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Updated: Jul 4, 2026
Microfluidic Preparation of Liquid Crystalline Elastomer Actuators
Published on: May 20, 2018
Darragh Murnane1, Christopher Marriott, Gary P Martin
1King's College London, Drug Delivery Research Group, Pharmaceutical Science Division, 150 Stamford Street, London SE1 9NH, United Kingdom.
This study compared two methods for making salmeterol xinafoate (SX) into microparticles for inhalation. One method used poly(ethylene glycol) solvents, while the other used propan-2-ol. The researchers found that SX crystallized from PEG solvents remained in a more stable polymorphic form (form I) with less crystal lattice disorder. Ball-milling SX samples caused a polymorphic transition, but untreated SX was stable. Micronization increased the differences in polymorphic stability between the two methods. The study suggests that using PEG solvents may result in better solid-state properties for SX in pharmaceutical applications.
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Area of Science:
Background:
Polymorphism in active pharmaceutical ingredients can significantly impact drug performance. Conventional milling processes often induce polymorphic changes in enantiotropic systems. Prior research has shown that micronization techniques may alter the solid-state properties of drugs. This gap motivated an investigation into how different crystallization methods affect polymorphic outcomes. The study addresses uncertainty around the stability of salmeterol xinafoate (SX) under various processing conditions. Knowledge exists about the role of solvents in polymorphic transitions, but specific data on SX remains limited. This work builds on established methods in powder X-ray diffraction and thermal analysis. The goal is to clarify how SX's polymorphic form is influenced by crystallization and micronization techniques.
Purpose Of The Study:
The study aimed to compare the polymorphic behavior of salmeterol xinafoate (SX) following two distinct crystallization methods. Researchers focused on antisolvent micronization from poly(ethylene glycol) solvents versus conventional crystallization techniques. The goal was to assess how these methods affect SX's solid-state properties. The work sought to determine if PEG-based crystallization preserves polymorphic integrity better than propan-2-ol. The study also aimed to evaluate the impact of micronization on SX's polymorphic form. Thermal analysis was used to compare the crystallization kinetics of SX samples. The research intended to clarify how different processing steps influence SX's enantiotropic purity. By comparing crystallization methods, the study aimed to inform better manufacturing practices.
Main Methods:
The study employed powder X-ray diffraction to analyze the polymorphic forms of salmeterol xinafoate (SX). A modified Avrami-Erofe'ev equation was used for thermo-kinetic analysis of differential scanning calorimetry data. SX was crystallized from poly(ethylene glycol) solvents and propan-2-ol as control. The samples were subjected to antisolvent micronization and ball-milling processes. Thermal behavior was evaluated through differential scanning calorimetry thermographs. The researchers compared the crystallization kinetics of SX from different solvents. Ball-milling was used to induce potential polymorphic transitions in SX samples. The study focused on quantifying crystal lattice disorder and enantiotropic purity differences.
Main Results:
Salmeterol xinafoate (SX) crystallized predominantly as form I following rapid precipitation from poly(ethylene glycol) solvents. Cooling crystallization from propan-2-ol also produced form I, but with higher crystal lattice disorder. SX crystallized from PEG solvents showed significantly less re-crystallization of form II from the melt. Ball-milled SX samples exhibited a polymorphic transition upon heating. Untreated SX was resistant to such transformations. Thermo-kinetic analysis revealed differences in crystallization kinetics between solvent systems. SX crystallized from PEG solvents had higher enantiotropic purity than propan-2-ol-derived samples. Micronization further amplified the differences in polymorphic stability between the two crystallization methods.
Conclusions:
The study found that salmeterol xinafoate (SX) crystallized from poly(ethylene glycol) solvents retained a more stable polymorphic form than propan-2-ol-derived samples. Ball-milling induced polymorphic transitions in SX, while untreated material remained stable. The thermal behavior of SX from PEG solvents suggested lower crystal lattice disorder. The authors propose that PEG-based crystallization preserves SX's polymorphic integrity better than conventional methods. Micronization amplified the differences in polymorphic stability between the two crystallization approaches. The findings suggest that solvent choice significantly influences SX's solid-state properties. The study highlights the importance of processing conditions in pharmaceutical crystallization. The results support the use of PEG solvents for SX formulations requiring stable polymorphic forms.
The main polymorphic form of salmeterol xinafoate following crystallization from PEG solvents is form I, with lower crystal lattice disorder and higher enantiotropic purity.
Salmeterol xinafoate crystallized from PEG solvents showed less re-crystallization of form II and higher enantiotropic purity compared to propan-2-ol-derived samples.
Ball-milling induced polymorphic transitions in salmeterol xinafoate, while untreated material remained stable, highlighting the impact of mechanical processing on solid-state properties.
Differential scanning calorimetry was used to analyze the thermal behavior and crystallization kinetics of salmeterol xinafoate samples from different solvents.
Micronization amplified the differences in polymorphic stability between salmeterol xinafoate samples crystallized from PEG solvents and propan-2-ol.
The authors propose that PEG solvents preserve salmeterol xinafoate's polymorphic integrity better than conventional crystallization methods.
