PHYSICOCHEMICAL CHARACTERIZATION OF LIPID NANOPARTICLES AND EVALUATION OF THEIR DRUG LOADING CAPACITY AND SUSTAINED-RELEASE POTENTIAL

Drug carrier systems based on lipid nanosuspensions prepared by melt e mulsification present a number of severe stability problems such as a high gelation tendency, considerable particle growth and drug expulsio n. Destabilization of the emulsified lipidic carriers is related to re crystallization of the lipids. The choice of stabilizers for colloidal lipid suspensions is, therefore, restricted. Systematic surface modif ications are thus limited. In addition, the drug payload of crystallin e nanosuspension particles is generally low. Improved stability and lo ading capacities were found for amorphous lipid nanoparticles which pr esent the characteristic signals of supercooled melts in high resoluti on LH-NMR. The NMR data indicate that such liquid but viscous carriers can, however, not immobilize the incorporated drug molecules to the s ame extent as a solid matrix. Sustained release over days or weeks as in slowly biodegraded solid matrices thus seems difficult to achieve w ith a supercooled melt. Attempts to combine the advantages of the soli d crystalline lipids and the amorphous nature of the supercooled melts by generating solid but amorphous lipid suspension particles with a s atisfactory long-term stability by a Variation of the lipid matrix mat erial have hitherto not been successful. Even a satisfactory stabiliza tion of the alpha i-modification using complex lipid mixtures to impro ve the loading capacity or to slow down the drug expulsion process cou ld not be achieved. The rates of the polymorphic transitions were much higher in the colloidal lipid dispersions than in the bulk for the ha rd fats under investigation. Despite the fact that the properties of t he lipids are superimposed with colloidal properties, significant diff erences between monoacid triglycerides and complex lipids were, howeve r, found. (C) 1997 Elsevier Science B.V.