The Stability of Cyclodextrin Complexes in Solution.

Cyclodextrins are cyclic oligomers of glucose that can form water-soluble inclusion complexes with small molecules and portions of large compounds. These biocompatible, cyclic oligosaccharides do not elicit immune responses and have low toxicities in animals and humans. Cyclodextrins are used in pharmaceutical applications for numerous purposes, including improving the bioavailability of drugs. Current cyclodextrin-based therapeutics are described and possible future applications discussed. Cyclodextrin-containing polymers are reviewed and their use in drug delivery presented. Of specific interest is the use of cyclodextrin-containing polymers to provide unique capabilities for the delivery of nucleic acids.

Cyclodextrin-based pharmaceutics: past, present and future

NMR Studies of Cyclodextrins and Cyclodextrin Complexes

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

The purpose of this review is to discuss and summarize some of the interesting findings and applications of cyclodextrins (CDs) and their derivatives in different areas of drug delivery, particularly in protein and peptide drug delivery and gene delivery. The article highlights important CD applications in the design of various novel delivery systems like liposomes, microspheres, microcapsules, and nanoparticles. In addition to their well-known effects on drug solubility and dissolution, bioavailability, safety, and stability, their use as excipients in drug formulation are also discussed in this article. The article also focuses on various factors influencing inclusion complex formation because an understanding of the same is necessary for proper handling of these versatile materials. Some important considerations in selecting CDs in drug formulation such as their commercial availability, regulatory status, and patent status are also summarized. CDs, because of their continuing ability to find several novel applications in drug delivery, are expected to solve many problems associated with the delivery of different novel drugs through different delivery routes.

Cyclodextrins in drug delivery: an updated review.

The use of supercritical fluids, and in particular supercritical carbon dioxide (SC-CO2), can be foreseen in a wide range of techniques and processes within pharmaceutical sciences. When dealing with both drugs and formulation adjuvants, the determination of the relevant solubilities in SC-CO2 represents a mandatory prerequisite, underlying the development of industrial scale operations. The aim of this work concerned the experimental determination of the solubility in SC-CO2 of vanillic acid and ketoprofen by means of an easy-to-use plant designed and assembled to operate in dynamic conditions. Its reliability was preliminarily checked by comparing solubility data obtained for salicylic acid and naphthalene with literature ones. Solubility measurements for ketoprofen and vanillic acid were carried out at 313 and 328 K in the 9−25 MPa pressure range. Crossover pressures of 16 MPa and 15 MPa were found for ketoprofen and vanillic acid, respectively. The solubility data were worked out according to a thermo...

Assessment of Solubility of Ketoprofen and Vanillic Acid in Supercritical CO2 under Dynamic Conditions

Carbon-13 nuclear magnetic resonance study of naproxen interaction with cyclodextrins in solution.

Binary systems of naproxen with statistically-alkylated s-cyclodextrins (methyl, hydroxyethyl and hydroxypropyl derivatives) were investigated for both solid phase characterization (differential scanning calorimetry, X-ray powder diffraction) and dissolution properties (dispersed amount and rotating disc methods) Kneading, coevaporation and colyophilization of the 1:1 (mol/mol) naproxen/methyl s-cyclodextrin combination, as well as colyophilization of analogous combinations of naproxen with hydroxyethyl and hydroxypropyl s-cyclodextrin, led to amorphous products with higher dissolution rates than the corresponding physical mixtures A conversion of crystalline to amorphous naproxen was also observed by heating the physical mixtures at about 393 K The amorphous statistically-alkylated s-cyclodextrins, in particular methyl s-cyclodextrin, can be employed as amorphizing agents for crystalline naproxen

Ferdinando Giordano

Papers

Assessment of Solubility of Ketoprofen and Vanillic Acid in Supercritical CO2 under Dynamic Conditions

Carbon-13 nuclear magnetic resonance study of naproxen interaction with cyclodextrins in solution.

Thermal behaviour and dissolution properties of naproxen in combinations with chemically modified ß-Cyclodextrins

The influence of water content on the binding capacity of β-cyclodextrin

Sobrerol enantiomers and racemates: solid-state spectroscopy, thermal behavior, and phase diagrams.