The Stability of Cyclodextrin Complexes in Solution.

Cyclodextrins as pharmaceutical solubilizers.

Artificial Organic Host Molecules for Anions

Drugs with low water solubility are predisposed to low and variable oral bioavailability and, therefore, to variability in clinical response. Despite significant efforts to "design in" acceptable developability properties (including aqueous solubility) during lead optimization, approximately 40% of currently marketed compounds and most current drug development candidates remain poorly water-soluble. The fact that so many drug candidates of this type are advanced into development and clinical assessment is testament to an increasingly sophisticated understanding of the approaches that can be taken to promote apparent solubility in the gastrointestinal tract and to support drug exposure after oral administration. Here we provide a detailed commentary on the major challenges to the progression of a poorly water-soluble lead or development candidate and review the approaches and strategies that can be taken to facilitate compound progression. In particular, we address the fundamental principles that underpin the use of strategies, including pH adjustment and salt-form selection, polymorphs, cocrystals, cosolvents, surfactants, cyclodextrins, particle size reduction, amorphous solid dispersions, and lipid-based formulations. In each case, the theoretical basis for utility is described along with a detailed review of recent advances in the field. The article provides an integrated and contemporary discussion of current approaches to solubility and dissolution enhancement but has been deliberately structured as a series of stand-alone sections to allow also directed access to a specific technology (e.g., solid dispersions, lipid-based formulations, or salt forms) where required.

Strategies to Address Low Drug Solubility in Discovery and Development

Surface active drugs: self-association and interaction with membranes and surfactants. Physicochemical and biological aspects

: The equilibrium constants and rate constants for the formation of inclusion complexes of cycloheptaamylose with small inorganic anions were measured by a spectrophotometric technique and an ultrasonic relaxation technique respectively. The stability of the complexes of anions with cycloheptaamylose decreased. Comparison is made between the equilibrium constants and the interaction of free anions with the solvent. Periodate and ClO4(-) exhibited a complexation rate constant 30 times greater than the remainder of the anions. A concentration independent relaxation was observed for aqueous cyclohexaamylose in the uncomplexed state. No like behaviour was observed for cycloheptaamylose. A conformational change in the cycloheptaamylose may be the rate determining step in the complexation of the more slowly reacting anions.

An Equilibrium and Kinetic Investigation of Salt-Cycloamylose Complexes

Une nouvelle methode de determination de la concentration critique micellaire (CMC) d'agents de surface ioniques en solution aqueuse, a partir des mesures de la conductivite electrique est developpee. Cette methode est appliquee a differents systemes eau/agents de surfaces cationiques (DETAB=decyltrimethylammonium bromure, DTAB=dodecyltrimethylammonium bromure, TTAB=tetradecyltrimethylammonium bromure et CTAB=cetyltrimethylammonium bromure)

Critical micelle concentration determination in binary mixtures of ionic surfactants by deconvolution of conductivity/concentration curves

Effect of PVP K-25 on the formation of the naproxen:β-ciclodextrin complex

Using Fourier transform infrared (FT-IR) spectroscopy and electrical conductivity measurements, the study of water-in-oil (w/o) microemulsions of Aerosol OT dissolved in toluene with different wate

Effect of the addition of water-soluble polymers on the structure of aerosol OT water-in-oil microemulsions : A fourier transform infrared spectroscopy study

Licesio J. Rodriguez

Papers

An Equilibrium and Kinetic Investigation of Salt-Cycloamylose Complexes

Critical micelle concentration determination in binary mixtures of ionic surfactants by deconvolution of conductivity/concentration curves

Effect of PVP K-25 on the formation of the naproxen:β-ciclodextrin complex

Effect of the addition of water-soluble polymers on the structure of aerosol OT water-in-oil microemulsions : A fourier transform infrared spectroscopy study

Ternary naproxen:β-cyclodextrin:polyethylene glycol complex formation