COMPARATIVE IN VITRO DISSOLUTION STUDY ON METFORMIN MARKET PRODUCTS USING DIFFERENT DISSOLUTION APPARATUSES

Objective: This study was proposed to evaluate and compare the in vitro dissolution profiles of six Metformin Hydrochloride (MH) market products. Methods: Different dissolution apparatuses (USP apparatus II, IV and beaker method) were used to evaluate the dissolution profiles (in phosphate buffer, pH 6.8) of two immediate release (IR) generic products of Metformin Hydrochloride (MH): Cidophage® 1000 mg (G1, Egyptian market) and Metformin arrow® 1000 mg (G2, French market) with respect to the reference products named Glucophage® 850 mg (R1, Egyptian market and R2, French market). In addition to a generic controlled-release (CR) product; Cidophage Retard® 850 mg (G3) versus the reference product; Glucophage XR® 1000 mg (R3) (both from Egyptian market). Dissolution efficiency (D. E.) and the similarity factor (f2) were calculated. Weight uniformity, hardness, tablet dimensions and MH content were measured. Results: Results of the three apparatuses showed that MH IR products studied (reference and generics) did not meet the 75% USP 30 specifications for MH dissolved at 30 min. For MH CR products, Glucophage XR® did not fulfill the USP release criteria, while Cidophage Retard® did. USP apparatus IV revealed the highest sensitivity and discriminative capability. Conclusion: Generally, MH IR generics (G1 and G2) might be interchangeable with the innovator product (Glucophage®). However, Cidophage Retard® might not be interchangeable with Glucophage XR®

PREPARATION AND EVALUATION OF METRONIDAZOLE SUSTAINED RELEASE FLOATING TABLETS

Objective: The objective of the present study is the preparation of metronidazole (MZ) floating tablets that are designed to retain in the stomach for a long time for better eradication of Helicobacter Pylori (H. pylori), a main cause of peptic ulcer disease. Methods: Synthetic and natural polymers were studied for their floating potential in the presence of sodium bicarbonate, namely: hydroxypropyl methylcellulose (HPMC), carbopol 974P, sodium alginate{low and medium viscosity (LV & MV) grades}, locust gum and guar gum. Hardness, floating ability, release profiles and kinetics as well as DSC / FT-IR were studied. Results: Results of both DSC and FT-IR spectroscopy revealed that there was no interaction between the drug and any of the proposed polymers. Carbopol 974P based tablets showed an unacceptable floating lag time (2 h) and did not maintain good tablet integrity. All other formulas were able to float after few seconds and showed buoyancy for more than 24 h. Meanwhile, sustained profiles of MZ release were obtained. After 6 h the amount of MZ released were: 75.11 %, 61.26 %, 54.56 %, 54.25 % and 43.42 % from sodium alginate-LV, HPMC-K4M, guar gum, locust gum and sodium alginate-MV based tablets, respectively. Kinetically, among the 5 assessed models, the release pattern of MZ from the tablets fitted best to Zero order and Hixson & Crowell Cube-Root models. Conclusion: These stomach targeted dosage forms could maintain the minimum inhibitory concentration for sufficient time to allow for local eradication and thereby achieve better efficiency of therapy with improved patient compliance, reduced costs and minimized side effects caused by immediate release dosage forms

IN VITRO EVALUATION OF IBUPROFEN HOT-MELT EXTRUDED PELLETS EMPLOYING DIFFERENT DESIGNS OF THE FLOW THROUGH CELL

Objective: Hot-melt extrusion technique (HME) was used to prepare a sustained release (SR) multiparticulate oral dosage form (pellets) containing Ibuprofen (IBU). Prepared IBU-HME pellets were in vitro evaluated by flow-through cell dissolution tester (FTC, USP Apparatus #4) using different flow conditions and FTC designs. Methods: In this study, Sucroester®WE15 was used as the polymeric carrier to prepare two different IBU loadings (60 % and 30 % w/w). In order to optimize the FTC conditions, different cell sizes, pellets loading and hydrodynamic conditions of FTC on IBU release rate from pellets were proposed. Results: The results showed that the IBU release rate was increased in the larger cell than the small cell. In addition, laminar flow showed more reproducible results than turbulent flow. It was found that the large cell with laminar flow rate and homogeneous mixing of the pellets with glass beads was the optimum conditions for in vitro evaluation of these preparations. Conclusion: Improper methods of sample loading as well as cell size may result in confusing or erroneous data if not analyzed carefully. Therefore, it might be critical to choose a specific cell design of the FTC for in vitro evaluation of pellets to obtain reliable and discriminative results reflecting the major as well as minor formulation variables

IN-VITRO DISSOLUTION STUDY OF MELOXICAM IMMEDIATE RELEASE PRODUCTS USING FLOW THROUGH CELL (USP APPARATUS 4) UNDER DIFFERENT OPERATIONAL CONDITIONS

Objective: To evaluate and compare the in-vitro dissolution profiles of five generic immediate release (IR) products of Meloxicam (MX) available in Egyptian market with the innovator reference product (Mobic®, R) using different operational conditions of the flow through dissolution cell (FTC, USP Apparatus 4), in phosphate buffer (pH=7.5). Methods: The comparative in-vitro dissolution studies were performed under different FTC operational conditions such as cell size, tablet position within the cell, open and closed loops setup and type of flow (laminar and turbulent) on MX dissolution rate from different IR products. Results: The study showed that two generic products, out of five, gave similar dissolution profiles with R using a specified well controlled condition of FTC. A selected generic product (Mobitil, G1) was tested versus R under different operational conditions of the FTC such as cell size, type of flow, tablet position and open & closed loops setup. The dissolution profile of MX from R was highly affected by changing the tablet position, slightly affected by the open & closed loops setup and not affected by cell size and type of flow. On the other hand, the dissolution profile of MX from G1 was affected by all the previous operational conditions. Comparing ƒ2 values between G1 against R among the different operational conditions proposed, only one in-vitro dissolution test showed similar dissolution profile of G1 with respect to R. Conclusion: Three generic products of MX might not be interchangeable with the innovator product (Mobic®)

Plasma ghrelin level in children with type 1 diabetes mellitus

Background: Type-1 diabetes mellitus(T1DM) is the commonest endocrine-metabolic disease in childhood. Ghrelin is a 28-amino-acid peptide hormone secreted predominantly by P/D1 cells lining the fundus of the stomach and epsilon cells of the pancreas that stimulates appetite with lesser amounts secreted by other cells. It is not clear which factors are involved in the regulation of ghrelin secretion in children with T1DM. Objective: This study aimed to estimate the level of pre-prandial plasma ghrelin level in children with T1DM and to clarify the relationship between its level and some parameters that may affect it as BMI, serum glucose and HbA1C levels and the effect of insulin therapy on its level. Methods: This study included 88 children, 66 diabetic children with type-1 diabetes mellitus(22 new-onset diagnosed diabetic children, 22 good glycemic controlled diabetic children on regular insulin therapy and 22 poor glycemic controlled diabetic children on insulin therapy) and 22 healthy controls. Diabetic children selected from the Diabetic Clinic and Inpatient Pediatric department, Minia University hospital from April 2009 to March 2010. Their ages ranged from 4 to 10 years with a mean 8.5 ± 1.53 years. All children were subjected to history taking, clinical examination, anthropometric measurements and laboratory investigations included: Fasting and two hours post-prandial blood glucose, HbA1C , liver and renal function tests and pre-prandial plasma ghrelin level using enzyme linked immunosorbant assay (ELISA). Results: Pre-prandial plasma ghrelin levels were significantly higher in diabetic children than controls(24.4±21.4 & 9.8±3.6 pg/ml respectively, p value=0.002).Both new-onset and poorly controlled diabetic groups were significantly higher in plasma ghrelin levels (37.03±24.2 & 25.1±19.5 pg/ml, p value=0.001 & 0.001 respectively),but no significant difference between good glycemic controlled diabetic group and controls(11.09±9.6 & 9.8±3.6 pg/ml respectively, p value=0.5). Significant negative correlations were found between ghrelin level and weight, weight on centile, BMI and BMI on centile, ,fasting and 2 hours post prandial glucose levels in all diabetic children. No significant difference between males and females as regards ghrelin level was present. Conclusions: Children with T1DM had significantly higher levels of pre-prandial plasma ghrelin level. Its level increased in both of new-onset and poorly controlled diabetic children. Significant negative correlations between pre-prandial ghrelin level and weight, BMI, fasting and 2-hours post-prandial levels were present. Insulin therapy plays an important role in normalizing plasma ghrelin level in good glycemic controlled T1DM children. No significant correlation between ghrelin and HbA1C was present.Keywords: T1-DM, Ghrelin, Children, Glucose, Insulin, HbA1CEgypt J Pediatr Allergy Immunol 2011;9(2):63-7

The PROVENT-C19 registry: A study protocol for international multicenter SIAARTI registry on the use of prone positioning in mechanically ventilated patients with COVID-19 ARDS

Background The worldwide use of prone position (PP) for invasively ventilated patients with COVID-19 is progressively increasing from the first pandemic wave in everyday clinical practice. Among the suggested treatments for the management of ARDS patients, PP was recommended in the Surviving Sepsis Campaign COVID-19 guidelines as an adjuvant therapy for improving ventilation. In patients with severe classical ARDS, some authors reported that early application of prolonged PP sessions significantly decreases 28-day and 90-day mortality. Methods and analysis Since January 2021, the COVID19 Veneto ICU Network research group has developed and implemented nationally and internationally the "PROVENT-C19 Registry", endorsed by the Italian Society of Anesthesia Analgesia Resuscitation and Intensive Care. . .'(SIAARTI). The PROVENT-C19 Registry wishes to describe 1. The real clinical practice on the use of PP in COVID-19 patients during the pandemic at a National and International level; and 2. Potential baseline and clinical characteristics that identify subpopulations of invasively ventilated patients with COVID-19 that may improve daily from PP therapy. This web-based registry will provide relevant information on how the database research tools may improve our daily clinical practice. Conclusions This multicenter, prospective registry is the first to identify and characterize the role of PP on clinical outcome in COVID-19 patients. In recent years, data emerging from large registries have been increasingly used to provide real-world evidence on the effectiveness, quality, and safety of a clinical intervention. Indeed observation-based registries could be effective tools aimed at identifying specific clusters of patients within a large study population with widely heterogeneous clinical characteristics. Copyright

Stability and bioavailability of diltiazem/polyethylene oxide matrix tablets

<p>The aim of this study was to prepare and evaluate <i>in vitro</i> and <i>in vivo</i>; Diltiazem-Hydrochloride (DTZ) in sustained-release matrix tablets. Stability of DTZ tablets prepared with polyethylene oxide (MWs 900 000, 4 000 000, and 8 000 000) with or without addition of electrolytes was carried-out for 1-month, under short-term storage at 40 °C/75% RH. Stability was evaluated by DTZ content, DSC and drug release using the Flow-Through Cell (USP # IV). The majority of stored tablets were stable for 1-month under short-term storage with respect to DTZ content and drug release. DSC curves of stored samples showed appearance of new exothermic peak after 1-month storage at 40 °C/75% RH, which was not observed after 5 years storage at room temperature. A selected formula was tested <i>in vivo</i> against reference product on eight healthy human volunteers. DTZ-plasma profiles were different between the two formulae. However, no statistically significant differences were detected between <i>C</i>_max, AUC_0–48 and AUC_0–∞. The two products were therapeutically in-equivalent, as 90% confidence intervals “T/R” were 88.82–205.76, 91.40–139.94, and 93.73–134.97 for <i>C</i>_max, AUC_0–48 and AUC_0–∞, respectively. This study highlighted possible differences observed between the two regimes frequently applied for stability testing.</p

Drug discovery utilizing biotechnological methodologies and Northern Africa biodiversity

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Hematite nanoparticles influence ultrastructure, antioxidant defenses, gene expression, and alleviate cadmium toxicity in Zea mays

The present study describes the response of Zea mays to hematite nanoparticles (NPs) using five concentrations ranged from 500 to 8000 mg kg−1, and Cd2+ concentrations (110 or 130 mg kg−1 Cd2+) only or combined with 500 mg kg−1 NPs, using soil culture. The endpoints measured were root/shoot growth, elements uptake, ultra-structural alterations, lipid peroxidation, some antioxidant enzyme activities, and their relative gene expressions. The results indicated that hematite NPs exhibited a dual behavior, in which 500 mg kg−1 NPs significantly enhanced maize growth, while 4000 and 8000 mg kg−1 NPs significantly increased lipid peroxidation and superoxide dismutase (SOD) activity displaying positive correlation with SOD expression in shoots (r = +0.472, p < .05). Ultrastructure micrographs revealed the appearance of aggregated NPs inside the vacuoles. The stunted growth, perturbed ultra-structure, and high lipid peroxidation were used as toxicity biomarkers for Cd2+. However, combined treatments of 500 mg kg−1 NPs and Cd2+ significantly stimulated growth and glutathione reductase activity, while significantly reduced catalase (CAT) activity displaying positive correlation with CAT expression in roots (r = +0.694, p < .01). In conclusion, hematite NPs could alleviate Cd2+ toxicity not at the level of antioxidant defense, but by affecting mechanisms of Cd2+ detoxification