Cyclodextrin Complexation as a Way of Increasing the Aqueous Solublity and Staility of Carvedilol

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 γCD 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 = 317 M−1 at 298 K) than that with γCD (K = 225 M−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.

Supercritical Carbon Dioxide as a Green Alternative to Achieve Drug Complexation with Cyclodextrins

Cyclodextrins are widely used in pharmaceutics to enhance the bioavailability of many drugs. Conventional drug/cyclodextrin complexation techniques suffer from many drawbacks, such as a high residual content of toxic solvents in the formulations, the degradation of heat labile drugs and the difficulty in controlling the size and morphology of the product particles. These can be overcome by supercritical fluid technology thanks to the outstanding properties of supercritical CO2 (scCO2) such as its mild critical point, its tunable solvent power, and the absence of solvent residue after depressurization. In this work the use of scCO2 as an unconventional medium to achieve the complexation with native and substituted cyclodextrins of over 50 drugs, which belong to different classes, are reviewed. This can be achieved with different approaches such as the “supercritical solvent impregnation” and “particle-formation” techniques. The different techniques are discussed to point out how they affect the complexation mechanism and efficiency, the physical state of the drug as well as the particle size distribution and morphology, which finally condition the release kinetics and drug bioavailability. When applicable, the results obtained for the same drug with various cyclodextrins, or different complexation techniques are compared with those obtained with conventional approaches.