Solid Phase Engineering and Solid Phase Quality Control of your API - Salts, Hydrates, Solvates, Polymorphs and Cocrystals (10695)

Course details

Course Solid Phase Engineering and Solid Phase Quality Control of your API - Salts, Hydrates, Solvates, Polymorphs and Cocrystals
Trainer Dr. Helmut Buschmann
RD&C Research, Development & Consulting GmbH

Dr. Norbert Handler
RD&C Research, Development & Consulting GmbH
Period 24/01/24 — 07/02/24
State scheduled
Category Webinar series
Language English
Free places
Fee €530.00 plus VAT.
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Salts, hydrates, solvates, and cocrystals have similar crystal structures comprising an API and a second component. Cocrystal lattices are held together by relatively weak interactions, whereas salts rely on stronger ionic forces. However, ascertaining whether a particular crystal is a salt or a cocrystal is frequently difficult. Crystals containing certain active ingredients (e.g., minoxidil) and organic acids are categorised as salts, cocrystals, or solvates, depending on the nature of the organic acid. The boundary between salts and cocrystals and methods to distinguish them have attracted increasing attention because of both, scientific interest and their different regulatory requirements. 

Polymorphism is the ability of a solid compound to exist in more than one crystalline form. Most drugs exhibit structural polymorphism or multiple crystalline forms. In order for a molecule to develop into a potential drug, the existence of a stable polymorph or a suitable pseudopolymorph needs to be established. The polymorphs (or pseudopolymorphs) of drugs show different chemical stability; it is generally observed that a more thermodynamically stable polymorph is more chemically stable than a metastable polymorph. 

Schematic representation of salts, hydrates, solvates and cocrystals in APIs present as a salt are composed of the active substance that possess a certain charge (either positive or negative) and interacts with a counter-ion (possessing the opposite charge to the API) to form the lattice. When the API interacts with water or a solvent, then hydrate or solvate crystals are formed, respectively. When an API forms a crystal lattice with a co-former via non-ionic interactions, then pharmaceutical co-crystals are formed. 

This webinar will present an overview and relevant aspects of this important topic together with a discussion of the differing positions and regulations of relevant authorities and cover the following aspects: 

Part 1:

24.01.2024 | 10:00 - 12:00 am

  • The landscape os salts, hydrates, solvates, polymorphs and cocrystals – an introduction 
    • Definition of different solid forms 
    • Analytical characterization 
    • Regulatory background and CMC aspects in the developmental and commercial phase 
    • Regulatory overview and differences between EMA and FDA 
  • Introduction to analytical techniques to control the solid phase of an API 
    • Overview of analytical methods 
      • XRPD 
      • TG 
      • DSC 
      • IR and Raman 
      • PDF 
      • Solid state NMR 
      • Hot-stage microscopy 
      • Dissolution profile: Thermodynamic vs kinetic dissolution profile 
  • Amorphous APIs 
    • Crystalline vs amorphous forms of APIs   
    • Control of the stability of amorphous forms in drug substance and drug product 
    • Preparation and characterization of amorphous forms 
    • Existence of different amorphous forms and how to characterize them 
    • Amorphous form stabilising excipients, impact on manufacture of drug products with amorphous APIs 
  • Interference of leachables with biopharmaceuticals during manufacturing, storage and administration
    • Influence of leachables on biopharmaceutical process performance
    • Influence of leachables on the stability of biopharmaceuticals
    • Influence of leachables on the analytics of biopharmaceuticals   
  • Polymorphic forms 
    • Characterization of polymorphic forms 
    • Polymorph screening approaches 
    • Polymorphic forms during development and in the commercial phase 
    • Case studies of polymorphic changes 
    • Polymorphic form over stability 
    • Interconversion studies: thermodynamic stable ones vs. kinetic stable ones 
    • How interconversion studies could be conducted 
    • Analytical techniques to control polymorphs in drug substance and in solid or semi-solid dosage forms 
    • CTD documentation (characterization and quality control) of polymorphs (3.2.S.1.3, 3.2.S.3.1, 3.2.S.7) 

Part 2:

07.02.2024 | 10:00 - 12:00 am

  • Salts
    • Overview of pharmaceutical salt forms 
    • Salt screening technologies and strategies 
    • Physiochemical properties of different salts 
    • Regulatory classification of salt forms 
    • Physicochemical properties: water adsorption, solubility 
    • Impact on stability studies 
    • Stability factors: Apparent pH in solid phase environment 
    • Hygroscopicity, DVS profile 
    • Hydrate interchanges 
    • Salts in the orange book 
    • How to provide the strength of APIs used in salt/hydrate forms 
    • Formation of cocrystals from alkali salts and free acid and impact on critical quality attributes 
  • Cocrystals 
    • Cocrystal preparation – Overview of solution-based and solid-based techniques 
    • Improvement of physicochemical properties of poorlysoluble APIs 
    • Regulatory impact on definition and quality control of cocrystal forms 
    • EMA Regulation 
    • FDA Guidance for Industry 
    • Cocrystals on the market 
    • Cocrystal development 
    • Specific analytical methods to control cocrystals during manufacturing and over shelf-life 
  • Other solid phase characteristics: Particle size distribution 
    • PSD analytical techniques 
    • Development and validation of PSD methods 
    • Reproducibility of PSD results 
    • Impact of homogeneity of samples and bulk 
    • How to control homogeneity of your API in bulk and stability samples 
    • PSD as critical quality attribute of APIs 
    • PSD changes over stability 
    • Micronization, Nanonization 
  • Crystal engineering 
    • Development of final crystallization step 
    • Optimization of crystallization conditions (solvent, concentration) 
    • In-process control during crystallization 
    • Scaling of crystallization batches: from lab to pilot plant 
    • In-silico simulation of crystallization processes 
    • Crystallization by seeds 
    • Regulatory control of seed material 
    • Stability of seed material 
    • Recrystallization: Re-processing or rather re-working - A critical analysis of aspects to be considered 

Duration: approx. 120 minutes per modul
Language: English | Handout: English

...more from your speaker Dr. Helmut Buschmann...
...more from your speaker Dr. Norbert Handler...

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Course times

Weekday Time
Wednesday 10:00 - 12:00


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