Cite this article:
Saoji, Rode, Saoji and Belgamwar (2016). Solubility and Dissolution Rate Improvement of Simvastatin via Phospholipid Complexation. Journal of Ravishankar University (Part-B: Science), 29(1), pp.146-147.
PP-C06
Solubility and
Dissolution Rate Improvement of Simvastatin via Phospholipid Complexation
Suprit D Saoji, Aniket Rode,
Vikas Saoji and Veena S Belgamwar
Department of Pharmaceutical
Sciences, R.T.M. Nagpur University, Nagpur - 440 033, India
Corresponding author email: vbelgamwar@gmail.com
[Received
15 January 2016, accepted 28 January 2016]
Abstract: The aim of
present investigation is to enhance the solubility and dissolution behaviour of
poorly soluble drug simvastatin. The simvastatin-phospholipid complex (SPC) was
prepared using a modified solvent evaporation method. A circumscribed central
composite design was used to analyze, and optimize the formulation and the
process variables to obtain acceptable simvastatin-phospholipid complex (SPC).
The influence of phospholipid-to-drug ratio (X1, w: w), reaction temperature
(X,"C) and the reaction time (X, h) on the entrapment efficiency of
simvastatin in SPC were evaluated. The prepared SPC was then characterized by
Fourier Transformed Infrared (FTIR) Spectroscopy, Differential Scanning
Calorimetry (DSC), Powder X-Ray Diffraction (PXRD) and Scanning Electron
Microscopy (SEM). Additionally, the SPC was evaluated for apparent aqueous
solubility, and in-vitro release of simvastatin. The optimum conditions identified
to obtain a high efficiency SPC were, phospholipid-to-drug ratio of 3:1, the
reaction temperature of 60°C, and a reaction time of 3 hours. The SEM images
indicated that SPC was composed of irregular size vesicles of hydrogenated soy
phosphatidylcholine, and simvastatin intercalated in the lipid layers. The
results showed that formulation of SPC significantly increased the aqueous
solubility of simvastatin. Additionally, the in-vitro dissolution results
showed that, at the end of 8 hours, free simvastatin showed about 16% release;
whereas, the drug release from SPC was over 98%. This increase in solubility
and the dissolution characteristics of the complex may be explained by the
amphiphilic nature of the complex, as well as possible amorphization of the drug
by the phospholipid. The prepared SPC showed a significant (27 fold)
enhancement in the apparent aqueous solubility, as well as the dissolution
behavior of simvastatin. Drug-phospholipid complexes can serve as a potential
alternative strategy for enhancing the aqueous solubility of poorly water
soluble drugs such as simvastatin.
Keywords: Simvastatin, Phospholipid, Complexation, Solvent evaporation method