Theophylline formulation by supercritical antisolvents.

Supercritical antisolvent precipitation has been used to produce theophylline particles as pure crystals or as a solid formulation with poly lactic acid (PLA). Experiments were carried out as batch or semi-continuous process and with carbon dioxide (CO2) or trifluoromethane (CHF3) as antisolvent. Both modes led to micronized theophylline, but the semi-continuous produced smaller particles than the batch. The particle morphology was sensitive to the antisolvent, since CO2- and CHF3-samples exhibited hexagonal and triangular shape, respectively. The most distinguish feature of CO2-powders was that theophylline exhibited a different crystal lattice than the crude- or the CHF3-materials, accredited by new diffraction peaks in the XRD patterns not attributable to hydration of samples. However, neither the shape nor the new crystal lattice influenced the dissolution kinetics of Theophylline. For co-precipitation with PLA, the successful recovery of a powder occurred only in conditions of CHF3-batch and CO2-semi continuous. The powder retained the shape and the crystallinity of the corresponding pure processed theophylline, indicating that PLA did not interfere with the precipitation behavior of the drug. Moreover, only the CO2-semi continuous products exhibited a decreased release rate and a prolongation of the total release time of the drug.

Preparation of acetazolamide composite microparticles by supercritical anti-solvent techniques.

The possibility of preparation of ophthalmic drug delivery systems using compressed anti-solvent technology was evaluated. Eudragit RS 100 and RL 100 were used as drug carriers, acetazolamide was the model drug processed. Compressed anti-solvent experiments were carried out as a semi-continuous or a batch operation from a liquid solution of polymer(s)+solute dissolved in acetone. Both techniques allowed the recovery of composite particles, but the semi-continuous operation yielded smaller and less aggregated populations than the batch operation. The release behaviour of acetazolamide from the prepared microparticles was studied and most products exhibited a slower release than the single drug. Moreover, the release could be controlled to some extent by varying the ratio of the two Eudragit used in the formulation and by selecting one or the other anti-solvent technique. Simple diffusion models satisfactorily described the release profiles. Composites specifically produced by semi-continuous technique have a drug release rate controlled by a diffusion mechanism, whereas for composites produced by the batch operation, the polymer swelling also contributes to the overall transport mechanism.