lipids.ConclusionSystematic study on comparison of mono-, di- and triglyceride of medium chain fatty acids will help formulators select components for optimal lipid-based formulation.

Prediction of Drug Solubility in Lipid Mixtures from the Individual Ingredients

“…It was recently noted that the simple weighted average equation worked well in estimating solubility of danazol in two and three component lipid mixtures using Cremophor EL and mono, di and triglyceride mixtures of caprylic/capric acid (15). Our research has demonstrated that this simple relation is broad in its application for acidic, basic and neutral drug molecules covering a wide range in physicochemical properties, and for the major lipids that are used in formulations.…”

Intestinal permeation enhancers for oral peptide delivery

“…In such complex dispersions, there is only a moderate intestinal permeation enhancement action of acyl glycerols compared to those of soluble surfactants (C 8 , or glyceride ethoxylates). The intestinal epithelial surface area exposed to acyl glycerols is increased by formulation in emulsified forms with soluble surfactants such as Cremophor®, demonstrating the positive interaction between the two types of surfactants [269].…”

In vivo treatment of Helicobacter pylori infection with liposomal linolenic acid reduces colonization and ameliorates inflammation

“…Such formulation minimizes chemical alterations on biological pathways but promotes physical-structural disruption of cell membrane, a mechanism previously reported to reduce the induction of bacterial drug resistance (13). For in vivo applications, this working mechanism is further ensured by a liposome formulation, in which the lipid bilayers protect LLA molecules from the damaging environment of the stomach and prevent potential oxidation and enzymatic degradation (12,13).…”

“…In particular, the amphiphilic properties of FFAs allow for direct incorporation into the lipid bilayer membrane of phospholipid liposomes with a high loading yield (12). The vast success of liposomes as an approved delivery vehicle bestows excellent opportunities on FFAs for translational testing and clinical use.…”