Solvates indinavir

U.S. Adopted Name Indinavir Sulfate International Non-Proprietary Name Indinavir International Non-Proprietary Name modified Indinavir Sulfate (This nomenclature will be used throughout to designate the sulfate salt (ethanol solvate) unless otherwise indicated.)... 

Crystallographic quality ciystals of indinavir sulfate salt were grown hy slow diffusion of methanol into an ethanol/water solution. As confirmed by TG/IR results, the crystals obtained were a mixed mono-methanol / mono-ethanol solvate. The compound crystallized in the P2, space group, (monoclinic crystal system) with 2 molecules per unit cell. The cell constants were found to be a= 14.321(1)A, 6 = 10.091(1)A, c = 15.192(1)A, P = 95.50(1)°, andV=2185.5A. The calculated density was 1.200 g/cm. A view of the crystallographic unit cell packing is shown in Figure 4, with the solvent molecules omitted [7]. 

To illustrate the ARS form selection process, two pharmaceutical examples of ARS form selection are provided. Indinavir sulfate is the API for Crixivan , a specific and potent inhibitor of the HIV-1 protease used in the treatment of AIDS. Indinavir sulfate is produced as a crystalline ethanolate sulfate salt. If the material is stored in double polyethylene liners within fiber containers or repeatedly exposed to ambient conditions changes occur in both crystallinity and solvation. Using XRPD, KF, and RP-HPLC, conversion of the crystalline ethanolate to amorphous material or to a hydrate crystal form has been detected and degradation is observed. However, the material is stable if stored in a tightly sealed container impermeable to ethanol/moisture transport under an inert nitrogen atmosphere at a controlled room temperature.82,83 These storage conditions are not practical for a routinely used ARS. Therefore, the free base monohydrate form of indinavir sulfate was evaluated and selected as the ARS. This form of the API was demonstrated to be extremely stable under ambient conditions needed for routine analysis. 

Indinavir sulfate ethanolate - a case of a salt hydrate/solvate... 

The judicious introduction of a fluorine atom into the HIV-1 protease inhibitor indinavir (33) and epi-indinavir (34) provided an opportunity to assess the effect of F-OH interactions on biological properties related to conformational disposition [71], The four fluorinated derivatives 35-38 were prepared with the anticipation of complex effects due to the F atom which was expected to affect the acidity of the OH and influence the population of conformers in addition to affecting steric interactions and solvation. The Kj data for the inhibition of HIV-1 protease are summarized in Table 2 and reveal interesting profiles. 

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