Session One: Dissolution
SPS Pharma Services, France
Prior to founding SPS Pharma Services in 2005, Samir Haddouchi spent more than 10 years in the industry, working on the analytical development of agrochemical compounds at Sandoz Agro (Basel, Switzerland) and, after the Novartis merger, in Novartis Pharma analytical group (Orleans, France) where he became responsible for dissolution.
In 2005, he resigned from Novartis to create SPS Pharma Services which is the first and only CRO specialized in Dissolution and Release Testing.
In April 2013, SPS Pharma Services moved to a new larger facility (Orleans, France) offering a broader range of services to its clients, including cGMP routine testing.
Mr Haddouchi's presentation is kindly sponsored by SOTAX.
Title of Research Sharing: API Characterization for Better Product Performance
Abstract of Research Sharing: Dissolution testing can be an extremely powerful tool to acquire knowledge about pharmaceutical products. Instead of considering dissolution profiles only when the agencies require to provide regulatory data (for a submission or for QC batch-to-batch consistency), one can use dissolution in order to learn more about the properties of the Active Pharmaceutical Ingredient, the composition of the formulation as well as the route of administration. The presentation highlights that the in vitro profiles can represent either the dissolution rate of the active ingredient or the release rate from the finished formulation. A case study is included to show how the dissolution testing of a simple immediate-release dosage form containing a BCS class 1 substance can be challenging in obtaining an in vitro profile able to predict the in vivo performance of the dosage form. By using additional dissolution tools, it is possible to investigate the root-cause of bio-In equivalence and further optimize the drug product appropriately.
Department of Pharmacy, National University of Singapore, Singapore
Institute of Pharmacy, Department of Biopharmaceutics and Pharmaceutical Technology, University of Greifswald
Werner Weitschies studied Pharmacy and received his Ph.D. in Pharmaceutical Sciences in 1990. From 1990 to 1995 he worked as a scientist in the research laboratories of Schering AG in Berlin in the field of nano- and microparticulate contrast agents. From 1996 to 1998 he was head of a research department in the field of magnetic nanoparticle relaxation measurements at the Institute for Diagnostic Research of the Free University of Berlin.
Since 1998 he is a Professor at the Institute of Pharmacy in Greifswald. His main research areas are the investigation of the behavior of dosage forms in the gastrointestinal tract, and the development of nanoparticle based techniques for molecular imaging and physical therapy.
Title of Research Sharing: Dynamic Dissolution Testing Using the GastroDuo Approach
Abstract of Research Sharing: The oral administration route is the most common way for the application of drugs. The rate and extent of drug absorption is determined by the physicochemical properties of the drug, the drug formulation as well as the gastrointestinal conditions of the patient. In recent years, various in vivo studies have been conducted to characterize the human gastrointestinal conditions. These studies have greatly improved our knowledge of gastrointestinal conditions during drug administration. The data collected in these studies also form the basis for the development of biorelevant test procedures and simulation calculations. For the simulation of the behavior of orally administered drugs and drug delivery systems, several in vitro test methods and test devices are available with the claim of a realistic prediction of in vivo behavior. Some test systems even attempt to fully mimic the complex in vivo situation with the goal of making predictive statements about drug absorption. Such models are often highly complex, and the experiments are therefore usually time-consuming. Another approach is to simulate selected conditions in specific compartments of the GI tract. Such approaches are not primarily intended to predict systemic drug exposure. However, they do allow conclusions to be drawn about the robustness of formulation principles and the ranking of parameters such as dissolution rate. Furthermore, such methods make it possible to evaluate critical drug formulation parameters in relatively simple experiments. In this talk, our "GastroDuo" approach to simulating the disintegration and dissolution behavior of dosage forms in the stomach will be presented. The main underlying in vivo data sets will be explained, the instrument setup will be demonstrated, and obtained data sets will be presented and discussed.
Harshvardhan Modh is a Research Fellow at the Department of Pharmacy, National University of Singapore. Here, he is optimizing in vitro drug release testing from nanoformulations using Dispersion Releaser technology, modelling and simulation of in vivo performance of novel formulations and formulation development. Prior to this role, he worked at Fraunhofer IME, Frankfurt developing release assay for formulations under clinical trials. He earned his PhD from Leibniz University Hannover in analytical methods development for the detection of small molecules in biological samples.
Title of Research Sharing: IVIVR of Injectable Nanomedicines – Standing on the Shoulders of Giants
Abstract of Research Sharing: Understanding the relationship between the performances of dosage forms in vitro and in vivo at the early stage of formulation development is highly valuable. In our recent work, we studied the in vitro release of doxorubicin from different nanomedicines including the drug product Lipodox®, and the investigational drug product NanoCore-7.4 using Dispersion Releaser (DR) technology. For the intravenous route of administration, the drug release plays a key role in the availability of the drug in the blood plasma. Lipodox® is slow-releasing liposomal formulation and NanoCore-7.4 is fast-releasing formulation. Based on available in vivo data, the in vitro-in vivo relationship (IVIVR) was developed using a physiologically-based biopharmaceutics model (PBBM). This IVIVR enabled a careful estimation of human pharmacokinetics of NanoCore 6.4 and nano-cellular vesicle technology-based delivery systems (nCVTs). The probability of each simulation was evaluated based on selected critical quality attributes with considerable impact on the pharmacokinetic profile such as the particle size and the carrier material.
James Mann is an associate principal scientist of in vitro product performance at AstraZeneca in the UK. He is an experienced analytical scientist with more than 15 years’ experience in the pharmaceutical industry specializing in all aspects of dissolution testing. At AstraZeneca, James is the global lead for the in vitro product performance scientific community with oversight of all dissolution related activities in product development. Prior to joining AZ, James was with Merck in the UK where he jointly led the global in vitro predictive technologies team as well as supervising a small team of product development analysts and more recently was the analytical manager at Molecular Profiles. James received his first degree from University of Strathclyde, followed by a PhD from the University of East Anglia.
Title of Research Sharing: Current & Future State of Quality Control (QC) Dissolution Testing
Abstract of Research Sharing: Dissolution is widely recognised as a key quality test within industry, and is used for several purposes during product development, including developing understanding of product performance, assessing the likely in vivo performance in patients, studying the in vivo impact of changes to formulation and process and ensuring batches of drug product are suitable for release to the clinic or market. The presentation will focus on the current state of how dissolution is used within AstraZeneca alongside other biopharmaceutics and in silico tools to advance projects, mitigate risks and expedite approvals. It will also address the challenges facing the dissolution scientist for the future and will focus on areas such as improved linkage with in silico tools, a greater patient focus of the dissolution test, developing release methodology for complex parenterals, and increasing the level of information gained from the dissolution test.
Lupin Ltd, India
Sajeev Chandran is currently at Lupin, and is involved in leading a diverse research group of formulators, analysts, biopharmaceutics & IVIVC experts in the design, development & filing of advanced drug delivery technologies & difficult to do generic products. The novel formulation developments are primarily aimed for advanced markets (US, Europe, Australia & Latin America). The product portfolio includes complex ANDAs, NDA & 505 b(2) NDA route for in-house filing, co-development projects for partnering companies and life cycle management idea based products for potential out-licensing. He also leads a group involved in design and development of bio-relevant methodologies and biopharmaceutical interventions that facilitates reverse engineering and development of complex generics. Dr. Sajeev Chandran completed his B.Pharm (Hons) at IIT Varanasi, India, and his M.Pharm and PhD in NDDS Design & Development from Birla Institute of Technology & Science, Pilani, India. He has also completed an MBA in Operations Management from IGNOU, New Delhi, India.
Title of Research Sharing: Novel Dissolution Techniques to Improve in vivo Predictiveness of Oral Formulations
Abstract of Research Sharing: Design of bioequivalent modified release (MR) formulations of BCS class II and IV drug (having poor aqueous solubility and/ or variable oral bioavailability) is challenging in the absence of a in vitro discriminatory/ biorelevant dissolution method or any other discriminatory tool. Development of in vitro biopredictive tools presents unique challenges related to drug property, product design and critical GI physiological variables. The presentation aims to discuss in the form of case studies the rationale basis for development various novel in vitro drug release methodologies for accurate prediction of in vivo performance for MR formulations.
Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, India
Amit Sanjay Lokhande is currently pursuing a PhD Tech. Pharmaceutics at Department of Pharmaceutical Sciences & Technology, Institute of Chemical Technology (ICT), Mumbai, under the supervision of Prof. Padma Devarajan. His research involves the development of innovative and affordable targeted drug delivery systems against intracellular infections. Another area of his research involves point of care, affordable diagnostic systems for human and veterinary use. He is a nominated AICTE/MHRD’s Innovation Ambassador Govt. of India. He is an Innovator cum Entrepreneur, supported through the India-South Korea Startup Exchange Program 2020 and recipient of Technology Incubation Start-up Grant 2020 from MHRD Govt. of India. Amit is a co-inventor of 4 Indian patent applications and has published 2 articles and 3 book chapters. He won 4 awards at various DISSO-INDIA International symposiums of the Society for Pharmaceutical Dissolution Sciences (SPDS). Amit also received over 30 awards and recognitions during his PhD tenure and his achievements received news and media attention. Amit has mentored over 15 undergraduate and postgraduate research students and is a recipient of Special research mentor Award 2017 and 2020 from Marathi Vidnyan Parishad Mumbai India. Amit also delivered over 18 invited talks at various institutions in India.
Title of Research Sharing: Developing a Discriminating Dissolution Test for Microparticulate Carriers Co-Loaded with Anti-Tubercular Drug Combinations
Abstract of Research Sharing: Tuberculosis, mainly a lung disease, fundamentally necessitates multidrug therapy. Particulate carriers are known to improve targeting, enhance efficacy and dose reduction. However, there is a quest to discriminate such particulate carriers' release performance when co-loaded with multiple drugs of varying solubility in different bio-relevant media, through an appropriate dissolution method. However as on date although number of methods are reported in literature there is no standard or official method for dissolution testing method for nano and microsystems. In this study, we present comparative evaluation of three dissolution methods for polymeric microparticles co-loaded with three anti-tubercular drugs. Dissolution was evaluated using the USP IV dissolution apparatus, the Dialysis membrane sac method employing USP type I (basket) and USP type II (paddle) apparatus. Microparticles co-loaded with Rifampicin, Isoniazid and Ethambutol were evaluated for drug release in two bio-relevant lung fluids ALF pH Float-A-Lyzer®4.5 and SLF pH 7.4.The release rate for all drugs was rapid in ALF pH 4.5 compared to SLF pH 7.4. Among the three methods evaluated the USP IV Apparatus with Float-A-Lyzer® provided data which was discriminatory and with minimal standard deviation, proposing promise for dissolution testing of particulate systems.