Elucidation of crystal form diversity of the HIV protease inhibitor ritonavir by high-throughput crystallization.

ABSTRACT: Pharmaceutical compounds are molecular solids that frequently exhibit polymorphism of crystal form. One high profile case of polymorphism was ritonavir, a peptidomimetic drug used to treat HIV-1 infection and introduced in 1996. In 1998, a lower energy, more stable polymorph (form II) appeared, causing slowed dissolution of the marketed dosage form and compromising the oral bioavailability of the drug. This event forced the removal of the oral capsule formulation from the market. We have carried out high-throughput crystallization experiments to comprehensively explore ritonavir form diversity. A total of five forms were found: both known forms and three previously unknown forms. The novel forms include a metastable polymorph, a hydrate phase, and a formamide solvate. The solvate was conve

SUBMITTER: Morissette SL 

PROVIDER: S-EPMC151315 | biostudies-literature | 2003 Mar

REPOSITORIES: biostudies-literature