Abbott, development phase drugs

Ritonavir (Norvir Abbott) is a drug for treating patients infected with human immunodeficiency virus-1 (HIV-1). In solid state the compound consists exclusively of one kind of monoclinic crystals. As this form, now called form I, was not sufficiently bioavailable by the oral route, a liquid formulation containing dissolved ritonavir in a hydroalcoholic solution was developed. It gave satisfactory results during the development and early manufacturing phases. However, in 1998, 2 years after the launch, a second form (form II) precipitated during shelf life. The new form is thermodynamically more stable and about 50% less water-soluble than form I. Within weeks-days, this new form was produced in all the production lines and Abbott had to stop the production of ritonavir. Finally, after considerable effort and expense, a new formulation of ritonavir was developed. 

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