6^th World Congress on Bioavailability & Bioequivalence: BA/BE Studies Summit August 17-19, 2015 Chicago, USA

Biography:

Keith Gallicano, PhD (Chemistry) is Vice President, Scientific Affairs, Novum Pharmaceutical Research Services. He has 27 years of diverse experience working in the pharmaceutical field, including various positions in government (Senior Research Scientist, Health Canada), academia (Assistant Professor of Medicine, University of Ottawa; Adjunct Professor of Pharmacology and Therapeutics, University of British Columbia), pharmaceutical manufacturing industry (Director, Biopharmaceutics, Watson Laboratories, Inc.) and the CRO service industry (Vice President, Research and Development, Axelson Biopharma Research, Inc.).

Abstract:

The vasoconstrictor assay (VCA) method published in FDA’s 1995 Guidance on bioequivalence of topical dermatologic corticosteroids is currently the only pharmacodynamic method approved by FDA for demonstrating bioequivalence of topical corticosteroid products (gels, creams, lotions, ointments, foams, tapes and sprays). The Guidance recommends a pilot dose duration-response study to determine the appropriate dose duration for use in the pivotal study. In general, evaluation of bioequivalence by the VCA method has worked well over the last 20 years, but there remain several challenges in design and data analysis. For example, for the dose-response study the fit of the simple Emax model is not always optimal with low potency products, with products that show delayed vasoconstrictor (skin blanching) response, or with subjects that have low skin blanching (low Emax); for the pivotal study a too short or very long ED50 duration products can pose operational challenges. Furthermore, the sample size recommendation in the Guidance of 40-60 qualifiers for pivotal studies may be too low for those products that show high intra-subject variability in vasoconstrictor response. Successful bioequivalence studies depend on the clinic’s ability to recruit a fair-skinned population of subjects that show high and consistent skin blanching to even low potency topical steroids so that within-subject variability in vasoconstrictor response is minimized. This presentation will discuss approaches for minimizing operational issues, estimating sample size, and evaluating reliability of blanching profiles for pivotal studies and will provide examples of design and data analysis challenges for dose-response and pivotal studies.

Biography:

He completed his PhD in pharmacokinetics/biopharmaceutics in Uppsala university in1997. He worked as a Senior research scientist and principle scientist at AstraZeneca Sodertalje (1997-2012). Presently he is a CEO, founder and method developer at PROSILICO.

Abstract:

Background: Prediction of in-vivo permeability (Pe), solubility, BCS-classing, food interactions, fraction absorbed (fa) and oral bioavailability(F) from in-vitro and animal data is a challenge, especially for compounds with low/moderate Pe, efflux and/or high lipophilicity/low solubility. For such compounds, in-vivo prediction from preclinical data is generally poor/uncertain and sometimes impossible. Thus, improvements are required. Methods: With extensive, diverse datasets (log P -9 to 9), new algorithms and various computational chemistry methods (including machine learning) we have developed and validated prospective in-silico prediction models (no retrospective data fitting) for the parameters described above. Results & Discussion: Models for fa and F (including compounds with low Pe, strong efflux, very low solubility, extensive gut-wall and hepatic extraction) showedQ^2 of 0.77 and 0.55 and median prediction errors of 1.1- and 1.4-fold, respectively. In direct comparison, the models outperformed lab methods. For the 100 compounds with lowest solubility (including albendazole, danazol, loperamide, lovastatin, ketoconazole and troglitazone), 74% correct in-vivo BCS-classing and 12% average absolute prediction error for fa was obtained. The mean prediction error for AUC-changes with food was 1.4-fold. Conclusion: The new in-silico models and algorithms enable improved and simplified prospective predictions of in-vivo Pe, fa, solubility, BCS-classing, food interactions and F. Benefits include reduced and defined uncertainty, reduced time and costs, and frontloaded and improved decision-making.

Biography:

She is a Professor in Shenyang Pharmaceutical University.

Abstract:

p21-activated kinases (PAKs) are a family of serine/threonine kinases that act downstream of Rho GTPases, Rac and Cdc42. PAKs play a critical role in cytoskeletal organization, cell cycle progression, migration and invasion, and cell survival. PAK4, as the principal member of group II PAKs, mainly regulate its functions via a kinase domain in the C terminal, where all of the existing PAK4 inhibitors target. In this study, a series of novel 1-phenanthryl- tetrahydroisoquinoline analogues have been designed and synthesized as a novel class of small-molecule PAK4 inhibitors to fit into the cavity of PAK4. All of the target compounds were evaluated for their in vitro PAK4 inhibitory activities and antiproliferative activities. Its affinity to C-termini of PAK4 was confirmed by BSA (Biotin-Streptavidin assay). Furthermore, this compound inhibits the invasion and migration of A549 tumor cells by regulating PAK4-Lim domain kinase 1 (LIMK1)-Cofilin signaling pathways in vitro, and exhibits anti-tumor activity in vivo in the A549 tumor xenografts model.

Biography:

Wenzhan holds a PhD. degree in Pharmaceutical Science. She has experiences in both academia and pharmaceutical industries. Wenzhan has been with AstraZeneca for about 10 years. She has worked on projects from preclinical stage through commercial products. Her current focus is on compound selection to support both infection and oncology projects from preclinical to first time in man. Her publications focuses mainly on delivering poorly soluble drugs by solubilization as well as drug delivery systems. Her research interests are in the area of solubilization, nanoparticles and targeted delivery.

Abstract:

Solution formulations are not all made equal. The type of excipients as well as the level of excipients in solutions can have either positive or negative impact on oral absorption of drug molecules. In this presentation, considerations and evaluation tools in selecting and optimizing solution formulations in order to maximize the oral absorption of drug molecules will be illustrated with case studies.

Biography:

S Samanta is Professor in the Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Jharkhand India. He is having 29 years of teaching and research experience and presently guiding 7 PhD students. He established CADD lab for the department. He is supported by UGC-MRP project for installation of FlexX and Reaction station in Medicinal Chemistry Research Labs. His area of interest includes anti-diabetics, analgesics, anti-inflammatory agents. He has a patent on product and process on peptide based oral anti-diabetic compounds. He has number of International publications and recognition in the field of research and teaching.

Abstract:

Pain is the most common symptom for most diseases and there is an urgent need of more receptor specific, potent and safe analgesics. The present study is based on docking studies of 30 designed molecules both linear and cyclic small peptides. Using Glide software (version: 5.0), on receptor [pdb: 4COX & OPRD_HUMAN_AD_JOM-13 the ADME studies were done using QikProp (version: 3.1) software. The cyclic peptides have shown good % Human oral absorption. The toxicity studies were validated using OSIRIS Property Explorer. 14 designed ligands having best docking scores were synthesized and screened for anti-inflammatory, analgesic activity. Peripheral analgesic activity was significant in acetic acid induced writhing test in mice, for injectable compounds SSLR-9 (72% of inhibition) and SSLR-12 (61% of inhibition) while orally given compounds SSLR-12 showed good analgesic activity (45% of inhibition) compared to standard compound Aspirin (67% of inhibition). Also, injectable compounds SSLR-9 (43% inhibition) & SSLR-12 (35% inhibition) showed significant degree of anti- inflammatory activity compared to standard compound indomethacin (55% inhibition) in carrageenan induced anti-inflammatory study in rats. Thus this study infers that in the near future different combinations of amino acids will be suitable for peripheral analgesic and anti-inflammatory activity. Peptide combinations can also be attached with the non peptide NSAIDs such as indomethacin etc. and can prove to be more receptor specific, potent, and bio-friendly analgesic and anti- inflammatory agents.

Biography:

Onursal Saglam has a graduated degree from Department of Mathematics of Middle East Tech University in 1996. He had special project at Computer Sciences and Statistics. He had worked for Turkish Pharmacist Association and participate number of IT project as project leader. He started to work in Novagenix as IT Manager and now he is Deputy General Manager. During his work he has participated over 550 BA/BE studies.

Abstract:

Citicoline is an essential intermediate in the synthesis of structural phospholipids of cell membrane. Citicoline is also related to acetylcholine metabolism (cholinergic action). Exogenously administered citicoline promotes rapid repair of injured cells in brain ischemia with two leading mechanisms: i) direct repair of neuronal membranes ii) reduced generation of free fatty acids. Also, citicoline downregulates phospholipases to avert apoptotic and necrotic cell death. Animal and clinical studies indicate the potential of citicoline to improve cognitive deficits, stroke rehabilitation, brain and spinal cord injuries, neurological diseases, and eye conditions. Citicoline is metabolized in the gut wall and liver. The byproducts of exogenous citicoline formed by hydrolysis in the intestinal wall are choline and cytidine. Following absorption, choline and cytidine are dispersed throughout the body, enter systemic circulation and cross the blood-brain barrier for re-synthesis into citicoline in the brain. However, in humans, plasma cytidine is converted to uridine, its circulating form, which is transformed in the brain to uridine diphosphate. The aim of the study was to evaluate the pharmacokinetics of citicoline for determining the bioequivalence, only a few methods have been publish which were only describing choline which is active metabolite of citicoline those were so far to be successful. The blood sampling was started from -48h for the clinical trial. The most feasible method was to determine the uridine levels and do base line correction for PK variables. At the end of study, the Cmax, AUC0-t and tmax had been achieved successfully.

Biography:

Aydin Erenmemisoglu has graduated from Ankara University Medicine Faculty in 1985. He held title of Assistant Professor at Erciyes University, Medicine Faculty, Pharmacology Department in 1995 and Professor in 2001. He is Principal Investigator of Erciyes University DEKAM GCP Centre and has completed 1400 BA/BE studies as well as Phase I & II.

Abstract:

Sponsors are spending billions of money to register their drugs. There are number of GCP, bioanalytical centers and CRO’s around the world in that business. BE/BA trials are designed and done with upmost care to protect subjects welfare and safety. When the outcome is positive, this is mostly product developer’s success. If the trial fails then everybody blames the Principal investigator about the unwanted results. The clinical center staff starts troubleshooting and tries to find-out possible mistakes through the clinical trial. They check all the quality records, the video recordings and monitoring reports. Are they looking right places? Sometimes the answer is yes. But there are some special cases that come out with surprising consequences. Those cases demonstrate that scientifically perfect designs could be ruined with uncalculated behaviors of subjects or staff. The clinical sites and Principal Investigators can avoid such consequences with right precautions and taking measures with root cause analysis. Those possible techniques could be documented and be part of quality system of GCP center.

Biography:

Marlene Teresa Llópiz-Avilés holds a BA from Austin College, a MD degree from Universidad Anahuac and a MPH from Harvard University School of Public Health. She has worked in the clinical research arena for over 25 years and is currently CEO at IFaB. She has published several papers in reputed journals and has served on several pharmaceutical boards including AMEIFAC (Association of Medical Specialists in the Pharmaceutical Industry)as its President, IFAPP (International Federation of Associations of Pharmaceutical Physicians), as its Secretary General, and CANIFARMA (Chamber of Commerce for the Pharmaceutical Industry) – as a member of its board, as well as Chair of the Mexican Chapter of ACRP (Association of Clinical Research Physicians) in the USA.

Abstract:

Investigación Farmacológica y Biofarmacéutica, SAPI de CV (IFaB) is a market-leading clinical research organization (CRO–Authorized Third Party) that focuses on bioavailability and bioequivalence testing studies in the Mexican healthcare market. The company is comprised by a group of highly qualified and renowned professionals in various areas of expertise related to the pharmaceutical industry who have worked together as a team for over ten years. IFaB is certified by the Mexican Federal Commission for the Protection against Health Risks (COFEPRIS–Ministry of Health) and the Brazilian National Health Advisory Agency (ANVISA) - the only Mexican company to have this certification. The company´s client base includes first-rate international and local pharmaceutical companies. Over the past 10 years, the bioequivalence market has witnessed a boom derived from new regulation aiming to renewal legacy drug licenses in Mexico. It is estimated that every year 300-350 bioequivalence studies are conducted, which represent a total market of $40 million dollars. With IFaB´s dual strategy, the Brazilian and Mexican regulatory requirements are fulfilled, and with this pharmaceutical companies can obtain licenses in Brazil, Mexico, Chile, Colombia, Peru, and several Central American countries–covering approximately 80% of the Latin American market with just one BE study. The pharmaceutical industry is experiencing significant changes: Biosimilar products provide cost savings, increases in patient access and innovations. The company believes that it can add value by developing new and complex products that can differentiate IFaB from competitors and increase its portfolio services with oncologicals, inhalables–combining complex drugs with sophisticate medical devices, patches–innovative alternative for controlled drug delivery through the skin, and biotechnological products including monoclonal antibodies, etc.

Biography:

Gulay Yelken Demirel completed his Bachelor’s degree in Chemistry from University of Gazi (Ankara, Turkey) followed by a Master’s degree at Medicinal and Pharmaceutical Chemistry (faculty of pharmacy) from same university. She is also a Turkish Patent Attorney. She has nine years experience in R&D department of generic pharmaceutical companies. She worked at the Pharmaceutical Technology Department and gained experience in pre-formulation and formulation studies, new combination and techniques for formulation development studies, OTC and herbal drugs formulations, bioequivalence batches preparation and in-vitro studies, drug product dossier preparing with main focus on generic drugs for different market applications. Presently, she owns the R&D Project Group Executive position at Sanovel Pharmaceuticals. She has several published papers in the academic areas and over 35 patents & patent applications in the industrial areas on pharmaceutical dosage forms.

Abstract:

Fast Dissolving Dosage Forms represent excellent opportunities for life cycle management to the pharmaceutical companies. They have many advantages like ease of swallowing, administration without water, quick onset of action for improving both patient convenience and compliance as benefits for patient; extended life cycle, product differentiation, patent protection. But there are some challenges for formulation development studies for the generic companies. In the sense of generic companies, developing a Fast Dissolving Formulation version of an existing immediate-release product means that the two formulations must be bioequivalent and this can be challenging for in-vivo studies especially if the method of taste masking retards the dissolution rate of the active ingredient after disintegration. On the other hand, what will be the effects on the BE studies if the API has significant degree of buccal or sublingual absorption occurs in this case?

Biography:

Wenzheng Ju, Chief Pharmacist, is now the Director of Clinical Pharmacology Laboratory at affiliated Hospital of Nanjing University of Chinese Medicine. He is also the Doctoral Supervisor at Nanjing University of Chinese Medicine. He obtained his Bachelor's degree from Nanjing University of Chinese Medicine (1984-1988). He continued his education at China Pharmaceutical University in 1996 and received his Master’s degree in 2000. Thereafter, he completed his Doctoral education at Nanjing University during 2002-2006, supervised by Professor Ren Xiang Tan. His major field of research interest is the pharmacokinetics (PK) of traditional Chinese medicine (TCM).

Abstract:

Celastrol is a natural compound extracted from the traditional Chinese medicinal herb, Thunder God Vine (TGV). Owing to its potential anti-inflammatory and anti-tumor effects, celastrol has been considered as a promising candidate for drug development. Sprague–Dawley rats were administrated an intravenous dose (100 μg•kg-1) of pure celastrol and an oral dose (1000 μg•kg-1) of pure celastrol and TGV tablets (corresponding to 534 μg•kg-1 of celastrol), respectively. At different time points, the concentration of celastrol in rat plasma was determined by a sensitive and well-validated LC–MS/MS method. Main pharmacokinetic parameters including AUC, Cmax, Tmax and MRT were estimated. The oral absolute bioavailability of celastrol significantly increased from 17.06% for pure celastrol to 94.19% for TGV tablets containing equivalent celastrol. After oral administration of TGV tablets, the Cmax and AUC values of celastrol in female rats were (32.03±8.41) μg•L-1 and (379.49±118.19) μg•h•L-1, which was significantly higher (p<0.01) than that in males with the values of (14.31±7.33) μg•L-1 and (188.17±92.33) μg•h•L-1.Celastrol administered orally in the rat was poorly absorbed into the systemic circulation. However, the poor absorption of celastrol could be greatly improved when celastrol-containing TGV tablets orally administered, and thereby the oral bioavailability of celastrol was significantly increased. As for gender difference, female rats showed significantly better absorption of celastrol than males. Plasma concentration–time profiles of celastrol following (a) intravenous injection and (b) oral administration of pure celastrol standard in female rats, as well as oral administration of TGV tablets in (c) female and (d) male rats.

Biography:

Aly H Nada, BPharm, MSc, PhD, is currently the Chairman of Pharmaceutics Department, Kuwait University. He joined the Faculty of Pharmacy in 2002 and he is involved in teaching many pharmaceutics courses for both undergraduate such as: Formulation and evaluation of liquid and solid dosage forms, Biopharmaceutics, Industrial Pharmacy, Cosmetics. He is serving as reviewer for many pharmaceutical journals and scientific organization, e.g. European Journal of Pharmaceutics and Biopharmaceutics, Drug Development and Industrial pharmacy, AAPS. He has published more than 50 peer reviewed articles and contributed in more than 100 conferences and meetings.

Abstract:

Meloxicam is a non-steroidal anti-inflammatory drug of the oxicam class, used to relieve the symptoms of dental pain, arthritis, etc. Meloxicam inhibits cyclooxygenase (COX) synthesis. It is characterized by dissolution-limited bioavailability. Co-grinding of poorly water soluble drug (Meloxicam) particles with different hydrophilic polymers like PEG and / or PVP-K25 resulted in the formation of amorphous powders having enhanced drug solubility and dissolution properties. According to percentage of drug dissolved, dissolution rate of MLX – PEG co-ground binary mixture prepared by ball mill or vibrational mill > MLX – PEG – PVP co-ground ternary mixture > MLX – PVP co-ground binary mixture > MLX – polymer physical mixture > MLX alone. Co-ground mixtures prepared with ball mill have a relatively higher dissolution rate than those prepared with vibrational mill. An increase in the concentration of carrier in the co-ground blends resulted in an increase in the dissolution rate of MLX.The enhancement of dissolution of MLX from co-ground mixtures could be due to the reduction of crystalline nature of the drug in co-ground mixtures. Co-ground mixture of MLX and PEG in 1:4 ratio by ball mill showed the best results in terms of extent and rate of dissolution in water and phosphate buffer. This effect was not only due to particle size reduction, but also loss of crystalline nature of the drug during co-grinding. DSC and PXRD studies indicated that crystalline nature of drug was reduced after co-grinding with PEG and / or PVP as compared to their corresponding physical mixtures.

Biography:

Subrata Deb received his PhD from The University of British Columbia (2009) and Postdoctoral fellowship from Vancouver Prostate Centre (2011). His areas of expertise and interests include cytochrome P450-mediated disposition of drugs and chemopreventive agents. Currently, he is an Assistant Professor in the Department of Biopharmaceutical Sciences, Roosevelt University College of Pharmacy (IL, USA). He has published more than 10 papers in reputed journals and currently serves in editorial boards and as reviewer for several journals of repute.

Abstract:

Glucocorticoids, primarily dexamethasone and prednisone, are routinely used in the cancer treatment regimens to minimize chemotherapy-induced nausea and vomiting, and to suppress inflammation. Interestingly, these corticosteroids are the agonists of glucocorticoid receptor and pregnane X receptor that regulate cytochrome P450 3A4 (CYP3A4) expression in humans and rodents. Since numerous anticancer agents (e.g. abiraterone, docetaxel) and chemopreventive agents (e.g. calcitriol, the biologically active vitamin D3) are substrates of CYP3A4 enzyme, glucocorticoids have the potential to alter the metabolism and bioavailability of anticancer agents. The effects of dexamethasone on the bioavailability of abiraterone (a steroidogenesis inhibitor) were evaluated by treating adult CD-1 mice with dexamethasone dissolved in 50% ethanol at a dosage of 80 mg/kg/day for three consecutive days by intraperitoneal injection. On the fourth day morning, a single dose of abiraterone (180 mg/kg) was administered by oral gavage, followed by collection of blood through tail bleeding method in time intervals between 0.5-24 hrs. Serum abiraterone levels in vehicle- or dexamethasone-treated mice were analyzed by an LC-MS/MS assay using deuterated testosterone as the internal standard. Estimation of peak serum concentration, area under the curve and serum half-life suggests that dexamethasone significantly reduced the bioavailability and increased elimination of abiraterone. Similarly, dexamethasone, but not prednisone, stimulated the metabolism of calcitriol in mouse liver. In conclusion, the results from our laboratory suggest that dexamethasone in cancer treatment regimens may alter the serum levels of anticancer agents and this may reflect in the recent preference of prednisone over dexamethasone as an adjuvant therapy.

Biography:

Abstract:

Anthocyanins are the main polyphenol components in extract of fresh red cabbage (Brassica oleracea) with inherent anti-oxidant activity. To protect them against harsh environmental conditions (e.g. pH and temperature), solid lipid nanoparticles were prepared by dilution of w/o microemulsion containing anthocyanins, in aqueous media. The formulations were characterized regarding particle size and encapsulation efficiency. The formulation parameters (e.g. % total lipid, volume of internal aqueous phase, homogenization time, % total surfactant, % stabilizer) were optimized by Placket-Burman and Box-Behnken experimental designs. The highest value of EE (89%) was obtained when mean particle size was 6 microns and the lowest particle size (417 nm) was achieved while EE value was 35.8%. SEM study revealed a spherical morphology of the particles.

Biography:

András Fodor has completed his PhD from Eötvös University of Budapest, Hungary. He is a Visiting Research Professor (a Fulbright Research Grantée) at the Department of Bacteriology of the University of Wisconsin-Madison. The research team is focusing on antimicrobial peptides of entomo-pathogenic nematode symbiotic bacteria. He has published more than 40 papers in reputed journals.

Abstract:

Research conception: Xenorhabdus species entomopathogenic nematode-symbiotic bacteria are produce NRP antimicrobial peptides to protect the monoxenic nematode-bacterium symbiotic complex in soil condition. The HPLC and MALDI analysis show that the profiles of the different species are different. The target specificities of the different peptides overlap. Aim: We determined the target specificities of some HPLC fractions of the antimicrobial peptide-rich fractions (APRF) uniformly prepared from antibiotics-producing strains. Method: We prepared antibiotic peptide-rich fractions (APRF) from X. budapestensis HGB2238, X. marinarium HGB2199, X, szentimaii HGB2239, and X. nematophila ATTC61019. We compared the HPLC and MALDI profile and also the antimicrobial activities of the different fractions against Gram positive (S. aureus) and negative (E. coli, Agrobacterium tumefaciens, Erwinia amylovora; some other plant and pathogenic) bacteria; fungi (Candida albicans) and Oomycete (Phytophthora infestans). Results: APR fractions active against (i) only Gram positive bacteria; some are produced in mutants of secondary phenotypes as well. X. marianensis has an anti-Gram (+) activity which could not be bound to reverse phase column; (ii) bacteria, oomycete and fungal target. Bicornutin A does not have antimicrobial activity but play a role in the Xenorhabdus antimicrobial scenario. The plant protection potential of X. budapestensis is demonstrated by in vitro and in planta experiments on fire-blight infested apple flowers. Significance: The spreading multidrug resistance occurring in both prokaryotic and eukaryotic pathogens urge to find new compound of strong antimicrobial potential and of novel mechanisms of action The Xenorhabdus genus is a golden mine of such compounds.

Biography:

Muneesh Garg has completed his MD Physician from DSMI, Russia and MD Pharmacology from BFUHS Faridkot, Punjab, India. He is the Principal Investigator of Sitec Labs Pvt. Ltd., Navi Mumbai, India, a premier contract research organization.

Abstract:

Nicotine Lozenges are used to aid smokers wishing to quit smoking or reduce prior to quitting. The aim of this study was to determine the bioequivalence of a test and reference formulation of Nicotine 2 mg Lozenge. This single dose, randomized, 2-period, 2 sequence, laboratory-blinded, crossover design study was conducted in 21 healthy adult Indian human male smoker subjects under fasting conditions with a washout period of 7 days. Study formulations were administered after a 10-hour overnight fast. Blood samples for pharmacokinetic profiling were taken post-dose up to 16 hours. Safety was evaluated through the assessment of adverse events, and laboratory tests. Plasma concentration of Nicotine was determined with a validated LC-MS/MS method. Bioequivalence between the products was determined by calculating 90% confidence intervals (90% CI) for the ratio of Cmax and AUC0-t values for the test and reference products, using logarithmic transformed data. The 90% confidence intervals of Cmax and AUC0-t for Nicotine were 96.16-119.10 and 92.16-111.51 respectively. Since the 90% confidence intervals for Cmax and AUC0-t were within the 80-125% interval, it was concluded that the two formulations of Nicotine 2 mg Lozenge are bioequivalent in their rate and extent of absorption.

Biography:

Jaswanth S Bhandaru has completed his Master’s degree in Pharmacy from Panjab University and has a 1.5 yr of industrial experience. He is currently doing his Doctoral research work on multi- component systems and supramolecular chemistry, particularly pharmaceutical cocrystals. He developed cocrystals of few antihypertensive drugs and proved their improved physicochemical properties. He is very enthusiastic in developing systems for improving the oral bioavailability of the molecules and studies their industrial applicability. He also has good publications to his credit.

Abstract:

Co-crystallization is a useful technique for the enhancement of the physicochemical properties of the molecules. The poor physiochemical properties of the API’s tend to show low oral bioavailability which leads to enhanced dosage and consequent adverse profiles of the drugs to the patients. Eprosartan mesylate (EM), an angiotensin II antagonist, is used in the treatment of hypertension exhibits poor bioavailability (13%) due to low absorption window. Hence we recently reported pharmaceutical co-crystals of EM (EM-SUC, EM-SAL & EM- PABA) with improved solubility and dissolution profiles. The present abstract focuses on the study of enhanced oral bioavailability of the EM cocrystals. Pharmacokinetic studies of EM cocrystals were performed using animal models (male Wister rats) to evaluate bioavailability of the drug. Four groups (n=6) of rodents were orally administered with pure EM (API suspended in water) and EM cocrystals (12.3 mg/ kg body weight in aq. solution) respectively. Serial blood samples were collected at predetermined time points and were analyzed for EM plasma concentration using a validated HPLC assay method. Pharmacokinetic and statistical data analysis was performed using Kinetica 5.0 and GraphPad Prism software. The results suggested that the EM cocrystals showed enhanced AUC and Cmax than the pure drug. Mean retention time of the cocrystals was observed to be high with low clearance values which suggest the enhanced absorption window of the prepared cocrystals. EM-SUC showed more than 3 times (3.4 fold) enhancement in the relative oral bioavailability than the pure EM suggesting that the succinic acid as preferred coformer for the preparation of the EM cocrystals.

Biography:

Gulcin Tok has completed her Master’s degree in Organic Chemistry from Gazi University in 2011. She has been working in pharmaceuticals industry for 5 years as a R&D Scientist. She develops generic drugs and she is responsible for all process to come onto the market from the beginning of product. Additionally, she has published patent about generic formulation and has published the papers in reputed journals.

Abstract:

Colesevelam is a second generation bile acid sequestrant that is used principally for treatment of elevated LDL cholesterol. Additionally, Colesevelam is indicated to improve glycemic control in adults with type 2 diabetes mellitus. Colesevelam is an insoluble, non-absorbed polymer that binds bile acids in the intestine, impeding their reabsorption. Conventional in vivo bioequivalence (BE) study with pharmacokinetic endpoints such as Cmax and AUC is neither appropriate nor feasible for this locally acting drug. The present abstract focuses on the study of in vitro BE in tablet formulation containing 625 mg of Colesevelam HCl. Bile acid sodium salts of glycocholic acid (GCA), glycochenodeoxycholic acid (GCDA) and taurodeoxycholic acid (TDCA) were used in vitro BE studies. The binding capacity HPLC method was developed and validated for these bile acid salts. The equilibrium binding study that is the pivotal BE study and in-vitro kinetic binding study that is the support the pivotal equilibrium binding study were repeated 12 times. In the in vitro equilibrium binding studies, the Langmuir binding constants k1 (affinity) and k2 (capacity) were calculated for the three salts, individually and combined (GC+GCDC+TDC) using linear Langmuir equation for the test and reference products. The calculated capacity (k2), the more important parameter, were obtained very similar between test and reference products in the 90% confidence interval and acceptance criteria of 80% to 120%. The test/reference ratio for k2 was obtained within 0.82-1.07 from the equilibrium binding study for without acid pre-treatment and 0.96-1.08 from the equilibrium binding study for with acid pre-treatment.