Day 1 :
Keynote Forum
Anand Kulkarni
Director, BioDuro- LLC, China
Keynote: Formulation selection matrix in early clinical formulation
Time : 10:10-11:10
Biography:
Anand has over 14 years of research experience in the pharmaceutical industry including generics and New Chemical Entities (NCE) development, scale up, technology transfer, registration, where he was involved in the overall end to end project management. He is currently working as a Director and Head of Formulation Development at BioDuro and supporting Yangtze River Pharmaceutical Group for formulation related technologies. Prior to joining BioDuro Anand worked over 7 years as a Director of Pharmaceutical Development Services at WuXi AppTec, Shanghai. In this role he was involved in building the formulation development team and infrastructure to support various dosage form development and pilot scale manufacturing. He also worked with over 35 global clients and over 120 projects to support various stages of clinical development. He was involved as a key SME for successful MPA (EU), US-FDA and C-FDA site inspections for GMP. He was also involved in successfully implementing several key technology platforms including microdoser, hot melt extrusion (HME), bilayer tableting, spray drying etc. He has received “Best team management” award in the year 2013. He is a recipient of several prestigious awards.
Abstract:
The pharmaceutical formulation development of early stage pre-clinical and clinical formulations poses various unique challenges during development. These challenges are mainly related to limited physicochemical data, limited availability of drug substances, uncertainty on dosage ranges, solubilization/ in-vivo exposure challenges, further scalability considerations for clinical manufacturing etc. The presentation covers an opportunity area for formulation selection matrix based on Data Driven Decision (DDD) making during developability assessment and solution engine that can facilitates overall development approach. Over 60% of New Chemical Entities (NCE’s) under development are poorly soluble therefore, it is always challenging to select appropriate development platform. The presentation covers and describes technology selection such as microevaporation, amorphous solid dispersions using spray drying or hot melt extrusion (HME) and few case studies describing the same. Overall, appropriate assessment of early stage data can help to successfully develop formulations within defined timeframe with limited usage of drug substances. These formulations can be further evaluated in animal models or first in human (FIH) clinical studies to understand in-vivo performance followed by phase appropriate scale up.
Keynote Forum
Tao Feng
Zai Lab, China
Keynote: Effective utilization of preformulation studies to guide drug product development
Time : 11:30-12:30
Biography:
Dr. Feng is currently Senior Director of CMC at Zailab, responsible for drug product development and manufacturing to support Zailab’s clinical and commercial programs. Dr. Feng has more than 12 years’ experience in new drug research and development including preclinical candidate characterization, preformulation, formulation development, and GMP manufacturing. Prior to joining Zai, Dr. Feng was Director of pharmaceutical development at WuXi Apptec, responsible for formulation development and GMP manufacturing of many new drug programs. Prior to WuXi Apptec, Dr. Feng worked at Schering-Plough in New Jersey US, where he led the preclinical candidate characterization activities to support multiple new drug discovery programs to progress into development phase. Dr. Feng received his PhD from Purdue University.
Abstract:
Preformulation study is starting point of new drug development program and defines the strategies for drug product development. It is critically important to utilize various preformulation characterization techniques to fully profile the preclinical candidates from various aspects to avoid any surprise in late stage of product development. The major preformulation aspects include molecular properties (solubility, stability, UV absorptivity, partition coefficient, etc.), solid-state properties (crystal form, thermal properties, particle size, etc.), API form development (salt screening, polymorph screening, particle size control, etc.), and formulation development support (toxicity formulation, enabling formulation development). Normally at early stage only very limited amount of API is available to be used in preformulation studies, thus a very full check list of all preformulation studies is not feasible for most drug development program. These studies need to be tailored based on the target product profile and unique properties of the drug candidate so that the appropriate development strategies can be well defined to mitigate any potential risk during the whole drug development process. Typical pitfalls and risk scenarios in new drug development will be discussed and explained to show how to effectively utilize preformulation studies to guide drug product development.
- Drug Formulation Procedures | Novel Drug Delivery System | Traditional Medicine
Chair
Peng Li
University of California, Irvine USA
Session Introduction
Peng Li
University of California, Irvine USA
Title: Neurotransmitters related to the acupuncture inhibitory effect on hypertension
Biography:
Peng Li In 1950 graduated from Shanghai first Medical College (Shanghai Medical College of Fudan University), Worked in Department Physiology from 1955-1999. Chair of this Department for 10 years. 1983-84 went to University of Birmingham, UK to learn electrophysiology & have studied over 55 years about electro acupuncture (EA) effect on cardiovascular diseases. Now he worked in the School of Medicine at UC Irvine & has examined the underlying mechanisms of EA with several animal models. Licensed to perform acupuncture in California, investigate the effects of EA in hypertensive patients. He have published over 153 articles and organized five international symposiums.
Abstract:
All antihypertensive medications have adverse side effects. However, physicians are reluctant to recommend acupuncture, owing to its controversial reports in treating hypertension and the unclear physiological mechanisms. Recently, according to the results of our data over 60 years animal experiments we conducted a clinical trial and showed that EA at certain acupoints reduced high blood pressure in 70 % patients with mild to moderate hypertension, and the effect showed a slow onset and long-lasting. In animal experiments we demonstrated that EA inhibited cardiovascular sympathoexcitatory neurons through activation of neurons in the hypothalamic arcuate nucleus, the ventrolateral PAG (vlPAG) in the midbrain and the nuclei raphe in the medulla, which in turn, inhibited the activity of premotor sympathetic neurons in the rostral ventrolateral medullar (rVLM) to reduce blood pressure. The arcuate also projects to the rVLM and contains endorphin. The neurotransmitters glutamate, acetylcholine, opioids, GABA, nociceptin, serotonin and endocannabinoids all participate in the EA hypotensive response, their importance varies between nuclei. The long-lasting inhibition of EA is related to opioids and GABA in the rVLM, neural circuitry between the arcuate and vlPAG, and prolongation of the increase in preproenkephalin mRNA and enkephalin expression in the rVLM and arcuate. The inhibition of sympathetic activity, renin, angiotensin and aldosterone are quite important. Thus, a number of mechanisms underlying the EA effect on hypertension have been suggested.
Ling Chen
Shanghai East Hospital, China
Title: What do we understand from clinical and mechanistic studies on acupuncture treatment for hypertension?
Biography:
Dr.Ling CHENG is Vice Chief to the Department of Acupuncture in East Hospital at Shanghai Tong-Ji University. She is currently the Deputy Head of Acupuncture-Moxibustion Group, Medical Association of Pudong New District, Shanghai. Pioneer Talent of Traditional Chinese Medicine (TCM) Practitioners in Pudong New District, Shanghai.
Abstract:
Our clinical study show that low current and low frequency electroacupuncture at P5-6 (overlying median nerve) and S36-37 (overlying deep peroneal nerve) reduces high blood pressure in a subset of patients (~70%) with mild to moderate hypertension. The effect is slow in onset (4-8 weeks) but is long-lasting (1-2 months). Experimental studies have shown that EA inhibits cardiovascular sympathoexcitatory neurons through activation of neurons in the arcuate nucleus of the hypothalamus, ventrolateral periaqueductal gray (vlPAG) in the midbrain and nucleus raphe pallidus (NRP) in the medulla, which in turn, inhibits the activity of premotor sympathetic neurons in the rostral ventrolateral medulla (rVLM) to ultimately reduce blood pressure. Several neurotransmitters such as glutamate, acetylcholine, opioids, GABA, nociceptin, serotonin and endocannabinoids participate in the EA hypotensive response although their importance varies between nuclei. The long-lasting inhibition of EA is related to opioids and GABA in the rVLM, neural circuitry between the arcuate and vlPAG, and prolongation of the increase in preproenkephalin mRNA and enkephalin expression in the rVLM and arcuate. The inhibition of sympathetic activity, renin, angiotensin and aldosterone may be quite important. Thus, a number of mechanisms underlying the actions and long-lasting effect of EA on cardiovascular function have been identified, but clearly further investigation is warranted.
Biography:
Yahdiana harahap completed her PhD from Pharmacy Department, Faculty of Mathematics and Natural Science, Institute Technology Bandung, Indonesia. She is now the Head of Biavailability 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 more than 40 papers published in both International and National Journals. She has been an invited speaker in many international conferences, 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, spesifically in BA/BE evaluation.
Abstract:
Curcumin is a polyphenol, found in the spice turmeric from the rhizome of Curcuma Longa. After oral administration, curcumin undergoes rapid metabolism by conjugation and reduction. Curcumin levels are generally low so that the required bioanalytical method is selective and sensitive. A simple, specific and rapid UPLC-MS/MS method has been developed and validated for the estimation of curcumin in human plasma, using diazepam as internal standard (IS). The separation was done using UPLC BEH C18 column (1.7 µm, 2.1 x 100 mm) Acquity® Waters; 0.15% formic acid - acetonitrile (50:50, v/v) as mobile phase; flow rate of 0.5 mL/min; using liquid-liquid extraction with the mixture of ethyl acetate-methanol (95:5) for the sample preparation. The ionization mode was performed using electrospray ionization (ESI) detection in multiple reaction monitoring (MRM) in positive ionization mode. The monitored MS/MS ion transitions were m/z 369.05 >176.95 and 284.95 > 193 for curcumin and diazepam respectively. The method fulfilled the requirement of EMEA Bioanalytical Method Validation Guidelines 2011 and the calibration curve was linear in concentration range of 1 – 100 ng/mL, thus LLOQ for curcumin was 1 ng/mL. The method was applied to determine the level of curcumin in healthy subject after 1800 mg oral administration of curcumin dosage form. There was no free curcumin determined in plasma sample, but curcumin glucuronides and sulfates were detected in plasma subject. The ratio of glucuronide to sulfate was 4:1.
Nasir Jalal
Tianjin University, China
Title: DNA strand break associated bystander effect (DSB-ABE) linked to gene mutations
Biography:
Nasir Jalal has completed his PhD from the Colorado State University, USA and currently engaged in postdoctoral studies at the School of Pharmaceutical Science and Technology, Tianjin University, China. He is an academician and researcher since 2007 working in the field of radiation induced DNA damage and repair mechanisms. He has published more than 10 papers in reputed journals and has served as the expert committee member for Biological drugs at the drug regulatory authority of Pakistan.
Abstract:
The goal of this project was to investigate whether radiation independent DNA damage, specifically a single induced DNA double strand break (DSB) can produce bystander signal, which is capable of inducing genomic instability in non-targeted cells. Previously uncharacterized E18 (modified TK6 cells) with a unique I-Sce1 insert in intron 2 of the thymidine kinase (TK1) gene were allowed to generate a bystander signal following electroporation of the rare cutting restriction enzyme I-Sce1 carried by a plasmid to induce DNA damage at the I-Sce1 site. Mutation assays were carried out to measure mutation fraction (MF) in directly targeted cells and using medium transfer, in non-targeted cells as a measure of bystander signal production. Transfection of the plasmid carrying I-Sce1 gene resulted in production of sufficient bystander signal into the medium to increase the bystander MF, when conditioned medium was applied from directly targeted to naïve E18 cells. The DSB-ABE exhibited temporal kinetics over a 10 hour duration. The relative direct and bystander MF increase due to the electroporation of three rare cutting restriction enzymes namely Not1 an 8 base cutter, Sfi1 a 13 base cutter (technically 8 because of the 5 non-specific bases in sequence) and I-Sce1 an 18 base cutter, showed that DSB-ABE does not show a dose-response. The bystander signal inhibition using superoxide dismutase (an enzyme that degrades reactive oxygen species) and PD 98059 (MEK1/2 inhibitor) indicated that the bystander signal activated the MAPK pathway in naïve cells. Higher levels of bystander mutation fraction were attempted through chemical inhibition of the three known enzymes of DNA repair (ATM, ATR and DNA PK) in directly targeted cells. Results reveal that inhibition of repair of I-Sce1 induced damage was not linked to bystander response. Further, sufficient bystander signal was produced by a presumably single I-Sce1 induced DNA break. The bystander signal produced, exhibited a dose-response in naïve cells and there was suggestion for the involvement of MAPK pathway.
Sevgi Gungor
Istanbul University, Turkey
Title: Vesicular nanocarriers designed for the topical treatment of psoriasis
Biography:
Dr. Sevgi Güngör currently is an Associate Professor of Pharmaceutical Technology at Faculty of Pharmacy, Istanbul University. She is a lecturer at since 2004. She has also worked visiting scientist at University of Bath in between 2005-2006; 2007-2008. Dr. Güngör has published more than 30 papers in peer reviewed journals, 7 book chapters in international books. She has given more than 50 oral and poster presentations in international conferences. Her research focuses on the enhancement of skin permeation of drugs with enhancers, colloidal, vesicular, and micellar nanocarriers, and iontophoresis; the characterization of skin transport mechanism of drugs; and the development of innovative topical&transdermal systems.
Abstract:
Psoriasis is a chronic inflammatory skin disease with unknown etiology. It affects significantly the quality of life of patients as much as other chronic diseases such as cancer or diabetes. Psoriasis therapy varies depending on its severity but there is still a need of more effective and safe treatments. Topical treatment is considered as first option to treat psoriatic skin. It offers targeted delivery to the dermis and epidermis with reduction of systemic absorption and consequently minimizing side effects. However, the skin represents an effective barrier in localized skin delivery. Thus, the available conventional formulations of anti-psoriatic agents suffer from the poor penetration through the skin, resulting in low topical bioavailability. Nanocarriers are promising approach used largely in the last decades to improve the drawbacks combined with the conventional preparations. Thet provide control the release of therapeutic agents into skin with localized effect by creating skin reservoirs. Vesicular systems such as as liposomes, ultradeformable liposomes, ethosomes and transethosomes are developed as drug carrier systems to target lower layers of skin with new approaches based on modification of vesicle ingredients. These vesicular nanocarriers could enhance the deposition of drug into target sites of the skin layers, consequently topical bioavailability may also be increased and dosing frequency decreased. In this context, vesicular nanocarriers of selected lipophilic antipsoriatic drugs were developed to provide a targeted topical delivery for the treatment of psoriasis.
Biography:
Dr. S. Rajendran. M.Sc., M.Phil., Ph.D., is an Associate Professor at Saraswathi Narayanan College and a Coordinator of Unit of Rural Biotechnology at Saraswathi Narayanan College, INDIA. He has over 50 scientific papers & projects either presented or published. He is an internationally recognized expert in many areas of Environmental Biology including Solid Waste management, Waste water treatment, Anaerobic digestion, Biofuel, Bioenergy production and formulator of Bio-Pesticide and Herbicide and serving as a reviewer in many biological journals. He has delivered a key note speech in various international conferences and also given invited lectures in various educational institutions and universities. He has also chaired the scientific sessions in conferences. He is one of the leading scientific writers in Tamil Dailies. He has conducted more than 30 scientific workshops for the upliftment of rural people and women self help groups. He also had given training to municipalities employees about garbage disposal. His excellence in environmental science he was awarded with Patron of Environment by Tamil Nadu Government in 2006. He also is serving as a consultant in many of the environmental organizations. His research group is actively working in the following aspects: MSW management, Mushroom culture, Biofuel generation, Waste water treatment and Bio pesticide and herbicide development. His work in biological derustification is a novel pioneer technique and growing area in the environmental biotechnology.
Abstract:
Rust is the reddish brown oxide of iron formed by the action of moisture and oxygen on the metal. It is an electrochemical corrosion which weaking the iron structures. It was estimated that the corrosion alone causing a loss of over $5000bn USD to global economy every year. According to a recent report of NACE the corrosion cost in any developing countries predicated by 5% of the GDP, for India the cost of corrosion is estimated to be Rs1.52lakh crore per year. All available methods for rust removal and corrosion prevention are having their own limitations. Therefore, it is an urgent need to find out suitable method to check the corrosion. A fungal based biological derustification process was observed and reported by us already. This present investigation deals with our further experiments and experiences on the fungal based technology for iron rust removal. The derustification process was repeated once again to conform the reproducibility of the technology in polybag fermenters. Rusty iron mesh which were rolled in the form of cylinders were placed in the fermenters to expose them to the aerosol particles generated by the fungus. The rate of derustification was noted. Attempts were also made to enhance the aerosol generation from the substrate (straw) by coconut water supplementation. It was observed that the rusty metals placed in the supplemented substrate where derusted quickly then the raw substrate. Various level of supplementation was also correlated with rate of derustification. Further works on rust removal process are under progress.