Materials Science in Pharmaceutical Industry

Temperature and Heat Flow

• Endothermic and exothermic processes occur in chemical reactions, involving heat absorption or release
• DSC (Differential Scanning Calorimetry) measures heat flow vs. temperature, providing information on melting points, crystallization, and phase transitions

DSC Applications

• Conversion of a monohydrated form of a drug compound to its anhydrous form
• Quantitative determination of the monohydrate and anhydrous forms in a mixture
• Calibration curve for quantitative determination of the monohydrate and anhydrous forms

Amorphous Solids

• Lack of a clear melt peak in DSC
• Presence of a Tg (glass transition temperature), indicating an endothermic process
• Amorphous solids have no long-range ordering of molecules, resulting in a high degree of disorder

Thermogravimetric Analysis (TGA)

• Measures the change in sample mass as a function of temperature and/or time
• Applications:
  • Changes in mass due to decomposition, oxidation, evaporation, or combustion
  • Absorbed moisture content
  • Volatilization rate of materials
  • Determination of processing or storage conditions

Dynamic Vapour Sorption (DVS)

• Interacts pharmaceutical solids with moisture, influencing material properties, processability, and stability
• Applications:
  • Characterization of amorphous content
  • Characterization of hydrate formation
  • Characterization of glass transition and crystallization behavior

Vibrational Spectroscopy

• Infrared spectroscopy (IR) and Raman spectroscopy
• Fingerprinting identification of known scans
• Identifies functional groups within the molecular structure
• Determines protein secondary structure
• Identifies resins and opaque/coloured materials using photoacoustic scans

Polymorphs

• Nifedipine exists as three polymorphic forms: α, β, and γ
• Degree of polymorphism is produced by the degree of conformational rotations within the large flexible Nifedipine molecule
• IR spectra can show differences between polymorphic forms

Powder X-ray Diffraction (PXRD)

• An array of X-ray diffraction techniques exist for characterizing structural and chemical properties of crystalline solids
• Applications:
  • Crystal structure determination
  • Compound identification
  • Determination of crystallographic orientation
  • Particle size analysis
  • Crystal strain measurement
  • Degree of crystallinity/crystal quality
  • Defect density and characterization

Particle Sizing

• Particle size influences physical and chemical properties
• Applications:
  • Solubility
  • Dissolution rate
  • Bioavailability
• Common techniques for particle size measurements include:
  • Sieving
  • Microscopy (with or without image analysis)
  • Electric stream sensing zone method (Coulter counter)
  • Laser diffraction
  • Sedimentation (by gravity or centrifugal)
  • Ultrasonic attenuation

Particle Size and Zeta Potential

• Dynamic light scattering (DLS) measures particle size and zeta potential
• Applications:
  • Analysing wet emulsion, suspension, and bulk dry dispersion
  • Diverse sample types: abrasive, fragile, cohesive, or agglomerated

Other Analysis Techniques

• UV/VIS spectroscopy:
  • Determines characteristic absorption patterns
  • Used for qualitative detection, quantitative calculation, and kinetic analysis
• NMR spectroscopy:
  • Solid-state characterization: crystal polymorphism, testing, and measuring polymorphic state
  • Impurity analysis
• Mass spectrometry:
  • Quantitative elemental analysis
  • Molecular weight/formula evaluation
  • Unknown purity evaluation

Polymorphism

• The ability of a solid to exist in two or more crystalline forms
• >50% of APIs in the pharmaceutical industry have polymorphs
• Chemically identical but with significant differences in physical properties (solubility, dissolution rate, Tm, hygroscopicity, etc.)
• Differences in bioavailability: low or high solubility
• Inattention to polymorphic forms of an API can be harmful and expensive for pharmaceutical companies

Multi-Tier Evaluation of API Candidates

• Tier 1: Crystallinity, optical microscopy, and powder X-ray diffraction (XRD)
• Tier 2: Thermal properties, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and dynamic vapour sorption (DVS)
• Tier 3: Polymorph and hydrate screening, XRD, Raman microscopy, and DSC
• Tier 4: Humidity/temperature-induced changes in crystal form, powder XRD, DSC, and DVS

Pharmaceutical Analysis

• Molecular level: Fourier Transform Infrared (FT-IR), Nuclear Magnetic Resonance (NMR) spectroscopy, and mass spectrometry
• Physical/Particulate/Morphology: thermal analyses, X-ray diffraction (XRD), and other techniques
• Quantitative: HPLC, UV/VIS spectroscopy, and other spectrophotometry methods

Solid Phase Transitions

• Knowledge of solid form transitions is important for pharmaceutical product preparation
• Processes may cause polymorph or amorphous form conversions
• Multi-tier evaluation of API candidates is necessary for thorough characterization

Polymer Classifications

• Based on source: natural, semi-synthetic, and synthetic polymers
• Based on structure: linear, branched, and cross-linked polymers
• Based on pharmaceutical applications: polymers in conventional dosage forms, controlled release dosage forms, and drug packaging
• Based on solubility: water-soluble and water-insoluble polymers

Polymer Properties

• Molecular weight
• Composition
• Mechanical/thermal properties
• Rheology

Pharmaceutical Applications of Polymers

• Natural polymers: starch, chitosan, and others
• Synthetic polymers: polythene, polyvinyl chloride, and others
• Applications: tablet and capsule diluents, disintegrants, glidants, binders, and others