Application of mixture experimental design to simvastatin apparent solubility predictions in the microemulsifion formed by self-microemulsifying.
Self-microemulsifying drug delivery systems (SMEDDS) are useful to improve the bioavailability of poorly water-soluble drugs by increasing their apparent solubility through solubilization. However, very few studies, to date, have systematically examined the level of drug apparent solubility in o/w microemulsion formed by self-microemulsifying. In this study, a mixture experimental design was used to simulate the influence of the compositions on simvastatin apparent solubility quantitatively through an empirical model. The reduced cubic polynomial equation successfully modeled the evolution of simvastatin apparent solubility. The results were presented using an analysis of response surface showing a scale of possible simvastatin apparent solubility between 0.0024 ~ 29.0 mg/mL. Moreover, this technique showed that simvastatin apparent solubility was mainly influenced by microemulsion concentration and, suggested that the drug would precipitate in the gastrointestinal tract due to dilution by gastrointestinal fluids. Furthermore, the model would help us design the formulation to maximize the drug apparent solubility and avoid precipitation of the drug.
Meng
Jian
J
Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, Liaoning, PR China.
Zheng
Liangyuan
L
D000284:Administration, Oral; D001682:Biological Availability; D011232:Chemical Precipitation; D002626:Chemistry, Pharmaceutical; D004304:Dosage Forms; D004655:Emulsions; D005750:Gastric Juice / Q000378:metabolism; D005990:Glycerol / Q000031:analogs & derivatives / Q000737:chemistry; D000960:Hypolipidemic Agents / Q000737:chemistry*; D007848:Laurates / Q000737:chemistry; D008962:Models, Theoretical; D011409:Propylene Glycols / Q000737:chemistry; D019821:Simvastatin / Q000737:chemistry*; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry*; D014280:Triglycerides / Q000737:chemistry
D004304:Dosage Forms; D004655:Emulsions; D000960:Hypolipidemic Agents; D007848:Laurates; D011409:Propylene Glycols; D013501:Surface-Active Agents; D014280:Triglycerides; C098387:propyleneglycol monolaurate; C000515:cremophor EL; D019821:Simvastatin; D005990:Glycerol