Cyclodextrin Complexation as a Way of Increasing the Aqueous Solubility and Stability of Carvedilol

Sebastien Rigaud (1) , David Mathiron (1) , Tarek Moufawad (2) , David Landy (2) , Florence Djedaini-Pilard (3) , Frederic Marcon (4)

1 PFA - Plateforme Analytique - UPJV
2 UCEIV - Unité de Chimie Environnementale et Interactions sur le Vivant
3 LG2A - Laboratoire de Glycochimie, des Antimicrobiens et des Agro-ressources - UMR CNRS 7378
4 AGIR - Agents infectieux, résistance et chimiothérapie - UR UPJV 4294

We studied the effect of several CDs on carvedilol's solubility and chemical stability in various aqueous media. Our present results show that it is possible to achieve a carvedilol concentration of 5 mg/mL (12.3 mM) in the presence of 5 eq of gamma CD or RAMEB in an aqueous medium with an acceptable acid pH (between 3.5 and 4.7). Carvedilol formed 1:1 inclusion complexes but those with RAMEB appear to be stronger (K = 317M(-1) at 298 K) than that with gamma CD (K = 225M(-1) at 298 K). The complexation of carvedilol by RAMEB significantly increased the drug's photochemical stability in aqueous solution. These results might constitute a first step towards the development of a novel oral formulation of carvedilol.

Mots clés: carvedilol; cyclodextrins; pharmaceutical solutions; NMR; ITC

Domaines: Sciences pharmaceutiques

Sebastien Rigaud, David Mathiron, Tarek Moufawad, David Landy, Florence Djedaini-Pilard, et al.. Cyclodextrin Complexation as a Way of Increasing the Aqueous Solubility and Stability of Carvedilol. Pharmaceutics, 13 (11), pp.1746, 2021, Special Issue Novel Cyclodextrin Based Systems for Drug Delivery and Related Issues, ⟨10.3390/pharmaceutics13111746⟩. ⟨hal-03684092⟩