Ribavirin (1-β-D-ribofuranosyl-1H-1,2,4-triazole-3-carboxamide) is a known synthetic nucleoside analog with broad spectrum antiviral activity. See, e.g., U.S. Pat. No. 3,927,216 to Witkowski et al. It is a colorless, water-soluble, stable material and is known to have two polymorphic forms.
Ribavirin compositions are also known as, for example, disclosed in U.S. Pat. No. 6,337,090; Canadian Patent No. 2,135,669; and U.S. Patent Application Publication 20030104050 A1. As noted in U.S. Pat. No. 6,337,090, there are many processing difficulties in preparing ribavirin compositions, including flowability, uniformity, etc. Ribavirin is known to have poor flow, which adversely affects its manufacture into solid dosage forms. A drug's manufacturing characteristic is important because it can affect weight variability, uniformity etc. of a dosage form of the drug, which in turns affects the drug's dissolution and bio-availability in a subject having ingested it.
Ribavirin is currently indicated for use as a combination therapeutic for Hepatitis C. As such, ribavirin is administered in large dosages, e.g., a dose as large as 1200 mg per day, together with interferon injections. Currently, however, ribavirin is only approved in the United States in the form of a 200 mg dosage. Hence, dosing regimens involve 4 to 6 capsules a day for treatment of Hepatitis C infections. The multiple capsules are typically taken twice daily so that the proper level of ribavirin can be maintained in the body. This dosage regimen is continued daily for a number of months and because of the frequency and number of capsules required for treatment, patient compliance becomes problematic. Additionally, the large dose of ribavirin needed for treating Hepatitis C causes undesirable side-effects for some patients.
Accordingly, a need exists to ameliorate the dosage regiment so that a more stable concentration of ribavirin can be achieved in a subject taking the medicament and to facilitate patient compliance. A continuing need also exists for improved ribavirin compositions.