Obesity is a metabolic disease that affects all ages; it is considered life-threatening condition as it leads to fatal complications such as; cardiovascular diseases and diabetes. The therapeutic options include; life-style modifications, pharmacotherapy intervention, and surgical intervention. Bariatric surgery (BS) is considered as the most effective option among the others for its rapid weight loss, maintaining the lost mass, and improving the quality of life of the patients. Nevertheless, BS leads to severe changes in the bioavailability of medications, especially for chronic diseases, which may reach to limit where the patient's life endangers. Recently, pharmaceutical formulations had developed several methods to improve the drug bioavailability of drugs though the implying of nanotechnology. Nonotechnology is responsible for reducing the size of the drugs to the nano range (<1000 nm), which increase the drug surface area, dissolution, absorption, and, most importantly, the bioavailability of these drugs. It is believed that BS malabsorption and drugs bioavailability problems can be solved using nanotechnology for its advantages in overcoming BS complications.

The purpose of this study was to formulate topically effective controlled release ophthalmic fluconazole liposomal formulations. Reverse-phase evaporation technique was used for the preparation of fluconazole liposomes consisting of phosphatidylcholine (PC) from soyabean and cholesterol (Ch) in weight ratios of (9:1), (7:2), (7:3), (7:4), (6:4), (7:6) and (5:5) with or without stearylamine (SA) or dicetyl phosphate (DP) as positive and negative charge inducers, respectively. The prepared liposomes were evaluated for their in-vitro release. The release mechanism was found to follow Higuchi and first order kinetics. Increasing cholesterol weight ratio in the prepared liposomal formulations progressively decreased the release of fluconazole from the vesicles. The positively charged liposomes showed slower rate of drug release compared to neutral ones. Negatively charged liposomes showed slight increase in the release rate and extent of fluconazole from the liposomal formulations 5:5:0.25 and 5:5:0.5; in comparison with neutral ones. Further increase in the amount of dicetyl phosphate 5:5:1 resulted in a significant decrease in the release rate.
Four fluconazole liposome eye drops were prepared. Physical stability study including, visual appearance, particle size and amount of drug leakage from liposome eye drops were studied. Approximately 82.82%, 76.55%, and 70.90% of fluconazole was retained in negative, positive and neutral liposomal ocular formulations up to a period of 24 weeks at 5°C.

The aim of this study was to evaluate a possible role of nitric oxide (NO)-cyclic guanylate monophosphate (cGMP) in antinociception induced by sildenafil (phosphodiesterase–5 inhibitor), celecoxib (selective cyclooxygenase-2 inhibitor), and indomethacin (nonselective cyclooxygenase inhibitor). Each of these drugs was administered intraperitoneally into experimental mice at different doses either alone or combined with either Ng -nitro-L-arginine methyl ester hydrochloride (L-NAME, NO synthase inhibitor) or methylene blue (guanylate cyclase inhibitor). Antinociceptive activity was assessed by using a writhing test as the pain model.

The three drugs showed dose-related antinociceptive activity as defined by a reduction in writhing episodes in comparison with controls. Pretreatment of the mice with L-NAME or methylene blue led to inhibition of the antinociceptive effect of any of the three analgesic drugs tested. Ineffective doses of either celecoxib (0.5 mg/kg) or indomethacin (2.5 mg/kg) achieved significant reduction of writhing episodes when concomitantly given with sildenafil at an ineffective dose (0.5 mg/kg). This possible synergistic effect of sildenafil was inhibited when animals were pretreated with either L-NAME or methylene blue. It is concluded that NO-cGMP may play an important role in induction of analgesia by sildenafil, celecoxib, and indomethacin.

Introduction: Developments in industrial pharmacy are often linked to the discovery of pharmaceutical excipients. Although recently introduced as a material for immediate release coatings, Kollicoat IR already has other applications.

Areas covered: In this review, the different properties and pharmaceutical applications of Kollicoat IR as an excipient are discussed. In the first part, the chemical structure and the physicochemical characteristics are examined. The second part is a presentation of the available Kollicoat IR products followed by a brief overview of the preclinical studies completed for its use as an instant release coating material.

Expert opinion: Although the polymer was intended as an immediate release coating material for tablets, grafting PEG with polyvinyl alcohol to form this polymer provides physicochemical properties that lead to ever-broadening applications. Understanding its properties can lead to the development of a new use for Kollicoat IR. The addition of Kollicoat IR to an ethylcellulose or polyvinyl acetate tablet coat was successful at modifying the drug release rate. Designing a successful controlled release coat simply requires acknowledgment of the drug release mechanism from the mixture of polymers that includes Kollicoat IR. Moreover, the interaction between Kollicoat IR and poorly soluble drugs produces fast-dissolving solid dispersions prepared using hot stage extrusion, spray drying, or freeze drying.

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.

Background: There are no studies reported on pharmacokinetics of opioids in patients with hepatocellular carcinoma, the fifth most common cancer in the world.
Methods: The authors have studied the pharmacokinetic profile of oral tramadol (50 mg) capsule in 20 patients with liver carcinoma (10 with primary carcinoma on top of chronic hepatitis C and 10 with secondary metastatic liver malignancy as a result of other primary) compared with 10 healthy controls. Plasma tramadol concentrations were measured in venous samples at intervals up to 12 hours by high-pressure liquid chromatography. All pharmacokinetic variables were evaluated using one-compartment model.
Results: Tramadol bioavailability showed a substantial increase in patients with primary liver cancer and secondary metastatic than that of control (98 percent, 75 percent, and 68 percent, respectively). The area under the serum concentration-time curve increased significantly in patients with primary and metastatic cancer of liver than in control [1,933 μg/h/L (SD = 41), 1,327 μg/h/L (SD = 51), 1,138.5 μg/h/L (SD = 31), respectively]. Also, a significant difference in Cmax and Tmax was found between patients with malignant liver and control. Reduced clearance and impaired elimination was significantly observed in patients with liver carcinoma than control. Clearance was reduced to 50 percent of control, and elimination halflife increased up to three folds in patients with primary liver carcinoma than that of control. Satisfactory pain relief with minimal side effects was observed all over study period.
Conclusion: It is recommended to lengthen the dose interval of oral tramadol, if it is to be used in patients with liver cancer for analgesic purposes, to 50 mg every 12 hours as it is proved to be effective and safe.

Aim: The 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.

Methods: Fifteen patients with liver cirrhosis were included They were given a fixed oral dose of propranolol 80mg on the morning of day 1 after overnight fasting. Blood samples were collected at fixed time intervals for 24h. Patients were given 12 sessions of rectal ozone of 300ml of 40% ozone/oxygen mixture. On day 14 another oral dose of 80mg 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.

Results: Plasma 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.

Conclusions: The 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.

Background: There are no studies reported on the pharmacokinetics of controlled release morphine (MST) in patients with hepatocellular carcinoma, the fifth most common cancer in the world.

Methods: We have studied the pharmacokinetic profile of MST (30 mg) in 15 patients with liver carcinoma (eight with primary carcinoma on top of chronic hepatitis C, and seven with secondary metastatic liver malignancy as a result of other primary) compared with our previously published data for 10 healthy controls. Plasma morphine concentrations were measured in venous blood samples at intervals up to 12 h by high-pressure liquid chromatography. Total body clearance (Cl) and systemic bioavailability were estimated using a compartmental method.

Results: Morphine bioavailability showed a substantial increase in patients with primary liver and secondary metastatic carcinoma than that of controls (64.8, 62.1, and 16.8%, respectively). The area under the serum concentration-time curve increased 4-fold in primary carcinoma (416 [sem25] microg h(-1) litre(-1)) and 3-fold (303 [21] microg h(-1) litre(-1)) in metastatic liver patients compared with healthy control (92.5 [3] microg h(-1) litre(-1)). No significant difference was found in T(max) between the two malignant groups but C(max) was significantly greater in primary liver carcinoma patients. Impaired morphine elimination was noted in primary carcinoma only (t(1/2) 5.99 [0.39] h).

Conclusion: Careful administration of morphine is recommended in patients with liver cancer.