Objective: The aim of this study was to develop a new dosage form as an alternative to the
classical tablet forms of atorvastatin calcium (AtrCa). The formulation strategy was to prepare an optimum
self micro emulsifying drug delivery system (SMEDDS) to overcome the problem of low solubility
of the active substance.
Methods: In this study, pseudo ternary phase diagrams were plotted determined by the solubility studies.
According to the solubility studies; oleic acid was used as the oil phase, Tween 20 and Span 80
were used as the surfactants and ethanol was used as the co-surfactant. SMEDDS formulations were
characterized according to pH, electrical conductivity, density, refractive index, viscosity, emulsification
time, dispersibility, robustness of dilution stability, droplet size, polidispersity index, zeta potential,
transmittance %, cloud point, content quantification %, chemical and physical stability. The lipolysis
study was conducted under fed and fasted conditions. In vitro release studies and kinetic evaluation
were carried out. Permeability studies were also examined with Caco-2 cell culture.
Results: The droplet size of the optimized formulation did not change significantly in different medias
over the test time period. Improved SMEDDS formulation will progress steadily without precipitating
along the gastrointestinal tract. Lipolysis studies showed that the oil solution had been exposed to high
amount of lipolysis compared to the SMEDDS formulation. The release rate of AtrCa from AtrCa-
SMEDDS formulation (93.8%, at 15 minutes) was found as increased when the results were compared
with commercial tablet formulation and pure drug. The permeability value of AtrCa from AtrCa-
SMEDDS formulation was found higher than pure AtrCa and commercial tablet formulation, approximately
9.94 and 1.64 times, respectively.
Conclusion: Thus, lipid-based SMEDDS formulation is a potential formulation candidate for lymphatic
route in terms of the increased solubility of AtrCa.