DRUG RELEASE FROM SOLID LIPID NANOPARTICLES
The release ofthe entrapped drug from the SLNs is governed by the following principles:
- • An inverse relationship exists between the release of the drug and the partition coefficient of the drug.
- • Smaller particle size promotes higher surface area, thereby leading to higher drug release.
- • Homogeneous dispersion of the drug in the lipid matrix causes slow release of the drug.
- • Lipid crystallinity and high drug mobility lead to rapid release of the drug from the SLNs .
Numerous studies have been carried out on the effect of formulation parameters and process conditions on the release of drug from SLNs. A crucial problem with SLNs is the initial burst release of drug. The burst release of drug from SLNs depends on the particle size and/or surface area. SLNs incorporated with tetracaine and etomidate demonstrated burst release with 100% release of the drug in less than 1 min (Fig. 12.2). This release pattern was attributed to the large surface area of nanoparticles and higher percentage
Solid Lipid Nanoparticles in Drug Delivery: Opportunities and Challenges 301
Figure 12.2 Drug release profile of etomidate from solid lipid nanoparticles (SLNs) and lipid microparticles of increasing particle size. (Reproduced with permission from zurMuhlen A, Schwarz C, Mehnert W. Solid lipid nanoparticles (SLN) for controlled drug delivery—drug release and release mechanism. Eur J Pharm Biopharm 1998;45:149-155.)
of drug in the outer layer of nanoparticles. The drug was found to be accumulated in the outer shell of nanoparticles with a relatively short distance of diffusion, which in turn resulted in a burst release. However, a prolonged drug release pattern was observed for lipid-soluble prednisolone-loaded SLNs. This could be explained with a “solid dispersion model” in which the drug is molecularly distributed into a lipid matrix. This study concluded that SLNs incorporated with lipophilic drugs follows prolonged release patterns . Thus the desired drug release can be fabricated by modulating the process parameters. The parameters that affect the release of drug from SLNs are temperature, amount of drug incorporated, lipid structure, and drug structure, duration of production, processing equipment, lyophilization process, and sterilization process . Among these, the two major parameters that influence the release of drug from the SLNs are temperature and presence of a surfactant.