Characterization of Physical Forms of Donepezil Hydrochloride

Miha Vrbinc,* Berta Jordan-Kotar, Matej Smrkolj, Franc Vrečer

Krka, d. d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, SI-Slovenia
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Different crystal forms and amorphous form of donepezil hydrochloride were prepared and characterized, using various analytical techniques. Hydrate form I is stable only at lower relative humidity (RH), while at higher RH it sorbes additional water. Forms II, III and V were identified as polymorphs, whereas form III is thermodynamically stable. Form V was prepared by heating of hydrate IV at high temperature (about 150 °C). Three different forms of hydrate IV were obtained and characterized. Differential scanning calorimetry and X-ray powder diffraction are the most promising analytical methods for differentiation between crystal forms, both polymorphs and hydrates. Methods could be also used in determination of physical form of a drug, incorporated into solid dosage form. Thermal methods explain the most significant difference in dehydration of different forms IV: transformation to pure polymorphic forms or mixture thereof. On heating of hydrates I and IV-1, two novel crystal forms were prepared and characterized, namely crystal forms VII and VIII.

Keywords: donepezil hydrochloride, polymorphs, hydrates, characterization