Polymorphic behaviour of Compritol888 ATO as bulk lipid and as SLN and NLC.
CompritolR888 ATO (glycerol behenate) is widely used as a pharmaceutical excipient in the field of solid dosage forms due to its lubricating properties. It is an amphiphilic material with a high melting point (approximately 70 degrees C) and, therefore, it can also be used to prepare aqueous colloidal dispersions. The aim of this paper is to study the suitability of CompritolR888 ATO for the production of solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) for the entrapment of a lipophilic model drug. This study assesses the crystalline structure of the bulk lipid, as well as the changes that occur in its crystal lattice with the addition of 'impurities', such as oil (alpha-tocopherol) and drug (ketoconazole), using DSC and X-ray diffraction analysis before and after thermal stress. Aqueous SLN and NLC dispersions were produced using an appropriate surfactant/co-surfactant system and their physicochemical stability was assessed by PCS, LD, DSC and by WAXS. It was found that the crystalline lattice of CompritolR888 ATO is composed of very small amounts of the unstable alpha polymorphic form characteristic of triacylglycerols, which disappears after thermal stress of bulk lipid. Mixing oils and drug molecules which are soluble in this lipid decreased its lattice organization and, thus, was revealed to be suitable for production of lipid nanoparticles containing ketoconazole. However, particle growth could not be avoided during shelf life.
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Department of Pharmaceutics, Biopharmaceutics and Biotechnology, Free University of Berlin, Berlin, Germany.
Mehnert
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W
Müller
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RH
D002152:Calorimetry, Differential Scanning; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D005227:Fatty Acids / Q000737:chemistry*; D007654:Ketoconazole / Q000737:chemistry; D008055:Lipids / Q000737:chemistry; D053758:Nanoparticles; D049329:Nanostructures; D014961:X-Ray Diffraction
D005079:Excipients; D005227:Fatty Acids; D008055:Lipids; C086409:glyceryl behenate; D007654:Ketoconazole