Faculty of Pharmacy

Three-Dimensional Presentations of Factorial Experimentation Data of Extrusion – Spheronization

Mon, 18 Apr 2016 00:00:00 GMT

Three-Dimensional Presentations of Factorial Experimentation Data of Extrusion – Spheronization El‑Mahdi, Idris; A El-Shehebia, Tariq Extrusion – spheronization technology is one of the major methods for production of multiparticulates in the pharmaceutical industry. The difficulty in this method is how to develop a formulation which provides high drug load and high yield of product of the desired size. In any spheronization operation, loss of significant amount of the formula to very large fraction or fine fraction is unavoidable. The aim of this work is to analyze the data obtained from 3 X 3 factorial experiment prepared using mixes of microcrystalline cellulose (MCC), ketoprofen, and water at three levels for each factor on production of large pellets, pellets, and fines. The factors studied were water content, spheronization speed, and spheronization time. The product obtained in each experiment was subjected to sieving analysis to three fractions, and the data was analyzed with the use of modified computerized method to allow for immediate analysis of such complex 3 X 3 experiment. The new 3-D plots allow for easy identification of the optimum conditions to allow for the maximum production of pellets and capable of identifying the possible interactions between the factors studied in the experiment. The data showed that the significance or non-significance obtained for the studied factors at their respective levels was observed during all the triplicate experiments which may provide for the desired “controlled spheronization”. Based on this work it was concluded that 3-D plots of factorial experiments are of great benefit to formulator than any other 2-D plots, especially in spheronization technology.

Effect of spheronizer plate design on the spheronization of ketoprofen

Wed, 26 Jul 2017 00:00:00 GMT

Effect of spheronizer plate design on the spheronization of ketoprofen A El-Shhibia, Salma; M.El-Mahdi, Idris Spheronization is a rapid process for production of microspheres. The process involves the dry mixing ofdrug with microcrystalline cellulose (MCC), which on subsequent wetting with water forms a plasticmass suitable for extrusion and spheronization. As in any pharmaceutical operation, large number offactors may affect the production of pellets, which can be related to formulation or processing ma-chinery. Among the factors related to spheronizers is the spheronization plate design. This work is aimedat evaluation of the effect of using the radial design and the cross-hatch design on product qualitythrough a factorial experiment using ketoprofen as a model drug. The factors studied were MCC level,spheronizer speed and spheronization time. The evaluation methods included sieving analysis, densityand porosity measurements, shape analysis, and dissolution testing. Preliminary experiments revealedthat MCC level is of great significance on pellets yield. Also, all the produced pellets were of acceptablesphericity score. The factorial experiments showed that an increase of pellets yield of desired size can beobtained when using the radial design of friction plate, while no significant changes were foundregarding density, porosity and dissolution rate

Bioavailability of Oral Colon-Specific Ketoprofen Microcapsules

Mon, 02 Oct 2017 00:00:00 GMT

Bioavailability of Oral Colon-Specific Ketoprofen Microcapsules M El-Mahdi, Idris; A El-Shhibia, Salma Oral, colon-specific drug delivery has attracted much interest recently. It is of considerable advantage to have an oral drug delivery system that could be targeted to the colon. This could be either for the local treatment of diseases such ulcerative colitis, irritable bowel syndrome and tumors, or to exploit the colon as a preferred region for systemic drug absorption, possibly as a site for polypeptides absorption. Delivery systems that rely on pH and/or time dependent mechanisms for drug release are less reliable in achieving consistent site-specific drug delivery to the colon. The successful delivery of prodrugs of 5- aminosalicylic acid is an evident of the potential of the bacterial flora. However, it has been less successful in the development of polysaccharide – based dosage forms or synthetic polymer coatings. This work was aimed at the development of ketoprofen microcapsules based on polysaccharide coating. The in-vitro release studies in simulated colonic media showed sensitivity of such dosage form to bacterial enzymes with subsequent increase in dissolution rate. The in -vivo profiles in dogs showed that the tested product exhibited a lagtime prior to commencement of drug absorption. The plasma profiles were not accompanied by a high initial plasma concentration associated with conventional dosage forms

Molecular Modeling Analysis of Atorvastatin Drug Enantiomers

Wed, 02 Dec 2020 00:00:00 GMT

Molecular Modeling Analysis of Atorvastatin Drug Enantiomers Alnajjar, Radwan; Kawafi, Nagwa; Elmhdw, Maraia; Kamunya, Stephanie; Eltumi, Salem; F. Mohamed, Najwa In this work, Atorvastatin, one of the most selling drugs in the world for cardiovascular disease, was studied theoretically. Density functional theory (DFT) calculations were carried out on the four optical enantiomers (SS, SR, RS, RR) of Atorvastatin drug at B3LYP/6-31+G* level in the gas phase. The spectroscopic profiling (1H and 13C NMR chemical shifts) were compared with the available experimental data. Frontier molecular orbital (FMO), thermodynamic properties, the molecular electrostatic potential (MEP), total density of states (DOS) of the four enantiomers were reported, investigated. EHOMO, ELUMO and HOMO-LUMO energy gap (Eg; Δ), Electron affinity (A), Ionization Potential (I), the electronic chemical potential (μ), chemical hardness (η), and electrophilicity (ω) also obtained. The four enantiomers were docked into HMG-CoA reductase active site; their interactions and binding energies were reported and analyzed.

Al-Zaytoonah University of Jordan and The University of Toledo Seventh International Pharmaceutical Conference (ZTIPC 2019)

Thu, 07 Nov 2019 00:00:00 GMT

Al-Zaytoonah University of Jordan and The University of Toledo Seventh International Pharmaceutical Conference (ZTIPC 2019) Al-Qirim, prof.Tariq; Al-Qerem, Dr. Waleed; Sari, prof.youssef; Bryant-Friedrich, Dr. Amanda; Hikmat, Dr. Suhair; Harb, Dr. Mohammad; Mohamed, Dr. Negia; Abul-Futooh, Dr. Hassan; Ali Al-Qirim, MSc. Rania; Abu Sheikha, Prof. Ghassan; Al-Essa, Dr. Luay; Hamed, Dr. Rania; Al-Hiari, Prof. Yusuf; Al Bawab, Dr. Abdel Qader; Hamadneh, Dr. Lama; Alhusban, Dr. Ala`

Bicyclo[1.1.1]Pentane as Phenyl Substituent in Atorvastatin Drug to improve Physicochemical Properties: Drug-likeness, DFT, Pharmacokinetics, Docking, and Molecular Dynamic Simulation

Mon, 09 Nov 2020 00:00:00 GMT

Bicyclo[1.1.1]Pentane as Phenyl Substituent in Atorvastatin Drug to improve Physicochemical Properties: Drug-likeness, DFT, Pharmacokinetics, Docking, and Molecular Dynamic Simulation Alnajjar, Radwan; Mohamed, Najwa; Kawafi, Nagwa Hyperlipidemia influences on numerous diseases, such as atherosclerosis, hypertension, and diabetes mellitus, however it still treatable. Atorvastatin is one of the most common statins; yet, it has poor solubility due to the three phenyl rings, which lead to low bioavailability issues. Herein, we used bicyclo [1.1.1] pentane a benzene bioisostere as a replacement for these phenyl groups. In total, seven analogous 1a, 1b, 1c, 2a, 2b, 2c, and 3 were designed and investigated theoretically. Their drug-likeness, physicochemical properties, bioactivity, and pharmacokinetics properties were reported and analyzed. Further DFT calculations at CAM-B3LYP/6-31+g in water were used to report the electronic properties and thermodynamic properties of the suggested analogues. Docking studied were conducted to mimic the interactions of the new derivatives with the active site of HMG-CoA reductase. Since docking results are not reliable, molecular dynamic simulations were carried out on analogous with the best docking score. Finally, binding free energy using MM-GBSA was calculated from the MD trajectories, reveals that compound 1a has promising properties as a drug with a docking score of -8.99 kcal/mol and MM-GBSA of -45.35kcal/mol

Reactive Dicarbonyls in Human Cataractous Nuclei

Mon, 02 Jun 2008 00:00:00 GMT

Reactive Dicarbonyls in Human Cataractous Nuclei El Mehdi, Eman; Sahoo, Rashmirekha; A Ahmed, Musa; Mohamed rghigh, Abir; Al Geilania, Abdelsalam; Sahoo, Soumendra Non-enzymic glycation of long-lived proteins has been implicated in several age related and diabetes related complications, including cataract. Dicarbonyl compounds such as methylglyoxal and glyoxal have been identified as the predominant source for the formation of advanced glycation end products in various tissues including the lens. Objective: Comparative assessment of the colour of nuclei and quantity of reactive Dicarbonyls present in removed senile cataractous lens nuclei in diabetic and non-diabetic senile cataract cases undergoing routine cataract surgery. Methods: 30 cases were recruited in this study. The preoperative assessment of types and grading of cataract were done after the cases admitted. All the cases were operated by one surgeon (SS) at Great River Eye Hospital Benghazi. The nucleus of the cataractous lens (core part of the human lens) from operated cases first examined for colour and then transferred in dry state to the laboratory for biochemical assay of reactive dicarbonyls. Results: Average concentration of detected reactive dicarbonyls in non diabetics was 2.5148x10 ± 1.2 w/w in comparison to 4.566x10 ± 1.5 w/w in diabetics (p<0.005) in our study. The average concentration of detected dicarbonyls in nondiabetic females is 2.55X10 ±1.2w/w.in comparison to2.45X10 ±1.2w/w in males, while the detected concentrations in diabetic females are 4.58X10 ±1.4 in comparison to 4.46X10 ±1.9w/w in males. Conclusion: We observed more browning of the removed cataract nuclei in cases that had diabetes in comparison to cases without diabetes. There has been significant high level of reactive dicarbonyls detected in removed nuclei from diabetic individuals than from non-diabetics.

Review of Biological Properties, Composition and Toxicity of Annonna Muricata

Thu, 24 Sep 2020 00:00:00 GMT

Review of Biological Properties, Composition and Toxicity of Annonna Muricata A. Algeryani, Safa; F. Al Shwihdy, Najwa; Omar, Ruwida; El-shinitri, Nouha; A. Alnajjar, Radwan Annona muricata also known as a Grviola is a fruit tree with a long history of traditional use. A. muricata has a wide array of ethnomedicinal activities and containing wide range of chemical compounds including Alkaloids (acetogenins); which represent the major constituents of A. muricata, there were more than 100 annonaceous acetogenins have been isolated from leaves, barks, seeds, roots and fruits of A. muricata. Furthermore; lipids, isoquinoline, lactones, Annomuricatina (protein), Bullatacin and Muricoreacinetc have been isolated from this plant. The plant extracts and secondry metabolites exhibit pharmacological properties such as anti-inflammatory, antibacterial, antioxidant, antiparasitic, hepatoprotective and bilirubin-lowering, anti-diabetic, wound healing, antiobesity, immunomodulatory, and anticancer activity. The present review summarizes the information concerning the traditional uses, phytochemistry, biological activity and two case studies one in-vitro on pancreatic cancer cells and other in-vivo study on breast cancer that had been carried recently to assess the effects of Graviola.

Computational, Pharmacological Evaluation and Comparative Similarity against Chloroquine for Some New Designed Hybridized Molecules and their Potential Use as Antiviral against COVID-19 and Malaria

Mon, 15 Jun 2020 00:00:00 GMT

Computational, Pharmacological Evaluation and Comparative Similarity against Chloroquine for Some New Designed Hybridized Molecules and their Potential Use as Antiviral against COVID-19 and Malaria Najar, Adel; MK Omar, Ruwida; Bobtaina, Eman Starting from the concept of "similar molecules exert similar biological activities" to modify structures of biologically active molecules or readily available drugs to improve their therapeutic activity or reduce side effects. Four designed 7- Chloroqunioline-N-Heterocyclic molecules that are derived from parent compound chloroquine (which recently has attracted wide international attention due to its potential activity against COVID-19) were investigated regarding QSAR and some electronic parameters compared to the original drug. Their chemical properties, biochemical properties, and physio-chemical properties were evaluated using computational chemistry. The method used for calculations was semi-empirical-geometry optimization-PM3. Single crystal X-ray crystallography data of Chloroquine and calculated data have been done using the same parameters. Surprisingly, the experimental and calculated data recorded the same values. Furthermore, in Silico evaluation of pharmacokinetics, drug-likeness and medicinal chemistry friendliness of four hybridized molecules compared to chloroquine by using SwissADME web tool confirm closeness of four hybrids to the chloroquine. The total energy, binding energy, dipole moment energy gap (HOMOLUMO) and log p of one of compounds coded AB1-4Py were -7.6647.710 Kcalmol-1, -3981.323, 4.531, 8.161 eV, and 4.25 respectively. AB2-4py compound calculated total energy was76007.6- , Binding energy at - 4109.424, dipole moment at 4.464, energy gap (EHOMO-ELUMO) at 8.131 and log p at 4.70. The AB1-4py, AB2-4py and chloroquine reported same stability and bioactivities. From QSAR study, the value of Log P indicates hydrophobic nature. The recorded values of AB1-4Py and AB2-4py were completely agreed with those of chloroquine. Therefore, this study may valuable in the discovery of a new series of potential drugs for treatment of malaria or COVID-19.

Reactive Dicarbonyls in removed cataractous lens nuclei, aqueous humor and plasma of senile cataract patients

Sun, 23 Sep 2012 00:00:00 GMT

Reactive Dicarbonyls in removed cataractous lens nuclei, aqueous humor and plasma of senile cataract patients Sahoo, Soumendra; Sahoo, Rashmirekha; El Mehendi, Iman; Abuajila Ahmad, Musa Background:- Dicarbonyl compounds such as methylglyoxal and glyoxal have been identified as the predominant source for the formation of advanced glycation end products (AGE) in various tissues contributing to aging and cataract formation in the lens. The aim of the study was to compare the level of reactive dicarbonyls in removed senile cataractous lens nuclei, aqueous humor and plasma of diabetic and non-diabetic cases. Methods: -. This was a cross sectional study done with sample size of 60 senile cataract cases. Half cases were known diabetic while other half non-diabetic. The reactive dicarbonyl levels were detected through UV spectrophotometry. Results: - The mean dicarbonyls level in lens nuclei, aqueous humor and plasma were 888.07 ± 14.95 nmol/L, 2.85 ± 0.44 nmol/L and 2.71 ± 0.44 nmol/L respectively in diabetic individuals where as in non diabetic cases the respective mean levels were 490 ± 8.72 nmol/L, 1.80 ± 0.34 nmol/Land 1.78 ± 0.45 nmol/L (p<0.001). Conclusion: - Diabetic cases were noted to have more browning of their cataractous nuclei. There was a significant elevation of dicarbonyls in the removed nuclei, plasma and in aqueous humor in diabetics.

Pryazolylpyridine and Triazolylpyridine derivative of hydroxychloroquine as Potential Therapeutic against COVID-19: Theoretical Evaluation

Sun, 16 Aug 2020 00:00:00 GMT

Pryazolylpyridine and Triazolylpyridine derivative of hydroxychloroquine as Potential Therapeutic against COVID-19: Theoretical Evaluation M.K. Omar, Ruwida; M. Najar, Adel; Bobtaina, Eman; F. Elsheikh, Awad In attempt to improve the biological activity of the well-known drug hydroxychloroquine (HQC), eight derivatives (HQ1-4Py – HQ8-4Py) based on the core of HQC were design and their electronic properties including frontier molecular orbitals, total energy and structural parameters were estimated at semi-empirical PM3 levels. Pharmacological parameters such as physicochemical, pharmacokinetics, drug-likeness and medicinal chemistry friendliness have been evaluated to estimate the drugs similarity. Introducing these moieties affect both electronic and drug likeness properties, HQ5-Py shows promised properties such large Eg and good clogP, The obtained results show that the suggested derivates may represent a potential drug candidate for COVID-19.