Indinavir Ethanol

Drugs that might affect amprenavir include abacavir, aldesleukin, antacids, anticonvulsants, azole antifungals, clarithromycin, cyclosporine, dexamethasone, buffered didanosine, disulfiram, ethanol, indinavir, methadone, metronidazole, nelfinavir, nonnucleoside reverse transcriptase inhibitors, oral contraceptives, rifamycins, ritonavir, saquinavir, St. John s wort, tacrolimus, and zidovudine. 

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.)... 

Indinavir sulfate (Compound X) as the crystalline ethanolate is then prepared by treatment of the free base monohydrate with sulfuric acid in anhydrous ethanol. 

Indinavir sulfate, produced as the ethanolate using the synthetic process described in Section 2, is crystalline as determined by the x-ray powder diffraction (XRPD) method. The XRPD pattern and associated data, obtained using a Phillips Model APD 3720 x-ray diffractometer, is shown in Figure 3 and Table 1 [7]. 

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]. 

Both a hydrated crystal and amorphous form of indinavir sulfate have been observed following prolonged exposure of the ethanolate to moisture [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. 

Solubility Indinavir Low solubility -limiting bioavailability Indinavir sulfate ethanolate salt with acceptable performance characteristics... 

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

Given that reliable performance is a critical feature of an antiviral compound, a key issue in the development of Indinavir was managing the problem of consistent oral bioavailability [25]. Indinavir sulfate ethanolate is a crystalline compound, which was selected for the drug product over the crystalline free base monohydrate form of Indinavir on the basis of superior oral pharmacokinetics in animals including humans. The base form, a material with less than 0.02 mg ml solubility in water at 22 °C, is only... 

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