Mechanisms of Drug Solubility Enhancement Induced by ß-Lactoglobulin-Based Amorphous Solid Dispersions.

Protein-based amorphous solid dispersions (ASDs) have emerged as a promising approach for enhancing solubility in comparison to crystalline drugs. The dissolution behavior of protein-based amorphous solid dispersions (ASDs) was investigated in various pH media. ASDs of four poorly soluble model drugs with acidic (furosemide and indomethacin), basic (carvedilol), and neutral (celecoxib) properties were prepared by spray drying at 30 wt % drug loading with the protein ß-lactoglobulin (BLG). The effect of spray-dried BLG (SD-BLG) solubility and protein binding ability with dissolved drugs in solution were investigated to retrieve the mechanisms governing the improvement of drug solubility from the BLG-based ASDs. Powder dissolution results showed that all ASDs obtained a higher maximum concentration (Cmax) compared to the respective pure crystalline drugs. It was found that the solubility increase of the drugs from the ASDs was to a large extent dependent on the solubility of the pure SD-BLG at the investigated pH values (low solubility at pH near the isoelectric point (pI) of BLG). Furthermore, drug-protein interactions in a solution were observed, in particular at pH values where the drugs were neutral. These drug-protein interactions also resulted, to some extent, in the stabilization of the drug in supersaturation.

Assessment of mean platelet volume and aortic intima media thickness in pediatric familial Mediterranean fever: as early markers of atherosclerosis.

OBJECTIVE: Familial Mediterranean fever is the most common auto-inflammatory disease in childhood. The aim of present study is to assess whether familial Mediterranean fever increases the risk of premature atherosclerosis. MATERIALS AND METHODS: It is a case-control prospective study. The study included 32 patients in attack-free period and 22 healthy children who did not have any chronic disease. Demographic features, clinical findings, response to colchicine therapy, Mediterranean Fever gene mutations were recorded in familial Mediterranean fever group. Mean platelet volume and intima-media thickness were evaluated as a possible marker of early onset atherosclerosis. Intima media thickness of abdominal aorta and common carotid arteries with color Doppler ultrasound, mean platelet volume and acute phase reactants were measured in both groups. RESULTS: No significant difference was documented between the patient and control groups regarding the intima-media thickness (p>0, 05). Familial Mediterranean fever patients had significantly higher mean platelet volume values compared with the controls (8.35±1.0 vs. 7.79±0.78 fl, p=0.026). Intima media thickness and mean platelet volume values of familial Mediterranean fever patients were not correlated with lipid profiles, inflammatory markers. CONCLUSIONS: The present study found out no evidence that intima media thickness of abdominal aorta and common carotid arteries in familial Mediterranean fever patients could predict early atherosclerosis. However, mean platelet volume value was found higher in children with familial Mediterranean fever. Mean platelet volume may be useful marker to show premature atherosclerosis in familial Mediterranean fever.