INTRODUCTION

In current drug discovery, more than 75% of potential drug candidates have low water solubility and belong to classes II and IV of the Biopharmaceutical Classification System [1]. The development of these new chemical entities into commercial drug products is often hampered by the hydrophobic nature of the compounds, resulting in drug precipitation and low drug bioavailability [2]. Potential strategies to overcome such problems are structure modification of the drug or incorporation of the drug into a carrier system. The in vivo fate ofa drug depends on the drug delivery system in which it is incorporated [3]. Lipid-based formulations were first commercialized in the 1950s. Intralipid was introduced as a safe fat emulsion for parenteral nutrition, followed by Diazemuls, an injectable emulsion of diazepam. One possible reason for the popularity of lipid delivery systems is the reduced pain and inflammation at the site of injection [4]. A particular advantage offered by lipid colloidal carriers is the increase in bioavailability of poorly water-soluble drugs.

In recent years, lipid-based systems such as solid lipid nanoparticles (SLNs) have received increasing interest in drug formulation due to their ability to carry and solubilize lipophilic drugs. SLNs offer several advantages over other polymeric colloidal carrier systems. Table 12.1 summarizes the advantages and disadvantages of SLNs. SLNs have a mean diameter, as measured by photon correlation spectroscopy, ranging from 50 to 1000 nm. SLNs are formulated from emulsions that are used for parenteral administration by replacing the lipids in the liquid state with lipids in the solid state. SLNs are normally stabilized physically using surfactants. The major advantage that makes SLNs unique compared with polymeric nanoparticles is that they can be produced/manufactured using high-pressure homogenization (HPH) techniques used industrially for preparing emulsions. The emulsion production is generally equipped with temperature control units,

Table 12.1 Few advantages and disadvantages of solid lipid nanoparticles [88,152,153]

Advantages

Broad spectrum of route of administration Good physical stability

Protection from degradation of incorporated labile drugs Modulated (fast or sustained) release of the drug is possible Targeted drug delivery

No use of organic solvents during preparation Ease of scale-up Excellent biocompatibility No need of special solvents

Conventional emulsion production techniques could be employed Raw materials used in the production of emulsions could be used Can be sterilized by commercial sterilization methods

Disadvantages

Particle growth Gelation tendency Unexpected polymorphic transitions Thermal degradation of heat-labile drugs Sophisticated equipment

as elevated temperature sometimes favors emulsion production, which is equally applicable for producing SLNs by the hot homogenization technique [5]. This chapter provides an overview of various aspects of SLNs, stability problems associated with SLNs, and diagnostic applications of SLNs.

 
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