9^th World Congress on Bioavailability & Bioequivalence April 16-18, 2018 Dubai,UAE

Biography:

Generic drugs are copies of innovator drugs that have exactly the same dosage, intended use, adverse effects, route of administration, risks, safety, and strength as the original drug. Since, the extensive preclinical and clinical studies were conducted by the innovator; these studies are not required for the generic products. The generic product must demonstrate the bioequivalence to the innovator product. Bioequivalence is also needed in case of post approval changes in pharmaceutical formulations, manufacturing process, batch size, excipients, which is going to be a costly and time consuming affair for a pharmaceutical company. Recent time brought a paradigm shift in the approach of both industry and regulators with respect to biowaiver leading to avoidance of unnecessary exposure of drugs to healthy subjects and huge investment of resources to prove the obvious, specifically, for generic players it is very critical to develop copycat product with very limited resources. In this regard, the concept and application of the in vitro-in vivo correlation (IVIVC) is the major focus in pharmaceutical product development in order to reduce time and efforts. This workshop will focus on step by step procedure to establish Level A correlation using a diclofenac sodium extended release tablet case study using simple Microsoft Excel software. With time permits Level B and C correlations will also be demonstrated.

Abstract:

Aliasgar Shahiwala is currently serving as a Professor in Department of Pharmaceutics and Program Director-Postgraduate studies at Dubai Pharmacy College, Dubai. Prof. Shahiwala received his masters and doctorate in pharmaceutics and pharmaceutical technology from The Maharaja Sayajirao University of Baroda, India with high research output in the area of novel drug delivery. His Postdoctoral Research at Northeastern University, USA was specifically focused on applications of nanotechnology in the field of drug delivery and drug targeting. Prof. Shahiwala published several international publications in high impact peer reviewed journals, four book chapters with internationally renowned publishers and one patent. He is also an editor of two books with international publishers. Prof. Shahiwala’s research credentials have established him as a reviewer, a member of editorial board, a speaker and an invited author for various pharmaceutical scientific journals and conferences. Prof. Shahiwala also has more than 3 years of rich research experience in Formulation & Development Division of large scale manufacturers of Pharmaceuticals in India as an added technical expertise in his field.

Biography:

Prof. Dr. heyamSaad Ali, M. Pharm., and Ph-D from U of K and Bradford universities, UK. She is working as a head of pharmaceutics departmentin Dubai Pharmacy College, UAE. Prof. contributed more than 50 articles to reputed international scientific journals in different conventional, controlled and targeted drug delivery systems in pharmaceutical product development. She has been invited as speaker to numerous International conferences .Reviewer and member of editorial board of many international journals.

Abstract:

The purpose of any delivery system is to enhance or facilitate the action of therapeutic compounds. It should now be apparent that conventional drug delivery systems are associated with a number of limitations which can reduce drug efficacy.

These limitations include an inability to:  facilitate adequate absorption of the drug, facilitate adequate access to the target site,  prevent non-specific distribution throughout the body (resulting in possible toxic side-effects and drug wastage),  prevent premature metabolism, prevent premature excretion, match drug input with the required timing (zero-order or variable input) requirements.

Limitations of conventional drug delivery systems are particularly acute for the new biotherapeutics, such as peptide and protein drugs and nucleic acid therapies. Advanced drug delivery and targeting systems are thus being developed in order to optimize drug therapy and overcome these limitations.

Utilization of nanoparticles as drug carriers promises a significant improvement In cancer treatment targeted delivery can reduce the systemic side effects that patients must endure under traditional chemotherapy by ensuring that pronounced cytotoxic levels of the drugs are only presents at the tumor sites Release their payloads in response to a variety of different stimuli, either those Specific to the tumor microenvironment, such as acidic pH values and elevated secretion of certain enzymes, or external ones

Nanoparticles can also offer multi-functionality, combining both diagnostic and therapeutic features a combination known as theranostics.  Smart emerging nanotechnologies, with reference to the various routes of delivery under investigation in various fields of nano-medicine.

Biography:

Dr. Sunil Kumar Dubey has been working in the area of clinical pharmacology, pharmacokinetics of racemic drugs (especially focused on CNS drug candidates) and also on designing nanocarriers like polymeric nanoparticles, micelles and polymersomes etc. for effective drug delivery. He also has expertise in the field pharmacokinetic and pharmacodynamic parameters modelling and simulation. He has been working in the thrust areas of CNS since long. His commitment to work and capability to successfully completing independent projects is reflected from his projects taken and international peer-reviewed publications.

Abstract:

Donepezil hydrochloride is a potent, acetylcholinesterase inhibitor used for the treatment of Alzheimer’s Disease. The objective of this study was to explore the compartmental pharmacokinetics and tissue distribution studies of donepezil after intravenous administration in Wistar rats. A simple HPLC–PDA assay method was developed and validated for rapid determination of donepezil hydrochloride, a potent acetylcholinesterase inhibitor in rat plasma and tissues. Solid-phase extraction method have been optimized using loratadine as an internal standard (IS). Chromatographic separation was detected on Waters Nova-Pak C18 column (3.9 × 150 mm, 5µm) using isocratic mobile phase of acetonitrile and ammonium formate (pH 6.4; 0.01M) (62:38 %v/v) at flow rate of 1 mL/min. All validation parameters were performed as per the guidelines of bioanalytical method validation. Weighted linear regression analysis was also performed on the calibration data. The method was successfully applied for exploring the compartmental pharmacokinetics and tissue distribution studies of donepezil after intravenous bolus administration at dose of 5 mg/kg in wistar rat. Experimental plasma concentration-versus-time profiles were fitted to compartmental pharmacokinetic models (Fig.1). One-, two-, three-compartment models were tested to characterize the pharmacokinetic parameters and statistically model was validated. Tissue distribution studies were also performed to assess the bio distribution studies (Fig.2). These parameters were analyzed for statistical significance by unpaired Student’s t-test. All validation parameter results were within the acceptable range described in guidelines. The method showed linearity in the concentration range of 50-5000 ng/mL with LOD of 20 ng/mL and LLOQ of 50 ng/mL. The mean absolute recoveries were found to be 79.86 ± 1.55 % for donepezil. Three-compartmental micro model was fitted to the plasma concentration-versus-time profiles and it was statistically validated by Akaike information criterion (AIC), Schwarz Bayesian criteria (SBC) and regression coefficient. Tissue distribution results showed that donepezil was well distributed in highly perfused tissues.

Biography:

Rolapitant (VARUBI^®/VARUBY^®), a selective and long-acting neurokinin-1 receptor antagonist, is approved in oral formulation for the prevention of delayed chemotherapy-induced nausea and vomiting in adults in the US and EU. This pivotal open-label, randomized, single-dose, multicenter, parallel-group study assessed the bioequivalence of a single oral dose of 180 mg rolapitant administered as tablets (2 × 90 mg tablets, commercial formulation) or capsules (4 × 45 mg capsules, formulation used in clinical development) in healthy subjects. Blood samples for pharmacokinetic analysis were collected pre-dose and at multiple time points up to 912 h post-dose. The pharmacokinetic analysis of the capsule group (n = 42) and tablet group (n = 42) were similar. The rolapitant tablet was considered bioequivalent to the rolapitant capsule if the 90% confidence intervals for the ratios of the geometric means for rolapitant, observed maximum plasma concentration (Cmax), and area under the curve (AUC0–∞) were within the 0.80–1.25 range. The geometric mean ratios of Cmax and AUC0–∞ were 0.99 (0.89–1.11) and 1.05 (0.92–1.19), respectively, establishing bioequivalence of the rolapitant tablet and capsule, and suggesting that data obtained during clinical development is translatable to the commercial formulation. Both formulations were well tolerated, with a similar incidence of treatment-emergent adverse events in the two groups.

Abstract:

Rolapitant (VARUBI^®/VARUBY^®), a selective and long-acting neurokinin-1 receptor antagonist, is approved in oral formulation for the prevention of delayed chemotherapy-induced nausea and vomiting in adults in the US and EU. This pivotal open-label, randomized, single-dose, multicenter, parallel-group study assessed the bioequivalence of a single oral dose of 180 mg rolapitant administered as tablets (2 × 90 mg tablets, commercial formulation) or capsules (4 × 45 mg capsules, formulation used in clinical development) in healthy subjects. Blood samples for pharmacokinetic analysis were collected pre-dose and at multiple time points up to 912 h post-dose. The pharmacokinetic analysis of the capsule group (n = 42) and tablet group (n = 42) were similar. The rolapitant tablet was considered bioequivalent to the rolapitant capsule if the 90% confidence intervals for the ratios of the geometric means for rolapitant, observed maximum plasma concentration (Cmax), and area under the curve (AUC0–∞) were within the 0.80–1.25 range. The geometric mean ratios of Cmax and AUC0–∞ were 0.99 (0.89–1.11) and 1.05 (0.92–1.19), respectively, establishing bioequivalence of the rolapitant tablet and capsule, and suggesting that data obtained during clinical development is translatable to the commercial formulation. Both formulations were well tolerated, with a similar incidence of treatment-emergent adverse events in the two groups.

Biography:

Over 12 years of experience working in the pharmaceutical industry. 17 years medical development as physician. 4 years in Basic Research Project CONICET Fellowship (National Scientific Council). 8 years of experience advising Oncologist Clinical Trials in Early and Late Phases for clinical research. Phase I and Bioequivalence studies, including First in Human/Healthy Volunteers studies, generic drugs and vasoconstriction assay (VCA).

Abstract:

The hypothesis   for the design of this project was that the extended release formulation containing dimethyl fumarate 240 mg, developed by Gador will present similar bioavailability with respect to the reference formulation, measured in terms of speed and absorption.

A clinical study of single-dose bioequivalence (in 2 stages) was designed to be carried out in healthy subjects. This study was opened of two periods, two sequences, crossed, randomized under fasting conditions.

Eight out of ten subjects involved in this pilot study (stage 1) were randomized and completed the 2 periods of administration of the treatments. Data of all the subjects who completed the 2 periods of treatment administration were used for pharmacokinetic purposes. The design of the study was adequate to determine the bioequivalence of the Test and Reference Products. The 7- day washout period was sufficient to allow the complete elimination of the formulations before the next dosing period.

Conclusion:

In relation to monomethyl fumarate;

The extended release formulation containing dimethyl fumarate 240 mg, developed by Gador presents similar bioavailability, measured in terms of speed and extension of absorption in relation to the reference formulation.

Intrasubject CVs were on the order of 30% to 40% for the 3 pharmacokinetic parameters; indicating that the molecule and/or the formulation shows high variability in absorption and must be considered for the calculation of sample size of Stage 2.This improved process will serve for clinical assessment in patients.

Individual plasma concentrations showed results lower than the lower limit of quantification of the validated analytical method. It is suggested to adjust the method by lowering said level for Stage 2.

It is possible to consider extending the range of Bioequivalence for Cmax to 70-143% in Stage 2; since the intrasubject CV was >30% and the Reference geometric mean is between 0.80-1.25 in Stage 1

Biography:

Aleksander Mendyk, PhD, DSc. is an expert in application of artificial&computational intelligence methods in pharmaceutical sciences, in vitro in vivo correlations development and bioequivalence assessment. With his background as a pharmacist and a programmer experience he’s a software developer and programmer both in Open Source and commercial applications. Currently employed in the Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, JUMC, Cracow, Poland (http://www.farmacja.cm.uj.edu.pl) and in the software company ThothPro^TM, Gdansk, Poland (http://thothpro.com).

Abstract:

Statement of the Problem: Dissolution testing has become standard tool for pharmaceutical industry both in quality control and product development. For generic companies it is a regulatory requirement to demonstrate similarity of dissolution profiles between reference product (R) and the generic product candidate (T). Several methods of dissolution profiles comparison could be classified into two main groups: (1) model based and (2) model independent. Application of any comparison method requires software to be developed for this purpose. This could be either in-house, commercial or open source. We propose open source software for calculation of FDA similarity factor (f2) and model based comparison of dissolution profiles.
Methodology: R statistical environment was chosen to write scripts and GUI (Shiny package). Bootstrap based bias corrected and accelerated confidence interval (BCa) was implemented for f2. In case of model based comparison, a method of Mahalanobis distance was chosen with Hotelling T2 test to determine similarity region for two dissolution curves. A multivariate statistical distance (MSD) for the raw dissolution profiles was also considered for the curves comparison.
Findings: Software was published on the sourceforge.net server [2, 4] under GNU GPL v3 license meaning that it is free of charge both for private and professional use. Due to the portability of R environment this software is OS–independent and was successfully tested under various Windows and Linux environments.
Conclusion & Significance: Implementation of BCa allows to use f2 for dissolution profiles comparison even when RSD exceeds 10% (20% at the first time point) and MSD is an alternative of direct curves comparison as per relevant EMA/FDA guidelines. Model based methods are commonly used for second opinion when inconclusive or borderline results of f2 analysis were found. Thus both packages enhance tooling for dissolution profiles comparison in difficult cases
 

Biography:

Over 12 years of experience working in the pharmaceutical industry. 17 years medical development as physician. 4 years in Basic Research Project CONICET Fellowship (National Scientific Council). 8 years of experience advising Oncologist Clinical Trials in Early and Late Phases for clinical research. Phase I and Bioequivalence studies, including First in Human/Healthy Volunteers studies, generic drugs and vasoconstriction assay (VCA)

Abstract:

Background: Perampanel is a glutamate non-competitive receptor antagonist that is effective as adjunctive treatment for epilepsy. No studies regarding comparative bioavailability between a generic perampanel formulation and the brand-name product have been published in the literature. The goal of the present investigation was to compare the bioavailability and to evaluate the bioequivalence between a novel pharmaceutical equivalent 12 mg film-coated tablet formulation and the reference product.

Methods: An open label, randomized-sequence, two-period, two-treatment, single-dose, crossover design study in healthy volunteers (n=24) was conducted. The treatment was split out by a 42 days wash-out period. The informed consent was signed by all volunteers. Healthy subjects of both genders, including non-pregnant and non-lactating females between 21-55 years with Quetelet index between 19-29 kg/m2 were enrolled. Blood samples were withdrawn in vacutainers with EDTA over 168 h and plasma levels of perampanel were measured by HPLC/ fluorescence method. Pharmacokinetic variables (Cmax, AUC0-last, and AUCinf) after a single oral administration dose of the test and reference treatments were analyzed by a non-compartmental PK model using natural log transformed data and were compared by ANOVA for a two-treatment crossover design. Bioequivalence between the two formulations was evaluated using the 90% Confidence Interval (CI) comprised between 80-125% corresponding to the ratio of the geometric means for log-transformed PK parameters.

Results: A similar bioavailability between products was determined. Test and reference formulations showed no statistically significant differences in relation to the fixed effect of period, sequence, treatment and volunteers within sequence as random effect for PK variables. The estimated point and 90% CI of the ratios of Cmax, AUC0-last and AUCinf were 0.92 (0.83-1.03), 1.04(0.98-1.10) and 0.98 (0.86-1.11), respectively. The formulations showed comparable safety/tolerability.

Conclusion: The new pharmaceutical equivalent perampanel 12 mg film-coated tablet formulation was also bioequivalent to the reference product. Therefore, both drugs are interchangeable.

Biography:

Ahmed Ahmed, BS, MBBS, Master of General Surgery- Imperial College, UK: bariatric surgical procedures in obesity: Sleeve,  gastric band, a gastric bypass, a gastric, Laparoscopic Roux-en-Y gastric bypass. Dr. Ahmed is  currently working as registrar in general surgery department for University Hospital Northampton NHS Foundation Trust,  UK., specialized in Surgical Gastroenterology: Upper GI endoscopy, Laparoscopy,  Colonoscopy. Destination: Consultant Gastroenterologist surgeon.

Abstract:

Bariatric surgery is categorized by surgical technique (i.e., restrictive procedure or a combination of restrictive and mal-absorptive procedures). Patients who have undergone this surgery are at risk for nutrient deficiencies. Selection of appropriate nutrient salts can improve nutrient replacement in patients who have undergone bariatric surgery. Changes in dosage forms based on drug characteristics can improve bioavailability. Several factors, such as pH and absorption sites, should be considered when providing these patients with appropriate supplementation. Drug solubility and surface area for absorption are also affected by gastric bypass procedures. By bypassing major portions of the small intestine, Roux-en-Y procedures drastically reduce the surface area for absorption. These changes may warrant manipulation in drug route or dose to ensure adequate delivery. Drugs with long absorptive phases that remain in the intestine for extended periods are likely to exhibit decreased bioavailability in these patients. The reduced size of the stomach after surgery can place patients at risk for adverse events associated with some medications. Medications implicated in such adverse events include (NSAIDS), salicylates, and oral bisphosphonates. Drugs that are rapidly and primarily absorbed in the stomach or duodenum are likely to exhibit decreased absorption in patients who have had combination restrictive-mal-absorptive procedures. Because reduced drug absorption may result in decreased efficacy rather than toxicity, increased patient monitoring for therapeutic effects can help detect potential absorption problems.

Biography:

R N Saha is Shri B K Birla & Shrimati Sarala Birla, Chair Professor (Senior Professor of Pharmacy) and Director of BITS Pilani Dubai Campus. In 2011 he has been awarded Shri B K Birla and Shrimati Sarala Birla Chair Professorship at BITS Pilani for contributions in teaching and research. He has vast experience in the field of Pharmacy especially in Pharmaceutics, novel drug delivery systems and Pharmacokinetics. He received “Pharmacy Professional of the Year 2013” Award given by Indian Association of Pharmaceutical Scientists and Technologists. He is also recipient of “The Best Pharmacy Teacher Award” for the year 2005, awarded by the Association of Pharmaceuticals Teachers if India (APTI), in recognition of his contribution in teaching and research in the fi eld of Pharmacy. He is also member of many scientific associations and societies like Association of Pharmaceutical Teachers of India (APTI); Indian Pharmaceutical Association (IPA); Indian Society of Technical Education (ISTE); Controlled Release Society Inc., USA; American Association of Pharmaceutical Scientists (AAPS), USA; American Chemical Society, USA; Controlled Release Society, Indian Chapter.
 

Abstract:

These are very important for formulation and drug delivery purpose as well as for new drug. This workshop will cover, what are bioavailability, bioequivalence, biodistribution studies, their importance, how they are studied and results are interpreted. Biodistribution study is very important for new drug to know where the drug is distributed and in what proportion. Mathematical modeling, experimental design will be covered. For design of novel drug delivery system, knowledge of biodistribution can help to modify distribution and make selective distribution. As analysis is very important for above studies, also analytical and statistical tools used for above studies will also be covered in brief.
 

Biography:

Sunil Kumar Dubey has been working in the area of clinical pharmacology, pharmacokinetics of racemic drugs (especially focused on CNS drug candidates) and also on designing nanocarriers like polymeric nanoparticles, micelles and polymersomes, etc. for effective drug delivery. He also has expertise in the field pharmacokinetic and pharmacodynamic parameters modeling and simulation. He has been working in the thrust areas of CNS. His commitment to work and capability to successfully completing independent projects is reflected from his projects taken and international peer-reviewed publications.
 

Abstract:

Analytical and boanalytical techniques play a very important role in drug discovery. The analytical and bioanalytical techniques are the important tools for identification and characterization of the newly discovered drug molecules. Statistical tools employed for assessing bioequivalence are critical in getting drug approvals during ANDA filings. Hence, this workshop will provide insights into following areas:

• Novel Approaches to Analytical and Bioanalytical Methods

• Analytical & Bioanalytical Method Development and Validation

• Applications of Analytical and Bioanalytical Methods

• LCMS/MS of Small Organic Molecules.

• Statistical tools for assessing Bioequivalence

Biography:

Dr. Taliyan is currently working as an Assistant Professor in the Department of Pharmacy, Birla Institute of Technology and Science, Pilani, Pilani-campus, Rajasthan. He has vast experience in the field of Neuropharmacology, Cardiovascular pharmacology and Drug toxicology. He has been awarded with many prestigious awards at international and national level including, Prof. Manjeet Singh Gold medal award at IPSCON-2015; PP Suryakumari Gold medal Award at IPSCON-2014. He has been invited by several Research and Academic institutes for delivering guest lectures. He has published several papers in peer reviewed international and national journals and in conferences of international and national repute. He is life member of Indian Pharmacological Society and Association of Pharmaceutical Teacher of India Society,

Abstract:

Numerous epidemiological studies have demonstrated that insulin resistance contributes to Alzheimer’s disease (AD) pathogenesis. However the molecular mechanisms is still remain elusive but various studies have highlighted the epigenetic alterations and involvement of histone deacetylases (HDACs) in insulin resistance and cognitive deficits^[1-2]. In our previous study, we have explored the potential of pan HDAC inhibitor, SAHA, in high fat diet induced insulin resistance ^[3-4]. In the present study, we have investigated the potential of isoform specific HDAC inhibitors in insulin resistance induced cognitive impairment in mice. Methods: Mice were subjected to either normal pellet diet (NPD) or high fat diet (HFD) for 8 weeks. Serum insulin, glucose, triglycerides, total cholesterol and HDL-cholesterol levels were measured weekly. A battery of behavioural parameters was performed to assess cognitive functions. HFD fed mice were treated with Class I specific HDAC inhibitor, CI-994 or Class II specific HDAC inhibitor, MC-1568 once daily for 2 weeks. Results: HFD fed mice exhibit characteristic features of insulin resistance, showed a severe deficit in learning and memory. HFD feeding results in significant increase in Amyloid beta1-42 levels as compared with NPD fed mice. By contrast, the mice treated with MC-1568 showed significant improvement in insulin resistance condition, marked decrease in Amyloid beta1-42 and significantly ameliorate the HFD induced decrease in BDNF and CREB level as compared to HFD group. Whereas, the mice treated with Class I HDAC inhibitor, CI-994 failed to show any improvement in insulin resistance and cognitive deficits. Conclusion: Based upon these results, it could be suggested that Class II HDAC inhibitors exert better neuroprotective effects as compared to Class I HDAC inhibitors associated with insulin resistant condition.

Biography:

Naglaa Gamil Shehab is graduated from Faculty of Pharmacy, Cairo University, Egypt and she received the PhD from the same college. She got the best research award three times from Egypt, Saudi Arabia and from Amsterdam, Netherland. She is a member in American society of Pharmacognosy and in Italo-Latin American Society of Ethnomedicine. She is also a reviewer for many international natural products Journals. She published at least 30 scientific papers also contribute in publication of scientific book. Her interest field is in bioactivity of medicinal plants. She have been an associate professor, the Head of Pharmacognosy and Phytochemsitry Department, Chief Academic Officer and a member in the research committee in Dubai Pharmacy College since 2005.
 

Abstract:

Dabigatran etexilate is a new oral drug with little side effects than other anticoagulant drugs. It has a direct thrombin inhibition and is used to treat deep vein thrombosis and pulmonary embolism. Escitalopram belongs to the group of medications called selective serotonin reuptake inhibitors (SSRIs). It works by increasing levels of a neurotransmitter called serotonin in the brain. Increased serotonin levels can lead to an improved mood. This study aims to evaluate the synergistic or the antagonistic interaction which may occur between some common remedies with the oral administration of Dabigitran and Cipralex.
 

Biography:

Aleksander Mendyk, PhD, DSc. is an expert in application of artificial&computational intelligence methods in pharmaceutical sciences, in vitro in vivo correlations development and bioequivalence assessment. On the pharmaceutical side he covers pharmaceutical technology, biopharmaceutics, pharmacokinetics, pharmaceutical compounding. On IT side he works in Windows and Linux environments using several languages like Pascal, Java, Python, bash and R/Shiny scripting language, He has developed and currently manages High Performance Computing system at the Faculty of Pharmacy Jagiellonian University-Medical College (JUMC). With his background as a pharmacist and a programmer experience he’s a software developer and programmer both in Open Source and commercial applications. Currently employed in the Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, JUMC, Cracow, Poland (http://www.farmacja.cm.uj.edu.pl) and in the software company ThothProTM, Gdansk, Poland (http://thothpro.com).

Abstract:

Statement of the Problem: In vitro in vivo correlation (IVIVC) is a tool designed for mapping dissolution tests results data into pharmacokinetic profile. It is an undisputed cost-savior for pharmaceutical industry and as such is still under heavy development. Currently, classical approach codified by FDA and EMA in their guidelines has several requirements, among them results from i.v. administration being the most difficult to fulfill. This work presents how to overcome limitations of the classical methods and get fully validated IVIVC Level A model using machine learning (ML) tools.
Methodology: Several ML techniques were applied: simulated annealing (SA), Nelder-Mead optimization (NM) and genetic programming (GP) for global and local optimization approaches. The code was written in R statistical environment scripts. Simulated data of 2-compartment model with oral administration together with simulated dissolution profiles were used for calculations.
Findings: As PK data were simulated with 2-compartment model, no Wagner-Nelson method could be applied. An application of Loo-Riegelman method also failed due to the  poor sampling with poor coverage of elimination and distribution phases. A “hybrid” approach was employed, where artificial impulse curve (i.v. administration) was generated based on the 2-compartment model and global optimization methods (SA&NM). This allowed to switch to the convolution based approach. Next, the RIVIVR tool was applied where no assumptions about the shape and physical nature of the impulse curve is employed resulting in the moderate improvement of the results. Finally, a direct mapping of dissolution data to the PK profile was performed with genetic programming tool. This tool delivered tailored mapping function represented by empirical equation with superior predictability.
Conclusion & Significance: This work presents suitable workflow for the development of IVIVC Level A model. In case of failure, classical methods could be replaced with empirical approaches delivering non-linear fully validated models suitable for pharmaceutical industry.
 

Biography:

Prof. Asmita Gajbhiye Patil is currently working as Professor and Head at  Department of Pharmaceutical Sciences, Dr. Harisingh Gour Vishwavidyalaya, Sagar (M.P.) India. She received her Doctoral degree in Pharmaceutical Sciences (2006) from Kakatiya University, Warangal (A.P.) India. She completed her Masters (1996) from the Department of Pharmaceutical Sciences, Dr. Harisingh Gour Vishwavidyalay, Sagar. Since 1998, she is working as Assistant Professor, Associate Professor and Professor in the University and has 20 years of teaching experience. She has authored 40 publications in various journals of national and international repute. Her publications reflect her research interests in both the fields of medicinal chemistry as well as pharmacology. She had filed a patent also. She has completed several major projects sponsored by various agencies eg DST, MPCST, ICMR, CSIR and UGC. Dr. Asmita was a member of member of Executive Council, member of Research Council, member of Mahila Kalyan Samiti of Dr. Harisingh Gour Vishwavidyalaya, Sagar (M.P). She was the Coordinator for conduct of University centralized evaluation. Presently she is holding the post of an Anti-Discrimination officer at Dr. Harisingh Gour Vishwavidyalaya, Sagar. She is honoured with the awards of National level i.e. Mother Teressa Shiksha Rattan Award 2016 by International Bussiness Council and National Mahila Rattan gold medal 2017 by International Institute of Education and Management, New Delhi.

Abstract:

Quercetin, mangifirin, kaempferol  are a well-known flavonoidal compounds found in plants, foods, and beverages. These flavonoids have shown several pharmacological activities including antioxidant, anti-inflammatory, anticancer, and antiviral properties. In spite of a variety of biological effects, they are very poorly soluble in water, which has limited their absorption upon oral administration and rapid clearance from intestine. Therefore, it is required to develop a drug delivery system   to resolve this problem.

Some phytoconstituents that are not effectively bioavailable, by binding them to phosphatidylcholine, they can be made in highly bioavailable form. One of the most important group of phytoconstituents is the flavonoid which can be bind with soya phosphatidylcholine (SPC). The resulting phytosomes formed are protected from distruction by digestive secretions and gut bacteria. The phytosomes intensifies herbal compounds by improving absorption, increasing bioavailablility and enhancing therapeutic potential. The phytosomes contains active ingredients of herb surrounded and chemically bound with phosphatidylcholine which is one of the chief components of the membranes in the human cells.  

Phytosomes of Quercetin, mangifirin and kaempferol were successfully prepared through complexation with soya phosphatidylcholine (SPC) which were characterized by spectroscopic (IR and NMR), microscopic (TEM) and colorimetric (DSC) analysis. The pharmacokinetic study was performed for the assessment of bioavailability.

The IR, NMR and DSC spectra of phytosomes were showed by different peaks as compared to that of phytosomes. Pharmacokinetic study revealed significant increased absorption of phytosomes.

The prepared complexes were characterized by solubility studies, DSC, TLC, FTIR and ¹H-NMR spectroscopic analysis. These physicochemical and spectroscopic investigations clearly showed evidence for the formation of quercetin–soya phosphatidylcholine complex.

The result of pharmacokinetic study clearly indicates that vesicular complex is more easily absorb than individual ingredients and hence it can be concluded that drug-SPC complex is more bioavaliable than individual ingredients.