Vol. 23, March, 2007.

1/23 PHYTOCHEMICAL AND BIOLOGICAL STUDIES OF THE FLOWERS AND FRUITS OF PONGAMIA PINNATA L.PIERRE GROWING IN EGYPT

A.O. El-Shabrawy, H.M. El-Gohary, M.M. Youssef, R.A. El Gedaily and A.A.Sleem*

Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Kasr El-Ainy, Cairo, Egypt

*Department of Pharmacology, National Research Center, Giza, Egypt.

The essential oil of the flowers of Pongamia pinnata L.Pierre was prepared by hydrodistillation and analysed using GS/MS technique. Thirty three components were identified, of which, β-citronellene (13.7%), limonene (13.35%) and trans caryophyllene (12.75%) were the major components. The retention indexes of the identified components were determined. GLC analysis of the fatty acid methyl esters prepared from the seed fixed oil and the petroleum ether extract of the flowers revealed the presence of oleic acid as the major fatty acid (84.8% and 34.86% respectively), while the major hydrocarbon detected in the unsaponifiable fraction was n-tetradecane (19.8%) and n-nonadecane (43.66%) respectively.Stigmasterol (3.12%) was the only sterol detected in the fixed oil of the seeds. The seed fixed oil and the aqueous and alcoholic extracts of the seed, flower and pericarp showed significant analgesic, antipyretic, anti-inflammatory, anti-ulcer and antidiabetic activities.

2/23 ENHANCED BIOAVAILABILITY OF FLURBIPROFEN USING GELUCIRE 44/14 AND LABRASOL AS SEMI-SOLID DISPERSIONS

M.S. Soliman, F.I. Abd Allah and A.B. Yassine

Pharmaceutics Department, Faculty of Pharmacy, Al-Azhar University

OBJECTIVES. This study was to investigated the in-vivo performance of semi-solid dispersion of flurbiprofen prepared with Gelucire 44/14 and Labrasol (F1) and pure drug (PD) filled in hard gelatin capsules. Methods: Oral bioavailability of 50 mg of semi-solid dispersion of flurbiprofen (F1) was compared with pure flurbiprofen filled into hard gelatin capsules (PD) after administration of a single oral dose to six healthy human volunteers. Two treatments were administered in crossover fashion, separated by a washout period of two weeks. Venous blood sample of 5 ml was taken immediately before dosing and after predetermined time intervals of 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 h. Flurbiprofen was monitored in serum by high- performance liquid chromatography. Results. The apparent rate of absorption of semi-solid dispersion of flurbiprofen from F1 was observed. The Cmax ± S.D. was found to be 50.45 ± 2.2634   µg/ml, and tmax ± S.D. was 1.5 ± 0 h and the AUC ± S.D. value was 367.47 ± 25.377 µg/ml which was significantly higher than that from PD with Cmax ± S.D. 16.06 ± 1.211     µg/ml, tmax ± S.D. was 2 ± 0 h, and AUC ± S.D. value was 201.28 ± 42.52 µg/ml . The relative bioavailability value as the ratios of mean total AUC for F1 relative to AUC for PD was 182.56 %. Conclusion. The results indicates that the bioavailability of flurbiprofen can be enhanced as semi-solid dispersions with Gelucire 44/14 and Labrasol, which would be advantageous with regards to rapid onset of action especially in various painful conditions where acute analgesic effect is desired.

3/23 BIOLOGICAL AND BIOCHEMICAL EVALUATION OF SOME PREPARED HIGH ANTIOXIDANT FRUIT BEVERAGES AS FUNCTIONAL FOODS

W.A. El-Malky

National Organization for Drug Control and Research (NODCAR)

In this study, six fruit beverages contains high antioxidant components were prepared as functional foods. Its sensory, physicochemical properties, antioxidant components and activity were evaluated. Hypolipidemic effect of this beverages as prophylactic agents on rats fed hyperlipidemic diet was biochemically studied. The results revealed that the beverages pH was between 3.5-5.9 while the total solids were between 17.1 to 20.2%. Minerals, Ca, P, Fe and Zn content of prepared beverages were similar in contents with commercial beverage. Good contents of vitamin C, carotenoids, flavonoids and polyphenolic compounds in the prepared beverages were indicated. Antioxidant activity of the prepared beverages were between 38.9 to 95%. The beverage which contain mango, red grape, carrot and tomato was the best prepared beverages according to the sensory evaluation, chemical composition and antioxidant activity. The high antioxidant content beverage was chosen for biochemical study as well as commercial beverage, complementary food Se-ACE and negative control compared to positive control. Insignificant differences were indicated in rats body weight and rats organs weight of rats fed either hyperlipidemic diet or its containing all treatments. The high antioxidant prepared beverage lowered the increasing of serum total cholesterol, triglycerides, LDL, VLDL and ALT. No marked changes were observed in the serum level of HDL cholesterol, AST and creatinine and slight increase in serum glucose level compared to positive control.

4/23 EFFECT OF GREEN LEAVES AND GERMINATION AND BOILING TREATMENTS OF FENUGREEK AND LUPIN SEEDS ON CHEMICAL COMPOSITION, SERUM GLUCOSE, LIPID PROFILE AND HEPATIC ENZYMES OF RATS

W.A. El-Malky and H.A. Gouda

National Organization for Drug Control and Research (NODCAR)

Raw, boiled and germinated fenugreek seeds of three kinds of fenugreek (Trigonella foenum graecum L.) were commercial, Giza 2 and Giza 30 and fenugreek green leaves and raw, boiled and germinated commercial sweet lupin seeds (lupinus termis forssk L.) were analyzed for its chemical composition, alkaloids and antioxidant activity. Essential fatty acids of fenugreek seed oil were also determined. Prophylactic effect of all treatments of the best kind of two legumes (commercial fenugreek and lupin seeds) in addition to fenugreek green leaves on serum glucose, lipid profile and liver enzymes of rats fed hyperlipidemic diet were studied. Also liver tissues of rats were histopathologically examined. The recorded analysis showed slight differences in chemical composition of treated seeds. However, commercial fenugreek seed oil was the best in fatty acids. Also commercial fenugreek and lupin seeds were the best in antioxidant components and activity especially germinated seeds. Germinated and boiled fenugreek seeds and fenugreek leaves and germinated lupin seeds reduced the increases of serum glucose, total cholesterol, triglycerides, LDL, VLDL risk ratio and hepatic enzymes ALT and AST and increased HDL and avoid the damage in liver tissues resulted from hyperlipidemic diet effect compared to positive control.

5/23 EFFECT OF FORMULATING ADDITIVES ON THE PROPERTIES OF IBUPROFEN TABLETS

M.M. Nafady

Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy,

Cairo University, Cairo, Egypt

A study of the comparative effects of different formulating additives and film coating on the properties of ibuprofen tablets was made. The tested properties were hardeness (H), friability (F), the disintegration time (D) and dissolution characteristics of ibuprofen tablets. The hardeness, friability, the hardeness friability ratio (HFR) and the disintegration time were affected by diluent-binder ratio and binder concentration. The ranking for the values of HFR for different coated tablet formulations and commercial tablet formulation )FC) was FVI>FV>FI>FII>FIV>FC>FIII. The ranking for disintegration times D of uncoated tablet formulations were FI>FII>FVI>FV>FIV>FIII and that of coated formulations and commercial formula was FI>FVI>FII>FV>FC>FIV>FIII. The ranking for the dissolution rates of uncoated tablet formulations after one hour were FIV>FV>FIII>FVI>FII>FI whereas those of coated formulations and commercial tablet formulation (FC) were FIV>FC>FV>FVI>FIII>FII>FI. It was found that, Film coating has a remarkable effect on both mechanical strength and drug release from different ibuprofen formulations. The results suggest that hydroxypropyl methylcellulose (HPMC) could be selected as a binding agent and film coating material. It produces tablets with acceptable mechanical properties and drug release pattern. Formula FIV gave the most acceptable properties and drug release profile compared to other tested formulations. The oral absorption profile of the selected formula (FIV) was studied and compared to that of the commercial tablet formulation (FC). The AUC of FIV was not significantly larger than that of FC. The maximum biological half life (tmax)of FIV was the same as that of FC. Statistical comparison of the biological half-life parameter did not indicate a significant difference between results from FIV tablets and FC tablets. Cmax of FIV was higher than that of FC. The results indicated that the adopted formulation technique gave ibuprofen tablets with acceptable properties. These results were comparable with FC.

 

6/23 CHEMICAL AND BIOLOGICAL STUDY OF AERIAL PARTS OF DILL (ANETHUM GRAVEOLENS L.)

W.M.A. Amin and A.A. Sleem*

Pharmacognosy Department, Faculty of Pharmacy, Cairo University,

Kasr El-Ainy, Cairo, Egypt.

* Pharmacognosy Department, National Reserch Centre, Cairo, Egypt.

The composition of the hydrodistilled volatile oil from the aerial parts (before flowering stage) of Anethum graveolens L. family Apiaceae was investigated by GC/MS. Twenty eight components representing 99.76% of the total chemical composition of the oil were identified. Monoterpene hydrocarbons were found predominating in the studied oil amounting (80.81%) where a- phellandrene (63 %) constituted the major compound. Meanwhile, oxygenated compounds reached up to (8.26%) with dill-ether (6.20%) which was the major compound. The unsaponifiable matter and fatty acids methyl esters of the aerial parts were identified and estimated by GLC analysis. b- Sitosterol (3.92%) was the major sterol, followed by campesterol (2.50%) and stigmasterol (2.01%) and n-dotriacontane (58.40%) represented the major hydrocarbon in the unsaponifiable fraction. Linoleic acid (20.51%) was the major fatty acid present followed by Nonadecanoic acid (9.95%). The aqueous infusion of the herb being the mode of administration in pharmaceutical formula in the market was studied. The n-hexane extract of the aqueous infusion showed spots similar to essential oil spots when compared by TLC. Also the ethyl acetate extract of the aqueous infusion showed spots of furanocoumarines which are characteristic to the family. The essential oil exhibited significant antibacterial activity against gram positive as well as gram negative bacteria and showed moderate antifungal effect. The petroleum ether extract showed broad spectrum antibacterial activity and antifungal effect but was being less active than essential oil. Meanwhile the aqueous extract had no antimicrobial and antifungal at the concentration used in the experiment (4 mg / disc). The essential oil showed high antimycobacterial effect at a minimum inhibitory concentration (MIC) ranging from 3 to 50 µl/ml. The LD50 for essential oil and aqueous extract was determined. The volatile oil as well as aqueous extract of the aerial parts exhibited a significant diuretic effect, anti-inflammatory effect and cytotoxic activity against three cell lines. The antispasmodic effect of aqueous infusion was also studied and showed to be significant.

7/23 Botanical and Biological Study of Oenotheraspeciosa Nutt. Cultivated in Egypt

H.H. Eid and A.A. Sleem*

Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Egypt

* Pharmacology Department, National Research Center, Giza, Egypt

A phytochemical screening of Oenothera speciosa Nutt. (Onagraceae) revealed the presence of steam-distilled volatile constituents in the flowers, as well as, sterols and/or triterpenes, carbohydrates and/or glycosides, tannins, flavonoids (aglycones and glycosides) in all the organs of the plant. The macro-and micro-morphology of the root, stem and leaf of Oenothera speciosa Nutt. (Onagraceae) were presented with the aim of finding out diagnostic characters by which the plant can be easily identified from other species in both entire and powdered forms. Furthermore, certain biological activities of the aqueous and alcoholic extracts of the roots, stems and leaves were evaluated. Extracts of roots and leaves showed variable degrees of anti-microbial effects against the tested microorganisms. All the extracts could be considered safe as deduced from their high LD50. Moreover, the anti-inflammatory, anti-ulcer, anti-pyretic and analgesic activities were explored and significant results were observed for the different extracts.

8/23 Seasonal Variation in the Essential Oil Composition of ORIGANUM SYRIACUM L. SUBSP. SINAICUM Greuter AND Burdet; EVALUATION OF its tocolytic activity

F.M. Soliman, M.F. Yousif, S.S. Zaghloul, M.M. Okba and E.M. El-Sayed*

Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Kasr El-Ainy, 11562, Cairo, Egypt and *Pharmacology & Toxicology Department, Faculty of Pharmacy, Al-Azhar University, Nasr City, Cairo, Egypt

The essential oil of Origanum syriacum L.subsp. sinaicum Greuter and Burdet obtained by hydrodistillation during four seasons was analyzed by GC-MS. The composition of the oil showed qualitative and quantitative variation. Carvacrol was the major component (64.71%, 36.50%) in summer and spring oils, respectively. The next major components in these seasons were sabinene hydrate<trans> (18.28%) and γ-terpinene (13.50%) in spring, and γ-terpinene (9.30%) and p-cymene (7.60%) in summer. The oil prepared in autumn revealed thymol as the major component (19.55%), followed by sabinene hydrate <trans> (18.32%) and sabinene (14.85%),while that prepared in winter showed sabinene hydrate<trans> as the major component (32.96%) followed by thymol (30.80%). In vitro study ofthe tocolytic activity of the essential oil and 70% ethanol extract of O. syriacum L.subsp. sinaicum Greuter and Burdet on rat uterus was carried out. Essential oil (18 mg/ml) and 70% ethanol extract (200 mg/ml) produced marked inhibitions in the uterine contractility of non-pregnant rats (50% and 65% in the normal frequency and 36% and 48% in the normal amplitude, respectively); the area under the curve was also decreased (60% and 82% respectively). Oxytocin-and KCL-induced uterine contractions were significantly decreased following addition of either the essential oil or the 70% ethanol extract.

9/23 ANTI-CANCER VOLATILE CONSTITUENTS FROM THE FLOWERS OF LONICERA JAPONICA THUNB. CULTIVATED IN EGYPT

E.A. El-Kashoury, A.E. Khaleel, O.M. Mousa and M.H. Daoud

Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Kasr-El-Ainy, Cairo, Egypt.

The volatile constituents of the flowers of Lonicera japonica Thunb. (Japanese honeysuckle), obtained by two methods [viz., floral absolute volatiles (FAV) and hydrodistilled/hexane extracted volatiles (HHV)], were comparatively investigated as regards composition and cytotoxicity. Hydrodistillation/hexane extraction was performed in Likens-Nickerson apparatus. The volatile constituents were identified and quantitated using GC/MS. Sixty compounds, 44 of which have not been previously reported in L. japonica, were identified among the volatiles prepared by the two methods. Linalool was the major constituent in both cases. However, its percentage is higher in the floral absolute volatiles (47.92%). On the other hand, 4-terpineol, nerolidol, cis-jasmone, cis-3-hexenyl tiglate, methyl palmitate and trans-linalool oxide, were detected in lesser but appreciable quantities in both samples. The volatiles prepared by the two methods were tested for their cytotoxic activities against four human cancer cell lines. The floral absolute showed a notable cytotoxic activity on the brain cancer cell line U251 (IC50 value of 7.92 μg/ml (and was found to be more potent than cisplatin reference drug (IC50 =8.66 μg/ml). Meanwhile, the volatiles prepared by hydrodistillation/hexane extraction showed a considerable cytotoxic activity on the liver cancer cell line Hepg2 with IC50 value of 7.58 μg/ml.

10/23 CHEMICAL COMPOSITION AND BIOLOGICAL STUDIES OF THE ESSENTIAL OIL OF THYMUS DECUSSATUS BENTH GROWING IN EGYPT.

A.A.A. El-Hela

Department of Pharmacognosy, Faculty of Pharmacy, Al-Azhar University,

Nassr City, Cairo Egypt

The essential oil of Thymus decussatus Benthherb growing in Egyptwasprepared by hydro distillation of the dried herb and analyzed by GC/ MS. It revealed the presence of 12 peaks, which were identified. The major component of the essential oil was thymol 94.14% w/w from the total (3%w/w). The essential oil showed strong anti microbial against the selected microorganisms. The cytotoxic activity against Ehrlich ascites carcinoma cell (EAC) as well as two human cancer cell – lines (U251: brain- tumor and Hepg 2: Liver carcinoma cell –lines) was tested and significant results were obtained.    

11/23 STUDY OF VOLATILE OIL AND LIPID CONTENT OF JASONIA MONTANA (Vahl.) BOTSCH.

F.M. Soliman, M.Y. Moussa and S.M. Osman

Department of Pharmacognosy, Faculty of Pharmacy, Kasr El-Ainy, Cairo, Egypt.

The volatile oils, prepared by hydrodistillation from the aerial parts of three patches of Jasonia montana (vahl.) collected in May, August and November were subjected separately to GC/Ms analysis. Camphor, endoborneol, endobornyl acetate, intermedeol, 1, 8-cineole, 1-α-terpineol, and α-pinene, represented the major components. Also saponifiable and unsaponifiable matters were subjected to GLC analysis. Seventeen hydrocarbons, two sterols and eighteen fatty acids were identified, through GLC technique adopted. The Volatile oil, was found to be more active against Gram (+ ve) bacteria more than Gram (-ve) bacteria and fungi.

12/23 PRODUCTION OF VITAMIN B12 BY STREPTOMYCES FULVISSIMUS

H.M. Atta

Botany and Microbiology Department, Faculty of Science (Boys);

Al-Azhar University, Cairo, Egypt.

Fifty five of actinomycete isolates were screened for vitamin B12 production by growing on soybean meal medium fortified with cobalt. Only one AZ-Z-88 among nine actinomycete cultures was found to produce significantly higher yield of the vitamin B12 (63.5 ug/ml). Determination of vitamin B12 production was carried out using E.coli, ATCC 14169 as the test organism. The actinomycete culture could be isolated from a soil sample collected from zagazig city. Taxonomical features of the most producer isolate were matches with Streptomyces fulvissimus in its morphological, physiological and biochemical characters, therefore, it was given the suggested nameStreptomyces fulvissimus, AZ-Z-88. The fermentation broth filtrates were extracted by using Chloroform. Purification of the active ingredient up to crystalloid form was performed by using both thin layer chromatography (TLC) and column chromatography technique. The spectroscopic analysis (UV, IR and HPLC spectrum) were used for comparative studies between vitamin B12 produced by Streptomyces fulvissimus, AZ-Z-88 and standard vitamin B12. Recorded data emphasized the fact that, the purified compound was suggestive of being belonging to vitamin B12.

13/23 EFFECT OF PHYTASE SUPPLEMENTATION ON THE PERFORMANCE, SERUM AND BONES BIOCHEMICAL CHANGES OF TURKEYS

A.M. Kamal and N. Atef

Animal Health Research Institute, Department of Biochemistry, Dokki, Gizza.

An experiment was conducted using 60 healthy Bronze turkey poult at the age 4 weeks in order to study the effect of microbial phytase on the performance of turkeys at the age of 16 weeks. The birds were classified into four comparable groups (15 each). The first group was consider as a control group received a basal ration, 2nd, 3rd and 4th groups received a basal ration plus 250, 500 and 1000 gm phytase /ton ration respectively. Phytase supplemented birds consumed more feed than the non-supplemented ones, Addition of 500 and 1000 gm at groups (3 &4) cause increased in Live weight gain and improvement in feed conversion. A significant increase in serum levels of calcium, phosphorus, Magnesium of birds received 500 and 1000 u/kg phytase while phytase supplementation show a significant reduction in serum alkaline phosphatase levels. Dietary phytase supplementation at a rate 500 and 1000 gm phytase show a significant increase in the percent of Ash, Calcium, phosphorus, magnesium and zinc of tibia at groups (3 and 4) than control one. Also, result of this study suggest that fecal calcium and phosphorus was decreased in the groups (3 and 4).

14/23 IN VITRO AND IN VIVO EVALUATION OF CONTROLLED-RELEASE BUCCOADHESIVE DISKS OF TIMOLOL MALEATE

S.A. Elkheshen, I.S. Ahmed, M.H. Aboul-Einien and M.A. Hassan

Pharmaceutics Department, Faculty of Pharmacy, Cairo University

The aim of the present work was to develop a buccoadhesive controlled-release dosage form of timolol maleate (TM) and to evaluate the feasibility of improving the bioavailability of TM via the buccal route. Buccoadhesive disks (BDs) of TM were prepared by the direct compression method using some selective polymers like carbopol 934(CP 934) and hydroxypropyl methylcellulose (HPMC K4M) in different amounts along with other tablet excipients. The disks were evaluated for thickness uniformity, weight variation, drug content uniformity, hardness, friability and surface pH. The buccal permeability of TM was assessed in one human subject and the drug was found to permeate through the buccal mucosa. The BDs were also evaluated for swelling index and bioadhesion time using rabbit buccal tissues. The swelling index was found to increase with an increase in HPMC and CP content in the disks and none of the disks detached from the rabbit buccal tissues until completely eroded. The in vitro drug release for 12 h in pH 6.6 phosphate buffer using a USP dissolution tester revealed that the rate of drug release was increased when the polymers were incorporated in the disks at low concentrations, but was decreased when incorporated at higher concentrations. When the release data were evaluated by a simple power equation (Mt/M = ktn); it was observed that drug release from most of the formulated BDs followed non-fickian release kinetics. A selected BD formulation was evaluated in vivo in rabbits. The selected BD gave controlled blood level profile with a 50% increase in area-under-the-curve (AUC) value in comparison to oral administration of aqueous drug solution.

15/23 PREPARATION AND CHARACTERIZATION OF ACYCLOVIR NANOPARTICLES BY DOUBLE EMULSION TECHNIQUE

A.O. Kamel, G.A.S. Awad, A.S. Geneidi and N.D. Mortada.

Department of Pharmaceutics, Faculty of Pharmacy, Ain Shams University,

Cairo, Egypt.

Acyclovir (ACV) is one of the most effective and selective agents against viruses of the Herpes group. Its t1/2 is about 2.5 hrs., hence repeated administration of high doses is required (200 mg 5 times daily). Parenteral ACV nanoparticles (NPs) for prolonged systemic delivery were prepared by w/o/w double emulsion (DE) technique using biodegradable polymers. The effect of formulation variables such as ratio of drug to polymer as well as the effect of polymer type [Polylactic acid (PLA), polylactic-co-glycolic (PLGA) 85/15, PLGA 75/25, PLGA 50/50] was studied. Dynamic light scattering system, transmission electron microscopy (TEM), zeta potential, differential scanning calorimetry (DSC) and X-ray powder diffractometry were employed to characterize the fabricated NPs for size and size distribution, surface morphology, surface charge and the physical state of drug in NPs respectively. Encapsulation efficiency (EE) and the in vitro release of ACV in NPs were investigated. Spherical NPs ranging between 590-770 nm in diameter with narrow size distribution were obtained. All particles exhibited a negative surface charge. ACV entrapped in NPs was found in the form of amorphous state. EE was in the range of 30.08% - 51.13%. The release behavior of ACV from the developed NPs exhibited an initial burst release within the first hour followed by a slower release (60% in 48 hrs).

16/23 CLINICAL PRESENTATION OF NASOPHARYNGEAL CANCER IN YEMEN.

A.O. Muthanna and A. Alaryani

Department of Ear, Nose and Throat, Faculty of Medicine and Health Sciences, Sana'a University, Sana'a, Yemen

Objective: To describe clinical presentation of nasopharyngeal cancer. Methods: Study performed on 100 patients who had been histologically diagnosed as having nasopharyngeal cancer between October 2002 and September 2005 in ENT department, Al-Thawra Teaching Hospital, Sana'a, Yemen. A detailed medical history, clinical examination, biopsy and histopathological study were performed. Results: One hundered diagnosed nasopharyngeal cancer patients were included in this study, 70 males 30 and females. Their age ranged from 10-59 years, the high incidence was in age group 40-49 years (32%). The least cases were in age group 10-19 years (14%). The most presenting symptoms of nasopharyngeal cancer were in the order of frequency: painless neck mass 60%, nasal obstruction 50%, headache, 34%, hearing loss 32%, epistaxis, 10%, trismus 4%, loss of vision 2%, diplopia and squint 2%. Conclusion: The majority of nasopharyngeal cancer were presented with painless cervical lymph node either unilateral or bilateral. Nasal obstruction and hearing loss associated with headache were found in high percentage of patients. Cranial nerve palsies and trismus found in the late stages.

17/23 PHARMACEUTICAL FACTORS AFFECTING THE FORMULATION OF VERAPAMIL HCL FLOATING CAPSULES

S.A. El-Adawy and A.A. Ramadan

Pharmaceutics Department, Faculty of Pharmacy (girls), Al-Azhar University,

Nasr City, Cairo, Egypt.

Floating sustained release Verapamil HCl capsules were prepared using different polymers. Hydroxypropylmethyl cellulose 4000 and 50 (HPMC 4000 & HPMC 50), Carbopol 934, sodium alginate (Na alginate), carboxymethyl cellulose (CMC) and Pectin were used to study their effect on the release of Verapamil HCl from its capsules. Three different ratios of drug: polymer were adopted namely 1:1, 1:0.5 and 1:0.25 w/w. The effect of the weight of the prepared capsules on the dissolution rate of the drug using avicel to adjust the weight of the capsule to 300, 400 and 500 mg. The incorporation of effervescent mixture in the prepared capsules was tried to prepare floating dosage form with an in – situ gas generating mechanism for the seek of buoyancy improved drug release characteristics. Monobasic potassium citrate and potassium bicarbonate (1:1 w/w) as an effervescent mixture were used to generate CO2 gas. The effervescent mixture was mixed with the polymers in each capsule in 0, 1 and 2% w/w of the total weight of the formula. In-vitro release studies were performed to observe the effect of effervescence on the duration of drug release. It was observed that increasing the ratio of the polymer in the formula retard the drug release. The release profile gave a faster release rate in case of light weight capsule than heavy weight capsule. Increasing the amount of effervescent mixture per capsule retarded the rate of the drug release.

 

18/23 EFFECT OF DIFFERENT DEGREES OF HEPATIC DYSFUNCTION ON THE PHARMACOKINETICS OF TELMISARTAN

M. El-Hamamsy, S. Hegazy*, W. Awara**

Clinical pharmacy department, Faculty of Pharmacy, Ain Shams University, *Clinical pharmacy department, Faculty of Pharmacy, Tanta University, **Pharmacology & Toxicology Department, Faculty of Pharmacy, Tanta University.

Background: Hypertension is a highly prevalent condition, as well as being one of the most powerful contributors to cardiovascular diseases; hypertension is also the leading cause of death in developed countries. Angitensin II receptorblockers represent a new class of effective and well tolerated orally active antihypertensive agents.Telmisartan is a nonpeptide angitensin II receptor antagonist, used for the treatment of hypertension. Objective: To describe the pharmacokinetics and safety of telmisartan in healthy volunteers and in subjects with different degree of hepatic impairment. Setting: Tanta University Hospitals, Faculty of Pharmacy, Ain Shams University and Faculty of Pharmacy, Tanta University, Egypt.Design: Prospective study. Single oral dose of telmisartan 80 mg was given to 10 healthy subjects served as a control group (group 1), and 20 subjects with hepatic impairment; divided into two groups; group 2(10 patients): patients with mild hepatospleenomegaly and group 3 (10 patients): patients with cirrhosis and ascitis. Plasma samples were collected and analyzed with high performance liquid chromatography (HPLC).Main outcome measures: Cmax, tmax, t 1/2, MRT, AUC0-∞, Cl/F and VdssResults: The pharmacokinetic profile of telmisartan was characterized by rapid absorption kinetics and a slow terminal elimination phase with mean half life of 25 hours. The maximum plasma concentration and area under the telmisartan plasma concentration-time curve (AUC0-∞} increased in all hepatically impaired subjects compared with healthy volunteers. There was a significant increase in the Cmax and AUC0-∞ of the cirrhotic patients and non significant increase in the patients with mild hepatospleenomegaly compared with the healthy volunteers. There was no change in the half life of telmisartan in all the patients and no adverse events were noticed in the patients during the study indicating the good tolerability of the drug in hypertensive patients with hepatic dysfunction.Conclusion:Lower doses of telmisartan should be considered in cirrhotic patients as well as in the patients with mild hepatitis.

 

19/23 PREPARATION AND EVALUATION OF FLUCONAZOLE GELS

M.M.A. Abdel-Mottaleb*, N.D. Mortada**, A.A. Elshamy** and G.A.S. Awad**

*Department of Drug technology, Faculty of Pharmacy, Ain Shams University, Egypt

**Department of Pharmaceutics, Faculty of Pharmacy, Ain Shams University, Egypt

Gels dosage forms are successfully used as drug delivery systems considering their ability to control drug release and to protect medicaments from a hostile environment. Thus, it was desired in this study to formulate fluconazole into a gel that could be used locally in the treatment of different skin fungal infections. Cellulose derivatives, chitosan and poloxamer-407 were used as the gelling agents. Different additives were used to enhance drug release from these preparations including PEG 400, glycerol, Tween 80 and Cetrimide. Different formulae were characterized in terms of spreadability, rheological properties and drug release. The formulae showing the best drug release were selected to study the effect of storage on various parameters over a period of 6 months and for microbiological evaluation. The best release enhancer was glycerol in the concentration of 10% and the formulae containing it were stable and proved to be effective in the inhibition of candidal growth in the in vitro microbiological evaluation.

 
 
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