1Pharmaceutical Technology Research Group, Department of Pharmacy, University of Bath, UK. prsrp@bath.ac.uk
This study used advanced imaging to examine how mechanical stress and humidity affect lactose crystal surfaces. Lactose is a key ingredient in many drugs, so understanding its behavior is important for drug stability. The researchers found that milling lactose crystals and exposing them to high humidity led to visible changes in surface structure. These changes suggest that the crystals may become less ordered or even amorphous under certain conditions. The findings could help improve drug formulation and storage practices by highlighting the sensitivity of lactose to mechanical and environmental factors.
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Area of Science:
Background:
Understanding surface behavior of pharmaceutical solids is essential for drug formulation stability. Prior research has shown that mechanical stress alters crystal structures. However, the exact nature of these changes remains unclear. This gap motivated the use of high-resolution imaging to explore surface transformations. Existing methods lack the detail needed to observe microstructural changes. The study addresses this by focusing on mechanical effects on lactose crystals. Lactose is a common excipient, making its behavior under stress clinically relevant. Humidity exposure is known to affect crystalline materials, but the mechanisms are not fully understood. This work provides a new perspective on how milling and humidity influence surface properties.
Purpose Of The Study:
The goal was to examine how mechanical damage and humidity affect lactose crystal surfaces. Lactose is a model compound for pharmaceutical excipients. The study aimed to visualize surface changes after milling. Phase Imaging AFM was selected for its ability to detect mechanical variations. The researchers wanted to determine if milling leads to amorphous regions. Humidity exposure was tested to observe its effect on re-crystallisation. This approach allows for detailed surface analysis at the micrometer scale. The findings could improve understanding of drug stability under storage conditions.
The study found that milling and humidity exposure cause morphological and physico-mechanical changes in lactose surfaces.
Atomic force microscopy Phase Imaging was used to visualize surface variations after mechanical and environmental stress.
70% RH was selected to observe how elevated humidity affects lactose crystal surface properties during re-crystallisation.
Phase Imaging showed ordered crystalline states with multiple platelets and altered surface characteristics after milling.
Main Methods:
Atomic force microscopy Phase Imaging was adapted from Tapping Mode AFM. Large lactose crystals were grown on sample stubs for imaging. The crystals were then subjected to a controlled milling process. After milling, the samples were imaged at specific humidity levels. Phase and Amplitude images were used to assess crystalline order. Surface morphology was analyzed using Topographical imaging techniques. The study compared pre- and post-milling crystal structures. Humidity exposure was tested at 70% relative humidity to observe changes.
Main Results:
Phase Imaging revealed ordered crystalline states in re-crystallised lactose samples. Multiple platelets were observed on the surface after milling and re-crystallisation. A 1-minute milling time caused significant changes in surface characteristics. The milled samples showed altered physico-mechanical properties. Exposure to 70% RH led to morphological changes in lactose crystals. These changes may indicate surface amorphous re-crystallisation. The data suggests humidity affects crystal structure during re-nucleation. The results highlight the sensitivity of lactose surfaces to mechanical and environmental factors.
Conclusions:
The study found that milling and humidity exposure alter lactose crystal surfaces. Phase Imaging provided evidence of surface amorphous re-crystallisation. The results suggest mechanical damage leads to changes in surface morphology. Humidity exposure was linked to physico-mechanical changes in lactose. The findings support the hypothesis that milling affects crystal structure. The authors propose that these changes may impact drug stability. The study demonstrates the utility of AFM in analyzing surface transformations. These conclusions are based on the observed data and imaging results.
The study compares Phase and Amplitude images before and after milling to detect structural changes.
The findings suggest that mechanical and environmental factors can affect lactose stability in drug formulations.