The work aims to prove the complexation of two models drugs (ibuprofen, IB and indomethacin, IN) by beta-cyclodextrin (βCD), the effect of the water in such process, and the comparison of their complexation yields. Two methods were considered: kneading of a binary mixture of the drug:βCD and inclusion of either IB or IN in aqueous solutions of βCD. In the latter method the water was removed by air stream, spray-drying and freeze-drying. To prove the formation of complexes in final products optical microscopy, UV spectroscopy, IR spectroscopy, DSC, X-Ray and NMR were considered. Each powder was added to an acidic solution (pH = 2) to quantify the concentration of the drug inside βCD cavity. Others media (pH = 5 and 7) were used to prove the existence of drug not complexed in each powder as the drugs solubility increases with the pH. It was observed that complexation occurred in all powders, and that the fraction of drug inside the βCD did not depend neither on the method of complexation nor on the processes of drying considered.

Cyclodextrins (CDs) are used in oral pharmaceutical formulations, by means of inclusion complexes formation, with the following advantages for the drugs: (1) solubility, dissolution rate, stability, and bioavailability enhancement; (2) to modify the drug release site and/or time profile; and (3) to reduce or prevent gastrointestinal side effects and unpleasant smell or taste, to prevent drug-drug or drug-additive interactions, or even to convert oil and liquid drugs into microcrystalline or amorphous powders. A more recent trend focuses on the use of CDs as nanocarriers, a strategy that aims to design versatile delivery systems that can encapsulate drugs with better physicochemical properties for oral delivery. Thus, the aim of this work was to review the applications of the CDs and their hydrophilic derivatives on the solubility enhancement of poorly water-soluble drugs in order to increase their dissolution rate and get immediate release, as well as their ability to control (to prolong or to delay) the release of drugs from solid dosage forms, either as complexes with the hydrophilic (e.g., as osmotic pumps) and/or hydrophobic CDs. New controlled delivery systems based on nanotechnology carriers (nanoparticles and conjugates) have also been reviewed.

Mixtures containing ibuprofen (IB) complexed with β-cyclodextrin (βCD) obtained by two complexation methods [suspension/solution (with water removed by air stream, spray-and freezedrying) and kneading technique] were processed into pharmaceutical dosage forms (minitablets and capsules). Powders (IB, βCD and IBβCD) were characterized for moisture content, densities (true and bulk), angle of repose and Carr's index, X-ray and NMR. 2.5 mm diameter minitablets and capsules were prepared from physical mixtures and IBβCD complexes without other excipients. Minitablets were characterized for the energy of compaction, tensile strength, friability, density and IB release (at pH 1.0 and 7.2), whereby capsules were characterized for IB release. The results from the release of IB were analyzed using different parameters, namely, the similarity factor (f 2 ), the dissolution efficiency (DE) and the amounts released at a certain time (30, 60 and 180 min) and compared statistically (α = 0.05). The release of IB from the minitablets showed no dependency on the amount of water used in the formation of the complexes. Differences were due to the compaction force used or the presence of a shell, for the capsules. The differences observed were mostly due to the characteristics of the particles (dependent on the method considered on the formation of the complexes) and neither to the dosage form nor to the complex of the IB.

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Cyclodextrins (CDs) were first isolated in 1891 as degradation products of starch from a medium of Bacillus amylobacter. They are cyclic water-soluble, nonreducing, macrocycle carbohydrate polymers constructed from a-(1-4)-linked D-glucopyranose units (naturally occurring a, b, and g formed by 6, 7, and 8 glucose units), in a ring formation and present a toroidal, hollow, truncated cone shape. Their most important property is the ability to establish specific interactions -molecular encapsulation -with various types of molecules through the formation of non-covalently bonded entities, either in the solid phase or in aqueous solution, taking up a whole molecule, or some part of it, into their cavities. This process in part mimics the "lock and key" mechanism of enzyme catalysis. Complexation may cause changes in physicochemical properties of the guest molecule (e.g., solubility, stability, kinetics and bioavailability, toxicity). Their negligible cytotoxic effects promoted them to the GRAS list and led them to be widely used in many industrial products and technologies.