Preparation, characterization, and dissolution studies of naproxen solid dispersions using polyethylene glycol ۶۰۰۰ and labrafil M۲۱۳۰

Naproxen is a poor water soluble, non-steroidal analgesic and anti-inflammatory drug. The enhancement of oral bioavailability of poor water soluble drugs remains one of the most challenging aspects of drug development. Although salt formation, solubilization and particle size reduction have commonly been used to increase dissolution rate and thereby oral absorption and bioavailability of low water soluble drugs, there are practical limitation of these techniques. However, the most attractive option for increasing the release rate is improvement of solubility through formulation approaches. In this study, solid dispersions (SD) of naproxen were prepared by hot melt method using various ratios of drug to polymers (PEG۶۰۰۰) separately and characterized for physical appearance, FTIR, DSC, X-Ray crystallography, and in-vitro dissolution studies. The influence of several amounts of Labrafil M۲۱۳۰ was also studied. FTIR study revealed that drug was stable in SDs, and great state of amorphous formed particles was proofed by DSC analysis. The in vitro dissolution studies were carried using USP type II (paddle) dissolution apparatus at medium (pH ۱.۵). Solubility of naproxen from SDs was increased in dissolution media. The prepared dispersion showed increase in the dissolution rate of naproxen comparing to that of physical mixtures of drug and polymers and pure drug. Percent of drug released in ۶۰ minutes was ۲۳.۹۲% for pure naproxen witch is increased in SDs and reached to۱۰۰% for best formulations of PEG۶۰۰۰ and labrafil based SDs respectively, considering ratio of drug to polymers.It is concluded that dissolution of the naproxen could be improved by the solid dispersion. Although physical mixtures have increased the rate of dissolution, dissolution shows faster release from SDs which would therefore be due to formation of amorphous particles through the hot melt process which was also revealed by DSC analysis and XRD.

Keywords:

Naproxen , Release rate , hot melt method , Solid dispersion