Pseudopolymorphs and Intrinsic Dissolution of Nevirapine

Nevirapine (C15H14N4O) is a lipophilic drug of low aqueous solubility used in AIDS treatment. Three different
crystal forms of this non-nucleoside reverse transcriptase inhibitor were obtained after recrystallization procedures. Physical
characterization was evaluated with DSC, TG, IR spectroscopy, and X-ray diffraction methods. Two new pseudopolymorphs have
been characterized:  nevirapine hemihydrate and nevirapine hemiethyl acetate. The pseudopolymorph identified as the hemiethyl
acetate is disordered. It is converted to the hemihydrate form at room temperature. The crystal structures of the hemihydrate and
hemiethyl acetate forms have been determined. The hemihydrate crystallizes in space group P21/n, while the ethyl acetate form is
in space group P1̄. Polymorphs and pseudopolymorphs of a drug may exhibit different chemical and physical properties, which can
affect dissolution, besides manufacturing, stability, and bioavailability. For this reason, an investigation on the behavior of the two
nevirapine pseudopolymorphs through the dissolution test has been described. The disk intrinsic dissolution rate of the solvent-free
form has been found to be 1.5-fold greater than the hemihydrate form in 0.01 mol L-1 HCl and in 0.1 mol L-1 HCl, which can be
explained by solubility results.