Day :
- Biomarkers and Biosimilars in Pharmaceutical Development | Current Trends in Pharmacology | Bio-Pharmaceutical Sciences
Session Introduction
Mathew George
Pushpagiri College of Pharmacy, India
Title: Pharmacological screening of oxazines for epilepsy
Biography:
Mathew George is currently working as Professor and Principal/Director of Pushpagiri College of Pharmacy, India. He has completed his Post-doctoral studies at USA and France. He has published more than 250 scientific research articles and authored different National and International text books. He has been awarded Best Teacher Pharmacist award by Kerala State Pharmacy Council.
Abstract:
Oxazines are six membered heterocyclic compounds with oxygen and nitrogen as heteroatoms in the ring. Many isomers exist depending on the relative position of the heteroatoms and relative position of the double bonds. Oxazine derivatives are promising heterocyclic with extensive biological properties. Oxazine derivatives have been reported to possess antifungal, antibacterial, cytotoxic, antiviral and analgesic activity. Twenty five oxazines derivatives synthesized and all structures characterized spectrally, CHN analysis done and subjected to screen for anticonvulsant property by two methods classical maximal electroshock (MES) and by chemically induced methods. Epilepsy is featured by recurrent unprovoked seizures. Acute toxicity of the compounds studied and experiments proceeded with safe dose. The structure-activity relationship among these compounds has also been discussed. This study highlighted the properties of new compounds with different functional groups exert promising antiepileptic properties, which may be more effective and selective, and possibly with less side effects. Compounds with halogen exhibited more activity.
Suliman Al-Fayoum
Al-Fayoumi Consulting, USA
Title: Navigating the biosimilar journey from bench to market: A general overview and case studies
Biography:
Al-Fayoumi is currently a Principal Consultant supporting several small biotech companies based in the US, Middle East and Australia. He served as the Vice President of Translational Sciences and Clinical Pharmacology at Cell Therapeutics Biopharma Inc., in Seattle, WA during 2013-2017. He has also worked as the Director of Preclinical and Clinical Pharmacology and Interim Head of Research at Acucela Inc., in Seattle, WA during 2010-2013, served as an Associate Director of Global PK/PD within the DMPK Department at Novartis Pharmaceuticals (East Hanover, NJ), where he supported the Cardiovascular & Metabolism (CVM) Franchise during 2006-2010 and served as a Senior Clinical Pharmacology Reviewer at US FDA between 1999-2006 supporting GI, anticoagulants, anesthetics, addiction and dermatology drug product divisions.
Abstract:
Bio similarity is the regulatory term used to denote the comparability between a biosimilar and its reference medicinal product. Regulatory bodies across the world recommend a stepwise approach to demonstrate bio similarity between a proposed medicine and the original biologic product. Biosimilars are required by regulatory authorities to meet strict criteria of quality and comparability to their respective innovator biologic. The nonclinical, clinical pharmacology and clinical requirements tend to be more subjective however, depending on the complexity of the biologic product as well as other nonclinical and clinical considerations. The non-clinical program usually comprises of single and/or repeat dose toxicity studies as well as Pharmaco-Kinetic and Pharmaco-Dynamic (PK/PD) studies in an appropriate animal model. The clinical comparability exercise typically consists of (1) Clinical PK and/or PD studies (2) Comparative clinical efficacy (equivalence design) and safety trial(s) in one or more representative indications (3) Comparable safety profile must be demonstrated. (4) Comparable immunogenicity profiles for the biosimilar and the reference products (5) PVG and RMP. Comparative clinical PK/PD study in lieu of clinical trial may suffice when (1) PK of reference biologic well characterized (2) Adequate knowledge of PD properties/mechanism of action (3) The selected surrogate marker is linked to efficacy (e.g. neutrophil count for G-CSF, early viral load reduction in chronic hepatitis C to assess the effect of alpha interferon and euglycemic clamp test to compare two insulins) (4) There may be PD-markers that are not established surrogates for efficacy but are relevant for the pharmacological action of the active substance and a clear dose-response or a concentration-response relationship has been demonstrated. In this case, a single or multiple dose-exposure response study at two or more dose levels may be sufficient to waive a clinical efficacy study.
Jia-You Fang
Chang Gung University, Taiwan
Title: Anti-MRSA activity of cationic lipid carriers in combination with oxacillin for eradicating skin infection
Biography:
Dr. Jia-You Fang is a Professor in the Graduate Institute of Natural Products at Chang Gung University in Taiwan. In addition, he is an Adjunct Professor in the Graduate Institute of Health Industrial Technology, Chang Gung University of Science and Technology and Department of Anesthesiology, Chang Gung Memorial Hospital. Over the past 25 years, he and his team have made outstanding contributions to the understanding of drug delivery, pharmaceutics, pharmacokinetics, nanomedicine, and cosmetology. His contributions add up to 271 peer-review articles, more than 6000 citations and H index of 45.
Abstract:
Nanoparticles have been the focus of being the antibacterial agents. The aim of this study was to evaluate the anti-methicillin-resistant Staphylococcus aureus(MRSA) activity of cationic nanostructured lipid carriers (NLC) combined with oxacillin against ATCC 33591 and clinical isolate. The cationic resource on NLC surface was the decoration of soyaethyl morpholinium ethosulfate (SME). NLC loaded with oxacillin was produced to assess antibacterial activity and the topical application for treating cutaneous infection. The hydrodynamic diameter and zeta potential of oxacillin-loaded NLC were 177 nm and 19 mV, respectively. Oxacillin exhibited synergistic MRSA eradication when combined with NLC. The minimum bactericidal concentration (MBC) of oxacillin was decreased from 250 to 62.5 μg/ml after NLC encapsulation. The combined NLC and oxacillin reduced MRSA biofilm thickness from 31.2 to 13.0 μm, which was less than NLC (18.2 μm) and antibiotic (25.2 μm) alone. The oxacillin-loaded NLC showed a significant reduction in the burden of intracellular MRSA in differentiated THP-1 cells. This reduction was greater than that of individual treatment. The mechanistic study demonstrated the ability of cationic NLC to disrupt bacterial membrane, leading to the protein leakage. The cell surface disintegration also increased oxacillin delivery into the cytoplasm for activating the bactericidal process. Topical NLC treatment of MRSA abscess in skin decreased bacterial load by 4 logarithm and improved skin architecture and barrier function. Our results demonstrated that a combination of nanocarriers and an antibiotic could synergistically inhibit MRSA growth. It can be a potential approach to resolve the risk of drug resistance.
Lincy Joseph
Pushpagiri College of Pharmacy, India
Title: Screening of novel oxazepines for anticonvulsant effect
Biography:
Lincy Joseph is currently working as Professor and HOD at Pushpagiri College of Pharmacy, India. She has completed her Post-doctoral studies at USA and France. She published more than 240 scientific research articles and authored different national and international text books.
Abstract:
Epilepsy is a neurological disease affecting people at all ages. In the disease burden epilepsy is in fourth position. With respect to magnitude, frequency and duration, the epilepsy experience varied individually. Mainly there will be deviation from normal conditions in movement, behavior, sensation, perception and consciousness. Oxazepine is oxygen and nitrogen containing seven membered heterocycle. With the aim of bringing a novel bioactive chemical pharmacophore for epilepsy at preclinical model, 25 oxazepine derivatives synthesized and their structures are confirmed through spectral analysis. Acute toxicity of the synthesized compounds done according to OECD 423 guidelines. Pentylenetetrazol at a dose level of 85 mg/kg (sc), used to induce convulsion in mice after 30 minutes of test drug treatment. Onset of convulsions and duration of convulsions noted. Maximal electroshock method also tried to find out the anticonvulsant effect of newly synthesized molecules. In the tested animals, current of 25 mA for 0.2 seconds applied through corneal electrodes. Protecting activity is considered as abolition of tonic extension. The change in degrees of anticonvulsant property varies with different functional group also discussed. Phenytoin has been used as the standard drug to compare the effects of test compounds.
Ming-Cheng Chang
Institute of Nuclear Energy Research, Taiwan
Title: Antibacterial activity of collagen/gelatin/sodium alginate biomaterial with liposomes immobilized releasing antibiotics
Biography:
Dr. Ming-Cheng Chang has his expertise in investigations in cancer vaccine and new therapeutic strategies development. He has generated several antigen-specific vaccines and combinational therapeutic strategies in treating gynecologic malignancy. He also built the novel dosage forms to prolong retention time in local area to improve the clinical application against infective illness. The foundation is based on the combination of liposome and bio-degradable matrix which is time-controllable, rapid drug releasing and persistent format. These investigations could provide innovative concepts and novel drugs releasing formulation for the future treatment of ophthalmological disease.
Abstract:
Eye-drops therapy is the conventional dosage forms that account for 90% of currently accessible ophthalmic formulations. The major problem of eye-drops therapy encountered is rapid pre-corneal drug loss. Besides, high administration frequency seriously affected the quality of life of ophthalmological patients. In the current study, we developed a liposomal nanoparticle encapsulated with chloramphenicol mixed with biodegradable materials against ophthalmological disease. We first established the protocol for chloramphenicol loaded into liposomal nanoparticle; Liposomal chloramphenicol (LipoCAP). Then we established the collagen/gelatin/sodium alginate (CGA) as the component of biodegradable polymers and calibrated the novel drugs releasing formulation. Finally we combined LipoCAP with CGA to generate 8 hours-degradable ophthalmic chloramphenicol gel CGA-LipoCAP-8. Evidences indicated that CGA-LipoCAP-8 could reach the effective working concentration in 75 minutes and the drug releasing time could last for 12 hours. Besides, CGA-LipoCAP-8 could stably and continuously inhibit E. coli proliferation. The inhibiting phenomenon could be more pronounced with the time prolonging. Furthermore, there were no significant toxicities observed when CGA-LipoCAP-8 co-cultured with ocular epithelial cells. Our results of this proposal will provide innovative concepts and novel drugs releasing formulation for the future treatment of ophthalmological disease.
Jaganmohan Somagoni
ClinSync Clinical Research Private Limited, India
Title: Design of bioavailability and bioequivalence studies through PK-Stat approach
Biography:
Jaganmohan Somagoni has completed his PhD from Kakatiya University, India and Post-doctoral studies from Florida A&M University, USA He is currently working as a Senior Research Scientist heading Pharmacokinetics, Bio-statistics and Medical Writing Departments and Phase trails in ClinSync Clinical CRO, India. He is also the Founder and Director of Lead2morrow Private Limited, India. He has published more than 25 papers and 50 presentations at national and international level and two books are in his credit. He is also a Subject Matter Expert, Scientific Speaker and Consultant for clinical trial designs with more than a decade of research experience in India and USA.
Abstract:
The concept of interchangeability of pharmaceutically equivalent drug products through bioequivalence test is not just a science but a noble idea to bring the drugs to a common man at an affordable cost. However, the study design and the way how the study is executed to prove that bioequivalence is a matter of concern to all the health authorities all over the world. In spite of an eagle eye watch with wide opened eyes by the pharma regulatory bodies on CROs and manufacturing companies, over the past 2-3 decades it has become evident that marketed products having the same amounts of the drug chemical entity are failing to demonstrate bioequivalence. In many cases, the reason behind the failure of the study is not an inefficient test formulation but inefficient study design. In view of the importance of the drug PK profile as a direct determinant of drug efficacy and safety a meticulous care has to be taken while designing the BE study so that the outcome of the study will be reliable and reproducible. The failure rate of BA/BE studies can be decreased drastically through combining the pharmacokinetic and statistical approaches. Therefore, an increased awareness of guidelines and training on the design of BE study with an appropriate PK-Stat approach will enhance the success rate of studies which will help the industry to launch better generic molecules. In addition, the increase in success rate of BE studies will also decrease unnecessary exposure of healthy subjects to investigational medications.