Stability Study of Naproxen in Solid State and Excipient Compatibility

Abstract

This study describes stability of Naproxen or (+)-6-methoxy-a methyla naphthalene acetic acid in solid state followed by different techniques (x-ray powder diffraction, DSC, HPLS and FTIR) at different temperatures during 18 weeks, using two excipients with different structure and solubility. In addition to its pharmaceutical importance, naproxen was chosen as a model to study the effect of excipients on the solid-state stability of an important class of compounds, aromatic carboxylic acids. The study used these techniques as methods to identify the stability of Naproxen at different temperatures and the compatibility between Naproxen and two excipients (microcrystalline cellulose and Magnesium stearate). The study by 18 weeks at 60ºC showed a small degradation of Naproxen 0.34%, with microcrystalline cellulose and with Magnesium stearate 3.30%. Founded that Naproxen was very stable alone and with the presence of the excipients at different temperatures (24 to 60ºC). The kinetic of degradation of naproxen was followed using the three principal peaks of the DRX profile. The main changes in the naproxen crystal were founded in 5.497, 22.611(111) and 28.544(210) degrees at magnesium stearate presence and in the Naproxen- Microcrystalline cellulose mixture, were 6.831(100), 22.611(111) y 28.544(210) degrees. Also, founded Naproxen was chemically compatible with microcrystalline cellulose and Magnesium stearate because the change on the intensity of the main peaks of diffraction was small to model with different solid state equations. Ilustrating the 3D structure, built the Naproxen unit cell and simulated the planes with Miller indices (100, 111 and 210). But was a surprise that calorimetric results detected a great change in the endothermic peak of Naproxen- magnesium stearate. This change was a decrease of 77% of the DH of Naproxen and 10 degrees of melting point depression, and consider magnesium stearate as an impurity compound to forms an eutectic solid between drug and Magnesium stearate. Then review different articles that mentioned the interaction between naproxen and other active pharmaceutical ingredients (API) and founded that many reports talked about the incompatibility between naproxen and APIs but the different authors did not check the incompatibility of naproxen with any other specific analytical technique. Then in some times magnesium stearate should not be considered incompatible, because it only causes the endothermic peak to disappear because the stearate is melted and dissolving the active ingredients that have a melting point higher than that of the stearate.