EMULSIFIER CONCENTRATION (%)
Figure 4 Effect of concentrations of emulsifier, Labrafac CM 10 BM 287, on partition coefficient (□) droplet size (o), and the release rate (V) of Ro 15-0778 from peanut oil based solution.
followed by emulsification by endogenous bile acids, leading to the creation of complex micellar species, which are intimately related to drug absorption. In general, lipids that are nondigestible, should be avoided due to the poor drug absorption typically associated with these excipients. In addition, the fatty acid chain length of glyceride excipients controls the rate of lipolysis and consequently, drug absorption. Glyceride excipients comprised of long chain fatty acids are lipolysed relatively slowly, whereas lipolysis of medium chain glycerides occurs more readily, which can be associated with more rapid and complete drug absorption (31). In addition, the surfactant component of a formulation can adversely affect the digestion process by sterically hindering the attachment of lipase enzymes at the oil-water interface, resulting in sub-optimal drug release (9,31). Given these limitation, lipid excipients that don't rely on preabsorptive lipolysis as a prerequisite to drug release (e.g., medium chain monoglycerides, fatty acids, and monoesters of fatty acids) are often preferred for lipid-based oral formulations.
Drug loading can influence both the physical characteristics and long-term physical stability of a lipid-based formulation. Thus, it is important to determine the saturation solubility of the drug in the chosen formulation. A plot of formulation viscosity as a function of drug concentration (Fig. 5) can be used to establish the approximate saturation solubility, which occurs in the region above the inflection point of the plotted data (32). Excessive drug loading in a lipid solution can result in gelling or drug crystallization under shear conditions or during storage, as well as drastic changes in the formulation dispersibility, which is associated with an
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