Potential SMEDDS formulations for the bioavailability enhancement of poorly water-soluble compounds were developed by mixing blends of {Miglyol 812/Imwitor 988} and Tagat TO as a non-ionic surfactant. 'Diffusion and stranding' appears to be the dominant mechanism of emulsification.

Objective: Parameters in the oil pre-concentrate which can affect the solvent capacity of the resultant dispersion such as, oil-cosurfactant ratio, type of surfactant used in the system, the inclusion of water soluble co-solvents and the solubilization capacity of native surfactants such as, bile salts and lecithin were studied in an attempt to circumvent crystallization of drug during its passage in the gut.Methods: Different types of self-emulsifying systems representing type II, IIIA and IIIB, were used to probe the influence of the various physicochemical properties of the resultant dispersions on the fate of dissolved model lipophilic drug. This was achieved by studying emulsification behavior of lipid systems in fed and fasted biological fluids, analyzing solubilization/drug crystallization kinetics and oil droplet diameter measurement.Results: Self-micro-emulsifying lipid systems lost solvent capacity on dispersion and were not able to keep the drug in solution at equilibrium. Miglyol 812/Imwitor ratio in the pre-concentrate mixture appeared to influence the kinetics of drug crystallization. Pre-microemulsion systems containing Tagat TO dispersions were found to hold more drugs in solution at equilibrium than in the case of systems containing Cremophor RH40. The inclusion of as little as 10-20% PEG in the lipid mixture accelerated drug precipitation. Bile salt-lecithin mixed micelles appears to some extent enhance the solubilization capacity of these systems after dispersionConclusion: Solvency of emulsions formed by self-emulsifying drug delivery in various emulsification media is a crucial parameter influencing the fate of dissolved drug after the dispersion of the formulations.

The field of SMEDDS is designed to enhance bioavailability of poorly-water soluble compounds. Yet, these systems have the capacity to solubilize aqueous-based materials within its lipid matrix as L2 phase (W/O microemulsion). This characteristic is utilized in this investigation to incorporate aqueous flavors within oil vehicle as an approach to mask bitter taste of drugs. Miscibility profiles and self-micro-emulsifying regions for various lipid composites were screened by constructing ternary phase diagrams using different types of oil, cosurfactant and surfactant. Solubility of bitter taste model drug was measured in various optimized vehicles. Dynamic equilibrium phase studies were performed and phase boundaries were determined for the lipid-aqueous flavors-water systems. Self-micro-emulsifying system comprising Crodamol GTCC/ Glycerox 767HC /Croduret 40 ss at ratios of {0/80/20}, {6/54/40} or {10/40/50} have shown capacity to solubilize, aqueous-based materials including; strawberry flavor, sucrose and citric acid as L2 phase. Phase behavior study has revealed that clear dispersions can be obtained at all dilutions with water. Potential flavored self-microemulsifying lipid formulations representing type III lipid class system were developed. Aqueous flavors loaded into these vehicles can be used to mask bitter tastes in oral pharmaceuticals.

Objective: There are many successful products on the market which are the culmination of the self-micro-emulsification lipid technology applications. Despite the importance of lipid-based formulations, these systems have some limitations including; stability, complexity during large scale manufacturing process and limited dosage forms to such as soft gelatin capsule. In order to overcome these limitations, the prospect of converting self-micro-emulsifying drug delivery systems (SMEDDS) into tablet dosage form was investigated in this study. Methods:A self-micro-emulsifying oil formulation representing type III A lipid class composed of glycerox 767HC/croduret 40 ss at ratios of (80/20) was converted into solid SMEDDS using solid carrier adsorption method. Powder blends containing magnesium trisilicate hydrate (MTSH) or magnesium lluminum silicate (MAS) at various oil loading factors were mixed with MCC with and without various binders and compressed into tablets using a fixed loading force of approximately of 5 KN. Hardness profiles of these oil loaded tablets were then analyzed. Results:Powder compacts which contained MTSH with and without SMEDDS oil had shown relatively better compaction properties than MAS. Adding SMEDDS oil solution to either MTSH or MAS at ratios of 1:9 has relatively reduced tablets hardness by almost 2 or 4 folds, respectively. Conclusion:Progressive inclusion of increasing amounts of SMEDDS oil solution adsorbed unto the solid carrier has incurred a further reduction in the hardness of SMEDDS tablets. It appears that manufacturing of tablet SMEDDS can only be attainable for highly potent drugs as minimal amounts of oil solution added to the powder blends can adversely affect the mechanical strength of compressed tablet.

Objective: Evaluation of the self-emulsifying behaviour of type III lipid systems comprising mixed medium chain glycerides (Miglyol 812-Imwitor 988) and wide range of hydrophilic surfactants in an attempt to identify self-emulsifying microemulsion formulations, prevaricate the crystallization tendency of Cremophor RH40 in the pre-microemulsion concentrate, to shed some light on the mechanistic behavior of these systems after aqueous dispersion. Methods: Non-ionic surfactants with HLB in the range 14 to 16.5 are investigated amongst these are; Cremophor RH40, Cremophor EL, Crillet 4 (polysorbate 80), Crillet 1 (polysorbate 20) and Tagat O2. Optimum oil blends of Miglyol 812-Imwitor 988 and various non-ionic surfactant systems were verified using self-emulsification performance studies, oil droplet diameter measurements and dynamic equilibrium phase studies. Results: Oil blends of Miglyol 812 as an oil and Imwitor 988 as a cosurfactant were optimized for microemulsion systems at ratios of 1:1 in the case of Cremophor RH40 or EL, and at 2:3 in the case of Crillet 4 or Tagat O2. In order to obtain small droplet size and fast dispersion rate for type III lipid systems, hydrophilic surfactants with HLB values between 13 and 15 were found to be the optimum. Conclusion: Spontaneous micro-emulsification in type III lipid system was attributed to the “diffusion and stranding” theory. Yet, the formation of liquid crystalline phases as intermediate phases during dilution of the oil formulation with water appears to be quintessential for the mechanistics of emulsification regardless type of lipid class system.