Crystallisation by design - PolyCrystalLine

download Crystallisation by design - PolyCrystalLine

of 40

  • date post

    16-Apr-2017
  • Category

    Science

  • view

    292
  • download

    1

Embed Size (px)

Transcript of Crystallisation by design - PolyCrystalLine

  • www.polycrystalline.it

  • www.polycrystalline.it

    OUTLINE

    WHO ARE WE?

    WHAT IS THE IMPORTANCE OF SOLID FORMS?

    SOLID FORMS AND DRUG DEVELOPMENT

    WHAT IS CRYSTALLISATION BY DESIGN?

    HOW CAN WE HELP YOU?

  • www.polycrystalline.it

    WHO ARE WE?

  • www.polycrystalline.it

    POLYCRYSTALLINE IN A NUTSHELL

    LEVEL OF CONTAINMENT

    FOR HPAPIs

    OEB5ANALYTICAL LABORATORY

    AND INSTRUMENTS

    cGMPDIFFERENT APIs

    WE HAVE STUDIED

    +300

    The company was born out of the Molecular Crystalline Engineering

    (MCE) group of research coordinated by Professor Dario Braga in the

    Department of Chemistry G. Ciamician of the University of Bologna. POLYCRYSTALLINE WAS FOUNDED

    2005

  • www.polycrystalline.it

    OUR PROVEN STRENGTH

    WE ARE A HIGH PERFORMING COHESIVE

    TEAM OF CHEMISTS AND ANALYSTS.

  • www.polycrystalline.it

    EVOLVING THROUGH RESEARCH

    WE CARE ABOUT RESULTS AND

    INNOVATION BASED ON THE USE OF

    MODERN TECHNOLOGIES.

  • www.polycrystalline.it

    HOW DO WE PERFORM OUR SERVICES?

    Manual/Semi-Automated Screening

    (PolyCrystalLine)

    Driven by science not robotics

    Scientific investigation tailored to your API

    properties, development phase and budget

    High-Throughput Screening

    (other CRO)

    Rapid but limited by its settings

    Fully automated and usually subject to large number of experiments required

  • www.polycrystalline.it

    REFERENCES

  • www.polycrystalline.it

    INSTRUMENTS FOR CRYSTALLISATION DEV. AND OPTIMIZATION

    PANalytical X'Pert3 Powder SMS DVS Intrinsic Malvern Morphologi G3

    Mettler-Toledo DSC 1 Beckman Coulter Particle Size Analyzer LS100Q Thermo Scientific Nicolet iS50 (FT-IR/FT-RAMAN)

    Mettler-Toledo TGA/DSC1 Thermo Scientific Nicolet iS10 TGA-IR Module

  • www.polycrystalline.it

    INSTRUMENTS FOR SOLID-STATE RESEARCH

    Mettler-Toledo EasyMax 102 Atlas Syrris Mettler-Toledo FBRM G400

    Avantium Crystalbreeder

  • www.polycrystalline.it

    INSTRUMENTS FOR ANALYTICAL RESEARCH

    Berghof EasyH2O Agilent 708-DS Dissolution Test Mettler-Toledo Karl-Fischer DL31

    Mettler-Toledo MP70 Melting Point System Thermo Scientifics Multiskan FC Thermo Scientifics UltiMate 3000 LC system with

    Coulochem III Electrochemical Detector

    Agilent HPLC 1260

  • www.polycrystalline.it

    WHAT IS THE IMPORTANCE OF SOLID FORMS?

  • www.polycrystalline.it

    DRUG DOSAGE FORMS

    Many pharmaceutical delivery technologies are available, such as:

    Pulmonary

    Delivery

    Nasal

    Delivery

    Transdermal

    Delivery

    Injectable

    Formulation

  • www.polycrystalline.it

    DRUG DOSAGE FORMS

    Year Oral Injection Other

    2012 54% 28% 18%

    2013 63% 26% 11%

    2014 46% 37% 17%

    2015 53% 40% 7%

    Route of Administration of Novel Drug Approvals by U.S. FDA

    However, oral administration is still the

    preferred route when developing a

    conventional dosage form for a new drug.

  • www.polycrystalline.it

    60% of novel drug approved by the U.S. FDA in 2015

    were solid dosage products.

    Year Tablet Capsule Powder Solution Other Solid Dosage Forms

    2012 15 5 5 13 1 64%

    2013 12 5 2 7 1 70%

    2014 10 9 3 19 0 54%

    2015 15 7 5 18 0 60%

    Dosage Forms of Novel Drug Approvals by U.S. FDA

    DRUG DOSAGE FORMS

    Oral dosage forms can have a variety of choices, but most common are solids:

  • www.polycrystalline.it

    WHY SOLID FORM?

    Solid is more stable than its liquid counterpart.

    Active Pharmaceutical Ingredients (APIs) are usually

    manufactured, transported and stored as solid.

    They are easy to administer (i.e. tablet, capsule,

    powder, etc. ).

  • www.polycrystalline.it

    TYPES OF SOLID FORMS

    SOLID

    CRYSTALLINE AMORPHOUS

    Long range order Short range order

    Multi components

    POLYMORPHS

    Single component

    Ionic Non-ionic

    SALT MOLECULAR ADDUCTS

    SOLVATE/HYDRATE CO-CRYSTAL

    Molecule solid at RT

    Free drug

    Solvent

    Protonated drug molecule

    Deprotonated acid

    The concept of pseudopolymorphism

    is used for crystalline forms which

    also comprise solvent molecules as

    an integral part of their structure.

  • www.polycrystalline.it

    WHAT IS THE IMPORTANCE OF SOLID FORMS?

    Different solid forms show different properties, such as:

    Spectral Properties Solubility, Bioavailability

    & Dissolution Rate

    Physical and

    Chemical Stability

    Manufacturability

    Hygroscopicity Crystal Shape

  • www.polycrystalline.it

    SOLID FORMS AND DRUG DEVELOPMENT

  • www.polycrystalline.it

    SOLID FORMS AND DRUG DEVELOPMENT

    Process

    Optimisation

    & Scale-Up

    Drug

    Discovery

    Pre-Clinical

    Studies

    Routine

    Production

    Synthetic Route

    Selection

    Final Dosage

    Form

    Drug Development Pipeline

    Drug development is a lengthy, complex, and costly process, entrenched with a

    high degree of uncertainty that a drug will actually succeed.

  • www.polycrystalline.it

    Process

    Optimisation

    & Scale-Up

    Drug

    Discovery

    Pre-Clinical

    Studies

    Routine

    Production

    Synthetic Route

    Selection

    Final Dosage

    Form

    Drug Development Pipeline

    SOLID FORMS AND DRUG DEVELOPMENT

    Many issues can affect the final dosage form, altering its appearance, friability,

    bioavailability, shelf-life, assay, etc.

  • www.polycrystalline.it

    Process

    Optimisation

    & Scale-Up

    Drug

    DiscoveryPre-Clinical

    Studies

    Routine

    Production

    Synthetic Route

    Selection

    Final Dosage

    Form

    Drug Development Pipeline

    SOLID FORMS AND DRUG DEVELOPMENT

    Often problems observed in the final dosage form may find their root causes in

    drug discovery and in a sub-optimal solid form screening.

  • www.polycrystalline.it

    1. What might go wrong?

    If anything can go wrong, it will.

    3. What are the consequences?

    It will be all your fault, and everyone will know it.

    2. What is the likelihood it will go wrong?

    If anything just cannot go wrong, it will anyway.

    MURPHYS LAWS FOR DRUG DEVELOPMENT

  • www.polycrystalline.it

    WHAT IS CRYSTALLISATION BY DESIGN?

  • www.polycrystalline.it

    The properties of products and processes are affected by many factors:

    TRADITIONAL APPROACH TO CRYSTALLISATION

    Physical StabilityDissolution Chemical Stability

    Process parameters

    Crystal form properties

    Crystallisation

    What influences my solid form?

    TemperaturePressureMixing speed

  • www.polycrystalline.it

    CRYSTALLISATION BY DESIGN

    Our mission is to support our clients during drug development, helping them to

    reduce batch failure, avoiding costly crystallisation issues and overall

    offering greater confidence in drug quality during manufacturing.

    Prepare the

    building blocks

    Crystal-oriented

    synthetic strategies

    Understand and control

    crystal properties

    Crystallisation

    by Design

    Arrange the building

    blocks in a desired way

    Understand and control over

    properties related to solid form

  • www.polycrystalline.it

    MOLECULE PARTICLE POWDER

    Chemistry Physics Functional

    Structure

    Molecular weight

    Melting point

    pKa

    Partition coefficient

    Solubility

    Particle size

    Surface properties

    Crystallinity

    Porosity

    Dissolution

    Flowability

    Mixability

    Wettability

    Compressibility

    The final goal to achieve with Crystallisation by Design is to understand and link

    together all the interconnections between properties of interest.

    CRYSTALLISATION BY DESIGN

  • www.polycrystalline.it

    After Crystallisation by Design the process is not seen as a black box anymore:

    CRYSTALLISATION BY DESIGN

    Input factors (X)

    Output responses (Y)

    TemperaturePressureMixing speed

    Physical StabilityDissolution Chemical Stability

    Crystallisation

    Y=f(X)

  • www.polycrystalline.it

    BENEFTIS OF CRYSTALLISATION BY DESIGN

    Proactive approach to drug development to quickly get to the root

    cause and resolution of any issue related to crystal form

    Better understanding and control of solid form properties of APIs and

    how they affect the final drug product

    Improve the manufacturing efficiency and product quality

    Identify critical chemical, physical and functional properties which are

    crucial for specific formulation requirements

  • www.polycrystalline.it

    HOW CAN WE HELP YOU?

  • www.polycrystalline.it

    HOW CAN WE HELP YOU?

    We support our clients from

    early-phase to kilogram supply.

    DISCOVER DESIGN DETERMINE DEVELOP

  • www.polycrystalline.it

    DISCOVER

    ...to obtain sight or knowledge of

    for the first time.

  • www.polycrystalline.it

    DISCOVER

    Determination and control of

    polymorphs is crucial to understand

    your product/process and enhance

    your patenting strength.

    Salts & Co-Crystals

    Screening

    Identification of

    H