Chemically fexofenadine hydrochloride is 4-[4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-hydroxybutyl]-α,α-dimethylbenzene acetic acid hydrochloride. It is also known as terfenadine carboxylic acid metabolite. It is represented by Formula 1.

Fexofenadine hydrochloride is useful as an antihistamine, and does not cause the adverse effects associated with the administration of terfenadine including abnormal heart rhythms in some patients with liver disease or patients who also take the antifungal drug ketoconazole or the antibiotic erythromycin.
U.S. Pat. No. 4,254,129 (“the '129 patent”) entitled Piperidine Derivatives issued on Mar. 3, 1981. The '129 patent relates to substituted piperidine derivatives and methods of making and using them. The disclosed compounds, including fexofenadine and its pharmaceutically acceptable salts and individual optical isomers, are purported to be useful as antihistamines, antiallergy agents and bronchodilators.
The '129 patent discloses a process for the preparation of fexofenadine having a melting point of 195-197° C. The recrystallization process exemplified therein in Example 3, column 13, involves use of a mixture of solvents for preparation of fexofenadine.
WO 95/31437 discloses processes for preparing hydrated and anhydrous forms of piperidine derivatives, polymorphs and pseudomorphs thereof, which are useful as antihistamines, antiallergic agents and bronchodilators.
WO 95/31437 discloses the preparation of anhydrous forms of fexofenadine hydrochloride by subjecting the hydrated fexofenadine hydrochloride to an azeotropic distillation or to water minimizing recrystallization. In the invention described in this application, unlike the process described in WO 95/31437, hydrated Fexofenadine Hydrochloride is not converted to anhydrous Fexofenadine Hydrochloride, but instead Fexofenadine is converted to Form A of Fexofenadine and then to anhydrous Form X of Fexofenadine Hydrochloride. The novel anhydrous crystalline form of Fexofenadine Hydrochloride is obtained according to the present invention directly from the novel precursor i.e. Fexofenadine without generating a hydrated form. The starting material used Fexofenadine (Base) is different than described in WO 95/31437.
WO 00/71124A1 discloses amorphous fexofenadine hydrochloride process, its preparation and a composition containing it.
Fexofenadine obtained in the prior art processes, is a mixture of regioisomers of fexofenadine containing 33% of para isomer and 67% of meta isomer. These components are referred to as inseparable and it is also stated that it is not possible to obtain either of the regioisomers in substantially pure form. On the other hand, Fexofenadine prepared according to the process of this invention has a purity of >99.5%. In the novel crystalline Fexofenadine of this invention, the meta isomer of Fexofenadine is at a level of below 0.1%. Purity of fexofenadine is critical when it is used for the conversion to its hydrochloride salt since it is very difficult to remove any undesired impurities, including regioisomers, from the desired compound in last late processing stage. Removing the impurities increases the cost of production. Hence it is generally preferred that the HPLC purity of fexofenadine is greater than 99.5%.
Another beneficial aspect of the present invention is that, the fexofenadine hydrochloride is obtained in almost quantitative yield from the precursor i.e. fexofenadine. Almost quantitative yield means that the pure fexofenadine is converted to fexofenadine hydrochloride quantitatively (>92% yield of theory), with almost no yield loss, as the fexofenadine base itself is >99.5% pure as compared to fexofenadine prepared by the prior art processes.