Proučavanje ravnoteža u heterogenim sistemima tricikličnog antidepresiva amitriptilina

Abstract

Cilj ovog rada bio je proučavanje ravnoteža u heterogenim sistemima tricikličnog antidepresiva amitriptilina (Am) koji sadrže hloride i/ili fosfate. Rastvorljivost Am u uslovima povećane jonske sile određena je pH–Ramp shake–flask metodom. Veća rastvorljivost Am u kiseloj sredini od očekivane, posledica je agregacije – analiza eksperimentalnih podataka pomoću programa pDISOL–XTM ukazuje na verovatno građenje pentamera Am5H5 5+. Kritična micelarna koncentracija i stepen disocijacije agregata određeni su primenom konduktometrijskih titracija. U baznoj sredini primećena je delimična degradacija Am. Eksperimentalno dobijeni podaci o rastvorljivosti biološki aktivnih supstanci i postojećim ravnotežama u heterogenim sistemima važni su u svim fazama dizajna i razvoja lekova.

The aim of this work was to study the equilibria in tricyclic antidepressant amitriptyline (Am) heterogeneous systems containing chloride and/or phosphate ions. Solubility of Am in high ionic strength conditions was determined using pH–Ramp shake–flask method.1, 2 Higher solubility of Am than expected in an acidic media is a consequence of self-aggregation – pentamer formation (Am5H5 5+) according to pDISOL–XTM analysis. Critical micelle concentration and the degree of the aggregate dissociation were determined by conductometric titrations. Partial degradation of Am in alkaline suspensions was observed. Experimental studies of solubility as well as the existing equilibria in heterogeneous systems of biologically active compounds are important at all stages of drug design and development.