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

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:

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:

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:

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.