BEHAVIOR OF MACROMOLECULAR DRUG CARRIER POLY(N-VINYLPYRROLIDONE-CO-MALEIC ACID) AND ITS BIOCONJUGATES AT DIFFERENT PH VALUES INVESTIGATED BY GEL-PERMEATION CHROMATOGRAPHY

Anionic poly(N-vinyl pyrrolidone-co-maleic acid) [referred later in th e text as P], which is utilized in Drug Delivery Systems as macromolec ular carrier of drugs was analysed by gel permeation chromatography. A nilide and quinoxaline derivatives were coupled to this drug-carrier t o form conjugates, which were also analysed with gel permeation chroma tography. Conjugate P-D1 was prepared by coupling the anilide derivati ve DI [2-cyano 3-hydroxy 5-amino 2 pentenoyc (4-trifluoromethyl anilid e)] to the carboxyl groups of the drag-carrier P, while conjugate P-D2 was prepared by coupling the quinoxaline derivative D2 [(6`,7' dimeth yl-1'-quinoxalinyl) 4-(2`amino) acetanilide] to the carboxyl groups of the drug-carrier P. Gel-chromatographic properties of the carrier P a nd its conjugates have been investigated on Biosil TSK 125 SW column i n 0.25 N triethyl ammonium phosphate buffer of different pH values (2. 25; 4.70 and 6.0). Applying appropriate pH (4.70) the method allowed u s to differentiate between conjugate molecules carrying strong or weak residual carboxyl groups. Strong molecular dispersity resulting in wi de, tailed chromatographic profiles could be detected in the case of t he conjugates. Various distributions of the residual charges along the polymer chains, as well as presence of residual carboxyl groups of di fferent acidity could be responsible for this molecular dispersity.