No abstract

Donepezil, a cholinesterase inhibitor with good central nervous system penetration, has been crystallized as a tertiary amine salt with a disordered oxalate anion to give the title compound, (R,S)-1-benzyl-4-[(5,6-dimethoxy-1-oxoindan-2-yl)methyl]piperidinium hydrogen oxalate trihydrate, C24H30NO3+.C2HO4-.3H2O. The indanone and piperidine ring planes are inclined at an angle of 33.4 (1) degrees. A comparison is made with the piperidinium cation bound in acetylcholinesterase in the solid state. The methylene units bridging the indanone-piperidine-benzyl groups determine the molecular shape and conformational features. The structure is stabilized mainly by O-H...O and N-H...O hydrogen bonds, with water molecules mediating interactions between oxalate anions and donepezilium cations.

Polymorphs have a tendency to undergo solution-mediated transformation from one form to another during crystallization. Various in situ techniques explored for understanding the crystallization process include, Raman spectroscopy, near-infrared spectroscopy (NIR), and focused beam reflectance measurement (FBRM). Both Raman and NIR techniques are used for polymorphic identification. FBRM has gained much popularity as an ideal technique for studying and improving particle size. The crystallization process can be improved using FBRM by studying the meta-stable zone, temperature of crystallization, and primary and secondary nucleation. This FBRM technique offers a quick and time-saving approach along with insight on the particle size of the product. The same technique can be used during scale up to understand and monitor crystallization processes. This report describes a different application of FBRM, which involves monitoring the changes in chord length distribution as a result of polymorphic transformation associated with temperature during crystallization. Needle-shaped Form III of acitretin undergoes solvent-mediated transformation to cube-shaped Form II. This polymorphic transformation is monitored by monitoring the chord length distribution.

Polymorphism is a solid-state phenomenon; hence, solid-state techniques such as XRPD, DSC, and FT-IR are used for characterization. Many a time, only XRPD is used. These techniques ignore the most important aspects, i.e., chemical purity and the chemical integrity of the polymorph, which can be confirmed by techniques such as 1 H NMR, HPLC, and elemental analysis. The aim of this article is to emphasize how techniques such as 1 H NMR, elemental analysis, and HPLC purity in addition to other solid-state characterization techniques would help to prove that the drug really exists in different polymorphic forms. H 1 NMR, HPLC, and elemental analysis reveal the formation of different compounds and not polymorphs in the case of pioglitazone•HCl and glyburide. In the cases of irbesartan and ropinirole•HCl use of a single solid-state characterization technique such as XRPD is not enough for establishing the existence of different polymorphic forms.