Yasmine Masmoudi

Impregnation of Fenofibrate on mesoporous silica using supercritical carbon dioxide

Low oral bioavailability can be circumvented by the formulation of the poorly water soluble drug in ordered mesoporous silica (OMS-L-7). Fenofibrate is an orally administered, poorly water-soluble active pharmaceutical ingredient (API), used clinically to lower lipid levels. Fenofibrate was loaded into silica using two methods: incipient wetness and supercritical impregnation. This study investigates the impact of loading and the impact of varying supercritical carbon dioxide (scCO2) processing conditions. The objective is to enhance Fenofibrate loading into silica while reducing degree of the drug crystallinity, so as to increase the drugs dissolution rate and its bioavailability. The comparison of both impregnation processes was made in terms of impregnation yields and duration as well as physical characterization of the drug. While incipient wetness method led to a Fenofibrate loading up to 300 mgdrug/gsilica in 48 h of impregnation, the supercritical impregnation method yielded loading up to 485 mgdrug/gsilica in 120 min of impregnation duration, at 16 MPa and 308 K, with a low degree of crystallinity (about 1%) comparable to the crystallinity observed via the solvent method. In addition to the enhancement of impregnation efficiency, the supercritical route provides a solvent-free alternative for impregnation.

Supercritical antisolvent co-precipitation of rifampicin and ethyl cellulose

&NA; Rifampicin‐loaded submicron‐sized particles were prepared through supercritical anti‐solvent process using ethyl cellulose as polymeric encapsulating excipient. Ethyl acetate and a mixture of ethyl acetate/dimethyl sulfoxide (70/30 and 85/15) were used as solvents for both drug and polymeric excipient. When ethyl acetate was used, rifampicin was crystallized separately without being embedded within the ethyl cellulose matrix while by using the ethyl acetate/dimethyl sulfoxide mixture, reduced crystallinity of the active ingredient was observed and a simultaneous precipitation of ethyl cellulose and drug was achieved. The effect of solvent/CO2 molar ratio and polymer/drug mass ratio on the co‐precipitates morphology and drug loading was investigated. Using the solvent mixture, co‐precipitates with particle sizes ranging between 190 and 230 nm were obtained with drug loading and drug precipitation yield from respectively 8.5 to 38.5 and 42.4 to 77.2% when decreasing the ethyl cellulose/rifampicin ratio. Results show that the solvent nature and the initial drug concentrations affect morphology and drug precipitation yield of the formulations. In vitro dissolution studies revealed that the release profile of rifampicin was sustained when co‐precipitation was carried out with the solvent mixture. It was demonstrated that the drug to polymer ratio influenced amorphous content of the SAS co‐precipitates. Differential scanning calorimetry thermograms and infrared spectra revealed that there is neither interaction between rifampicin and the polymer nor degradation of rifampicin during co‐precipitation. In addition, stability stress tests on SAS co‐precipitates were carried out at 75% relative humidity and room temperature in order to evaluate their physical stability. SAS co‐precipitates were X‐ray amorphous and remained stable after 6 months of storage. The SAS co‐precipitation process using a mixture of ethyl acetate/dimethyl sulfoxide demonstrates that this strategy can be successful for controlling rifampicin delivery. Graphical abstract Figure. No caption available.

Supercritical impregnation and optical characterization of loaded foldable intraocular lenses using supercritical fluids

PURPOSE To prepare drug-loaded intraocular lenses (IOLs) used to combine cataract surgery with postoperative complication treatment through supercritical impregnation while preserving their optical properties. SETTING Aix-Marseille Université, CNRS, Centrale Marseille, Laboratoire de Mécanique, Modélisation & Procédés Propres, Marseille, France, and He University Eye Hospital, Liaoning Province, China. DESIGN Experimental study. METHODS Supercritical impregnations of commercial foldable IOLs used in cataract surgery with ciprofloxacin (an antibiotic) and dexamethasone 21-phosphate disodium salt (an antiinflammatory drug) were performed in a noncontinuous mode. Impregnation amounts were determined through drug-release kinetic studies. The optical characterizations of IOLs were determined by evaluating the dioptric power and the imaging quality by determining the modulating transfer function (MTF) at a specified spatial frequency according to the International Organization for Standardization (ISO 11979-2:2014). RESULTS Transparent IOLs presenting an effective impregnation were obtained with a prolonged drug delivery during approximately 10 days. Optical characterizations (dioptric powers and MTF values) show preserved optical properties after supercritical treatment/impregnation. CONCLUSION Supercritical treatments/impregnations do not damage the optical properties of IOLs and are therefore adequate for the preparation of delivery devices used for cataract surgery.