Solid-state characterization of tacrine hydrochloride.

Area of Science:

• Pharmaceutical Sciences
• Solid-State Chemistry
• Drug Development

Background:

• Tacrine monohydrochloride (TCR) is a key acetylcholinesterase inhibitor used for Alzheimer's disease.
• Understanding TCR's solid-state properties is crucial for its formulation and therapeutic efficacy.
• Polymorphism and hydration significantly impact drug stability and bioavailability.

Purpose of the Study:

• To comprehensively characterize the physicochemical properties of different solid forms of tacrine monohydrochloride (TCR).
• To investigate the formation of new hydrates and anhydrous phases of TCR.
• To elucidate the hydration behavior of anhydrous TCR under varying relative humidity conditions.

Main Methods:

• Recrystallization from various solvents to obtain different solid forms.
• Differential scanning calorimetry (DSC) and simultaneous thermogravimetric analysis (TGA/DSC) for thermal characterization.
• X-ray powder diffractometry (PXRD) and Fourier transform infrared spectroscopy (FT-IR) for structural analysis.
• Thermo optical analysis (TOA) to observe solid-state transitions.

Main Results:

• A new dihydrate form (TCR·2H₂O form I) was successfully isolated via recrystallization.
• A unique anhydrous crystalline phase of TCR was confirmed through desolvation studies.
• Anhydrous TCR rehydrated to TCR·H₂O at 32% RH and formed a distinct polymorph (TCR·2H₂O form II) at 100% RH.

Conclusions:

• TCR exhibits complex solid-state behavior, including the formation of multiple hydrates and a stable anhydrous form.
• The identified solid forms (TCR·H₂O, TCR·2H₂O form I, TCR·2H₂O form II, and anhydrous TCR) possess distinct physicochemical characteristics.
• Understanding these solid forms is essential for optimizing tacrine-based Alzheimer's therapies.