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Solid State Characterization

Solid State Characterization

Understanding what happens inside the crystal, so your API stays stable from process to patient.

Solid State Characterization

At a fundamental level, micronization involves the transfer of mechanical energy to a solid material. When mechanical energy is accumulated (ΔE), the material undergoes a thermodynamic transition from a stable crystalline structure to a high-energy state. To return to stability, the material releases this excess energy through three primary mechanisms: initial heat generation, material comminution (creating new surfaces), and plastic deformation, which can induce crystal defects or amorphous structures. High specific energy is often required to reach narrow particle size distributions (PSD), but this can unintentionally alter the solid state and stability of the API.


Increased surface area often leads to poor flow properties and electrostatic charges. High energy also risks surface amorphization, where unstable amorphous content reverts to crystalline form, causing particles to agglomerate. Advanced analytical techniques like XRPD, DSC, and DVS are employed to monitor these solid-state changes.


Customers

  • Small biotechs to Big Pharma
  • CDMO’s (API, Dosage Form, Integrated)
  • Functional Excipient Companies

Phases of Development Supported:

  • Lifecycle Presence: From Pre-Clinical to Commercial Phase
  • Fully Equipped from few grams up to metric Ton Batches
  • One Independent R&D Lab and 3 fully inspected GMP Buildings

Types of Molecules

  • Small Molecule APIs and HPAPIs
  • Functional Excipients
  • NCEs, 505b2s, Generics
Solid State Characterization

The importance of Solid State Characterization

Micronization’s high specific energy can trigger unstable amorphization or polymorphic transitions. Therefore, robust solid-state characterization using XRPD, DSC, and DVS is essential to guarantee long-term stability and performance.

DVS +

Dynamic Vapor Sorption (DVS) is an analytical method used to determine a material’s susceptibility to moisture and its amorphous content. Because micronization significantly increases a powder's surface area and could generate surface amorphization, this could lead to stability issues. DVS measures changes in sample mass as it is exposed to varying levels of relative humidity and temperature, providing sorption and desorption curves. This technique is vital for predicting product performance, as high moisture uptake can trigger the rapid conversion of surface amorphous content back to a crystalline phase, potentially causing the particles to agglomerate and increase in size.

XRPD +

X-ray Powder Diffraction (XRPD), is a fundamental technique for identifying solid-state modifications and verifying the crystalline form of an API after processing. The high mechanical energy involved in jet milling can disrupt a material's stable lattice, leading to polymorphic transitions or amorphization. XRPD characterizes these changes by measuring diffraction peak intensities. A reduction in peak intensity, or the emergence of a broad amorphous "halo“, confirms a loss of crystallinity. This analysis is essential to highlight physical differences before and after micronization, ensuring the drug maintains the required physical form for stability and performance.

DSC +

Differential Scanning Calorimetry (DSC) is a thermo-analytical technique used to monitor the impact of micronization on the solid state of an API. By measuring the heat flow associated with thermal transitions, DSC detects physical changes such as polymorphic transitions, dehydration, or the formation of amorphous content. Specifically, a progressive reduction in the enthalpy of fusion peak indicates a decrease in material crystallinity. This allows researchers to quantify the degree of amorphization induced by high specific energy during milling. Identifying these changes is critical, as unstable amorphous surfaces can revert to crystalline forms, causing unwanted particle aggregation.

Solid State Characterization explained

Solid State Characterization explained

Solid state characterization is like a high-tech "health check" for the physical structure of a medicine. When we break medicine down into microscopic pieces, the high energy used during the process can sometimes scramble its internal crystalline "blueprint". If this happens, the powder might clump together or not dissolve correctly in your body. To prevent these issues, scientists use specialized tests to see how the crystals react to heat or moisture. These checks ensure the medicine stays stable, safe, and high-quality until it reaches the patient.

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