Acta Pharm. 49 (1999) 89–98

Increased aqueous solubility of N-(7- oxododecanoyl)-L-alanyl-D-isoglutamine by coprecipitating with various pharmaceutical carriers

ODON PLANINSEK,^1,2  ROBERT PISEK, ¹ ALBIN KRISTL,¹ 
PETER C. SCHMIDT,³  and  STANKO SRCIC^1*

¹ University of Ljubljana, Faculty of Pharmacy, Askerceva 7, 1000 Ljubljana, Slovenia
² Institute of Pharmacy and Drug Research, Ptujska 21, 1000 Ljubljana, Slovenia
³ Pharmaceutical Institute, University of Tübingen, Auf der Morgenstelle 8, 7276 Tübingen, Germany

N-(7-oxododecanoyl)-L-alanyl-D-isoglutamine, which is a modified N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP, the smallest immunologically active glucopeptide's subunit of the bacterial cell wall), was chosen after immunorestorement tests for further preclinical testing. For the preparation of an appropriate parenteral formulation, the solubility of the compound has to be increased. For this purpose different physical mixtures and solid dispersions prepared by solvent evaporation method with different carriers were investigated. The solubility of N- (7-oxododecanoyl)-L-alanyl-D-isoglutamine increased from 0.16 g L^-1 to 27 g L^-1 for the dispersion with nicotinamide, to 40 g L^-1 for the dispersion with sodium salicylate and to 24 g L^-1 for the complex with 2- hydroxypropyl-beta-cyclodextrin.

Keywords: solid dispersion, nicotinamide, sodium salicylate, 2-hydroxypropyl-beta -cyclodextrin, increased water solubility, thermal analysis