• Priemel, Petra Alexandra
• Rades, Thomas
• Diego, Heidi Lopez De
• Grohganz, Holger
• Doreth, Maria
• Holm, René
• Löbmann, Korbinian

Abstract

Previously, the concept of in situ amorphization of indomethacin/Eudragit® E compacts was introduced. In the current study, in situ amorphization of naproxen and ibuprofen with Eudragit® E was investigated to gain a better understanding of in situ amorphization and to investigate if this approach is applicable to other drugs. Compacts of drug and Eudragit® E were compressed at a 2:1, 1:1 and 1:2 drug-to-polymer ratio (w/w) and immersed in water for 1 h. Physicochemical characteristics, potential interactions and dissolution behavior were analyzed and compared to non-immersed compacts.<br/><br/>Both drugs formed a glass solution with Eudragit® E when immersed into water. In XRPD, reflections of the respective drugs decreased or disappeared completely. All samples showed a single glass transition temperature in the DSC, suggesting the formation of single phase amorphous systems. Ionic interactions between drug and polymer were identified by infrared spectroscopy. In the dissolution study (pH 4.1), especially the 1:1 (w/w) in situ amorphized samples showed an improved dissolution behavior compared to their non-immersed counterparts. It can be concluded that in situ amorphization is a promising method to amorphize poorly water-soluble drugs immediately prior to administration, and thereby avoid the physical stability problems connected to amorphous formulations during storage.

Topics

• impedance spectroscopy
• polymer
• amorphous
• phase
• glass
• glass
• glass transition temperature
• differential scanning calorimetry
• infrared spectroscopy