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The present research investigates the enhancement of the dissolution rate of celecoxib by using spray-drying to prepare a solid dispersion with various polymers, namely Kollicoat IR® (Kollicoat), polyvinyl alcohol (PVA) 22000, or polyethylene glycol 6000 (PEG). The investigated drug-to-polymer mass ratios were 1:1, 1:2, and 1:4 by weight. Hydroalcoholic or methylene chloride solvent systems were used. The obtained yields ranged from 65% to 78%, whereas the entrapment efficiencies were between 68% and 82%. The results revealed an increase in the dissolution rate of the prepared particles up to 200% within 20 min. The prepared particles were investigated using differential scanning calorimetry, scanning electron microscopy, X-ray diffraction, and Fourier transform infrared spectroscopy. The increased dissolution rate was attributed to hydrogen bond formation between celecoxib and each polymer together with the reduced size of the formed particles offering a greater overall surface area. It was concluded that spray-drying may be considered a successful one-step technique to improve the dissolution rate of celecoxib when using Kollicoat, PVA, or PEG as the carrier polymer.

We have studied the kinetic profile of controlled release morphine (MST) in 12 patients with posthepatitic cirrhosis, caused by HCV and HBsAg, with portal hypertension, given MST 30 mg for endoscopic sclerotherapy and compared the data with those from 10 healthy controls. Plasma drug concentrations were measured in venous blood samples at intervals up to 12 h by high-pressure liquid chromatography (HPLC). Total body clearance (Cl) and systemic availability were estimated using a compartmental method. Patients with cirrhosis had less clearance (0.586 litre h-1) than controls (0.729 litre h-1). Mean residence time (MRT) was prolonged in cirrhotic patients (19.57 h) compared with controls (7.03 h). Elimination half-life in cirrhotic patients (mean 7.36 (SEM 0.45) h) was nearly twice that of controls (4.01 (0.15) h). Serum concentrations were higher at all sampling times in the cirrhotic patients (peak concentration 35.2 (3.2) ng ml-1 compared with 12.8 (0.4) ng ml-1 in controls). For these changes in the kinetic profile of morphine (as MST) in cirrhotic patients, who experienced more sedation than controls, a smaller dose study together with longer dosing intervals is recommended.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Experimental work has shown that ozone protected both the liver and kidney from reperfusion injury through release of mediators of nitric oxide. Rectal ozone increased oxygenation in the intestinal wall (250%), portal vein (134%) and liver parenchyma (127%) in experimental animals. The kinetics of propranolol and other oxidation-dependent drugs have been reported to be affected due to liver cirrhosis. Several experimental studies have reported improved propranolol clearance through increased hepatic blood flow. WHAT THIS STUDY ADDS• This current study looked for evidence in man of improved hepato-splanchnic oxygenation after rectal ozone. Changes in metabolic pathway via measurement of portal vein oxygenation and the kinetic profile changes of propranolol as an index drug for metabolic oxidation in the liver were measured.• This small preliminary clinical study showed that improved propranolol clearance was obtained by rectal ozone in humans for the first time. In addition there was also evidence of improved portal vein oxygen tension and saturation after rectal ozone. This study has a potential clinical significance. AIMThe aim of this study was to investigate the effect of rectal ozone on portal vein oxygenation and the pharmacokinetic changes of propranolol in patients with liver cirrhosis. METHODSFifteen patients with liver cirrhosis were included They were given a fixed oral dose of propranolol 80 mg on the morning of day 1 after overnight fasting. Blood samples were collected at fixed time intervals for 24 h. Patients were given 12 sessions of rectal ozone of 300 ml of 40% ozone/oxygen mixture. On day 14 another oral dose of 80 mg propranolol was given and blood samples were collected as on day 1. Plasma concentrations of propranolol were measured by HPLC. Portal vein oxygen tension and saturation were measured before and after rectal ozone. RESULTSPlasma concentrations of propranolol were reduced after ozone therapy with pronounced decreases in the maximum plasma concentration and the area under the plasma concentration-time curve. The changes were consistent with a decrease in propranolol bioavailability. There was a decrease in the elimination half-life and mean residence time. Portal vein oxygenation significantly increased after rectal ozone. CONCLUSIONSThe changes in the pharmacokinetics of propranolol probably reflect an increase in the rate and extent of its metabolism resulting from improved portal vein oxygenation attributable to the ozone therapy. The present work highlights that ozone can be an alternative medical measure to improve portal vein oxygenation in liver cirrhosis.