Advanced Technologies for Oral Controlled Release: Cyclodextrins for oral controlled release

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 nanotechonology carriers (nanoparticles and conjugates) have also been reviewed

Particle formation of ibuprofen-supercritical CO2 system from rapid expansion of supercritical solutions (RESS): A mathematical model

10.1016/j.powtec.2005.03.020Powder Technology1542-383-94POTE

Solubility of Diflunisal in Supercritical Carbon Dioxide

The solubility of diflunisal, a nonsteroidal anti-inflammatory drug (NSAID), in supercritical carbon dioxide (scCO2) was measured at (308.2, 318.2, and 328.2) K and in the pressure range from (9.0 up to 25.0) MPa. Results were obtained using a static analytical method. Experimental solubility was found to be between 0.54·10−6 and 8.07·10−6 (in terms of diflunisal mole fraction). Experimental data were satisfactorily correlated with an equation-of-state (EOS) model: the Peng−Robinson cubic equation of state (PR−EOS) together with the conventional van der Waals mixing and combining rules. Solid properties were estimated by different methods available in the literature. The solubilities of several NSAIDs in SCFs, namely in scCO2, were obtained from the literature and plotted and represented as a function of the corresponding sublimation pressures and fusion temperatures

Application of dense gas techniques for the production of fine particles

The feasibility of using dense gas techniques such as rapid expansion of supercritical solutions (RESS) and aerosol solvent extraction system (ASES) for micronization of pharmaceutical compounds is demonstrated. The chiral nonsteroidal anti-inflammatory racemic ibuprofen is soluble in carbon dioxide at 35°C and pressures above 90 bar. The particle size decreased to less than 2 μm while the degree of crystallinity was slightly decreased when processed by RESS. The dissolution rate of the ibuprofen (a poorly water-soluble compound) was significantly enhanced after processing by RESS. The nonsteroidal anti-inflammatory drug Cu2(indomethacin)4L2(Cu-Indo); (L=dimethylformamide [DMF]), which possessed very low solubility in supercritical CO2, was successfully micronized by ASES at 25°C and 68.9 bar using DMF as the solvent and CO2 as the antisolvent. The concentration of solute dramatically influenced the precipitate characteristics. The particles obtained from the ASES process were changed from bipyramidal to spherical, with particle size less than 5 μm, as the concentration increased from 5 to 100 mg/g. A further increase in solute concentration to 200 mg/g resulted in large porous spheres, between 20 and 50 μ, when processing Cu-Indo by the ASES method. The dissolution rate of the micronized Cu-Indo was significantly higher than the commercial product

Experimental Determination and Correlation of Artemisinin's Solubility in Supercritical Carbon Dioxide

The measurement and correlation of the experimental solubility of the antimalarial artemisinin (Artemisia annua L.) in supercritical carbon dioxide is reported. Results were obtained using a static analytical method at 308.2, 318.2, and 328.2 K, and in a pressure range from 10.0 up to 25.0 MPa. Solubility experimental data were correlated with three density-based models (Chrastil, Bartle, and Méndez-Santiago−Teja models) and with two cubic equation of state (EOS) models, namely, the Peng−Robinson EOS and the Soave−Redlich−Kwong EOS, together with the conventional van der Waals mixing and combining rules. Good correlation results were obtained between the calculated and the experimental solubility to all fitted models. Results clearly show the feasibility of processing this antimalarial drug using supercritical fluid technologies and processes