Pharmaceutics

Title: Solubility of Budesonide, Hydrocortisone, and

Prednisolone in Ethanol + Water Mixtures at
298.2 K
1,2 1 1
Authors: Hany S. M. Ali , Peter York , Nicholas Blagden ,
Shahla Soltanpour3, William E. Acree, Jr4,
Abolghasem Jouyban4

Source: Journal of Chemical and Engineering Data, 55 (1), 578-582

(2010)

Address: 1Institute of Pharmaceutical Innovation, University

of Bradford, Richmond Rd., Bradford, BD7 1DP,
U.K., 2Department of Pharmaceutics, Pharmacy
Faculty, Assiut University, Assiut 71515, Egypt,
3Biotechnology Research Center and Pharmacy,

Faculty and Drug Applied Research Center, Tabriz

University of Medical Sciences, Tabriz 51664, Iran,
4Department of Chemistry, University of North

Texas, Denton, Texas 76203-5070, 5Pharmacy

Faculty and Drug Applied Research Center, Tabriz
University

Experimental solubilities of budesonide, hydrocortisone, and prednisolone in

ethanol + water mixtures at 298.2 K are reported. The solubility of drugs was
increased with the addition of ethanol and reached the maximum values of the
volume fractions of 90%, 80%, and 80% of ethanol. The Jouyban-Acree model
was used to fit the experimental data, and the solubilities were reproduced using
previously trained versions of the Jouyban-Acree model and the solubility data in
monosolvents in which the overall mean relative deviations (OMRDs) of the
models were 5.1%, 6.4%, 37.7%, and 35.9%, respectively, for the fitted model, the
trained version for ethanol + water mixtures, and generally trained versions for

-1-
various organic solvents + water mixtures. Solubilities were also predicted by a
previously established log-linear model of Yalkowsky with the OMRD of 53.8 %.
Pharmaceutics

Title: Nanosizing and In-vitro Characterization of

Budesonide Dispersions Prepared by
Microfluidic Reactors

Authors: Hany S.M. Ali1,2, Peter York1, Nicholas Blagden1,

Amir Amani3

Source: Journal of Aerosol Medicine and Pulmonary Drug Delivery.

Abstracts from the Aerosol Society Drug Delivery to the
Lungs 20 (in press) (2010)

Address: 1Institute of Pharmaceutical Innovation, School of

Pharmacy, University of Bradford, Richmond Road,
Bradford BD7 1DP, United Kingdom,
2Pharmaceutics Department, Faculty of Pharmacy,

Assiut University, Egypt, 3Department of Medical

Nanotechnology, School of Advanced Medical
Technologies, Tehran University of Medical Sciences,
Tehran, 1417614411, Iran

Budesonide, a poorly aqueous soluble steroid, is commonly used in the

treatment of asthma in adults and children due to its anti-inflammatory effects.
In this work a microfluidic technique was employed as a bottom-up approach to
prepare nano-sized particles of budesonide. Budesonide nanodispersions were
produced as a result of mixing budesonide solution in ethanol with water as
antisolvent within a set of microreactors. Particle size of the produced dispersion
was analyzed by photon correlation spectroscopy (PCS), while the shape of the
dispersed particles was studied using transmission electron microscopy (TEM).
Results of particle size analysis showed that budesonide nanodispersions (150 to

-2-
350 nm) with narrow size distributions (polydispersity index < 0.25) can be
obtained. TEM showed that budesonide nano-sized particles were spherical with
smooth surfaces. The impact of different factors affecting the nanoprecipitation
process (drug saturation level, flow rate of drug solution and antisolvent, inlet
angle of microreactors and internal diameters of microreactors) was reported. A
marked effect on drug particle size was noticed with changes in flow rates of
solvents and antisolvent. The in vitro aerosolization performance of one of the
prepared nanodispersion was studied and compared with a commercial product of
budesonide for nebulization using the Sidestream jet nebulizer. Overall results
revealed that MMAD of the generated aerosol was significantly smaller (p <
0.05) than that produced the commercial microsuspension (3.9 ± 0.48 µm vs. 6.2
± 1.09 µm, respectively). Also, a significantly higher fine particle fraction (p <
0.05) was achieved with budesonide nanodispersion versus the marketed
suspension of budesonide (56.88 ± 3.37 vs. 38.04 ± 7.81, respectively).

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 Pharmaceutics

Title: Formulation and Evaluation of Ketorolac

Tromethamine-Eudragit Solid Dispersions of
Potential Sustained-Release Properties

Authors: M.A. Ibrahim, M.A. Amin, G. Fetih, A. Abou Ela

Source: STP Pharma Pratiques, 20 (3), 189-200 (2010)

Ketorolac tromethamine (KT) is a non-steroidal anti-inflammatory drug

having a half half-life around 6 h. This study aims to formulate sustained release
forms of KT by preparing solid dispersion in the matrices of Eudragit polymers
(Eud) using coevaporation technique. Tow Eud polymers, namely Eud RS100 and
Eud RL100, were used in preparing KT-coprecipitates at different drug:polymer
ratios. The prepared KT-Eud coprecipitates were characterized for their yield,
drug content and drug in vitro release patterns as well. In addition,
physicochemical characterization was carried out on some KT-Eud coprecipitates
by differential scanning calorimety (DSC) and infrared spectroscopy (IR) so as to
study the possibility of solid-state KT-Eud interaction. Also, KT interaction with
the tested Eud polymers was carried out in solution in phosphate buffer saline
(PBS, pH 7.4) along twenty days. Moreover, the analgesic activity of KT-Eud RS
100 (1: 5) coprecipitate was assessed by tail-flick method and compared to that of
untreated KT. The in vitro release results indicated that the dispersions made of
pure Eud RS exhibited a slower when compared to those prepared using RS/RL
blends. DSC scans of KT-Eud RS 100 (1:5) systems indicated that a complete
suppression of the drug fusion peaks suggesting a homogeneous dissolution of the
drug in the polymer matrix. Eud RL 100 had a greater adsorptive capacity than
Eud RS 100 due to the greater number of quaternary ammonium functions on RL

-4-
surfaces. The maximum analgesic activity of KT-Eud RS100 (1:5) coprecipitate
was between 5 and 6 h extended to 10 h while the maximum analgesic activity of
untreated Ketorolac was between 2 and 2.5 h.

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 Pharmaceutics

Title: Meloxicam Formulations for Transdermal

Delivery: Hydrogels Versus Organogels

Authors: G. Fetih

Source: J. Drug Del. Sci. Tech., 20 (6), 451-456 (2010)

Address: Department of Pharmaceutics, Faculty of Pharmacy,

Assiut University, Assiut, Egypt

The objective of this work was to evaluate the efficacy and suitability of
different organogel formulations as transdermal delivery systems of meloxicam
(MX) compared to hydrogel formulations. Hydrogels and hydroalcoholic gels were
prepared using either carbopol 940 or pluronic F-127 as gelling agents. The
organogels used glyceryl monostrearate (GMS), a glyceryl fatty acid ester as
organogelator in view of the good skin tolerability of this group of organogelators.
The liquid phase was oleic acid, Mygliol 812 or Labrasol. In vitro drug release
through cellophane membrane was studied. The effect of some formulation
variables (organogelator concentration, type of liquid phase, drug concentration
and method of drug incorporation) on the release patterns of meloxicam (MX)
from different organogels was investigated. In vitro skin permeation through
excised rat skin in phosphate buffer (pH 7.4) was carried out. The in vivo skin
penetration was evaluated by measuring the anti-inflammatory effect in rats by
the paw edema test. The highest drug release was obtained from Mygliol 812
organogel, Labrasol organogel and hydroalcoholic pluronic gel. The results
revealed an inverse correlation between the drug release rate and organogelator
concentration and direct correlation between the drug release rate and the initial
drug concentration. The release rate of the drug was dependent on the nature of

-6-
the gel’s liquid component (which influences drug solubility), but not on the
method of drug incorporation. Permeation across rat skin showed that Mygliol
812 and Labrasol organogels were superior to hydrogels and hydroalcoholic gels.
The anti-inflammatory activity of the drug in different formulations was studied
using carragenan-induced rat paw edema method. The results showed an excellent
anti-inflammatory activity for the tested formulations, but the anti-inflammatory
activity of organogels was significantly higher than that of hydroalcoholic gel.
Histopathological examination of rat skin treated with the selected formulations
showed normal skin histology. These findings suggest that these organogels could
be effective vehicles for transdermal delivery of meloxicam.

-7-
 Pharmaceutics

Title: Tailoring the Efficacy of Nimodipine Drug

Delivery using Nanocarriers Based on A2B
Miktoarm Star Polymers

Authors: Soliman GM, Sharma R, Choi AO, Varshney SK,

Winnik FM, Kakkar AK, Maysinger D

Source: Biomaterials, 32, 8382-92 (2010)

-8-
 Pharmaceutics

Title: Robust Polymeric Nanoparticles for the Delivery

of Aminoglycoside Antibiotics Using
Carboxymethyldextran-b-poly(ethyleneglycols)
Lightly Grafted with n-Dodecyl Groups

Authors: Soliman GM, Szychowski J, Hanessian S, Winnik

FM

Source: Soft Matter, 6, 4504-4514 (2010)

-9-
 Pharmaceutics

Title: Minocycline Block Copolymer Micelles and their

Anti-Inflammatory Effects on Microglia

Authors: Soliman GM, Choi AO, Maysinger D, Winnik FM

Source: Macromolecular Bioscience, 10, 278-88 (2010)

-10-
 Pharmaceutics

Title: Film Forming Gel for Treatment of Oral

Mucositis: In-vitro Studies

Authors: Mohamed Attia, Heba Y. El Badawy

Source: International J. of Drug Delivery, 2, 314-21 (2010)

-11-
 Pharmaceutics

Title: Indomethacin Sustained Release Pellets

Prepared by Extrusion-Spheronization

Authors: M. El-Badry, Gamal M. Mahrous, Mohamed A.

Ibrahim, F.K. Al-Anazi

Source: J. Drug Del. Sci. Tech., 20 (2), 119-125 (2010)

-12-
 Pharmaceutics

Title: Preparation and Investigation of Acetyl Salicylic

Acid Caffeine Complex for Rectal Administration

Authors: M. El-Badry, Ehab A. Fouad, Fars K. Alanazi,

Maha M. Arafah, Ibrahim A. Alsarra, Riyad Al-
Ashban

Source: Pharm. Dev. Tech., 15 (3), 249-257 (2010)

-13-
 Pharmaceutics

Title: Design and Evaluation of Ciprofloxacin

Hydrochloride Ocular Inserts

Authors: Mohamed Attia, Mohamed El Azizi, Mohamed S.

Hashish

Source: J. Pharmacy and Pharmacology, (2010, In press)

-14-
 Pharmaceutics

Title: Formulation and Evaluation of Sustained

Release Tablets Containing Antioxidants

Authors: J. Cantoni1, S. Shawky Tous2*, B. Bataille1, P.

Prinderre3, J. P. Reynier3, S. Hansel-Esteller1

Source: Bull. Pharm. Sci., Assiut University, 33 (1), 9-18 (2010)

Address: 1Department of Pharmacy, Lapeyronie Hospital,

Montpellier, France, 2Department of Pharmaceutics,
Faculty of Pharmacy, Assiut University, Assiut,
Egypt, 3Department of Galenic Pharmacy and
Biopharmacy, Faculty of Pharmacy, Marseille,
France

Deficiency in nutrients especially antioxidants play an important role in the

pathogenesis of acquired immuno-deficiency syndrome (AIDS). Antioxidants;
vitamin A, vitamin C, vitamin E, zinc and selenium are available in market as
capsules. The release rate is very fast followed by fast elimination. It is necessary
to prolong the residence time of antioxidants. Sustained release tablet formulation
was designed and evaluated on small scale and on large scale preparations. Low
attention has been discuss the use of sustained release formula in treatment of
AIDS. Sustained release tablet formulation was designed and evaluated on small
scale and on large scale preparations. The formulated tablets contained beta-
carotene, vitamin C, tocopherol acetate, selenium, yeast and zinc pidolate.
Vitamin C was chosen as tracer for detection and evaluation of tablet dosage
form. Vitamin C was found to be stable in 0.1 N HCl (pH 1.2) along 8 hrs at
37°C. The formulated tablets passed the pharmacopeial requirements for all tablet

-15-
tests. The formulated tablets showed sustained release characteristics of vitamin
C as a tracer, within 8 hrs.

-16-
 Pharmaceutics

Title: Mucoadhesive Buccal Patches of Lornoxicam: I-

Development and In-Vitro Characterization

Authors: Fawzia Habib, Maha Abdel Azeem, Gihan Fetih,

Mohamed Safwat

Source: Bull. Pharm. Sci., Assiut University, 33 (1), 59-68 (2010)

Address: Department of Pharmaceutics, Faculty of Pharmacy,

Assiut University, Assiut, Egypt

Lornoxicam as a non-steroidal anti-inflammatory drug (NSAID) has the

same side effects of this group if taken orally (GIT, renal, and hepatic disorders).
Lornoxicam and its metabolites bind extensively to plasma albumin (99%), beside
that, it has a relatively short half-life (3 to 5 hrs). The drug was formulated in
mucoadhesive buccal patches using different polymers including, hydroxyethyl
cellulose (HEC), hydroxypropyl cellulose (HPC), hydroxypropylmethyl cellulose
(HPMC), chitosan, polyvinyl alcohol (PVA), gelatin, sodium alginate and sodium
carboxymethyl cellulose (Na CMC).
The physical characteristics of the formulated patches as mass uniformity,
patch thickness, surface pH, folding endurance, swelling, residence time as well as
mucoadhesion (in-vitro and ex-vivo mucoadhesion force) were evaluated. The in-
vitro release of the drug from the formulated patches was studied using the USP
dissolution apparatus, and the results indicated that HEC, HPC and chitosan
showed the lowest drug release (70%, 76%, and 81%, respectively) while gelatin,
sodium alginate and Na CMC gave the highest release (nearly 100%). Permeation
of lornoxicam formulated in different patches through rabbit buccal mucosa was
also studied and the results showed that gelatin and chitosan patches resulted in
the highest drug permeation. Kinetics of drug release from the different patches
was found to follow zero order or diffusion kinetics.

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 Pharmaceutics

Title: Formulation and Characterization of Gelucire

Pellets for Sustained Release of Ibuprofen

Authors: Gihan Nabil Fetih

Source: Bull. Pharm. Sci., Assiut University, 33 (2), 217-224 (2010)

Address: Deptartment of Pharmaceutics, Faculty of

Pharmacy, Assiut University, Assiut, Egypt

The aim of the present study was to develop ibuprofen (IBU) - loaded pellets
by melt solidification technique using Gelucire 50/13 (GL) as a lipid carrier in
different concentrations. This system was intended to prolong the drug release in
order to minimize the drug related adverse effects and improve bioavailability in
different gastrointestinal tract conditions. The prepared pellets were evaluated
using scanning electron microscopy (SEM), Infrared spectroscopy (IR), and
Differential scanning calorimetry (DSC) studies. Process yield, drug loading,
encapsulation efficiency, and particle size distribution were also investigated. The
effect of agitation speed and amount of GL on pellets properties was evaluated.
In-vitro drug release of ibuprofen from prepared pellets was studied in HCl buffer
(pH1.2) for 2 hrs, and in phosphate buffer (pH 7.4) for up to 8 hrs. The obtained
pellets were spherical in shape with smooth surfaces; and GL showed no
interaction with the drug. The release of drug from the pellets showed low
percentage of drug release in pH 1.2. However, at pH 7.4 the obtained results
showed that optimum levels of drug were released in a sustained manner.

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 Industrial Pharmacy

Title: Design and Evaluation of Novel pH-Sensitive

Chitosan Nanoparticles for Oral Insulin Delivery

Authors: Makhlof A.1,2, Tozuka Y.2, Takeuchi H.2

Source: Eur. J. Pharm. Sci., doi:10.1016/j.ejps.2010.12.007

Address: 1Department of Industrial Pharmacy, Assiut

University, Assiut, Egypt, 2Laboratory of
Pharmaceutical Engineering, Gifu Pharmaceutical
University, 1-25-4 Daigaku-nishi, Gifu 501-1196,
Japan

Chitosan nanoparticles (CS NPs) have been commonly regarded as potential

carriers for the mucosal delivery of therapeutic peptides because of their
biocompatibility, bioadhesion and permeation enhancing properties. However,
they have limited colloidal stability and readily dissociate and dissolve in the
acidic gastric conditions. In the current study, CS NPs were formulated by ionic
cross-linking with hydroxypropyl methylcellulose phthalate (HPMCP) as a pH-
sensitive polymer and evaluated for the oral delivery of insulin. In vitro results
revealed a superior acid stability of CS/HPMCP NPs with a significant control
over insulin release and degradation in simulated acidic conditions with or
without pepsin. Furthermore, fluorescently-labeled CS/HPMCP NPs showed a 2-
to 4-fold improvement in the intestinal mucoadhesion and penetration compared
to CS/TPP NPs as evidenced by quantitative fluorescence analysis and confocal
microscopy. After s.c. injection to rats, no significant difference in the
hypoglycemic effect of insulin solution or insulin-loaded CS/HPMCP NPs was
observed, confirming the physico-chemical stability and biological activity of the
entrapped peptide. Following peroral administration, CS/HPMCP NPs increased
the hypoglycemic effect of insulin by more than 9.8 and 2.8 folds as compared to

-19-
oral insulin solution and insulin-loaded CS/tripolyphosphate (TPP) NPs,
respectively.

-20-
 Industrial Pharmacy

Title: In-vitro and In-vivo Evaluation of WGA-

Carbopol Modified Liposomes as Carriers for
Oral Peptide Delivery
1,2 2 2 2
Authors: Makhlof A. , Fujimoto S. , Tozuka Y. , Takeuchi H.

Source: Eur. J. Pharm. Biopharm., doi:10.1016/j.ejpb.2010.12.008

Address: 1Department of Industrial Pharmacy, Assiut

University, Assiut, Egypt, 2Laboratory of
Pharmaceutical Engineering, Gifu Pharmaceutical
University, 1-25-4 Daigaku-nishi, Gifu 501-1196,
Japan

Surface modification of liposomal nanocarriers with a novel polymer-lectin

conjugate was proposed for enhancing the systemic uptake of encapsulated
peptide and protein therapeutics after oral administration. Wheat germ
agglutinin (WGA) was covalently attached to carbopol (CP) using the
carbodiimide method. The prepared WGA-CP conjugate retained the biological
cell binding activity of WGA without any evidence of cytotoxicity to Caco-2
monolayers. Cationic liposomes in the size range of 100 nm were prepared by the
lipid film hydration method followed by probe sonication and surface
modification with negatively charged WGA-CP. The uptake of WGA-CP
liposomes by Caco-2 cells was significantly higher than non-modified or CP
liposomes. The uptake was dependent on the surface concentration of WGA,
temperature, and incubation period, and was significantly inhibited in the
presence of chlorpromazine and 10-fold excess of free WGA. These results suggest
the involvement of active transport mechanism for the cellular uptake of the
modified liposomes, mediated mainly by binding of WGA to its specific cell

-21-
membrane receptors. Dual channel confocal microscopy confirmed the
simultaneous association and internalization of the polymer conjugate and the
liposomal carrier by Caco-2 cells and intestinal membrane of rats. In addition, the
pharmacological efficacy of calcitonin, a model peptide drug, was enhanced by
more than 20 and 3 folds following peroral administration of calcitonin-loaded
WGA-CP liposomes as compared to non-modified and CP liposomes, respectively.

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 Industrial Pharmacy

Title: A Mucoadhesive Nanoparticulate System for the

Simultaneous Delivery of Macromolecules and
Permeation Enhancers to the Intestinal Mucosa
1,2 1 1 1
Authors: Makhlof A. , Werle M. , Tozuka Y. , Takeuchi H.

Source: J. Control. Release, doi:10.1016/j.jconrel.2010.02.001

Address: 1Laboratory of Pharmaceutical Engineering, Gifu

Pharmaceutical University, 1-25-4 Daigaku-nishi,
Gifu 501-1196, Japan, 2Current address: Department
of Industrial Pharmacy, Assiut University, Assiut,
Egypt

The feasibility of combining safe permeation enhancers in a mucoadhesive

particulate system for the oral delivery of peptide drugs was investigated in this
study. Polyelectrolyte complex nanoparticles (NPs) were prepared by ionic
interaction of spermine (SPM) with polyacrylic acid (PAA) polymer. Cytotoxicity
studies in Caco-2 monolayers revealed the safety of the delivery system in the
concentration range used for permeation enhancement. The cellular transport of
fluorescein isothiocyanate dextran (FD4) showed higher permeation enhancing
profiles of SPM-PAA NPs, as compared to SPM solution or PAA NPs prepared
by ionic gelation with MgCl2 (Mg-PAA NPs). These permeation enhancing
effects were associated with a reversible decrease in TEER values, suggesting a
paracellular permeation pathway by reversible opening of the tight junctions.
Furthermore, confocal microscopy results revealed strong association of the NPs
prepared using fluorescence labeled PAA to Caco-2 cells. The permeation
enhancing properties of SPM-PAA NPs were further evaluated in vivo after oral
administration to rats, using FD4 and calcitonin as models of poorly permeating

-23-
drugs. Confocal microscopy images of rats’ small intestine confirmed previous
findings in Caco-2 cells and revealed a strong and prolonged penetration of FD4
from the mucosal to the basolateral side of the intestinal wall. In addition, the
proposed NPs were efficient in improving the oral absorption of calcitonin, as
evidenced by the significant and prolonged reduction of the blood calcemia in rats.

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 Industrial Pharmacy

Title: Nanoparticles of Glycol Chitosan and its

Thiolated Derivative Significantly Improved the
Pulmonary Delivery of Calcitonin
1,2 1 1 1
Authors: Makhlof A. , Werle M. , Tozuka Y. , Takeuchi H.

Source: Int. J. Pharm., 397, 92-95 (2010)

Address: 1Laboratory of Pharmaceutical Engineering, Gifu

Pharmaceutical University, 1-25-4 Daigaku-nishi,
Gifu 501-1196, Japan, 2Current address: Department
of Industrial Pharmacy, Assiut University, Assiut,
Egypt

A novel thiomer derivative of glycol chitosan (GCS) was synthesized by

coupling with thioglycolic acid (TGA) and evaluated for the pulmonary delivery
of peptides. Nanoparticles (NPs) based on GCS and GCS-TGA were obtained by
the ionic gelation method and demonstrated a particle size in the range of 0.23-
0.33 μm with positive surface charge and high calcitonin entrapment. Fluorescent
GCS-TGA NPs resulted in a 2-fold increase in mucoadhesion to lung tissue after
intra-tracheal administration to rats as compared to non thiolated NPs.
Evaluation of pulmonary toxicity revealed the biocompatibility of the two
nanoparticulate formulations with lung tissue. The efficacy of the prepared NPs
to enhance the pulmonary absorption of peptides was evaluated after pulmonary
administration to rats using a liquid micro-sprayer technique. Calcitonin-loaded
GCS and GCS-TGA NPs resulted in a pronounced hypocalcemic effect for at least
12 and 24 h, and a corresponding pharmacological availability of 27 and 40%,
respectively. These findings suggest that both GCS and its thiomer derivative are
promising and safe carriers for pulmonary peptide delivery.

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 Industrial Pharmacy

Title: Carbopol-Lectin Conjugate Coated Liposomes

for Oral Peptide Delivery

Authors: Werle M.1, Makhlof A.1,2, Takeuchi H.1

Source: Chem. Pharm. Bull., 58, 432-434 (2010)

Address: 1Laboratory of Pharmaceutical Engineering, Gifu

Pharmaceutical University, 1-25-4 Daigaku-nishi,
Gifu 501-1196, Japan, 2Current address: Department
of Industrial Pharmacy, Assiut University, Assiut,
Egypt

Within the current study, a delivery system based on a novel polymer-lectin

conjugate (carbopol-lectin) was evaluated for the oral delivery of therapeutic
peptides and proteins. It was demonstrated that covalent attachment of lectin to
carbopol does neither decrease nor abolish the specific binding properties of lectin.
Bioadhesion studies revealed that liposomes coated with carbopol lectin are more
bioadhesive than liposomes coated with unmodified carbopol. Finally, the in vivo
data suggest that carbopol-lectin conjugate coated liposomes are effective oral
peptide delivery systems which are capable of increasing the pharmacological
effect of orally administered calcitonin.

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 Pharmacognosy

Title: New 2-(2-Phenylethyl)chromone Derivatives

from the Seeds of Cucumis melo L var.
reticulatus
Authors: Sabrin R. M. Ibrahim

Source: Natural Product Communications, 5 (3), 403-406 (2010)

Address: Department of Pharmacognosy, Faculty of

Pharmacy, Assiut University, Assiut 71526, Egypt

Chemical investigation of the methanolic extract of the seeds of Cucumis

melo L. var. reticulatus (Cucurbitaceae) afforded three new chromone derivatives;
5,7-dihydroxy-2-[2-(4-hydroxyphenyl)ethyl]chromone 3, 5,7-dihydroxy-2-[2-(3,4-
dihydroxyphenyl)ethyl]chromone 4, and 7-glucosyloxy-5-hydroxy-2-[2-(4-
hydroxyphenyl)ethyl]chromone 6, together with three known compounds; β-
amyrin 1, β-sitosterol 2, and β-sitosterol-3-O-β-glucopyranoside 5. Their
structures were established by UV, IR, 1D and 2D NMR, in addition to mass
spectroscopic data and comparison with literature data. The hexane and
methanolic extracts were evaluated for their antimicrobial activity, as well as
cytotoxic activity using the brine shrimp bioassay.

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 Pharmacognosy

Title: Methods for Preparing Heterocyclic Rings

Authors: Schofield C. J., Hamed R. B., Batchelar E. T.,

Ducho C.

Source: WO Patent WO/2010/046,713 (2010)

-28-
 Pharmacognosy

Title: Monitoring the Activity of 2-Oxoglutarate

Dependent Histone Demethylases by NMR
Spectroscopy: Direct Observation of
Formaldehyde

Authors: Hopkinson R. J., Hamed R. B., Rose N. R.,

Claridge T. D. W., Schofield C. J.

Source: ChemBioChem., 11, 506-510 (2010)

-29-
 Pharmacognosy

Title: Carboxymethylproline Synthase Catalysed

Syntheses of Functionalised N-Heterocycles

Authors: Hamed R. B., Mecinovic J., Ducho C., Claridge T.

D. W., Schofield C. J.

Source: Chem. Commun., 46, 1413-1415 (2010)

-30-
 Pharmacognosy

Title: Evidence for the Slow Reaction of Hypoxia-

Inducible Factor Prolyl Hydroxylase 2 with
Oxygen

Authors: Flashman E., Hoffart L. M., Hamed R. B., Bollinger

Jr, J. M., Krebs C., Schofield C. J.

Source: FEBS J., 277, 4089-4099 (2010)

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 Pharmacognosy

Title: Laurefurenynes A–F, new Cyclic Ether Aceto-

genins from a Marine Red Alga, Laurencia sp.

Authors: Wael M. Abdel-Mageed1,2, Rainer Ebel2, Fred A.

Valeriote3, Marcel Jaspars2

Source: Tetrahedron, 66, 2855–2862 (2010)

Address: 1Department of Pharmacognosy, Faculty of

Pharmacy, Assiut University, Assiut, Egypt, 2Marine
Biodiscovery Centre, Department of Chemistry,
University of Aberdeen, Old Aberdeen, AB24 3UE,
Scotland, UK, 3Ford Cancer Center, 1 Ford Place,
Detroit, M148202, USA

We report here on the discovery and structure determination of three new

diastereomeric pairs of cyclic ether acetogenins, laurefurenynes A–F, isolated from
the aqueous extract of the alga Laurencia sp. collected in the Philippines.
Extensive use was made of NMR spectroscopic data and high resolution MS to
determine the structures of the pure compounds. The most stable and the lowest
energy conformation was determined using molecular modelling, and their
cytotoxic activity was tested against different tumour cells, a significant
indication that laurefurenyne C and F are moderately cytotoxic, but non selective
whilst the others are inactive.

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-33-
 Pharmacognosy

Title: Dermacozines, A New Phenazine Family from

Deep-Sea Dermacocci Isolated from a Mariana
Trench Sediment
1,2 3
Authors: Wael M. Abdel-Mageed , Bruce F. Milne , Marcell
Wagner4, Marc Schumacher5, Peter Sandor6,
Wasu Pathom-aree7, Michael Goodfellow7, Alan T.
Bull8, Koki Horikoshi9, Rainer Ebel1, Marc
Diederich5, Hans-Peter Fiedler4, Marcel Jaspars1

Source: Org. Biomol. Chem., 8, 2352–2362 (2010)

Address: 1Marine Biodiscovery Centre, Department of

Chemistry, University of Aberdeen, Old Aberdeen,
Scotland, UK AB24 3UE. E-mail: m.jaspars@,
abdn.ac.uk; Fax: +44 1224 272921; Tel: +44 1224
272895, 2Department of Pharmacognosy, Faculty of
Pharmacy, Assiut University, Assiut, Egypt, 3Center
for Computational Physics, Physics Department,
University of Coimbra, Rua Larga, 3004-516,
Coimbra, Portugal, 4Mikrobiologisches Institut,
Universit¨at T¨ubingen Auf der Morgenstelle 28, D-
72076, T¨ubingen, Germany, 5Laboratoire de Biologie
Mol´eulaire et Cellulaire du Cancer, Hˆopital
Kirchberg, 9 rue Edward Steichen, L-2540,
Luxembourg, Grand-Duchy of Luxembourg, 6Varian
Deutschland GmbH, Alsfelder Strasse 6, 64289
Darmstadt, Germany, 7School of Biology, University
ofNewcastle, Ridley Building, Newcastle upon Tyne,
UK NE1 7RU, 8Department of Biosciences,
University of Kent, Canterbury, Kent, UK CT2 7NJ

Dermacoccus abyssi sp. nov., strains MT1.1 and MT1.2 are actinomycetes
isolated from Mariana Trench sediment at a depth of 10 898 m. Fermentation

-34-
using ISP2 and 410 media, respectively, lead to production of seven new oxidized
and reduced phenazine-type pigments, dermacozines A–G (1–7), together with
the known phenazine-1-carboxylic acid (8) and phenazine-1,6-dicarboxylic acid
(9). Extensive use was made of 1D and 2D-NMR data, and high resolution MS
to determine the structures of the compounds. To confirm the structure of the
most complex pentacyclic analogue (5) we made use of electronic structure
calculations to compare experimental and theoretical UV-Vis spectra, which
confirmed a novel structural class of phenazine derivatives, the dermacozines. The
absolute stereochemistry of dermacozine D (4) was determined as S by a
combination of CD spectroscopy and electronic structure calculations.
Dermacozines F (6) and G (7) exhibited moderate cytotoxic activity against
leukaemia cell line K562 with IC50 values of 9 and 7 mM, respectively, while the
highest radical scavenger activity was observed for dermacozine C (3) with an
IC50 value of 8.4 mM.

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-36-
 Pharmacognosy

Title: Organic Structure Determination Using Atomic

Resolution Scanning Probe Microscopy

Authors: Leo Gross1, Fabian Mohn1, NikolajMoll1, Gerhard

Meyer1, Rainer Ebel2, Wael M. Abdel-Mageed2,3,
Marcel Jaspars2

Source: Nature Chem., 2, 821-825 (2010)

Address: 1IBM Research - Zurich, 8803 Ru¨schlikon,

Switzerland, 2Marine Biodiscovery Centre,
Department of Chemistry, University of Aberdeen,
AB24 3UE, UK, 3Department of Pharmacognosy,
Faculty of Pharmacy, Assiut University, Assiut,
Egypt

Nature offers a huge and only partially explored variety of small molecules
with potential pharmaceutical applications. Commonly used characterization
methods for natural products include spectroscopic techniques such as nuclear
magnetic resonance spectroscopy and mass spectrometry. In some cases, however,
these techniques do not succeed in the unambiguous determination of the chemical
structure of unknown compounds. To validate the usefulness of scanning probe
microscopy as an adjunct to the other tools available for organic structure
analysis, we used the natural product cephalandole A, which had previously been
misassigned, and later corrected. Our results, corroborated by density functional
theory, demonstrate that direct imaging of an organic compound with atomic-
resolution force microscopy facilitates the accurate determination of its chemical
structure. We anticipate that our method may be developed further towards
molecular imaging with chemical sensitivity, and will become generally useful in
solving certain classes of natural product structures.

-37-
SPM measurements of the unknown compound.

-38-
 Pharmacognosy

Title: Antimicrobial Effects of Pepper, Parsley, and

Dill and their Roles in the Microbiological
Quality Enhancement of Traditional Egyptian
Kareish Cheese
1 2
Authors: Nahed M. Wahba , Amany S. Ahmed , Zedan Z.
Ibraheim2

Source: Foodborne Pathogens and Disease, 7 (4), 411-418, April

(2010). doi:10.1089/fpd.2009.0412

Address: 1Animal Health Research Institute, Assiut Regional

Laboratory, Assiut University, Assiut, Egypt,
2Department of Pharmacognacy, Faculty of

Pharmacy, Assiut University, Assiut, Egypt

This study was designed to assess the application of some edible plants
including cayenne, green pepper, parsley, and dill to Kareish cheese and to
evaluate the antimicrobial activity of these plant materials against natural
microflora, coliforms, molds, and Staphylococcus aureus. Twelve different
concentrations of ethanol extract of the plants were prepared for determination of
the minimal inhibitory concentration. Cayenne and green pepper extracts showed
highest activity followed by dill and parsley against S. aureus. Addition of
cayenne or green pepper to Kareish cheese during manufacture revealed that both
plants were able reduce the S. aureus population to undetectable level within the
first and second days of storage. To study the effect of combining plant materials
on the microbiological quality of ready-to-eat Kareish cheese, the total bacterial
count, coliform count, and yeast and molds counts were determined. It has been
found that addition of plant materials to Kareish cheese reduced the total

-39-
bacterial and coliform populations. All concentrations of cayenne, green pepper,
dill, and parsley (9%) completely reduced the yeast count within 2 hours. Cayenne
and green pepper completely reduced the mold count within 2 days, whereas
parsley and dill were found to be less effective. Kareish cheese prepared with 1%
cayenne pepper and 3% and 6% each of green pepper, dill, and parsley were found
strongly acceptable to the consumer and considered the most preferable type.
Therefore, this study revealed that pepper, parsley, and dill exhibited antibacterial
activity against natural microflora, coliforms, yeast and molds, and S. aureus in
Kareish cheese, and the addition of these plants is acceptable to the consumer and
may contribute to the development of new and safe varieties of Kareish cheese.

-40-
 Pharmacognosy

Title: Constituents and Secondary Metabolite Natural

Products in Fresh and Deteriorated Cassava
Roots
1,3 1
Authors: Soad A.L. Bayoumi , Michael G. Rowan , John R.
Beeching2, Ian S. Blagbrough1

Source: Phytochemistry, 71, 598-604 (2010)

Address: 1Department of Pharmacy and Pharmacology,

University of Bath, Bath BA2 7AY, UK, 2Department
of Biology and Biochemistry, University of Bath,
Bath BA2 7AY, UK, 3Current Address: Department
of Pharmacognosy, Faculty of Pharmacy, Assiut
University, Assiut, Egypt

A phytochemical analysis of cassava (Manihot esculenta Crantz) fresh roots

and roots suffering from post-harvest physiological deterioration (PPD) has been
carried out. The first isolation and identification of galactosyl diacylglycerides
from fresh cassava roots is reported as well as -carotene, linamarin, and -
sitosterol glucopyranoside. The hydroxycoumarin scopoletin and its glucoside
scopolin were identified from cassava roots during PPD, as well as trace
quantities of esculetin and its glucoside esculin. There is no isoscopoletin in
cassava roots during PPD.

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 Pharmacognosy

Title: Cassava: An Appraisal of its Phtytochemistry

and its Biotechnological Prospects

Authors: Ian S. Blagbrough1, Soad A.L. Bayoumi1,3, Michael

G. Rowan1, John R. Beeching2

Source: Phytochemistry, 71, 1940-1951 (2010)

Address: 1Department of Pharmacy and Pharmacology,

University of Bath, Bath BA2 7AY, UK, 2Department
of Biology and Biochemistry, University of Bath,
Bath BA2 7AY, UK, 3Current Address: Department
of Pharmacognosy, Faculty of Pharmacy, Assiut
University, Assiut, Egypt

The present state of knowledge of the phytochemistry of small molecules

isolated from the roots and leaves of cassava, Manihot esculenta Crantz
(Euphorbiaceae), is reviewed. Cassava roots are an important source of dietary
and industrial carbohydrates, mainly eaten as a source of starch, forming the
staple food to over 500 million; additionally, the roots have value as a raw
material for industrial starch production and for animal feed giving the crop high
economic value, but it suffers markedly from post-harvest physiological
deterioration (PPD). The hydroxycoumarins scopoletin and its glucoside scopolin
as well as trace quantities of esculetin and its glucoside esculin are identified from
cassava roots during PPD. The biotechnological prospects for cassava are also
reviewed including a critical appraisal of transgenic approaches for crop
improvement, together with its use for bioethanol production, due to cassava's
efficient ability to fix carbon dioxide into carbohydrate.

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 Pharmacognosy

Title: Photoactivable Peptides for Identifying Enzyme-

Substrate and Protein-Protein Interactions

Authors: Rotili D., Altun M., Hamed R. B., Loenarz C.,

Thalhammer A., Hopkinson R. J., Tian Y.-M.,
Ratcliffe P. J., Mai A., Kessler B. M., Schofield C. J.

Source: Chem Commun, Accepted (2010)

-43-
 Pharmacognosy

Title: The 2-Oxoglutarate Dependent Oxygenase

JMJD6 Catalyses Oxidation of Lysine Residues
to Give 5S-Hydroxylysine Residues

Authors: Mantri M., Loik N. D., Hamed R. B., Claridge T. D.

W., McCullagha J. S. O., Schofield C.J.

Source: ChemBioChem, Accepted (2010)

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 Pharmacognosy

Title: Pentacyclic Triterpenes from Ficus pandurata

Hance. Fruit

Authors: Amany Sayed Ahmed

Source: Bull. Pharm. Sci., Assiut University, 33 (1), 1-7, (2010)

Address: Department of Pharmacognosy, Faculty of

Pharmacy, Assiut University, Assiut, Egypt

From Ficus pandurata Hance fruits, six triterpenes and three sterols were
isolated. The structure of these compounds were elucidated using physical and
spectral characters including IR, 1H, 13C-NMR including DEPT experiment and
MS.

-45-
 Pharmacognosy

Title: Phytochemical and Biological Study of

Eranthemum nervosum (Vahl) R. Br., Cultivated
in Egypt
1 1
Authors: Mahmoud H. Assaf , Yaser G. Gouda , Ehab S. El-
Khayat2, Reda A. Abd El-Hamid2

Source: Bull. Pharm. Sci., Assiut University, 33 (1), 19-31, (2010)

Address: 1Department of Pharmacognosy, Faculty of

Pharmacy, Assiut University, Assiut, Egypt,
2Department of Pharmacognosy, Faculty of

Pharmacy, Al-Azhar University, Assiut, Egypt

Fractionation and purification of the methanolic extract of the aerial parts

of Eranthemum nervosum (Vahl) R. Br. (Acanthaceae) cultivated in Egypt
yielded eleven compounds named: β-amyrin (1), α-amyrin (2), Lupeol (3), β-
sitosterol (4), Apigenin (5), Kaempferol (6), β-sitosterol 3-O-β-D-glucopyranoside
(7), Benzoic acid (8), Kaempferol-3-O-β-D-glucopyranoside (9), Syringin (10) and
Apigenin 7-O-neohesperidoside (11). Identification of these compounds has been
established by physical, chemical and spectral data as well as comparison with
authentic samples. The LD50; anti-inflammatory; antipyretic; hepatoprotective
and the effect on CNS were studied.

-46-
 Pharmacognosy

Title: Macro- and Micromorphology of the Leaves,

Stems and Flowers of Chrysanthemum
carinatum L.
Authors: A. A. Ali, M. A. El-Shanawani, A. A. Khalifa, M. A.
Mohammad

Source: Bull. Pharm. Sci., Assiut University, 33 (2), 141-168 (2010)

Address: Department of Pharmacognosy, Faculty of

Pharmacy, Assiut University, Assiut, Egypt

The genus Chrysanthemum L. is sometimes called Ismelia, it comprises about

150 species native to tropical and temperate North and South America.
Chrysanthemum carinatum L. is known as Painted daisy, German flag and
Tricolor Chrysanthemum. Some species of genus Chrysanthemum are used
medicinally to cure influenza symptoms, liver and menstrual disorders and have
anti-inflammatory and antispasmodic effects.

-47-
 Pharmacognosy

Title: Minor Constituents from Rubia cordifolia L. Root

Authors: Zedan Z. Ibraheim, Yaser G. Gouda

Source: Bull. Pharm. Sci., Assiut University, 33 (2), 225-233 (2010)

Address: Department of Pharmacognosy, Faculty of

Pharmacy, Assiut University, Assiut, 71526, Egypt

Reinvestigation of the chloroform soluble fraction of the chloroform-

methanol (1:1) extract of the dried roots of Rubia cordifolia L. using different
chromatographic techniques led to isolation of one new naphthohydroquinone
dimer (1) and four known compounds identified as 3--friedelinol (2), atraric acid
(3), vanillic acid (4) and D-3-O-methoxy-chiro-inositol (5). The identification of
the isolated compounds was carried out using different physical, chemical and
spectral methods of analysis.

-48-
 Medicinal Chemistry

Title: Pharmacophoric Model Building for

Antitubercular Activity of the Individual Schiff
Bases of Small Combinatorial Library
Authors: Wesam S. Abdel-Aal, Hoda Y. Hassan, Tarek
Aboul-Fadl, Adel F. Youssef
Source: European Journal of Medicinal Chemistry, 45, 1098-1106
(2010)

Address: Department of Medicinal Chemistry, Faculty of

Pharmacy, Assiut University, Assiut 71526, Egypt

Synthesis and evaluation of anti-TB activity of individual compounds of

Schiff bases combinatorial library were done against Mycobacterium tuberculosis
H37Rv at a single concentration of 6.25 µg/mL according to the protocol of
TAACF. Compounds 2C and 3D produced 99% inhibitory activity on the
investigated organism, while the other tested compounds showed lower activity
ranging from 35 to 84%. It was found that there are no relation between the
anti-TB activity of the tested compounds and their lipophilicity expressed by C
log P of these compounds. A 3D pharmacophoric model has been generated by
Molecular Operating Environment (MOE) using a training set of 10 reported
anti-TB compounds and testing the synthesized compounds (1A, 1B, 1D, 1E, 2C,
3A, 3C, 3D, 3E and 4A–4E). The generated pharmacophoric features include, F1:
hydrogen bond donors (Don), F2: aromatic rings (Aro), F3: hydrogen bond
acceptors (Acc)/metal ligator (ML), F4: Aro/hydrophobic (Hyd). In all hit set, it
was found that the amidic nitrogen CONH–N=C fitted the region of the Don,
F1, while the amidic carbonyl group fitted the region of the Acc/ML, F3. The
distances bridging F1 to F2, F3 and F4 were essential for anti-TB activity in the
developed pharmacophore model, as it was confirmed from model validation
procedure.

-49-
 Medicinal Chemistry

Title: Design of Pentapeptide Inhibitors with

Carboxylic Acid Bioisosteres at P1’ and P4
Positions

Authors: Harichandra D. Tagad, Yoshio Hamada, Jeffrey-Tri

Nguyen, Takashi Hamada, Hamdy Abdel-Rahman,
Abdellah Yamani, Ayaka Nagamine, Hayato Ikari,
Naoto Igawa, Koushi Hidaka, Youhei Sohma,
Tooru Kimura, Yoshiaki Kiso

Source: Bioorg. Med. Chem., 18, 3175-3186 (2010)

-50-
 Medicinal Chemistry

Title: Synthesis and Anti-Mycobacterial Evaluation of

Some Pyrazine-2-Carboxylic Acid Hydrazide
Derivatives.

Authors: Mohamed Abdel-Aziz, Hamdy M. Abdel-Rahman

Source: European Journal of Medicinal Chemistry, 45 (8), 3384-3388

(2010)

-51-
 Medicinal Chemistry

Title: Specific Brain Delivery of Pyridyl Chloro-

ethylurea Derivatives as Potential Antitumor
Agents: Synthesis, Evaluation and Molecular
Modeling Study

Authors: Nawal A. El-Koussi

Source: Bull. Pharm. Sci., Assiut University, 33 (1), 69-78 (2010)

Address: Department of Medicinal Chemistry, Faculty of

Pharmacy, Assiut University, Assiut, Egypt

The present investigation describes the synthesis; evaluation and molecular

modeling studies of a series of 1-substituted-1,4-dihydropyridine-3-
chloroethylurea derivatives IIIa-e as potential agents for treatment of brain
tumors. The incorporation of the 1,4-dihydropyridine moiety in the structure
attains an efficient site specific chemical delivery system (CDS) of the
chloroethylurea (CEU) as a known antitumor pharmacophore to the brain. The
target compounds IIIa-e were synthesized through reduction of the corresponding
quaternary compounds IIa-e. The in-vitro oxidation studies showed that,
compounds IIIa-e could be oxidized into their corresponding quaternary
compounds IIa-e, respectively which attains their “locked in” characteristics as
brain antitumor agents. The in-vivo studies showed that compound IIIa was able
to cross the BBB at detectable concentration. In addition the in-vitro alkylating
activity studies using 4-(4-nitrobenzyl)pyridine (NBP) revealed that compound
IIe is an efficient alkylating agent with activity comparable to reference drug
chlorambucil. The target compounds were tested for their binding to the
colchicine-binding site (CBS) of -tubulin using Molecular Operating
Environment (MOE) software.

-52-
 Organic Chemistry

Title: Synthesis of New 4,5-3(2H)pyridazinone

Derivatives and their Cardiotonic, Hypotensive,
and Platelet Aggregation Inhibition Activities
1 1
Authors: Enas N. Amin , Abdel-Alim M. Abdel-Alim , Samia
G. Abdel-Moty1, Abdel-Naser A. Elshorbagi1,
Mahran Sh. Abdel-Rahman2

Source: Arch. Pharm. Res., 33 (1), 25-46 (2010)

Address: 1Department of Pharmaceutical Organic Chemistry,

Faculty of Pharmacy and 2Department of
Pharmacology, Faculty of Medicine, Assiut
University, Assiut 71526, Egypt

4,5-dihydro-3(2H)pyridazinones such as CI-914, CI-930 and pimobendan

along with tetrahydropyridopyridazine (endralazine) and perhydropyridazino-
diazepine (cilazopril) have been used as potent positive inotropes,
antihypertensives as well as platelet aggregation inhibitors. Accordingly, the
present work involves the synthesis of 24 target compounds; 4,5-dihydro-
3(2H)pyridazinones in addition to seven reported intermediates. The chemical
structures of the new compounds were assigned by microanalysis, IR, 1H-NMR
spectral analysis and some representatives by mass spectrometry. The positive
inotropic effect of the final compounds and the intermediates (12a-12d) as well as
the reported intermediate compound 10 was determined in-vitro on isolated rabbit
heart in comparison to digoxin. Data obtained revealed that twelve of the test
compounds exhibited higher effective response than digoxin, nine compounds
elicited comparable effects to digoxin and eight compounds were less active than

-53-
digoxin. In addition, four compounds approved marked significant hypotensive
effect better than that of the previously reported compound 10.
Moreover, two compounds induced complete platelet aggregation inhibition.
The last two compounds were also subjected to determination of their LD50 and
they showed no signs of toxicity up to the dose level 300 mg / kg (i.p.), while the
reported oral LD50 of digoxin is 17.78 mg / kg. Correlation of cardiotonic and
hypotensive activities with structures of compounds was tried and
pharmacophore models were computed to get useful insight onto the essential
structural features required for inhibiting phosphodiesterase-III in the heart
muscles and blood vessels.

-54-
 Organic Chemistry

Title: Albumin-Based Nanoparticles as Magnetic

Resonance Contrast Agents: I. Concept, First
Syntheses and Characterisation
1 2
Authors: M. M. Stollenwerk , I. Pashkunova-Martic , C.
Kremser3, H. Talasz4, G. C. Thurner3, A. A.
Abdelmoez5,9, E. A. Wallnöfer3, A. Helbok6, E.
Neuhauser5, N. Klammsteiner5, L. Klimaschewski8,
E. Von Guggenberg6, E. Fröhlich7, B. Keppler2, W.
Jaschke3, P. Debbage5

Source: Histochem. Cell Biol., 133 (4), 375-404 (2010); DOI

10.1007/s00418-010-0676-z

Address: 1Faculty of Health and Society, Malmö University,

205 06 Malmö, Sweden. 2Institute of Inorganic
Chemistry, University of Vienna, Währinger Str. 42,
1090 Vienna, Austria. 3Department of Radiology,
Innsbruck Medical University, Anichstrasse 35, 6020
Innsbruck, Austria. 4Section for Clinical
Biochemistry, Biozentrum of the Medical University
Innsbruck, Fritz-Pregl-Straße 3, 6020 Innsbruck,
Austria. 5Department of Anatomy, Histology and
Embryology, Innsbruck Medical University,
Mu¨llerstrasse 59, 6020 Innsbruck, Austria.
6Department of Nuclear Medicine, Innsbruck

Medical University, Anichstrasse 35, 6020

Innsbruck, Austria. 7Center for Medical Research,
Stiftingtalstrasse 24, 8010 Graz, Austria. 8Division of
Neuroanatomy, Department of Anatomy, Histology
and Embryology, Innsbruck Medical University,
Müllerstrasse 59, 6020 Innsbruck, Austria. 9Current
address: Department of Pharmaceutical Organic
Chemistry, Assiut University, Assiut, Egypt

-55-
 To develop a platform for molecular magnetic resonance imaging, we
prepared gadolinium-bearing albumin-polylactic acid nanoparticles in the size
range 20–40 nm diameter. Iterative cycles of design and testing upscaled the
synthesis procedures to gram amounts for physicochemical characterisation and
for pharmacokinetic testing. Morphological analyses showed that the
nanoparticles were spheroidal with rough surfaces. Particle sizes were measured
by direct transmission electron microscopical measurements from negatively
contrasted preparations, and by use of photon correlation spectroscopy; the two
methods each documented nanoparticle sizes less than 100 nm and generally 10–
40 nm diameter, though with significant intrabatch and interbatch variability.
The particles’ charge sufficed to hold them in suspension. HSA retained its
tertiary structure in the particles. The nanoparticles were stable against turbulent
flow conditions and against heat, though not against detergents. MRI imaging of
liquid columns was possible at nanoparticle concentrations below 10 mg/ml. The
particles were non-cytotoxic, non-thrombogenic and non-immunogenic in a range
of assay systems developed for toxicity testing of nanoparticles. They were
micellar prior to lyophilisation, but loosely structured aggregated masses after
lyophilisation and subsequent resuspension. These nanoparticles provide a
platform for further development, based on non-toxic materials of low
immunogenicity already in clinical use, not expensive, and synthesized using
methods which can be upscaled for industrial production.

-56-
 Organic Chemistry

Title: Albumin-based Nanoparticles as Magnetic

Resonance Contrast Agents: II. Physico-
chemical Characterisation of Purified and
Standardised Nanoparticles
1,5 1
Authors: A. A. Abdelmoez , G. C. Thurner , E. A.
Wallnöfer1, N. Klammsteiner2, C. Kremser1, H.
Talasz3, M. Mrakovcic4, E. Fröhlich4, W. Jaschke1,
P. Debbage2

Source: Histochem. Cell Biol., 134 (2), 171-196 (2010);

DOI 10.1007/s00418-010-0726-6

Address: 1Department of Radiology, Innsbruck Medical

University, Anichstrasse 35, 6020 Innsbruck,
Austria. 2Department of Anatomy, Histology and
Embryology, Innsbruck Medical University,
Müllerstrasse 59, 6020 Innsbruck, Austria.
3Biozentrum of the Medical University Innsbruck,

Section for Clinical Biochemistry, Fritz-Pregl-Straße

3, 6020 Innsbruck, Austria. 4Center for Medical
Research, Stiftingtalstrasse 24, 8010 Graz, Austria.
5Current address: Department of Pharmaceutical

Organic Chemistry, Faculty of Pharmacy, Assiut

University, Assiut, Egypt

We are developing a nanoparticulate histochemical reagent designed for

histochemistry in living animals (molecular imaging), which should finally be
useful in clinical imaging applications. The iterative development procedure
employed involves conceptual design of the reagent, synthesis and testing of the
reagent, then redesign based on data from the testing; each cycle of testing and
development generates a new generation of nanoparticles, and this report

-57-
describes the synthesis and testing of the third generation. The nanoparticles are
based on human serum albumin and the imaging modality selected is magnetic
resonance imaging (MRI). Testing the second particle generation with newly
introduced techniques revealed the presence of impurities in the final product,
therefore we replaced dialysis with diafiltration. We introduced further testing
methods including thin layer chromatography, arsenazo III as chromogenic assay
for gadolinium, and several versions of polyacrylamide gel electrophoresis, for
physicochemical characterisation of the nanoparticles and intermediate synthesis
compounds. The high grade of chemical purity achieved by combined application
of these methodologies allowed standardised particle sizes to be achieved (low
dispersities), and accurate measurement of critical physicochemical parameters
influencing particle size and imaging properties. Regression plots confirmed the
high purity and standardisation. The good degree of quantitative physicochemical
characterisation aided our understanding of the nanoparticles and allowed a
conceptual model of them to be prepared. Toxicological screening demonstrated
the extremely low toxicity of the particles. The high magnetic resonance
relaxivities and enhanced mechanical stability of the particles make them an
excellent platform for the further development of MRI molecular imaging.

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 Analytical Chemistry

Title: Fluorometric Study for the Reaction between

Sertraline and 7-Chloro-4-nitrobenzo-2-oxa-1,3-
diazole: Kinetics, Mechanism and Application
for the Determination of Sertraline in Tablets
1 2
Authors: Ashraf M. Mahmoud , Ibrahim A. Darwish , Nasr Y.
Khalil2

Source: Journal of Fluorescence, 20, 607–613 (2010)

Address: 1Department of Pharmaceutical Analytical

Chemistry, Faculty of Pharmacy, Assiut University,
Egypt,
2Department of Pharmaceutical Chemistry, College

of Pharmacy, King Saud University, Riyadh, Saudi

Arabia

A fluorometric study has been carried out, for the first time, to investigate
the reaction of the new generation antidepressant sertraline (SRT) with 7-chloro-
4-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl). In an alkaline buffered medium (pH
8.0), a green fluorescent product exhibiting maximum fluorescence intensity at
532 nm after excitation at 470 nm was produced. The factors affecting the
reaction were carefully studied and the conditions were optimized. The kinetics of
the reaction was investigated, the stoichiometry of the reaction was determined,
and the mechanism was postulated. The activation energy of the reaction was
determined and found to be 27.34 KJ mole−1. Under the optimum reaction
conditions, a linear relationship with good correlation coefficient (r = 0.9998, n =
6) was found between the fluorescence intensity of the reaction product and SRT
concentrations in the range of 0.3–20.0 µg ml−1. The limit of detection and limit
of quantitation were 0.07 and 0.21 µg ml−1, respectively. The intra- and inter-

-59-
assay precisions were satisfactory; the relative standard deviations did not exceed
2.61%. The proposed method was successfully applied to the determination of
SRT in its pharmaceutical tablets with good accuracy; the recovery percentages
were 96.97–102.23 ± 1.01–1.62%. The results were compared favorably with
those of the reported method.

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 Analytical Chemistry

Title: Highly Sensitive HPLC Method with Automated

Co-Sense System and Fluorescence Detection
for Determination of Sertraline in Human
Plasma
1 2
Authors: Nasr Y. Khalil , Ashraf M. Mahmoud , Ibrahim A.
Darwish1, Abdul-Rahman A. Al-Majed1

Source: Chromatographia, 72, 825-831 (2010)

Address: 1Department of Pharmaceutical Chemistry, College

of Pharmacy, King Saud University, Riyadh, Saudi
Arabia, 2Department of Pharmaceutical Analytical
Chemistry, Faculty of Pharmacy, Assiut University,
Egypt

A highly sensitive HPLC method with column-switching “Co-sense” system

and fluorescence detection has been proposed for trace determination of sertraline
(SRT) in human plasma. A simple pre-column derivatization procedure with 7-
chloro-4-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) reagent was employed.
Fluxetine (FLX) was used as an internal standard. Plasma samples were simply
deproteinated with acetonitrile and then derivatized with NBD-Cl in borate
buffer of pH 7.9 at 70 C for 30 min. The derivatized samples were injected into a
pretreatment column (Shim-pack MAY1-ODS) with a washing mobile phase
(acetonitrile: 2% acetic acid, 40: 60) at a flow rate of 5 mL min-1 for 2 min. After
an automated on-line column switching (by Co-sense system) to the analytical
Nucleosil C8 column (150  4.6 mm, 5 µm), the separation of the derivatized SRT
and FLX was achieved using a mobile phase consisted of acetonitrile:10 mmol L-1
sodium acetate buffer (pH 3.5):tetrahydrofuran (40:40:20, v/v) at a flow rate of

-61-
1.0 mL min-1. The derivatized samples were detected at emission wavelength of
531 nm after excitation at 470 nm. Under the optimum chromatographic
conditions, a linear relationship with good correlation coefficient (r = 0.9997) was
found between the peak area ratio and SRT concentration in the range of 5 –
5000 ng mL-1. The limit of detection and limit of quantitation were 1.41 and 4.28
ng mL-1, respectively. The intra and inter-assay precisions were satisfactory; the
relative standard deviations did not exceed 5.63%. The accuracy of the method
was proved; the recovery of SRT from the spiked human plasma was 99.76-
102.62  2.19-5.63%. The proposed method had high throughput as the analysis
involved simple sample pre-treatment procedure and short run-time (~12 min).
The results demonstrated that the method would have a great value if applied in
bioavailability and pharmacokinetic studies for SRT.

-62-
 Analytical Chemistry

Title: Spectral Investigation and Analytical Application

of the Vinylamino-Substituted Haloquinone
Derivatives of Nizatidine and Ranitidine
1 2
Authors: Ibrahim A. Darwish , Samiha A. Hussein , Ashraf
M. Mahmoud2, Ahmed I. Hassan3

Source: Int. J. Res. Pharm. Sci., 1, 1-7 (2010)

Address: 1Department of Pharmaceutical Chemistry, College

of Pharmacy, King Saud University, Riyadh 11451,
Saudi Arabia. 2 Department of Pharmaceutical
Analytical Chemistry, Faculty of Pharmacy, Assiut
University, Assiut 71526, Egypt. 3Department of
Pharmaceutical Analytical Chemistry, Faculty of
Pharmacy, Al-Azhar University, Assiut, 71524,
Egypt

Studies were carried out, for the first time, to investigate the formation and
spectral characteristics of Nvinylamino-substituted haloquinone derivatives of
nizatidine and ranitidine. The reactions involved the condensation of N-
alkylvinylamine formed from the interaction between the free secondary amino
groups in the investigated drugs and acetaldehyde with each of chloranil,
bromanil, and 2,3-dichloronaphthoquinone. The experimentalconditions affecting
the reactions were optimized and the characteristics of the absorption spectra of
the formed colored derivatives were established. Under the optimum reaction
conditions and at the max of the formed derivatives, linear relationships were
found between the absorbances and the concentrations of the investigated drugs
in a concentration range of 10-250 g.ml-1. The limits of assays detection were 2.1-
7.77 g.ml-1. The precisions of the methods were satisfactory; the relative standard
deviations were 1.13-1.73%. The proposed methods were successfully applied to
the analysis of the studied drugs in pure and pharmaceutical dosage forms with

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good accuracy; the recovery percentages were 98.1-101.8 0.58-1.57%. The results
were compared favorably with those of the official methods.

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 Analytical Chemistry

Title: N-Bromosuccinimide/Fluorescein System for

Spectrophotometric Determination of H2-
Receptor Antagonists in Their Dosage Forms
1 1
Authors: Ibrahim A. Darwish , Samiha A. Hussein , Ashraf
M. Mahmoud1, Ahmed I. Hassan2

Source: Int. J. Res. Pharm. Sci., 1, 86-93 (2010)

Address: 1Department of Pharmaceutical Analytical

Chemistry, Faculty of Pharmacy, Assiut University,
Assiut 71526, Egypt, 2Department of Pharmaceutical
Analytical Chemistry, Faculty of Pharmacy, Al-
Azhar University, Assiut, 71524, Egypt

Studies were carried out, for the first time, to investigate the formation and
spectral characteristics of N-vinylamino-substituted haloquinone derivatives of
nizatidine and ranitidine. The reactions involved the condensation of N-
alkylvinylamine formed from the interaction between the free secondary amino
groups in the investigated drugs and acetaldehyde with each of chloranil,
bromanil, and 2,3-dichloronaphthoquinone. The experimental conditions affecting
the reactions were optimized and the characteristics of the absorption spectra of
the formed colored derivatives were established. Under the optimum reaction
conditions and at the max of the formed derivatives, linear relationships were
found between the absorbances and the concentrations of the investigated drugs
in a concentration range of 10–250 g ml–1. The limits of assays detection were
2.61–7.77 g ml–1. The precisions of the methods were satisfactory; the relative
standard deviations were 1.13–1.73%. The proposed methods were successfully
applied to the analysis of the studied drugs in pure and pharmaceutical dosage
forms with good accuracy; the recovery percentages were 98.1–101.8  0.58–
1.57%. The results were compared favorably with those of the official methods.

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 Analytical Chemistry

Title: New Sensitive HPLC Method for Evaluation of

the Pharmacokinetics of New Amantadine
Prodrugs as Hepatic Delivery Systems to
Enhance its Activity Against HCV
1 1
Authors: Ibrahim A. Darwish , Tarek Aboul-Fadl , Nasr Y.
Khalil1, Ashraf M. Mahmoud2, Abdul-Rahman M.
Al-Obaid1

Source: Int. J. Res. Pharm. Sci., 1, 151-157 (2010)

Address: 1Department of Pharmaceutical Chemistry, College

of Pharmacy, King Saud University, Riyadh, Saudi
Arabia, 2Department of Pharmaceutical Analytical
Chemistry, Faculty of Pharmacy, Assiut University,
Egypt

To improve the efficacy of amantadine (AMD) in chronic hepatitis C

therapy, various prodrugs were designed and synthesized to enhance its hepatic
delivery based on the incorporation of AMD into modified bile acid or cysteine
derivatives. A new sensitive and selective HPLC method with fluorescence
detection has been developed and vali- dated for determination of AMD in
human plasma for evaluation of the pharmacokinetics of these prodrugs. Be-
taxolol hydrochloride (BTX) was used as internal standard. AMD and BTX were
isolated from plasma by protein precipitation with acetonitrile and derivatized by
heating with 1,2-naphthoquinone-4-sulphonate (NQS) in alkaline medium (0.01
M NaOH) at 90±5˚C for 45 min. Separations were performed in isocratic mode
on Nucleosil CN column (250 mm leng 3.9 mm i.d., 5 µm particle diameter) using
a mobile phase consisting of acetonitrile:10 mM sodium acetate buffer (pH
3.5):methanol (20:70:10, v/v) at a flow rate of 1.5 mL min-1. The derivatized

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samples were extracted with chloroform and reduced with 0.03% potassium
borohydride. The reduced fluorescent AMD- NQS derivative was monitored at
emission wavelength of 382 nm after excitation at 293 nm. Under the optimum
chromatographic conditions, a linear relationship with good correlation coefficient
(r = 0.9989, n = 5) was found between the peak area ratio of AMD to BTX and
AMD concentration in the range of 30–3200 ng mL-1. The limit of detection and
limit of quantification were 6.7 and 21 ng mL-1, respectively. The intra and inter-
assay precisions were satisfactory; the relative standard deviations did not exceed
1.57%. The accuracy of the method was proved; the recovery of AMD from spiked
human plasma were 97.51-100.95 ± 0.26-1.57%. The method had higher
throughput as it involved simple sample preparation procedure and short run-time
(<15 min). The results demonstrated that the proposed method would have a great
value in the pharmacokinetic studies for AMD released from the synthesized
produgs.

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 Analytical Chemistry

Title: Current Exposure to Persistent Polychlorinated

Biphenyls (PCBs) and Dichlorodiphenyldichloro-
ethylene (p,p′-DDE) of Belgian Students from
Food and Dust
1
Authors: Laurence Roosens , Mohamed Abou-Elwafa
Abdallah2,3, Stuart Harrad2, Hugo Neels1, Adrian
Covaci1,4

Source: Environmental Science and Technology, 44, 2870–2875

(2010)

Address: 1Toxicological Centre, Department of Pharmaceutical

Sciences, University of Antwerp, Universiteitsplein
1, 2610 Wilrijk, Belgium
2Division of Environmental Health and Risk

Management, Public Health Building, School of

Geography, Earth, and Environmental Sciences,
University of Birmingham, Birmingham, B15 2TT,
United Kingdom
3Department of Analytical Chemistry, Faculty of

Pharmacy, Assiut University, 71526 Assiut, Egypt

4Laboratory for Ecophysiology, Biochemistry and

Toxicology, Department of Biology, University of

Antwerp, Groenenborgerlaan 171, 2020 Antwerp,
Belgium

Human exposure to individual polychlorinated biphenyl (PCB) congeners and

dichloro-diphenyldichloroethylene (p,p′-DDE) through food (duplicate diets) and
indoor dust ingestion was assessed for 19 Belgian students. The serum
concentrations of the persistent PCB congeners in serum (PCB 118, 138, 153,
170, and 180) have been correlated with the individual intake through food and
dust. Dietary intakes of ΣPCBs ranged between 40 and 204 ng/day (median

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133). PCB exposure through dust ingestion ranged between 0.1 and 0.8 ng/day
(median 0.3) or 0.3 and 1.7 ng/day (median 0.8), assuming average dust ingestion
(20 mg/day) and high dust ingestion rates (50 mg/ day), respectively. Dietary
intake of p,p′-DDE was comparable to that of PCBs with a range from 21 to 214
ng/day (median 92). The exposure to p,p′-DDE via dust ingestion ranged between
0.02 and 0.43 ng/day (median 0.17) or 0.05 and 1.09 ng/day (median 0.43),
assuming average and high dust ingestion rates, respectively. Concentrations
measured in blood serum were 28-153 ng/g lipid weight (lw) (median 74) and 32-
264 ng/g lw (median 45) for ΣPCBs and p,p′-DDE, respectively. Serum
concentrations in the studied population are slightly lower compared to other
European populations. Inspite of the uncertainty associated with the dust
ingestion rates, food was the predominant exposure pathway for each PCB
congener and for p,p′-DDE in the studied population. Food intake contributed
more than 99% of the combined PCB intake from food and dust. No significant
positive correlations (p>0.05) were observed between the serum concentrations of
PCBs and p,p′-DDE and the total intake through food and dust for each
participant. Instead, it is hypothesized that past and episodic higher current
intakes are more important determinants of body burden than continuous
background exposures at low levels.

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 Analytical Chemistry

Title: Modification and Calibration of a Passive Air

Sampler for Monitoring Vapor and Particulate
Phase Brominated Flame Retardants in Indoor
Air: Application to Car Interiors
1,2 1
Authors: Mohamed Abou-Elwafa Abdallah , Stuart Harrad

Source: Environmental Science and Technology, 44, 3059-3065

(2010)

Address: 1Division of Environmental Health and Risk

Management, School of Geography, Earth and
Environmental Sciences, University of Birmingham,
Birmingham, B15 2TT, United Kingdom
2
Department of Analytical Chemistry, Faculty of
Pharmacy, Assiut University, 71526 Assiut, Egypt

A passive air sampler was modified to monitor both vapor and particulate
phase brominated flame retardants (BFRs) in indoor air using polyurethane foam
disks and glass fiber filters (GFF). Significant correlation (p<0.01) was observed
between passive (ng day-1) and active sampler (ng m-3) derived BFR
concentrations in an office microenvironment (r = 0.94 and 0.89 for vapor and
particulate phase BFRs respectively). A calibration experiment was performed
where concentrations of target BFRs were obtained for an office using a low
volume active sampler operated over a 50 d period alongside passive samplers. The
passive uptake rates of each studied BFR ranged between (0.558-1.509 ng day-1)
and (0.448-0.579 ng day-1) for vapor and particulate phases respectively. The
passive entrapment of particles by the GFF was investigated using environmental
scanning electron microscopy which revealed gravitational deposition of particles
as the main mechanism involved. The developed sampler was applied to monitor

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BFR concentrations in 21 cars. Average concentrations of ΣHBCDs, TBBP-A
and Σtetra-deca BDEs were 400, 3 and 2200 pg m-3 in cabins and 400, 1 and
1600 pg m-3 in trunks. No significant differences (p<0.05) were observed between
levels of ΣHBCDs and Σtri-to hexa- BDEs in cabins and trunks. However,
TBBP-A, BDE-209 and ΣPBDEs concentrations were significantly higher in
vehicle cabins.

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 Analytical Chemistry

Title: Indoor Contamination with Hexabromocyclo-

dodecanes, Polybrominated Diphenyl Ethers,
and Perfluoroalkyl Compounds: An Important
Exposure Pathway for People?
1 2
Authors: Stuart Harrad , Cynthia A. de Wit , Mohamed
Abou-Elwafa Abdallah1,3, Caroline Bergh4, Justina
A. Björklund2, Adrian Covaci5, Per Ola Darnerud6,
Jacob de Boer7, Miriam Diamond8, Sandra Huber9,
Pim Leonards7, Manolis Mandalakis10, Conny
Östman4, Line Småstuen Haug11, Cathrine
Thomsen11, Thomas F. Webster12

Source: Environmental Science and Technology, 44, 3221-3231

(2010)

Address: 1Division of Environmental Health and Risk

Management, School of Geography, Earth, and
Environmental Sciences, University of Birmingham,
Birmingham B15 2TT, U.K.
2Department of Applied Environmental Science

(ITM), Stockholm University,SE-106 91 Stockholm,

Sweden
3Department of Analytical Chemistry, Faculty of

Pharmacy, Assiut University, 71526 Assiut, Egypt

4Department of Analytical Chemistry, Stockholm

University, SE-106 91 Stockholm, Sweden

5Toxicological Centre, Department of Pharmaceutical

Sciences, University of Antwerp, Universiteitsplein

1, 2610 Wilrijk, Belgium
6National Food Administration, P.O. Box 622, SE-

751 26 Uppsala, Sweden

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 7Institute for Environmental Studies (IVM), VU
University Amsterdam, De Boelelaan 1087, 1081 HV
Amsterdam, The Netherlands
8Department of Geography, 100 St George Street

fifth floor, University of Toronto, Toronto, Canada

M5S 3G3
9Norwegian Institute for Air Research, The Polar

Environmental Centre, NO-9296 Tromsø, Norway

10Hellenic Center for Marine Research, Institute of

Marine Biology and Genetics, GR 71003, Heraklion,

Crete, Greece
11Norwegian Institute of Public Health, P.O. Box

4404, Nydalen, N-0403 Oslo, Norway

12Department of Environmental Health, Boston

University School of Public Health, Boston,

Massachusetts 02118

This review underlines the importance of indoor contamination as a pathway

of human exposure to hexabromocyclododecanes (HBCDs), polybrominated
diphenyl ethers (PBDEs), and perfluoroalkyl compounds (PFCs). There is ample
evidence of substantial contamination of indoor dust with these chemicals and
that their concentrations in indoor air exceed substantially those outdoors.
Studies examining the relationship between body burden and exposure via indoor
dust are inconsistent; while some indicate a link between body burdens and
PBDE and HBCD exposure via dust ingestion, others find no correlation.
Likewise, while concentrations in indoor dust and human tissues are both highly-
skewed, this does not necessarily imply causality. Evidence suggests exposure via
dust ingestion is higher for toddlers than adults. Research priorities include
identifying means of reducing indoor concentrations and indoor monitoring
methods that provide the most “biologically-relevant” measures of exposure as
well as monitoring a wider range of microenvironment categories. Other gaps

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include studies to improve understanding of: emission rates and mechanisms via
which these contaminants migrate from products into indoor air and dust;
relationships between indoor exposures and human body burdens; relevant
physicochemical properties; the gastro-intestinal uptake by humans of these
chemicals from indoor dust; and human dust ingestion rates.

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 Analytical Chemistry

Title: Selective Densitometric Determination of Four

-Aminocephalosporins Using Ninhydrin

Authors: Gamal A. Saleh, Fardous A. Mohamed, Salwa R.

El-Shaboury, Azza H. Rageh

Source: Journal of Chromatographic Science, 48, 68-75 (2010)

Address: Department of Pharmaceutical Analytical

Chemistry, Faculty of Pharmacy, Assiut University,
71526 Assiut, Egypt

A simple, selective, and precise densitometric method for analysis of four αα-
aminocephalosporins, namely cefaclor monohydrate, cefadroxil monohydrate,
cefalexin anhydrous, and cefradine anhydrous, both in bulk drugs and in
formulations was developed and validated. The method employed thin-layer
chromatography (TLC) aluminium sheets precoated with silica gel G 60 F254 as
the stationary phase. The solvent system consists of ethyl acetate–methanol–
water with different ratios for all studied drugs (Rf values of 0.40–0.60). The
separated spots were visualized as blue to violet color after spraying with
ninhydrin reagent. The linear regression analysis data for the calibration plots of
all studied drugs produced a good linear relationship with correlation coefficients
ranging from 0.9990 to 0.9996 and coefficients of determination ranging from
0.9986 to 0.9992 over the concentration range 2–10 μg/spot. The limits of
detection and quantitation for all studied drugs ranged from 0.09 to 0.23 and
from 0.27 to 0.84 μg/spot, respectively. The developed method was applied
successfully for the determination of the studied drugs in their pharmaceutical

-75-
dosage forms with good precision and accuracy. Also, the method can be employed
as a promising stability-indicating assay.

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 Analytical Chemistry

Title: Kinetic Spectrophotometric Determination of

Certain Cephalosporins Using Iodate/Iodide
Mixture

Authors: Salwa R. El-Shaboury, Fardous A. Mohamed,

Gamal A. Saleh, Azza H. Rageh

Source: Natural Science, 2 (5), 432-443 (2010)

Address: Department of Pharmaceutical Analytical

Chemistry, Faculty of Pharmacy, Assiut University,
71526 Assiut, Egypt

A simple, precise and accurate kinetic spectrophotometric method for

determination of cefradine anhydrous, cefaclor monohydrate, cefadroxil
monohydrate, cefalexin anhydrous and cefixime in bulk and in pharmaceutical
formula-tions has been developed. The method based on a kinetic investigation of
the reaction of the free carboxylic acid group of the drug with a mixture of
potassium iodate and potassium iodide at room temperature to form yellow
coloured triiodide ions. The reaction was followed up spectrophotometrically by
measuring the increase in absorbance at 352 nm as a function of time. The initial
rate, fixed time, variable time and rate-constant methods were adopted for
constructing the calibration curves but fixed time method has been found to be
more applicable. The analytical performance of the method, in terms of accuracy
and precision, was statistically validated; the results were satisfactory. The
method has been successfully applied to the determination of the studied drugs in
commercial pharmaceutical formulations. Statistical comparison of the results
with a well established reported method showed excellent agreement and proved
that there is no significant difference in the accuracy and precision.

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-78-
 Analytical Chemistry

Title: Spectophotometric Method for Determination of

Certain Cephalosporins Using 4-Chloro-7-
nitrobenzo-2-oxa-1,3-diazole (NBD-Cl)

Authors: Azza H. Rageh, Salwa R. El-Shaboury, Gamal A.

Saleh, Fardous A. Mohamed

Source: Natural Science, 2 (8), 828-840 (2010)

Address: Department of Pharmaceutical Analytical

Chemistry, Faculty of Pharmacy, Assiut University,
71526 Assiut, Egypt

A simple, accurate and precise spectrophotometric method has been proposed

for the determination of eleven cephalosporins, namely; cefaclor monohydrate,
cefadroxil monohydrate, cefalexin anhydrous, cefradine anhydrous, cefotaxime
sodium, cefoperazone sodium, ceftriaxone sodium, ceftazidime penthydrate,
cefazolin sodium, cefixime and cefpodoxime proxetil in bulk drug and in
pharmaceutical formulations.The method depends on hydrolysis of the studied
drugs using 0.5M NaOH at 100°C and subsequent reaction of the formed sulfide
ions with NBD-Cl (4-chloro-7-nitrobenzo-2-oxa-1,3-diazole) to form a yellow-
colored chromogen measured at 390 nm. Different variables affecting the reaction
(e.g. NaOH concentration, hydrolysis time, NBD-Cl concentration and diluting
solvent) were studied and optimized. Under the optimum conditions, linear
relationships with good correlation coefficients (0.9990-0.9999) were found in the
range of 5-160 μg mL-1 for all studied drugs. The limits of assay detection and
quantitiation ranged from 0.289 to 5.867 and from 0.878 to 17.778 μg mL-1;
respectively. The accuracy and precision of the proposed method were satisfactory.
The method was successfully applied for analysis of the studied drugs in their

-79-
pharmaceutical formulations and the recovery percentages ranged from 96.6 to
103.5%.

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 Analytical Chemistry

Title: High-Performance Liquid Chromatographic

Determination and Pharmacokinetic Study of
Cefepime in Goat Plasma and Milk After Pre-
Column Derivatization with Hg(I)
1 1
Authors: Nawal A. El-Rabbat , Hanaa M. Abdel-Wadood ,
Mohammed Sayed2, Heba S. Mousa3

Source: J. Sep. Sci., 33, 2599-2609 (2010)

Address: 1Department of Pharmaceutical Analytical

Chemistry, Faculty of Pharmacy, Assiut University,
Assiut, Egypt. 2Department of Food Hygiene, Faculty
of Veterinary Medicine, Assiut University, Assiut,
Egypt. 3Drug Research Center, Assiut University,
Assiut, Egypt

A highly sensitive and selective HPLC method with UV detection was

developed for the determination of cefepime in goat plasma and milk. The
proposed method was based on the complexation of cefepime with Hg(I) ions that
imparts the high selectivity of the proposed method with enhancement of the
sensitivity which enabled the analysis of cefepime in complex matrices such as
plasma and milk. Detection was performed at 263 nm, using cefuroxime sodium
as an internal standard. Chromatographic separation of cefepime and the internal
standard was achieved with Aqua RP-C18 column using methanol/triethylamine-
acetate buffer, pH 3.5 (18:82, v/v) as mobile phase at a flow rate of 1 mL/min.
Linear detector responses were observed spanning the range of 1.3–20 mg/mL.
The LOD for standard cefepime was 0.43 mg/mL, whereas the LOD for cefepime
in goat plasma was 0.84 mg/mL and the corresponding value in goat milk was
1.1 mg/mL. No interference from endogenous substances in plasma and milk was
observed. The developed HPLC method has been successfully applied for the

-81-
pharmacokinetic study of cefepime in goat plasma and milk, for the first time,
after a single intramuscular injection of 50 mg cefepime/kg body weight.

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 Analytical Chemistry

Title: The Profile of Free Amino Acids in Latent

Fingerprint of Healthy and Beta-Thalassemic
Volunteers

Authors: Alaa Khedr

Source: J Chromatogr. B., 878, 1576-1582 (2010)

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 Analytical Chemistry

Title: Influence of Various Concentrations of

Terpene-4-ol Enhancer and Carbopol-934
Mucoadhesive Upon the In-vitro Ocular
Transport and the In-vivo Intraocular Pressure
Lowering Effects of Dorzolamide Ophthalmic
Formulations Using Albino Rabbits

Authors: Mohsen I. Afouna, Alaa Khedr, Ashraf A. Naiem,

Adnan Al-Marzoqi

Source: J. Pharm. Sci., 99, 119-127 (2010)

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 Analytical Chemistry

Title: Kinetic Spectrophotometric Method for

Determination of Ciprofloxacin and
Lomefloxacin in their Pharmaceutical
Formulations

Authors: Ibrahim A. Darwish, Maha A. Sultan, Hessa A. Al-

Arfaj

Source: Int. J. Res. Pharm. Sci., 1, 43-50 (2010)

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 Analytical Chemistry

Title: Selective Kinetic Spectrophotometric Method for

Determination of Gatifloxacin Based on
Formation of its N-Vinylchlorobenzoquinone
Derivative

Authors: Ibrahim A. Darwish, Maha A. Sultan and Hessa A.

Al-Arfaj

Source: Spectrochim. Acta A, 75, 334-339 (2010)

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 Analytical Chemistry

Title: HPTLC-Densitometric Method for Simultaneous

Determination of Salmeterol Xinafoate and
Fluticasone Propionate in Dry Powder Inhalers

Authors: Lantider Kasaye, Ariaya Hymete, Abdel-Maaboud I.

Mohamed

Source: Accepted for publication in Vol. 18, no. 3, July (2010) of SPJ

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 Analytical Chemistry

Title: Simultaneous Determination of Candesartan

Cilexetil and Hydrochlorothiazide by High-
Performance Liquid Chromatography

Authors: Alaa Khedr

Source: J. King Abdulaziz Univ. Med. Sci., (2010) In Press

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 Analytical Chemistry

Title: Spectrophotometric and Spectrofluorimetric

Determination of 1,4-Dihydropyridine Drugs
Using Potassium Permanganate and Cerium
(IV) Ammonium Sulphate
1 2
Authors: H. F. Askal , Osama H. Abdelmegeed , Sayed
M.S. Ali2, Mohamed Abo El-Hamd3

Source: Bull. Pharm. Sci., Assiut University, 33 (2), 201-215 (2010)

Address: 1Department of Pharmaceutical Analytical

Chemistry, Faculty of Pharmacy, Assiut University,
Assiut 71526, Egypt, 2Department of Pharmaceutical
Analytical Chemistry, Faculty of Pharmacy, Minia
University, Minia 61519, Egypt, 3Department of
Pharmaceutical Analytical Chemistry, Faculty of
Pharmacy, Al-Azhar University, Assiut 71524, Egypt

Simple and sensitive spectrophotometric and spectrofluorimetric methods

have been developed for determination of 1,4-dihydropyridine (1,4-DHP) drugs
based on the oxidation of the investigated 1,4-DHP drugs with acidic KMnO4
(method I) or Ce (IV) (method II). The first method is based on the decrease in the
colour of the permanganate solution due to the presence of the studied drug was
measured at 525 nm. And the second method is based on monitoring the
fluorescence of the produced cerium (III) at emission 355 nm (excitation at 255
nm). All variables that affect the performance of the proposed methods were
carefully studied and optimized. The analytical performance of the methods was
validated according to International Conference of Harmonization guidelines.
The proposed methods were applied successfully to the determination of the drugs

-89-
in commercial tablets and capsules. The results of the proposed procedures were
statistically and compared with those obtained by the reference methods.

-90-