Understanding polymer-lipid solid dispersions--the properties of incorporated lipids govern the crystallisation behaviour of PEG.
A deeper insight into the crystallisation process of semi-crystalline polymers during formation of solid dispersions is crucial to improve control of product qualities in drug formulation. In this study we used PEG 4000 with 12 different lipids as a model system to study the effect that incorporated components may have on the crystallisation of the polymer. The lipids were melted with PEG 4000 and the crystallisation of the polymer studied with differential scanning calorimetry (DSC) and small angle X-ray diffraction (SAXD). PEG 4000 can crystallise into lamellar structures with either folded or fully extended polymer chains. All lipids increased the fraction of the folded form and lowered the crystallisation temperatures. Some lipids were incorporated to a high extent into the amorphous domains of the PEG lamellae and thereby swelling the structure, which also resulted in a high degree of chain folding. Partial least squares (PLS) modelling indicated that small hydrophilic lipids increased the folding of PEG and that large non-polar lipids retarded the unfolding during secondary crystallisation. This work shows that there is a large difference in the behaviour of PEG depending on lipid added. Differences are explained in terms of molecular properties for the lipids, demonstrated by the use of PLS modelling to describe the behaviour of PEG solid dispersions.
Unga
Johan
J
Department of Chemical and Biological Engineering, Chalmers University of Technology, Göteborg, Sweden.
Matsson
Pär
P
Mahlin
Denny
D
D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D018360:Crystallography, X-Ray; D004337:Drug Carriers; D016018:Least-Squares Analysis; D008055:Lipids / Q000737:chemistry*; D008956:Models, Chemical; D008968:Molecular Conformation; D011092:Polyethylene Glycols / Q000737:chemistry*; D025341:Principal Component Analysis; D013678:Technology, Pharmaceutical / Q000379:methods; D013696:Temperature
D004337:Drug Carriers; D008055:Lipids; D011092:Polyethylene Glycols