712 B. K. Nanjwade et al.: Tab. 1. Commonly used lipid vehicles for lipid-based formulations. Classification Fatty acids Ethyl esters Triglycerides of long-chain fatty acids Triglycerides of medium-chain fatty acids Lipophilic vehicles Oleic acid, Myristic acid, Caprylic acid, Capric acid Ethyl Oleate Soybean Oil, Peanut Oil, Corn Oil Miglyol® 812, Captex® 355, Labrafac® Crucial Issues during Development of Isotropic Lipid Solutions The physico-chemical properties of the API as well as the choice of lipids play a major role in designing isotropic solutions and will decide whether it will be a simple lipid solution, a SEDDS or a SMEDDS. Some of the physico-chemical parameters, which influence the design of isotropic solution, include: Solubility of API in the Lipid System Solubility is one of the major factors that limit the use of lipid-based delivery systems. The amount and the solubility of the drug in the lipid vehicle are decisive whether an isotropic lipid formulation is formed or not. Factors that can impact solubility include: Solubility Parameters The solubility characteristics are useful as a predictive tool for the selection of a solvent or solvents for a particular application. Solubility parameters give a systematic estimate for the compatibility between two components. As a rule of thumb two substances are miscible when their Hildebrand solubility parameters are close to each other or when the difference in their solubility parameters is less than 2 MPa1/2. Checking the Hildebrand solubility parameters is an effective way to predict the formulation characteristics of a particular compound. Hydrophilic-Lipophilic Balance (HLB) The HLB is an empirical formula that is used to characterize surfactants and to select those appropriate for preparation of microemulsions [23, 24]. Non-ionic and ionic surfactants are often considered for pharmaceutical applications because they are less toxic [26] and less affected by pH and ionic strength changes. The HLB value of each lipid vehicle is calculated according to: HLB = 20 1 – S A where S is the saponification number of the ester and A is the acid number of the fatty acid [27]. The higher the HLB value of the surfactant, the broader is the range to obtain micro- emulsions. Emulsifiers with HLB > 10, which are commonly used in isotropic lipid-based solutions, are summarized in table 2. Co-emulsifiers with HLB values ranging from 4 to 6, which are commonly used in isotropic lipid-based solutions, are given in table 3. Sci Pharm. 2011; 79: 705–727