Antoine Al-Achi

Erythrocytes as Oral Delivery Systems for Human Insulin

The use of different forms of human red blood cells as oral carrier systems for human insulin in vivo was the subject of this investigation. Male Wistar rats were made diabetic by a single intraperitoneal injection of streptozocin (100 mg/kg). Three days after the injection, rats were found diabetic as evidenced by elevated fasted blood glucose concentration (200 mg/dl or higher). Rats received orally one of the following (100 U, 2 ml): an insulin solution, a ghosts-insulin suspension, a vesicles-insulin suspension, a liposomes-ghosts-insulin suspension, or a liposomes-vesicles-insulin suspension. Free carrier suspensions or sodium chloride solution (0.9%) were also given orally as controls. Blood glucose concentration was determined just before administration and at 1, 2, 3, 4, 5, 6, and 7 hr post administration. The results show that all treatment groups, except liposomes-ghosts-insulin, were significantly different statistically from their respective controls (i.e., the free carriers).

Does incorporation of thromboelastography improve bleeding prediction following adult cardiac surgery

Cardiopulmonary bypass (CPB) coagulopathy increases utilization of allogenic blood/blood products, which can negatively affect patient outcomes. Thromboelastography (TEG) is a point-of-care measurement of clot formation and fibrinolysis. We investigated whether the addition of TEG parameters to a clinically based bleeding model would improve the predictability of postoperative bleeding. A total of 439 patients’ charts were retrospectively investigated for 8-h chest tube output (CTO) postoperatively. For model 1, the variables recorded were patient age, gender, body surface area, clopidogrel use, CPB time, first post-CPB fibrinogen serum level, first post-CPB platelet count, first post-CPB international normalized ratio, the total amount of intraoperative cell saver blood transfused, and postoperative first ICU hematocrit level. Model 2 had the model 1 variables, TEG angle, and maximum amplitude. The outcome was defined as 0–8-h CTO. The predictor variables were placed into a forward stepwise regression model for continuous outcomes. Analysis of variance with adjusted R2 was used to assess the goodness-of-fit of both predictive models. The predictive accuracy of the model was examined using CTO as a dichotomous variable (75th percentile, 480 ml) and receiver operating characteristic curves for both models. Advanced age, male gender, preoperative clopidogrel use for 5 days or less, greater cell saver blood utilization, and lower postoperative hematocrit levels were associated with increased 8-h CTO (P < 0.05). Adding TEG angle and maximum amplitude to model 1 did not improve CTO predictability. When TEG angle and maximum amplitude were added as predictor factors, the predictability of the bleeding model did not improve.

Human Insulin Binding to Erythrocyte-Membrane

AbstractThe binding of human insulin to erythrocyte membrane in the form of ghosts, vesicles (ultrasonicated ghosts), lipid-coated-ghosts or lipid-coated-vesicles was the subject of this study. Insulin was found to associate with ghosts in two mechanisms, by encapsulation and adsorption on the surface. Insulin binding reached equilibrium with a much faster rate with ghosts than the other carriers, due to these two mechanisms. The findings from this study suggest that the use of these carrier-insulin systems may be of value in the delivery of insulin in the treatment of diabetes.

Physico-Mechanical Properties of Coprocessed Excipient MicroceLac® 100 by DM(3) Approach.

PurposeTo determine the effect of relative humidity (RH) and hydroxypropyl methylcellulose (HPMC) on the physico-mechanical properties of coprocessed MacroceLac® 100 using ‘DM3’ approach.MethodsEffects of RH and 5% w/w HPMC on MacroceLac® 100 Compressibility Index (CI) and tablet mechanical strength (TMS) were evaluated by ‘DM3’. The ‘DM3’ approach evaluates material properties by combining ‘design of experiments’, material’s ‘macroscopic’ properties, ‘molecular’ properties, and ‘multivariate analysis’ tools. A 4X4 full-factorial experimental design was used to study the relationship of MacroceLac® 100 molecular properties (moisture content, dehydration, crystallization, fusion enthalpy, and moisture uptake) and macroscopic particle size and shape on CI and TMS. A physical binary mixture (PBM) of similar composition to MacroceLac® 100 was also evaluated. Multivariate analysis of variance (MANOVA), principle component analysis, and partial least squares (PLS) were used to analyze the data.ResultsMANOVA CI ranking was: PBM-HPMC > PBM > MicroceLac®100 > MicroceLac®100-HPMC (p < 0.0001). MANOVA showed PBM’s and PBM-HPMC’s TMS values were lower than MicroceLac®100 and MicroceLac®100-HPMC (p < 0.0001). PLS showed that % RH, HPMC, and several molecular properties significantly affected CI and TMS.ConclusionsSignificant MicroceLac®100 changes occurred with % RH exposure affecting performance attributes. HPMC physical addition did not prevent molecular or macroscopic matrix changes.

Intraduodenal Administration of Biocarrier-Insulin Systems

AbstractSuccessful oral administration of insulin for systemic therapeutic effects has long been a major pharmaceutical challenge. Intraduodenal administration of insulin to rats, free or in a form of carrier-insulin, was the subject of this study. Several erythrocyte-membrane carrier systems (ghosts, vesicles, liposomes-ghosts, and liposomes-vesicles) were tested. Insulin (100 U) was incubated with each of the carriers at 37°C for 24 hr. The carrier-insulin system, insulin solution, sodium chloride solution, or carrier-free insulin was then introduced into the duodenum of anesthetized male Wistar diabetic rats. Blood samples were collected from the tail at different time intervals and then analyzed for glucose content using an o-toluidine method. There was no significant difference in blood glucose concentrations among the control groups. However, ghosts-insulin, vesicles-insulin, and liposomes-vesicles-insulin all showed a statistically significant difference in lowering blood glucose levels when compar...

Evaluation of the Moisture Prediction Capability of Near-Infrared and Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy Using Superdisintegrants as Model Compounds

The superdisintegrants (SDs) moisture content measurement by near-infrared (NIR) spectroscopy and attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy has been evaluated against thermogravimetric analysis as a reference method. SDs with varying moisture content were used to build calibration and independent model verification data sets. Calibration models were developed based on the water-specific NIR and ATR-FTIR spectral regions using partial least-square regression methods. Because of the NIR water low molar absorptivity, NIR spectroscopy handled higher moisture content (∼81%, w/w) than ATR-FTIR (∼25%, w/w). A two-way ANOVA test was performed to compare R(2) values obtained from measured and predicted moisture content (5%-25%, w/w) of SDs. No statistically significant difference was observed between the predictability of NIR and ATR-FTIR methods (p = 0.3504). However, the interactions between the two independent variables, SDs, and analytical methods were statistically significant (p = 0.0002), indicating that the predictability of the analytical method is material dependent. Thus, it would be important to recognize this highly dependent material and analytical method interaction when using NIR moisture analysis in process analytical technology to analyze and control critical quality and performance attributes of raw materials during processing with the goal of ensuring final product quality attributes.

Human insulin absorption from the intestine in diabetic rats

AbstractThe ability of human insulin to produce hypoglycemia in streptozocin-diabetic rats (average weight 500 g) was investigated. A simple solution of human insulin (insulin in hypotonic buffer solution) was administered intraduodenally. Rats received a dose of insulin of either 200 U/kg, 400 U/kg, or 600 U/kg. The hypoglycemic response was most significant when 600 U/kg solution of insulin was administered. The 200 U/kg dose was of two forms; one form was a solution of insulin with a concentration of 25 U/ml, 4 ml, and the other was a solution of insulin with a concentration of 50 U/ml, 2 ml. The dose of 25 U/ml, 4 ml produced a more significant hypoglycemic response than that of 50 U/ml, 2 ml. Carrier-insulin systems were also introduced intraduodenally in streptozocin-diabetic rats. The results indicate that the carrier systems without insulin had glucogenic effect. Despite this glucogenic effect, carrier-insulin systems at 200 U/kg dose were as effective as that of 600 U/kg of insulin solution. We c...

A brief report on some physiological parameters of streptozocin-diabetic rat

Several biological changes occur when streptozocin is given to experimental animals. The rat streptozocin (STZ) model is extensively used in diabetic experiments. In this brief report, the main physiological characteristics of rats injected with streptozocin are presented. These characteristics are manifested by weight loss, organ weight reduction, serum glucose elevation, decrease in serum insulin level, and other enzyme and hormonal changes. A collection of these parameters may be helpful in establishing a database to describe this model.

Suppository Preparation: Density Factor Determination for Some Over-the-Counter Analgesic Products:

Background: The formulation of analgesic suppositories by the compounding pharmacist may offer an alternative to patients who cannot take medications orally. Objective: To determine the density factor (DF) for 9 nonprescription nonsteroidal antiinflammatory drugs, aspirin, and acetaminophen for use in compounding suppositories. Methods: Nine nonprescription analgesic products were purchased from local stores in North Carolina. All products were solid dosage forms (ie, tablets, caplets, or geltabs). The solid units were pulverized with a porcelain mortar and pestle and then incorporated into a cocoa butter base for formulating the suppository. The DF estimation was evaluated according to the Paddock method. Results: The highest DF value (mean ± SD) among the products tested was for St. Joseph Aspirin (1.45 ± 0.78); the lowest value was for Motrin IB (ibuprofen) (1.06 ± 0.23). Overall, 11.1% (40/360) of all compounded suppositories had some sort of defect. The most often encountered defect was chipping (3.6%; 13/360); the least encountered was sticking to molds (0.83%; 3/360). Conclusions: A practical method for preparing compounded suppositories provides a viable alternative for patients who require analgesic medications but cannot take them orally.

Diffusion Profile of Human Insulin Through Polycarbonate Membrane

AbstractThe aim of this study was to investigate the diffusion of human insulin through polycarbonate membrane, a common mechanical support used in cell culture studies. The pore size of the polycarbonate membranes, the presence of collagen on the surface of the membrane, and the pH of the medium affected the diffusion of insulin through the membrane. Minimum diffusion occured at pH near the isoelectric point of insulin (5.3). The larger the pore size of the polycarbonate membrane the higher the amount diffused. The transfer rate of insulin was slower when membranes were coated with collagen.