Effect of temperature and fat content on the solubility of hydrochlorothiazide and chlorothiazide in milk

The solubility of hydrochlorothiazide and chlorothiazide in milk has been studied. Experiments were carried out at 5, 15, 25, and 37 degrees C on a buffer solution of pH 6.5, a 2.6% solution of casein, bovine skim milk samples, and bovine milk samples with fat contents of 0.75, 1.70, and 3.50%. The "total" solubility of both drugs in the media studied was higher than the buffer solubility. The highest "total" solubility for both drugs was observed in skim milk. Based on binding data of thiazides to milk, the "total" solubility was split into "free" and "bound" solubility. The increases of solubility noted cannot be explained on the basis of drug-milk binding data. The enhancement of solubility was attributed to the increase of intrinsic solubility of drugs in milk. Results of the thermodynamic analysis of solubility data showed that a different solubilization process of hydrochlorothiazide may be responsible for the high solubility values found in skim milk for this drug. In contrast, the thermodynamic parameters of chlorothiazide in all types of milk are similar, indicating a common solubilization mechanism. The biopharmaceutical significance of the findings is discussed in light of the freeze-dried drug-milk formulations and coadministration of drugs with milk in general.     

Dissolution studies of drug formulations using ion-selective electrodes as sensors in an air-segmented continuous flow analyzer

The application of drug ion-selective electrodes as sensors for the direct determination of the released drug in a continuous-flow analyzer for automated dissolution studies is described. Flow-through electrodes, selective to chlorpromazine, amitriptyline, propantheline, cimetidine, and ranitidine, have been constructed and used for the dissolution studies of 18 dosage forms using the rotating basket apparatus. The dissolution profiles are obtained in the form of potential peaks versus time.     

Improvement of an enhanced recovery protocol for radical cystectomy

IntroductionEnhanced recovery protocols (ERPs) aim to improve outcome following major abdominal surgery. Our ERP for radical cystectomy focuses on reduced bowel preparation and standardised feeding and analgesic regimens. Although the ERP safely decreased hospital stay, time to return of bowel function has not been affected. The current study aims to assess the addition of chewing gum on return of bowel function as part of an ERP.Patients and methodsWe examined the addition of chewing gum to our ERP. Data was obtained retrospectively from 112 consecutive patients, 56 before and 56 after implementing chewing gum in to the EPR. The primary outcome measured was return of bowel function signified by first defecation after surgery.ResultsThe demographics of the two groups showed no significant difference in age, gender distribution, American Society of Anesthesiologists grade, or type of urinary diversion. A significant reduction in the time to return of bowel function was observed in patients using chewing gum post-operatively (4 versus 6 days, p < 0.0001). The median inpatient stay was 13 days in both groups; however there was a trend to an earlier discharge in those patients receiving chewing gum.ConclusionThe introduction of chewing gum to our ERP is associated with a faster return of bowel function and may lead to a reduced inpatient stay.     

Reactive oxygen species and erectile dysfunction: possible role of NADPH oxidase

Erectile dysfunction (ED) is a widespread condition, the incidence of which is increasing globally. ED is also indicative of underlying vasculopathy and represents a predictor of more serious cardiovascular disorders. Understanding the aetiology of ED may therefore provide invaluable pointers to the pathobiology of other cardiovascular diseases (CVDs) and syndromes. It follows, too, that therapeutic interventions that are successful in treating ED may, ipso facto, be effective in treating the early stages of conditions that include atherosclerosis, angina, plaque rupture and diabetic angiopathy. One common pathological denominator in both CVD and ED is oxidative stress, that is, the overproduction of reactive oxygen species (ROS), in particular, superoxide (O(2)(*-)) and hydrogen peroxide (H(2)O(2)). In this review, therefore, we consider the aetiology and pathobiology of O(2)(*-) in promoting ED and focus on NADPH oxidase as an inducible source of O(2)(*-) and H(2)O(2). Therapeutic strategies aimed at reducing oxidative stress to improve erectile function are also discussed.     

Improved antibody coating protocol using a second antibody antiserum. Application to total thyroxin immunoassay

A complete antibody coating protocol for the preparation of dry antibody coated tubes is presented. This protocol is based on a recently described antibody immobilization principle. We modify this immobilization principle in order to improve and simplify the coating procedure. In addition, we propose a drying procedure that provides long-term storage stability of the antibody coated tubes. According to the modified protocol, polystyrene plastic tubes are first coated with rabbit gamma-globulins. The tubes are incubated with a sheep anti-rabbitIgG antiserum dilution. After incubation, antigen-specific antibody antiserum raised in rabbits is added directly into the tubes containing the sheep anti-rabbit IgG antiserum solution (difference from the original protocol). Finally, the tubes are washed, blocked, and dried following the drying procedure developed. The suitability of the modified protocol for the development of immunoassays requiring high loading of antibody was exemplified through the development of a RIA for total thyroxin. The estimated assay characteristics (detection limit 4 microg/L, dynamic range up to 210 microg/L, within-run CV 2.7-5.7%, between-run CV 5.1-7.3%, recovery 84.4-112%, cross-reactivity for T3 1.9%) were comparable with those provided by commercially available RIA kits for the determination of thyroxin.     

Automated flow injection determination of salicylates using Trinder reaction for clinical analysis, assays and dissolution studies of formulations

An automated flow-injection technique is described for salicylate (25-250 or 80-800 mg l(-1)), salicylamide (30-300 mg l(-1)), methylsalicylate (100-1000 mg l(-1)) and acetylsalicylic acid (after alkaline hydrolysis), based on their colour reaction with iron (III) in weak acid medium. The method was evaluated for the determination of salicylate in serum, the assay of the drugs in commercial formulations and automated dissolution studies of drug tablets. There were decreased interferences because of the short reaction time. The precision was good with RSD less than 1% in all cases. Recoveries of salicylate from spiked sera (100-1000 mg l(-1)) varied from 96.4-102.5% (mean 99.3%), and from spiked sample solutions of acetylsalicylic acid, 97.8-103.0% (mean 99.6%). The results of the analysis of commercial drug formulations obtained with the proposed method agreed well with the current USP and BP procedures, with differences of 0.4-1.5% (mean 0.8%). High measurement rates of 180 or 95 per hour were achieved using manifolds without and with predilution respectively.     

Penicillamine administration reverses the inhibitory effect of hyperhomocysteinaemia on endothelium-dependent relaxation in the corpus cavernosum in the rabbit

OBJECTIVE: To elucidate the role of copper in mediating the impact of homocysteine on vasculogenic erectile dysfunction (VED), by investigating the effect of dietary supplementation with the copper-chelator penicillamine to rabbits rendered hyperhomocysteinaemic (HHC) with a methionine-rich diet, as a raised plasma level of homocysteine might be a risk factor for VED. MATERIALS AND METHODS: Homocysteine inhibits the nitric oxide (NO)-dependent relaxation of the corpus cavernosum (CC), an effect which appears to be mediated via the generation of superoxide (O2*-), and H2O2. Copper is a catalyst for the generation of H2O2 in the presence of homocysteine and in the presence of copper, H2O2 undergoes reactions resulting in the generation of O2*-, which reacts with NO to produce peroxynitrite (ONOO-), thereby reducing the bioavailability of NO and impairing NO-mediated relaxation of CC. Smooth muscle strips from CC were obtained from two groups of adult New Zealand White rabbits, one rendered HHC with a diet supplemented with methionine (group 1) and another HHC group that had additional dietary supplementation with penicillamine (group 2). Tissue O2*- levels were measured in each group. After pre-contraction with phenylephrine, relaxation responses of CC strips to carbachol were also assessed in both groups. RESULTS: Methionine supplementation led to profound HHC in all rabbits. Penicillamine in group 2 reduced the total plasma Cu2+ compared to group 1. There was a markedly lower carbachol-stimulated relaxation of CC from HHC rabbits in group 1, with a mean (sem) maximum relaxation of 37 (4)% (six samples), than in group 2, at 58 (6)%. CONCLUSION: These data show that elevated levels in vivo of homocysteine in the rabbit markedly impair NO-dependent relaxation of the CC. Furthermore, this effect appears to be augmented by copper. Further clinical studies on homocysteine and copper status in patients with VED are warranted.