Drug/lactose co-micronization by jet milling to improve aerosolization properties of a powder for inhalation.

The aim of this work was to formulate a powder for inhalation with fusafungine, a drug substance initially highly cohesive. The classical approach based on micronization by jet milling to prepare respirable drug particles and then blending with a carrier was first applied. A fractional factorial experimental design was implemented to screen six formulation parameters. The effect of drug/lactose co-micronization on aerosolization was then evaluated. In vitro deposition studies were performed with the twin stage glass impinger and the inhaler Spinhaler. Micronization did not induce DSC-detectable amorphization and gave a highly cohesive, poor flowable powder with a theoretical aerodynamic diameter of 5 microm. The powder was then blended with coarse lactose and optionally fine lactose. Unfortunately, the respirable fraction could not be optimized and remained below 10%. On the other hand, a co-micronized powder drug/fine lactose 50:50 gave a respirable fraction of 16%. Following blending with a carrier, the respirable fraction and the emitted dose fraction reached 23% and 69%, respectively. The use of a fine lactose grade for co-micronization was essential. In conclusion, this study demonstrated that co-micronization with a fine lactose is an efficient and simple strategy to formulate a powder for inhalation with enhanced aerosolization properties, especially for highly cohesive drug substance.

A supercritical fluid-based coating technology 1: process considerations.

A novel solvent-free particle coating process, based on the solvent properties of supercritical fluids (SCF) is described. It consists of dissolving one or more coating materials in supercritical CO(2) and then adjusting T/P conditions in the autoclave so that the coating material becomes insoluble in the CO(2). This insolubilization step causes a coating to deposit on the surface of suspended particles. This process has been applied to bovine serum albumin and sugar granules. Coating was effective, but different morphologies were obtained depending on the coating material used. A discontinuous coating has been made using trimyristin, since this material precipitates as micro-needles. Conversely, a smooth, regular coating has been obtained with a commercially available mixture of glycerides and glyceride esters of PEG (Gelucire 50/02) acting like a film-forming agent.

Antivitamin K prevents heterotopic ossification after hip arthroplasty in diffuse idiopathic skeletal hyperostosis. A retrospective study in 67 patients.

We investigated the risk of heterotopic ossification (HO) after total hip arthroplasty in 67 patients, 16 of whom had diffuse idiopathic skeletal hyperostosis (DISH). DISH was diagnosed on chest, dorsolumbar and pelvic radiographs. HO was graded according to DeLee et al. (1976). After a 1.4 year follow-up, 21 patients had HO. The risk of HO was 5 times higher in DISH than in non-DISH patients, but lower in patients receiving antivitamin K than in those receiving other anticoagulant therapy (relative risk 0.2). Our findings lead us to recommend that DISH should be diagnosed preoperatively for preventive therapy. They also suggest a preventive effect of antivitamin K against heterotopic ossification after hip arthroplasty.