La maladie goutteuse

Gout is a chronic disease due to the deposition of monosodium urate microcrystals in joints and tissues. Its incidence and prevalence are increasing worldwide in close relation with the epidemic of obesity and metabolic syndrome. Gout is related to chronic hyperuricemia that should be treated to ensure the reduction or even the disappearance of acute attacks (“gout flares”) and to reduce the size and number of tophi. If arthritis of the first metatarsophalangeal joint is the most typical form, other joints may be affected, including the spine. Demonstration of urate microcrystals arthritis allows diagnosis of gout but, in the absence of possibility of performing joint puncture, imaging may be useful for providing complementary diagnostic elements. Appropriate care is essential to reduce the number of flares and the evolution towards gouty arthropathy but also in terms of public health in order to reduce costs related to this pathology.     

Effects of particle size on the pharmacokinetics of puerarin nanocrystals and microcrystals after oral administration to rat

Puerarin, which is extracted from traditional Chinese medicine, is widely used in clinic in China and mainly used as a therapeutic agent to cardiovascular diseases. Owing to its poor water solubility and adverse drug reactions caused by cosolvents after intravenous administration, the development of oral formulation is urgently needed. Nowadays, nanocrystals technique has become a preferred way to develop oral dosage form. In this study, we used high pressure homogenization (HPH) to prepare puerarin nanocrystals and microcrystals with different sizes ranged from 525.8 nm to 1875.6 nm and investigated the influence of particle size on pharmacokinetics. The nanocrystals and microcrystals prepared were characterized using DLS, DSC, XRD and SEM, and we found that the crystalline state of puerarin was changed during the preparation process and the drug was dispersed into HPMC. In the pharmacokinetic study, we observed an increasing of C_max and AUC and a decreasing of CL/F with the decreasing of particle size. The AUC of the puerarin nanocrystals (525.8 nm) was 7.6-fold of that of raw puerarin suspension, with an absolute bioavailability of 21.44%. From the above results, we can conclude that nanocrystal technique is an efficient technology to improve the oral bioavailability of puerarin.     

Adsorption of pharmaceutical excipients onto microcrystals of siramesine hydrochloride: Effects on physicochemical properties

A common challenge in the development of new drug substances is poor dissolution characteristics caused by low aqueous solubility. In this study, microcrystals with optimized physicochemical properties were prepared by precipitation in the presence of excipients, which adsorbed to the particle surface and altered particle size, morphology, and dissolution rate. The poorly water-soluble drug siramesine hydrochloride was precipitated by the antisolvent method in the presence of each of various polymeric and surface active excipients. Powder dissolution studies of six of the resulting particle systems showed a significant increase in percent dissolved after 15 min compared to the starting material.A quantitative determination of the amount of excipient adsorbed to the surface of the drug particles proved that only a very small amount of excipient was needed to exert a marked effect on particle properties. The adsorbed amount of excipient constituted less than 1.4% (w/w) of the total particle weight, and thus powders of very high drug loads were obtained. Sodium lauryl sulphate (SLS), hydroxypropyl methylcellulose (HPMC), and hydroxypropyl cellulose (HPC), which exhibited the greatest degree of adsorption, also had the greatest effect on the physicochemical properties of the particles. X-ray Photoelectron Spectroscopy (XPS) analysis of the surface composition and scanning electron microscopy studies on particle morphology suggested that the excipients adsorbed to specific faces of the crystals.     

Intra-Articular injection of acid-sensitive stearoxyl-ketal-dexamethasone microcrystals for long-acting arthritis therapy

Despite advances in treatment of chronic arthritis, there is still a strong need for the development of long-acting formulations that can enable local and sustained drug release at the inflamed tissues. In this work, we fabricated microcrystals of an acid-sensitive stearoxyl-ketal-dexamethasone prodrug for treatment of arthritis. Microcrystals of the prodrug with two sizes were successfully engineered and showed pH-dependent hydrolysis kinetics in vitro. In a collagen-induced arthritis rat model, we evaluated the influence of particle size and injection dose on anti-inflammatory effect after intra-articular injection. Such prodrug demonstrated long-acting anti-arthritis effects with good safety. Our results indicate ketal-based prodrugs are promising for the development of long-acting injectables and may stimulate the development of new treatments for chronic diseases.     

Benznidazole microcrystal preparation by solvent change precipitation and in vivo evaluation in the treatment of Chagas disease

Benznidazole (BNZ) is traditionally used to treat Chagas disease. Despite its common use, BNZ has a poor water solubility and a variable bioavailability. The purpose of this study was to prepare BNZ microcrystals by solvent change precipitation and to study the effects of BNZ micronisation on therapeutic efficiency using a murine model of Chagas disease. The solvent change precipitation procedure was optimised in order to obtain stable and homogeneous particles with a small particle size, high yield and fast dissolution rate. The thermal and crystallographic analysis showed no polymorphic change in the microcrystals, and microscopy confirmed a significant reduction in particle size. A marked improvement in the drug dissolution rate was observed for micronised BNZ particles and BNZ tablets in comparison with untreated BNZ and commercial Rochagan®. In vivo studies showed a significant increase in the therapeutic efficacy of the BNZ microparticles, corroborating the dissolution results.     

Combining cytology and microcrystal detection in nonpurulent joint fluid benefits the diagnosis of septic arthritis

Objective

To evaluate the performance of combined cytology and microcrystal detection in joint fluid for diagnosing septic arthritis.

Synovial,articular cartilage and bone changes in rapidly destructive arthropathy (osteoarthritis) of the hip

Summary We studied ten femoral heads from eight patients suffering from rapidly destructive arthropathy (RDA) of the hip. At surgery, 1–3.5 ml of synovial fluid, ranging from citrous to hemorrhagic, was aspirated from six joints. This fluid was viscous, pauci-cellular and did not contain calcium pyrophosphate dihydrate (CaPPD) crystals, although significant amounts of alizarin S-positive material was found in three joints. Significant synovial hyperplasia was found in four joints and moderate hyperplasia in two. Synovium was hypertrophic, hypercellular and slightly to moderately fibrotic. It lacked evidence of perivascular inflammatory infiltrates. Synovium often contained amyloid micro-deposits and alizarin S-positive osteocartilagenous debris surrounded by macrophages. Synovial hyperplasia had a good correlation with osteocartilagenous debris and a poor correlation with amyloid infiltration. Femoral heads were usually flattened and exhibited large areas of exposed bone spotted by plugs of fibro-cartilagenous tissue. Subchondral bone contained large ischemic and necrotic areas, remodeling. Subchondral bone necrosis and ischemia were the most significant findings of this study and their role in the development of RDA is discussed.