Influence of the composition of glycerides on the solid-state behaviour and the dissolution profiles of solid lipid extrudates.
A monoacid triglyceride and a partial glyceride were extruded below their melting ranges alone and together in different mixture ratios to investigate the influence of the chemical composition of the lipid matrix on the solid-state properties and dissolution characteristics. The partial glyceride exhibits a faster release of the drug compared to the triglyceride due to its surfactant properties. The lipid mixtures show rather complex solid-state behaviour and hence unexpected dissolution characteristics. Adding 10% (w/w) partial glyceride to a triglyceride matrix led to increased incidence of the unstable alpha-form of the triglyceride leading to recrystallization of the stable beta-form over time which causes fractal structures on the extrudate surface which decrease the dissolution rate. Adding 50% (w/w) partial glyceride to the triglyceride matrix also results in tristearin alpha-formation subsequently followed by recrystallization to the beta-form. But as 50% of the matrix consists of the partial glyceride the dissolution rate was faster than the rate obtained by pure triglyceride or the 9+1 (w/w) mixture of triglyceride and partial glyceride. The results of this study help in understanding the complex solid-state behaviour of solid lipid extrudates with different composition and to manufacture suitable lipid-based oral dosage forms.
Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine-University Düsseldorf, Germany; Centre for Drug Research, Faculty of Pharmacy, University of Helsinki, Finland; Division of Pharmaceutical Technology, Faculty of Pharmacy, University of Helsinki, Finland.
Maike
M
Windbergs
Clare J
CJ
Strachan
Peter
P
Kleinebudde
D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D004339:Drug Compounding / Q000379:methods*; D004356:Drug Storage; D005989:Glycerides / Q000737:chemistry*; D006358:Hot Temperature; D008055:Lipids / Q000737:chemistry*; D033362:Powder Diffraction; D011208:Powders / Q000737:chemistry; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013499:Surface Properties; D013501:Surface-Active Agents / Q000737:chemistry; D013806:Theophylline / Q000737:chemistry; D044366:Transition Temperature; D014280:Triglycerides / Q000737:chemistry
D004337:Drug Carriers; D005989:Glycerides; D008055:Lipids; D011208:Powders; D013501:Surface-Active Agents; D014280:Triglycerides; C048159:glyceryl monostearate; D013806:Theophylline; C022618:tristearin