Mechanochemically induced solid state transformations: The case of raloxifene hydrochloride

Area of Science:

• Pharmaceutical Science
• Materials Science
• Solid-State Chemistry

Background:

• Raloxifene hydrochloride, a benzothiophene derivative, is crucial for osteoporosis management.
• Its therapeutic efficacy is limited by poor water solubility and low oral bioavailability.
• Developing novel solid forms is essential to enhance raloxifene hydrochloride's pharmaceutical properties.

Purpose of the Study:

• To explore mechanochemical methods for producing new solid forms of raloxifene hydrochloride.
• To characterize the physical and chemical properties of these novel forms.
• To evaluate the solubility and stability of the new raloxifene hydrochloride forms.

Main Methods:

• Mechanochemical processing: neat grinding and liquid-assisted grinding.
• Solid-state characterization: powder X-ray diffraction (PXRD), thermal analysis (DSC/TGA), infrared (IR) and Raman spectroscopy.
• Solubility and stability assessments.

Main Results:

• Mechanochemical grinding successfully produced solvated and amorphous forms of raloxifene hydrochloride.
• Raman spectroscopy effectively differentiated between amorphous and crystalline forms and monitored recrystallization.
• The amorphous form exhibited notably enhanced solubility compared to the commercial raloxifene hydrochloride salt.

Conclusions:

• Mechanochemical techniques offer a viable route to generate novel solid forms of raloxifene hydrochloride.
• The amorphous form presents a promising strategy for improving raloxifene hydrochloride's bioavailability.
• Further investigation into the amorphous form could lead to more effective osteoporosis therapies.