Understanding polymer-lipid solid dispersions-The properties of incorporated lipids govern the crystallisation behaviour of PEG
Journal article, 2010
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. (C) 2009 Elsevier B.V. All rights reserved.
Stability
Partial least
polyethylene-glycol
system
dry
Polyethylene glycol
poly(ethylene glycol)
Solid state
squares projection to latent structures
Principal component analysis
Multivariate data analysis
drug-release
molecular-weight
Solid dispersions
water
state characterization
oral delivery
emulsion
pharmaceutical applications
Lipids
Author
Johan Unga
Chalmers, Chemical and Biological Engineering
P. Matsson
Uppsala University
D. Mahlin
Uppsala University
International Journal of Pharmaceutics
0378-5173 (ISSN) 1873-3476 (eISSN)
Vol. 386 1-2 61-70Subject Categories
Pharmacology and Toxicology
DOI
10.1016/j.ijpharm.2009.10.049