5^th Annual European Pharma Congress July 18-20, 2016 Berlin,Germany

Chair

Djebbar Atmani

test

Co-Chair

Shirly Kumala

test

Session Introduction

Pierre Lutgen

IFBV-BELHERB, Luxembourg

Title: Artemisia plants are deadly weapons against malaria

Time : 9.30 - 10.00

Biography:

Dr Pierre Lutgen was born 1940 in Luxembourg, studied at the University of Louvain in Belgium and obtained diplomas in chemistry, social sciences and philosophy. He worked during 25 years for the Dupont CY, in research, and during 8 years in the steel industry, mainly in the environmental field. Since his retirement he worked as consultant for health and environment as invited professor at the University in Medellin and for the European Communities in several countries. Over the last ten years he has organized the association IFBV-BELHERB studying and fighting tropical diseases with some 30 academic and medical partners in Africa, South America and Europe. Numerous peer reviewed papers have been published by this team, mainly on herbal medicine.

Abstract:

Since 7 years the association IFBV-BELHERB from Luxembourg has established a working relationship with African and South American universities, in close cooperation with other European research institutions. Several of these partners have run clinical trials with Artemisia annua team. In all these trials a therapeutical effect of 95 % or higher was confirmed by the use over 7 days of whole leaf infusion, capsules or tablets. One of the surprising effects noticed in these trials was that that the artemisinin content had very little impact on the results. This lead us to make an analysis as complete as possible of all the constituents, organic and inorganic, in a large series of A. annua samples from different origins. A. annua from Luxembourg which had shown very promising antimalarial results, excellent bactericidal properties and a strong anti-inflammatory effect contained very little artemisinin but higher concentrations of certain essential oils. The effect of water soluble polysaccharides, phytosterols and saponins has been neglected in the past because most of the A. annua extracts had been obtained with organic solvents. Several papers have shown that A. annua ingested as powdered leaves or in conjunction with fatty food significantly increases the artemisinin concentration in the blood. It is well documented in the literature that A. afra or sieberi which contain little or no artemisinin are extensively used as antimalarials. They contain at least 5 molecules of the same antimalarial efficacy as artemisinin. At Leiden it was found that the anti-HIV activity of A. afra is even higher than for A. annua. More recent research from the Al Quds University has shown that aqueous infusions of several Artemisia species strongly inhibit beta-hematin, like chloroquine did. But the most important finding in several of the clinical trials, especially in Kenya and Uganda, was that people who drink one or two cups of A. annua tea per week become immune against malaria. Similar strong prophylactic results have been obtained with ARTAVOL, a mixture of herbs developed by the Ministry of Health in Uganda, mixture containing Artemisia without artemisinin. Resistance in this case is not related to the killing power of one single molecule like artemisinin but to the polytherapy of the whole plant which not only eliminates the parasites but boosts the immune system, avoiding thus infection, reinfection or recrudescence. Recent clinical trials in Senegal and RD Congo also have shown that Artemisia inusions are more efficient against Schistosomiasis mansoni than Praziquantel

Djebbar Atmani

University of Bejaia, Algeria

Title: Antidiabetic, anti-lipoperoxidation and hepatoprotective activities of Fraxinus angustifolia and Pistacia lentiscus extracts

Time : 13:15-13:35

Biography:

Professor Djebbar Atmani has completed his Master of Science degree at California State University, Los Angeles (USA) in 1987 and his PhD at the University of Sétif (Algeria) in 2004. He is the acting Dean of the Faculty of Nature and Life Sciences, University of Bejaia (Algeria). He has published more than 15 papers in reputed journals and has been serving as reviewer of many journals.

Abstract:

Fraxinus angustifolia (Lamiaceae) and Pistacia lentiscus L. (Anacardiaceae) are two common Mediterranean plants used extensively in Algerian traditional medicine to cure inflammatory-related disorders as well as symptoms of diabetes. The anti-diabetic effect of F. angustifolia (leaves and bark) and P. lentiscus (leaves and fruits) extracts was evaluated using the streptozotocin-induced diabetes model in rats, whereas anti-lipoperoxidation activity was assessed with the malonaldehyde assay after injection of paracetamol to mice. The results indicate that F. angustifolia leaf extract (50 mg/Kg of body weight) and P. lentiscus leaf extract (100 mg/kg of body weight) induced a significant reduction (60%) of blood glucose level after 2 hours of administration of the extracts. Furthermore, extracts from both plants significantly reduced α-amylase activity. Analysis of liver homogenates showed an important decrease in the concentration of malonaldehydes in the group of mice treated with plant extracts (0.25 ± 0.006 and 0.26 ± 0.03 for F. angustifolia and P. lentiscus extracts, respectively), compared to that of non-treated animals (0,45± 0.005). Furthermore, plant extracts tested with concentrations up to 200mg/kg of body weight showed no signs of toxicity. Moreover, histological examination of the liver revealed significant protection against paracetamol-induced hepatic necrosis. Phenolic compounds identified in plant extracts could take, at least, partial responsibility for the observed anti-hyperglycaemic and antioxidant activities, thereby conferring these plants a promising protective capacity against oxidative stress.

Shirly Kumala

Pancasila University, Jakarta

Title: Antimicrobial activity and Identification of Chemical Compounds of Secondary Metabolites Bioproduction of Endophytic Fungi from Jamblang Plant (Eugenia cumini L.)

Time : 14:05:14-25

Biography:

Shirly Kumala has completed her PhD from Biomedik Faculty of Medical, University of Indonesia, Jakarta. She is the Dean of Faculty Pharmacy. Pancasila University Jakarta, Indonesia. She has published more than 25 papers in accredited journals and has been serving as a reviewer in journal of Pharmacy.

Abstract:

Colletotrichium capsici endophytic fungi isolated from Jamblang plant (Eugenia cumini L.). Endophytic microbes were microbes that spent part or all of their life within plant tissue or of a host plant. They produce secondary metabolites with potent anti-microbial activity. Jamblang (Eugenia cumini L.) is one of the traditional medicinal plants that grow in Indonesia and were known by the layman as a plant that has efficacy as anti-diarrheal and anti-diabetic.This research focussed on isolation of the endophytic microbes from branches of Jamblang plants and their secondary metabolites. Isolation of endophytes were performed in PDA(potato dextrose agar) using direct seed plant. Endophytic fungi isolates that have the greatest antimicrobial activity against the bacteria Staphylococcus aureus, Escherichia coli, and then fermented in Potato Dextrose Yeast (PDY) in large scale. Supernatant was extracted with ethyl acetate solvent.. Ethyl acetate extract fractionated by column chromatography (SiO3, n-hexane- ethyl acetate = 50:1 ~ 1:1) and obtained three fractions. Further, agar diffusion method was performed to assess their anti-microbial activity Antibacterial test results indicate the fraction III had the antibacterial activity against Staphylococcus aureus with the inhibition diameter of 10.7 mm and but no antibacterial activity against Escherichia coli. Identification of chemical compounds by GC-MS showed that the fraction III is dominated by compound fatty acids and phenolic groups. In conclusion, secondary endohpytes isolated from Jamblang plants branches contained predominantly fatty acid and phenol related compounds that could be responsible for its potent anti-microbial activity.

I.Ermolina

De Montfort University School of Pharmacy, Leicester, UK

Title: Physicochemical and pharmaceutical properties of HEA-HEMA hydrogels

Biography:

Irina Ermolina has completed her PhD from Kazan Institute of Biochemistry and Biophysics, Russian Academy of Sciences in 1995, following by postdoctoral studies from Hebrew University of Jerusalem, Glasgow University and South Hampton University. Currently, she is a senior lecturer at De Montfort University, Leicester, UK, theaching the pharmaceutical technology, pharmaceutical material sciences and analytical techniques. She has published 45 papers in the peer reviewed journals and has been serving as a reviewer for several sceintific Journals.

Abstract:

Over the last years the hydrogels have attracted considerable attention due to their capability to be used for numerous pharmaceutical and biomedical applications (i.e. drug delivery systems, contact lenses and wound dressings). Hydrogels are swell able polymeric materials capable of imbibing a large amount of liquid and, therefore, a large amount of drug. Recently we have described novel cross-linked 2-hydroxyethylacrylate-co-2-hydroxyethylmethacrylate (HEA-HEMA) hydrogels with different co-polymer compositions synthesized by three-dimensional free-radical copolymerisation. The aim of the present work is to characterize the physicochemical and pharmaceutical properties of HEA-HEMA hydrogels, which potentially can be used as sustain drug delivery systems. The effects of the hydrogel composition (HEA/HEMA ratios) and liquid medium (aqueous PEG and glycerol solutions) on morphology, swelling and mechanical properties were examined using different analytical techniques. The molecular dynamics results for hydrogels were obtained by Broadband Dielectric Spectroscopy. The current study has been specifically focused on the analysis of the free/bound water redistribution in the hydrogels using thermo analytical techniques. Also the effect of different methods of sterilization was studied with respect to the stability of hydrogels. The pharmaceutical aspect of this study included the analysis of drug loading and release for the cases of low molecular weight drugs (riboflavin, ibuprofen) and proteins (lysozyme). The results show that HEA-HEMA hydrogels can be used as a sustain drug delivery system for both small drugs and bio macromolecules. The variation of the HEA-HEMA composition as well as liquid medium permits controlling the properties of hydrogels allowing producing the hydrogels with the drug release rate desired.

Atmani-Kilani Dina

University of Bejaia, Algeria

Title: Hepatoprotective activity of the ethanolic extract of C. flammula against paracetamol toxicity in mice

Time : 14:45-15:05

Biography:

Atmani-Kilani Dina has completed her master degree from California State University, Los Angeles and her PhD from University of Bejaia in Algeria and postdoctoral studies from University of Bejaia. She is the director of a project on the biological activities of Clematis flammula and is involved in two other projects on the biological activities of other local plants in Algeria. She has published more than 7 papers in reputed journals and is pursuing her research in order to identify many novel molecules in C. flammula with the collaboration of Dr. Tristan Richard in Bordeaux France and José Ignacio Ruiz Sanz in the University of the Basque Country in Bilbaoa

Abstract:

Paracetamol is widely used to treat pain and fever. However, it creates oxidative stress by causing the depletion of glutathion which leads to hepatic lesions and necrosis Clematis flammula is a plant widely used in folklore medicine in Algeria to treat inflammatory diseases. The hepatoprotective activity of this plant extracts were evaluated in vivo against paracetamol toxicity by the assessment of MDA levels superoxide dismutase and catalase activities. Histopathological analysis was equally carried out to confirm our results. Results demonstrated an increase in MDA levels (6.61±0.75 nmol/mg prot) and a decrease in the activities of superoxide dismutase (3.557±0.91 U/mg protein), catalase (2.41±0.49 U/mg protein), glutathione (2.45± 0.60 μmol/mg de protéine) in paracetamol (400mg/kg)-treated group (positive control), compared to negative control. Clematis flammula plant extracts, on the other hand, contributed at reducing MDA levels (2.34±0.47) and increasing the activities of superoxide dismutase (6.068±0.85 U/mmg protein), glutathion (17.80±2,42 μmol/mg proteins) and catalase (10.64±2,01 U/mg protein) at 100 mg/kg. Histopathological analysis confirmed the hepatoprotective activity of this plant against paracetamol toxicity.

Walid El Azab

Technical Services Manager for STERIS Life Sciences

Title: EU GMP changes – impact on cleaning and process validation

Time : 12:30-12:50

Biography:

Walid El Azab is a Technical Services Manager for the Life Sciences Division of STERIS Corporation. He currently provides technical support related to cleaning chemistries, disinfectants and sterility assurance products and their application and validation. His areas of expertise include both upstream and downstream biopharmaceutical operation and validation. Walid has held various positions including Project Manager, Inspection Readiness Manager, Quality and Regulatory Manager, and Qualified Person (QP). Walid’s responsibilities and experience have also included handling deviations and complaints, releasing raw materials and drug products, conducting external audits of suppliers, and leading customer and regulatory (FDA, EMA…) audits. Walid earned a Master’s degree in Industrial Pharmaceutical Sciences from the University of Liège, Belgium and is a certified Lean Six Sigma green belt. Walid also gives Industrial Pharmaceutical Sciences Master courses at the University of Liège (Belgium). Finally, Walid is an active member of the PDA, ISPE, Pharmaprocess, ECA, A3P and is Secretary of the Belgium Qualified Person (UPIP-VAPI) association.

Abstract:

The presentation will shed light on the current European GMP changes and how these changes are now linked to each other. The presentation will also detail and explain the changes of recently effective and draft documents as the annex 15, annex 16, chapter 2, chapter 3, chapter 5 and finally the EMA guidance on setting limit. Following that, the presentation will explain the impact of these changes on cleaning, process validation and how senior management and the qualified person need to ensure compliance. In addition, the presentations will deep dive on how to assess setting limits in cleaning validation and explain the difference with the ISPE and EMA guidance. Finally, the presentation will share common questions asked by manufacturers on cleaning and process validation in Europe and what regulatory agencies are expecting to be in place.

Chair

Arik Dahen

Ben-Gurion University of the Negev, Israel

Co-Chair

Adalberto Rezende Santos

Oswaldo Cruz Institute – Brazil

Session Introduction

Hulya Ozdemir

Yuzuncu Yil University, Turkey

Title: The effect of resveratrol therapy on serum total sialic acid and lipid-bound sialic acid in male rats with chronic fluorosis

Time : 15:05-15:25

Biography:

Hulya Ozdemir has completed her PhD in Faculty of Medicine; she is working as a Professor at the Medicine Faculty of Yuzuncu Yıl University. She’s the head of department of Pharmacology and Toxicology. She has published more than 70 papers and her research areas are mainly with plant therapy on the diabetes and cancer diseases, antioxidants and behavioural pharmacology. 

Abstract:

Fluor is strongest electronegative element, a potent anion and cumulative toxin. This study was designed to evaluate the effect of resveratrol on serum total sialic acid (TSA) and lipid bound sialic acid in the rats chronically exposed to fluoride. The study was administered using 32 male Sprague Dawley rats weighing 200-250 g. Rats were divided into four groups (n=8/group). Group I comprised the control group, group II was treated with NaF (10 mg/lt/day), group 3 was treated resveratrol (50 mg/lt/day) and group IV was treated NaF+resveratrol for 90 days period. Total sialic acid (TSA) and lipid-bound sialic acid (LSA) were determined using spectrophotometric method. As a result of the analysis, It was seemed that LSA level compared with the control group increased in NaF group (p<0.05). On the other hand the resveratrol group was also significantly lower than the NaF group regarding LSA and TSA levels (p<0.05 and p<0.01 respectively). Whereas, the resveratrol + NaF group was significantly higher than the resveratrol group regarding TSA levels (p<0.05). Results from this study suggest that resveratrol may be partially effective in preventing the negative effects of fluorosis in male rats.

Adalberto Rezende Santos

Oswaldo Cruz Institute –Brazil

Title: Pharmacogenetics research in different disease models: genetic diversity in an ethnic admixture population

Time : 15:45-16:05

Biography:

Adalberto Rezende Santos is Ph.D in Cellular and Molecular Biology from Oswaldo Cruz Foundation, Rio de Janeiro, Brazil. Actually, he is a Senior Investigator and Head of the Laboratory of Molecular Biology Applied to Mycobacteria of Oswaldo Cruz Institute, Supervisor at the post-graduation programs of Cellular, Molecular Biology, and Clinical Medicine from Fiocruz and Federal University of Rio de Janeiro respectively. He is ad hoc consultant of the Executive Secretariat of Science Technology and Environment and of the Ministry of Health, Brazil. He is also referee of the Journal of Infectious Diseases and Pharmacogenomics.

Abstract:

In humans, the enzyme N-acetyltransferase2 (NAT2), coded by NAT2 gene, is the main metabolizer of isoniazid, dapsone and hydralazine, used for the treatment of tuberculosis, leprosy and resistant hypertension, highly incident diseases in Brazil. We studied NAT2 in different Brazilian populations for these three diseases. In the first study, we showed the predominance of NAT2 slow acetylation alleles in Rio and Goias states. However, population from Rio showed a higher heterogeneity in NAT2 allele distribution and significant higher frequency of intermediate phenotype. We identified six new SNPs allowing characterization of seven new alleles. Further, we performed an in silico molecular modelling and structural protein analyses of NAT2. The results strongly indicates the direct involvement of the new SNP (152G>T-Gly51Val) in substrate recognition, SNP (203G>A-Cys68Tyr) in the modification of the catalytic site by the loss of a functional group and SNPs (458C>T, 578C>T, 683C>T and 838G>A) in enzyme degradation, all altering the acetylation activity to slow acetylation. In a subsequent study to evaluate the influence of CYP2E1, GSTT1, GSTM1 and NAT2 genotypes on isoniazid-induced hepatitis in TB patients, we found that only the NAT2 slow acetylation phenotype represented a risk factor for the occurrence of this outcome during TB treatment. In a more recent study, the influence of the acetylation phenotypes in anti-hypertensive effect of hydralazine in patients with RH was evaluated. Again, the predominance of slow acetylation phenotype was observed and only slow acetylators had significant blood pressure reductions after hydralazine use, however, with a high incidence of ADRs.

Ronny Martien

Gadjah Mada University, Indonesia

Title: Formulation Insulin Nanoparticle Using Chitosan and Pectin Polymers and their pharmacokinetic profile with oral application

Time : 16:05-16:20

Biography:

Ronny Martien has completed his PhD at the age of 30 years from Innsbruck University Austria (2007) and postdoctoral studies from Univ. Innsbruck (2010). He is the head of research group, BINDR (Biopolymer and Nano Delivery Research). He is a head of PhD Program at Faculty Pharmacy, Gadjah Mada University, Indonesia. He has published more than 10 papers in reputed journals and has been serving as an editorial board member of repute. His research topic are nano particulated drug delivery system, expecially with biopolymers as a matrix.

Abstract:

Parenteral insulin is one of the major therapeutic for patients with Diabetes Mellitus (DM) especially in Type 1, which often leads to patient discomfort and other problems due to the use of it within a certain period. Formulate insulin in oral dosage form is the main choice to resolve the issue. However, application of insulin orally encounters obstacles such as degradation by protease enzyme and poor insulin permeability of the gastrointestinal tract. One solution offered is insulin formulation into the nanoparticles form. In this study, nanoparticle formulation of insulin will use a combination of low molecular weight chitosan and pectin that serves to protect insulin from degradation and also enhance insulin absorption through the gastrointestinal mucosa. The aim of this study was to obtain the optimum formula of insulin nanoparticles that can be used as an alternative therapy for patient with DM. Preparation of insulin nanoparticles carried by ionic gelation method utilizing polyelectrolyte interaction between (-NH3+) of chitosan and (-COO-) of pectin to form nanoparticles that are compact and stable charge. Formula optimization was performed using Factorial Design 22 with Design Expert® 7.1.5 software. Concentration and pH of the pectin were used as factors, while the entrapment efficiency, particle size and polydispersity index were used as responses. The optimum formulas were further evaluated like zeta potential, particle morphology, profile spectra of FT-IR and in vitro release study. The obtained optimum formula consist of chitosan of 0.05% and 0.4% pectin (pH 5.0) with the mean entrapment efficiency of 63,59% ± 2,17, particle size of 228,3 nm ± 26,3, polydispersity index of 0,354 ± 0,042, zeta potential 49,40 mV ± 11,59, particle round and dark, polymer complexation was confirmed by FT-IR and release profile following the kinetics Korsmeyer-Peppas models with non-Fickian release mechanism on media HCl buffer pH 1.2 (n = 0.454) and Fickian release mechanism on PBS buffer pH 6.8 (n = 0.369). Nanoparticle insulin have AUC [(114,9917 ± 11,88) ng.menit/mL] higher than unmodified insulin [AUC = (67,8830 ± 2,17) ng.menit/mL] and PBS as negative control [AUC = (62,9713 ± 9,12) ng.menit/mL] with p < 0,05. Conclution from these results are insulin nanoparticle significantly improved insulin concentration in the blood serum higher than unmodified insulin per oral.

Emad B. Basalious

Cairo University, Egypt

Title: Self-nanoemulsifying self-nanosuspension (SNESNS) for enhancing oral bioavailability of diacerein: Simultaneous portal blood absorption and lymphatic delivery

Time : 16:25-16:45

Biography:

Emad B. Basalious has completed his PhD and postdoctoral studies from Faculty of Pharmacy, Cairo University. He is an associate professor in department of pharmaceutics and Industrial pharmacy, Cairo University. He has published more than 20 papers in reputed journals. He is working as R&D technical consultant for several Egyptian pharmaceutical companies.

Abstract:

The application of self-Nano emulsified drug delivery system (SNEDDS) to improve bioavailability of diacerein (D) has been hampered by its large dose and limited solubility. This work aimed to prepare diacerein loaded self-Nano emulsifying self-Nano suspension (D-SNESNS) containing high drug load. DSNESNS was prepared by homogenizing D into MaisineTM-based SNEDDS that gave the highest drug solubility. D-SNESNS was evaluated for particle size, zeta potential and in vitro dissolution. Significant increase of D solubility was observed from D-SNESNS ( 309 mg/mL) than traditional SNEDDS (162 mg/mL) due to the spontaneous simultaneous formation of Nanoemulsion and Nano suspension (top–down approach). When exposed to water with mild agitation, the drug micro particles in D-SNESNS are temporarily surrounded by unsaturated aqueous layer (containing optimum concentrations of surfactant and co-solvent) that facilitates the erosion of the suspended drug particles into Nano sized ones. Nanoemulsion-based nano suspension (NENS) was confirmed using transmission electron microscopy and particle size analysis. D-SNESNS equivalent to 50 mg D exhibited complete and very rapid dissolution after 15 min in phosphate buffer pH 6.8 due to the existence of D as solubilized molecules inside Nanoemulsion globules and Nano sized suspended drug particles forming D-NENS. The relative bio availabilities of rhein from D-SNESNS in rats with normal and blocked chylomicron flow were about 210% and 164%, respectively in comparison to aqueous D suspension. The significant increase in the dissolution, portal absorption and lymphatic delivery of D propose that SNESNS could be promising to improve oral bioavailability of poorly water soluble drugs that have limited drug load in SNEDDS.

Christina Yuen Ki Leung

The University of Hong Kong – Shenzhen Hospital (HKU-SZH), Shenzhen, China

Title: Advanced Clinical Pharmacy System in a Reformed Hospital in China aiming to improve the quality of patient care and to enhance the job satisfaction level for the clinical pharmacists

Time : 16:25-16:45

Biography:

Christina Leung completed two Bachelor degrees in England, Management Sciences degree followed by a Pharmacy degree. Following the registration as a pharmacist in England, she worked in a number of teaching hospitals in London. After the completion of junior pharmacist training, Ms Leung spent 12 years as Women’s and Children’s Pharmacist, mainly specialising in Paediatric ICU, Paediatric Liver, Obstetrics and Gynaecology. She published a number of articles including two articles relating to drugs use in paediatric liver diseases published in UK Healthcare magazine. Ms Leung is also a registered pharmacist in HK and she is currently working as the Senior Pharmacist (Clinical Pharmacy Service) at the HKU-SZH in China. She is also the Honorary Lecturer of the Department of Pharmacology and Pharmacy at the University of Hong Kong.

Abstract:

HKU-SZH adopts the good pharmacy practices from the West and has implemented an advanced clinical pharmacy system. We have been using near-patients and near-doctors approach to provide high quality of clinical pharmacy service to patients and healthcare professionals to ensure safety and efficacy of drugs use. The clinical pharmacists join the doctor-led ward rounds regularly on selected wards such as ICU and Medicines wards. For all newly admitted in-patients, the clinical pharmacists carry out medication reconciliation, and the information is recorded in the electronic prescribing system permanently. They also check the in-patient prescriptions for clinical appropriateness using approved and updated reference sources. In addition, pharmacists involve actively in the warfarin patient counselling service and the stroke clinical pathway for our in-patients. Since early 2015, clinical pharmacists have participated in the smoking cessation clinic, paediatric respiratory out-patient clinic, diabetic clinic to provide patient counselling services. In addition, clinical pharmacists deliver drugs-related talks for patients in the cardiac rehabilitation centre and on endocrine ward, and have prepared medication-related patient leaflets. Furthermore, clinical pharmacists give talks to patients in the Out-Patient Forum regarding drugs use for smoking cessation, drugs use in hepatitis B, safe use of insulin injection, effective use of inhalation devices, medication safety in children including use of oral syringe. All these quality improvement plans are to enhance medication safety and optimistation of drugs use. Clinical pharmacists in China find this experience rewarding and they gain lots of job safisfaction by noticing the positive impact on the quality of patient care.

Chair

Moses S S Chow

Western University of Health Sciences, USA

Co-Chair

Anna Szemic-Hojniak

University of Wroclaw, Poland

Session Introduction

Suad Yousif Abdalla Alkarib

University of Karary, Sudan

Title: Gum Arabic Acacia for Manufacturing of Hard & Soft empty capsule shell in Sudan 2011

Biography:

Suad Yousif Abdalla Alkarib has completed her PhD at the age of 37 years from University of Khartoum. She is the founder of College of Pharmacy in Karary University. Before she was a Director General Manager for the “Wafrapharma Laboratories Ltd. She is the Member of the Sudanese Medical Council. She is the Member of Scientific Researches committee in Gum Arabic Board(Sudan). She is the Member of the Arab Administrative Development Organization(League of Arab States). She is the Rapporteur of the Industrial Pharmacy Committee in the Pan Arab Colleges of Pharmacy.(October-2012) . She is the Member of the proposed fellowship in Technology of Industrial Pharmacy. (Council of pharmaceutical specialties-Sudan). She has got a Certificate of honor as a leader in the field of pharmacy, and the first female major-general (Jan-2011) Sudan. She has got a MAJOR AWARDS AND DECORATIONS in Competency - Duty - The national Rescue - Golden defence. She has published more than ten papers in deferent Journals and Conferences.

Abstract:

Gum is a dried exudate from stems and branches of acacia senegle linne willdenow and other related African species of acacia Family Leguminosae. It is a safe nontoxic material utilized in production of capsule shell compared to the gelatin. Capsule hardness and elasticity are influenced by changes in gum: water: plasticizer ratio. This study described the use of gum Arabic in the manufacturing of capsules, using water and plasticizer to fine-tune the elasticity. Hand pick gum Arabic grinded and treated by adding glycerine B.P, polyethylene B.P glycol, sorbitol and purified water in a ratio of 5:2:1 per volume in Wafrapharma industry. A flexible sheet was produced from the mucilage to confirm the formula reliability. Then after capsules shells were produced by process of dipping molds in the mucilage and let to dry. The influence of gum: water: plasticizer ratio on capsule formulation showed the difference in ratio of gum solution formula affects the elasticity degree of the sheet. When the quantity of the plasticizer is increased, the ratio of water: plasticizer decreased. Gum Arabic is a stable suitable natural material to be used in capsule shell production in Sudan. Both gum solution and plasticizer loading level were found to influence the initial rate of elasticity. Elasticity shown to be controlled by the added quantity of plasticizer.

Yahdiana Harahap

Universitas Indonesia, Indonesia

Title: Analysis of Valproic Acid with Dried Blood Spot Method by Ultra Performance Liquid Chromatography – Mass Spectrometer

Time : 13:50-14:10

Biography:

Yahdiana harahap has completed her PhD at the age of 39 from Department of Pharmacy, Institute Technology Bandung, Indonesia. Now she is the Head of Bio availability and Bioequivalence laboratory Faculty of Pharmacy, Universitas Indonesia. Prior to this position, she was the Dean of Faculty of Pharmacy, Universitas Indonesia. She has published 40 papers published in both International and National Journals. She has been invited to be the speakers in many international conference, especially in the field of BA/BE and Bioanalysis technique. She currently serves as an expert at Indonesia National Agency of Drug and Food Control, specifically in BA/BE evaluation.

Abstract:

Valproic Acid is an anticonvulsant, which can be used to treat all types of epilepsy and has also been developed to be used as an adjuvant therapy for bipolar disorder. Valproic acid has narrow therapy index therefore it needs therapeutic drug monitoring with dried blood spot method which is simple, easy, and accurate. The objective of this research is to obtain optimum and validated method of Valproic acid in whole blood as Dried Blood Spot (DBS) using Ultra Performance Liquid Chromatography – tandem mass spectrometry (UPLC-MS/MS). The quality control and calibration samples were obtained by pipetting as much as 20 µL blood sample onto CAMAG DBS paper and then left to dry at room temperature for 1 hour. Then the disc was transferred into micro tube and added 200 µL extraction solution (acetonitrile – methanol mixed solution (1:3) containing benzoic acid as internal standard with concentration of 1000 µg/mL. Chromatographic separation was conducted using Waters Acquity UPLC Class BEH C18 1.7 µm (2.1 x 100 mm) with mobile phase of 0.1% acetic acid - acetonitrile (40-60) under isocratic elution and flow rate of 0.4 mL/minute. Mass detection was performed with an Electrospray Ionization (ESI) source at negative ion mode in the Multiple Reaction Monitoring. Detection of Valproic acid was performed at m/z 142.95 > 142.95 value; and benzoic acid was at m/z 121.1 > 77.1. This method was linear on range concentration of 0.5 – 100 µg/mL with r > 0.9991. Dried Blood Spot sample was stable for minimum of 16 days in room temperature and the validated analysis method was applied on one healthy subject.

Hiwa K. Saaed

University of Sulaimani KRG-Iraq

Title: QRT-AAGEL-Quantitative Real Time PCR Analysis of Apoptotic Gene Expression In Chronic Lymphocytic Leukemia Patients and Their Relationships With Chemosensitivity

Time : 14:10-14:30

Biography:

Hiwa K Saaed currently the Dean of The School of Pharmacy, Faculty of Medical Sciences at the University of Sulaimani since 2010, where he has been a faculty member since 2007. He is currently a lecturer of Pharmacology, Toxicology, and Communication skills in Pharmacy Practice. Hiwa K Saaed received his B.Sc in pharmacy and a Higher Diploma in Clinical Pharmacy from the College of Pharmacy and M.Sc and Ph.D. (1st Rank) in Clinical Pharmacology and Toxicology from the College of Medicine University of Baghdad. He has over 20 years of experience in Pharmacy practice/ Hospital and Community settings. He is a director of Joint Higher Diploma (in Clinical Pharmacy) Studies with Ministry of Health KRG-Iraq, since 2010. His academic research explores the different aspects of Pharmacodynamics and –kinetics; permeability of Hydatid (Echinococcus granulosus) Cyst to drugs, GABA Receptor, Apoptotic gene expression in Leukemic patients... etc. He is supervising several postgraduate students in the area of clinical and basic pharmacology leading to MSc in Pharmacology and higher Diploma in Clinical Pharmacy. He is a member of the University Council of Sulaimani, Scientific Promotion Committee of Faculty of Medical Sciences, Federal International Pharmacist Society, Royal Pharmaceutical Society, Syndicate of Iraqi Pharmacists and Kurdistan Pharmacists Associations and Faculty Affiliate of College of Pharmacy at Belmont University, Tennessee USA

Abstract:

To determine the role of Bcl-2 and p53 apoptosis related genes expressions in chronic lymphocytic leukaemia (CLL) patients concerning the response to different chemotherapy regimens and number of treatment courses. The study conducted on 55 CLL patients (44 CLL and 11 CLL/SLL; small lymphocytic leukaemia) and forty healthy individuals as control, at Hiwa Hospital of oncology & haematology in Sulaimaniyah during three-month period, October 1st- Dec 13th 2013. The RNA was extracted by exploitation total RNA extraction kit, treated with DNAse, then cDNA was synthesized and qRT-PCR used to analyse anti-apoptotic Bcl-2 and tumour suppresser p53 gene expressions. CLL/SLL showed higher Bcl-2 and p53 gene expression than CLL. CLL patients showed one-third increase in Bcl-2 gene expression compared to healthy controls (p<0.05), and one-half decrease in p53 gene expressions (p<0.05). Bcl-2 gene expression was higher, particularly, for those who were treated with higher range of treatment courses and fludarabine cyclophosphamide rituximab (FCR) regimen. P53 gene expression reciprocally related with Bcl-2 and vice versa. In conclusion, the results of this study indicated that both of the anti-apoptotic Bcl-2 family members and additionally the tumour suppresser p53 may be thought-about as a result of the key choices of cancer and significantly contributes to the impact of current treatment modalities on cancer cells. Moreover, a marked role for p53 gene in the chlorambucil resistance in CLL is elucidated.

Shinya Uchida

University of Shizuoka, Japan

Title: Evaluation of the ease of taking mini-tablets compared with other tablet formulations in healthy volunteers

Time : 14:30-14:50

Biography:

Shinya Uchida, PhD, received his Ph.D. degree from University of Shizuoka in 1999. Dr. Uchida served as a clinical pharmacist at University Hospital of Hamamatsu School of Medicine. He is associate professor at University of Shizuoka and his major interests include clinical pharmaceutical science, clinical pharmacology and pharmacokinetics. He has published more than 50 papers in reputed journals.

Abstract:

Tablets are the most widely used drug formulation. However, problems may arise in paediatric or elderly patients, whose swallowing functions are inferior. Mini-tablets (MTs) are considered easier to swallow than conventionally sized tablets (CTs). Although several trials suggest that MTs are the most acceptable oral formulation, reports comparing MTs with other tablet formulations and quantitative data for the ease of intake of a unit of several tablets are lacking. We aimed to evaluate the ease of taking MTs in comparison with that of other tablet formulations, as well as to evaluate the ease of taking different numbers of MTs. We prepared 4 types of tablets in 2 diameters (3 mm for MTs and orally disintegrating mini-tablets (ODMTs) vs 8 mm for CTs and orally disintegrating tablets, ODTs) and two formulations (MTs and CTs vs ODMTs and ODTs). Our randomized crossover trial in 18 healthy volunteers indicated that the visual analogue scale (VAS) score for the ease and amount of water required for intake of MTs was significantly lower than those of CTs. An ODMT required the least amount of water and smallest VAS score for ease of taking a tablet. The advantages of MTs, namely the ease of intake and the low amount of water required, were the most prominent for a unit comprising < 5 tablets. In conclusion, MTs could reduce the problems and risks associated with taking tablets and improve patient adherence, especially in paediatric and geriatric patients who have difficulty with taking CTs.

Arik Dahan

Ben-Gurion University of the Negev, Israel

Title: Implications of Segmental-Dependent Intestinal Permeability in Oral Drug Delivery

Time : 14:50-15-10

Biography:

Arik Dahan is an Associate Professor of Pharmaceutics and Biopharmaceutics at the Department of Clinical Pharmacology and the School of Pharmacy, Ben-Gurion University of the Negev in Beer-Sheva, Israel. He is also an Adjunct Professor of Pharmaceutical Sciences at the College of Pharmacy, University of Michigan. Dr. Dahan received his Ph.D. (2007) from the Hebrew University of Jerusalem. He was a Post-Doctoral Research Fellow at the University of Michigan (2007-2010) with Professor Gordon Amidon. Dr. Dahan's research interest is the integration of up-to-date molecular/cellular mechanistic investigations of drug disposition in the context of the human body. In implementing this molecular biopharmaceutical approach to ADME research, Dr. Dahan is seeking to enable mechanistic-based successful solutions to drug delivery/therapy, in challenging scenarios e.g. low-solubility, low-permeability, extensive metabolism, poor site targeting, various pathophysiological conditions, and paediatrics. He has published over 60 top-notch Journal papers

Abstract:

On several levels, the dissolution and the permeability are related and should maintain a certain relationship between them. For instance, Tsume and Amidon (Mol Pharmaceutics 2010) have shown that the higher the permeability is, the more lax the dissolution criterion for granting a bio waiver can be. In this talk, regional-dependent intestinal permeability will be discussed, including dissolution aspects, as well as pathophysiological conditions. Permeability is location dependent, and pertains to each point throughout the gastrointestinal tract. A drug may exhibit significantly different intestinal permeability not only between the small and large intestine, but even within the small intestine, i.e. between the proximal jejunum and the distal ileum. The asymmetrical pH profile throughout the small intestine may be the underling mechanism for such segmental-dependent permeability of certain ionisable drugs. An asymmetrical expression pattern of different transporters throughout the intestinal tract may also cause such regional-dependent permeability. Asymmetrical intestinal enzymes expression may significantly influence the systemic bioavailability of a drug, although not necessarily affect the permeability. In these cases, rapid vs. sustained dissolving drug products may result unexpectedly different systemic drug levels. In conclusion, it is prudent to consider the intestinal permeability pattern when deciding on a certain dissolution profile.

Pierre Lutgen

IFBV-BELHERB, Luxembourg

Title: Artemisia afra will save Africa

Time : 15:10-15:30

Biography:

Dr Pierre Lutgen was born 1940 in Luxembourg, studied at the University of Louvain in Belgium and obtained diplomas in chemistry, social sciences and philosophy. He worked during 25 years for the Dupont CY, in research, and during 8 years in the steel industry, mainly in the environmental field. Since his retirement he worked as consultant for health and environment as invited professor at the University in Medellin and for the European Communities in several countries. Over the last ten years he has organized the association IFBV-BELHERB studying and fighting tropical diseases with some 30 academic and medical partners in Africa, South America and Europe. Numerous peer reviewed papers have been published by this team, mainly on herbal medicine.

Abstract:

A team of medical doctors in R.D.Congo, Jerome Munyangi and Michel Idumbo, have run randomized clinical trials in Maniema province with the participation of some 1000 malaria infected patients. The trials were run in conformity with the WHO procedures. For all the parameters tested herbal treatment was significantly better than ACTs. The efficiency was equivalent for Artemisia annua and Artemisia afra. More important even is the observation for the total absence of gametocytes after 7 days treatment with the herb. A tremendous hope for malaria eradication. The results have been communicated to the local health authorities, and to the Ministries of Health and Research in the RD Congo who were supportive of these trials. The draft of a paper is almost ready and will be submitted to a peer reviewed scientific journal. The large scale trials confirm those of Dr Constant Kansango in Katanga who had found in a trial with 44 Plasmodium falciparum infected patients that after 7 days of treatment with 20 gr of capsules containing a afra powder the gametocytes had completely disappeared, except for one patient. Artemisia afra does not contain artemisinin. The best explanation available is the high arginine content of Artemisia plants (see "Arginine, a deadly weapon against gametocytes" on malariaworld.org). In 2012 already Dr Saint-Hillier worked with capsules containing powdered leaves from the French Artemisia annua genotype with a content of 0.1 % artemisinin only. A total of 40 000 capsules containing one gram was administered, to adults, children, but also to neonates and pregnant women. The therapeutic effect of the capsules against fever and other clinical signs of malaria are always very fast. These results confirm results obtained by the association IFBV-Belherb and her partners in many small scale trials in several African countries. Therapeutic efficiency always was > 95% and prophylaxy was noticed and documented. The abstracts or peer reviewed papers of all these trials are available on request.

Session Introduction

Noor Mohammed

University of Birmingham School of Bioscience, UK

Title: Regucalcin protects HepG2 cells from Doxorubicin-induced apoptosis and Autophagy

Time : 15:50-16:05

Biography:

Noor has completed her master degree (MSc) in Histology on March 2010 from university of Duhok (Kurdistan Region Government of Iraq) and has published her master thesis as two papers in local university journal. Noor worked as an assistant lecturer in biology department, university of Duhok since 2010 then she started her PhD on September 2013 focusing on the mechanism effect of chemotherapy drugs on liver and kidney cell line.

Abstract:

Regucalcin (RGN) is a cytosolic Ca2+-binding protein that was discovered in 1978 and is known to be a multi-functional protein involved in number of cellular processes including – calcium homeostasis by regulating Ca²+ binding protein activity such as Ca2+-ATPases, calmodulin kinase and PKC. This protein is mostly found in liver and kidney tissues. Furthermore, RGN also plays a defence role in Ca2+-mediated stress protection and apoptosis. Doxorubicin (DOX) is a potent anti-cancer drug that is used either in isolation or in combination with other drugs for treating variety of cancers. Several studies have shown that DOX induces p53 activation leading to apoptosis in both normal and tumour endothelial cardiomyocytes cells; by causing cytochrome c release from the mitochondria, resulting in caspase 3 activation and induction of apoptosis. Moreover, this drug has the ability to damage DNA by producing reactive oxygen species. A major problem of DOX treatment is that it is highly cardio- and hepato-toxic. In the current study we have investigated the molecular mechanisms of DOX-induced hepatic cell death and show that DOX can induce cell death in human HepG2 liver cells through a number of different mechanisms including; apoptosis, DNA damage and autophagy. However, necrosis does not appear to be involved in this process. Furthermore, over-expression of RGN in HepG2 cells was found to protect against the toxicity by DOX. Therefore increased expression of RGN in the liver could be a mechanism for protection against DOX-induced toxicity.

Juan Wang

Jilin University, China

Title: MUC1-MBP/BCG anti-tumor vaccine, an attractive anti-tumor vaccine

Time : 16:05-16:20

Biography:

Juan Wang is a Ph.D student, whose supervisor is professor Guixiang Tai from Department of Immunology, College of Basic Medical Sciences, Jilin University. Hers research is focus on the biological function of MUC1 and the therapy of cancer by targeting MUC1. She has participated in several projects, including the China National Natural Science Foundation and the Major Development Programs for New Drugs of the Chinese Academy of Sciences during the 12th Five-Year Plan Period . To date, she has been published 4 SCI indexed papers

Abstract:

Mucin 1 (MUC1), as an oncogene, plays a key role in the progression and tumorigenesis of many human adenocarcinomas and is an attractive target in tumour immunotherapy. To develop an effective anti-tumour vaccine for the treatment of MUC1-expressing human tumours, our research group generated a recombinant MUC1-MBP fusion protein combined with Bacillus Calmette-Guerin (MUC1-MBP/BCG) anti-tumour vaccine, the repeated animal experiments demonstrated that MUC1-MBP/BCG anti-tumour vaccine not only induced the release of MUC1-specific antibody and a MUC1-specific Th1-dominant immune response, but also enhanced the cytotoxic T lymphocyte killing activity and the activation of macrophage and NK cells. Furthermore, the results from tumour-bearing nude mouse model revealed that MUC1-MBP/BCG anti-tumor vaccine significantly inhibited the growth of Lewis lung cancer, B16-MUC1 (MUC1+) and human breast cancer cells. To help move the vaccine into a Phase I clinical trial, the pilot production process and quality control standard of pharmaceutical research have been accomplished, and a majority of pharmacodynamics, pharmaceutical and toxicology pre-clinical studies have been accomplished as well. A pre-clinical toxicity evaluation that comprised of a single-dose acute toxicity study in mice, repeat-dose chronic toxicity and immunogenicity studies in rats, and pilot toxicity and immunogenicity studies in cynomolgus monkeys showed that treatment with the MUC1-MBP/BCG anti-tumour vaccine did not cause any organ toxicity. Collectively, these data are beneficial to move the MUC1-MBP/BCG anti-tumour vaccine into a Phase I clinical trial, and suggesting that MUC1-MBP/BCG vaccine is an attractive anti-tumour vaccine.

Lanja Ibrahim Saeed

University of Sulaimani School of Pharmacy, KRG-Iraq

Title: T-VDMS- Therapeutic Potential of Vitamin D3 as an add on to Interferon Beta in Patients with Multiple Sclerosis in Sulaimaniyah, KRG-Iraq

Biography:

Lanja Ibrahim Saeed recently graduated from Master Degree, she is currently in charge of Multiple sclerosis pharmacy at Multiple Sclerosis Center at Shar Hospital of Sulaimaniyah. Lanja Ibrahim Saeed received her B.Sc in pharmacy and M.Sc in Clinical Pharmacology from the College of Pharmacy University of Sulaimani. She has 12 months of experience in Hospital as clinical pharmacist / 2 years of experience in hospital pharmacy management and 5 years of experience in Pharmacy practice and Community pharmacy. She is a member of the Syndicate of Iraqi Pharmacists and Kurdistan Pharmacists Associations

Abstract:

Treatment of Multiple Sclerosis (MS) has received substantial attention due to devastating symptoms, disability progression, mental health and cost of polytherapy. To investigate the effect of vitamin D supplementation as an add on to interferon beta on immunological, biochemical, radiological and clinical outcomes. Patients and methods: Double-blind, placebo-controlled, randomized study conducted in 54 MS patients on interferon beta at MS Center in Sulaimaniyah City, KRG-Iraq. Total of 43 patients completed the study. On vitamin D3 arm 13 patients received 10000 IU/day, 14 patients received 5000IU/day and on placebo arm 16 patients treated with placebo. Serum cytokines IL-2 and TGF-β₁ were measured. Modified Fatigue Impact Scale, cognition (MFIS), Expanded Disability Status Scale (EDSS), 9-hole peg test, 25-foot walk, lesion numbers at T2 and T1 enhancing lesion, brain atrophy, relapse occurrences were assessed twice for every patient at baseline and after six months of treatment. Results: after six months of treatment; serum vitamin D level significantly increased MFIS, EDSS and cognition function improved significantly, relapse rate reduced very significantly, TGF-β₁ serum level increased, IL-2 level and MS Functional Composite changed but not significantly, Gadolinium-enhancing lesions reduced significantly compared to placebo. Conclusions: Vitamin D deficiency is considered as both risk factor and consequences of MS. The optimum serum vitamin D level (40ng/ml) can be achieved faster by 10000IU vitamin D3/daily which can be considered as a loading dose, also favoured for prevention of relapse occurrences this level can be maintained by 5000IU vitamin D3/daily and keeping its therapeutic potential without causing hyperkalaemia.

Maria Sala-Cîrtog

University of Medicine and Pharmacy “Victor Babes”, Timisoara, Romania

Title: Identification of potentially conserved microRNAs in Calendula officinalis using homology-based approaches

Time : 16:35-16:50

Biography:

Maria Sala-Cîrtog is a third year PhD student at the University of Medicine and Pharmacy "Victor Babes", Timisoara (Romania) where she works as an Assistant professor in the Department of Biochemistry and Pharmacology. She is also a Pharmacy resident at the Clinical Municipal Hospital, Timisoara. In the last year, she received a grand from the Ministry of European Funds.

Abstract:

MicroRNAs (miRNAs) are a group of small, noncoding endogenous RNA (21-25 nucleotides long) with an important role in gene expression regulation by targeting specific mRNAs in plants, animals and humans. To date, no miRNAs from marigold (Calendula officinalis), one of the best known medicinal plants, have been identified. This may be due to the lack of genome data regarding Calendula off. because the majority of available miRNA identification tools require a reference such as EST database or genomic sequence to discover novel miRNAs. Materials and Methods: - Certified plant material (Calendulae flos) and standard growth conditions - Plant small RNA isolation and extraction - Sequencing data analysis and plant miRNA identification Results: The cDNA libraries of two tissues from Calendula (petals and inflorescence) were prepared and small RNA-seq were conducted according to Illumina's protocols. To identify potential miRNAs, previously known miRNAs from Arabidopsis thaliana, Ricinus Communis, Linum Usitatissimum and Physcomitrella patens were downloaded from MirBase. The reference set miRNAs were compared against Calendula small RNA sequences using homology approaches. A total of 3 miRNAs, with 0 mismatches, (mir166a, lus-mir166e, ppt-mir894 and ath-mir8175), were identified based on their sequence complementarities. Conclusion: The potentially conserved miRNAs from Calendula were identified only in the inflorescence, which is the part used for medicinal purposes. This could lead to a better understanding of the relationship between plant exogenous genetic material and the changes in mammal upon oral ingestion. Acknowledgement: We would like to thank for financial support received from the Romanian Ministry of Education and Research (Grant PN-II-PT-PCCA-2013-4 No 165/2014)

Chair

aravind

test

Co-Chair

chudamani

web