β-cyclodextrin complex formation and protonation equilibria of morphine and other opioid compounds of therapeutic interest.

The inclusion complex formation of morphine and its 18 opioid derivatives with β-cyclodextrin has been studied using nuclear magnetic resonance spectroscopy. Initially, the protonation equilibria and the acid-base properties of dibasic opioid compounds have been fully characterized. Apparent protonation constants and the relative concentration of the microspecies in cyclodextrin excess were also determined.

Physico-chemical profiling of semisynthetic opioids.

Species-specific acid-base and partition equilibrium constants were experimentally determined for the therapeutically important semisynthetic opioid receptor agonist hydromorphone, dihydromorphine, and mixed agonist-antagonist nalorphine and nalbuphine. The acid-base microequilibria were characterized by combining pH-potentiometry and deductive methods using synthesized auxiliary compounds. Independent of the pH, there are approximately 4.

Species-specific lipophilicity of morphine antagonists.

Complete sets of microscopic acid-base and partition equilibrium constants were experimentally determined for therapeutically important morphine derivatives, including the widely used antagonists naloxone and naltrexone. The acid-base microequilibria were characterized by combining pH-potentiometry and deductive methods using synthesized auxiliary compounds. Microscopic protonation equilibria show that approximately three times as many zwitterionic microspecies than non-charged ones exist in oxymorphone and naltrexone solutions.

Drug delivery: a process governed by species-specific lipophilicities.

Drug delivery is a cascade of molecular migration processes, in which the active principle dissolves in and partitions between several biological media of various hydrophilic and lipophilic character. Membrane penetration and other partitions are controlled by a number of physico-chemical parameters, the eminent ones are species-specific basicity and lipophilicity. Latter is a molecular property of immense importance in pharmacy, bio-, and medicinal chemistry, expressing the affinity of the molecule for a lipophilic environment.