EFFECT OF PHYSICOCHEMICAL PROPERTIES OF EMULSIONS FORMED BY SELF-EMULSIFYING DRUG DELIVERY SYSTEMS (SEDDS) ON THE SOLUBILIZATION STATE OF DRUG: IN VITRO STUDY
DOI:
https://doi.org/10.22159/ijap.2019v11i1.28664Keywords:
SEDDS, SMEDDS, Lipid formulations, Medium chain mono-and glycerides, Poorly water-soluble compoundsAbstract
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 dispersion
Conclusion: 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.
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