Oral ribavirin pharmaceutical compositions

2- Oral ribavirin composition possibly according to claim 1, wherein the modified release form of ribavirin has a release profile, in a dissolutest in which the pH is maintained at a pH=1.4 for 1.5 h then increased to a pH=6.8, such that 70% of the ribavirin is released over a period of time of between 1.5 and 16 h.

3- Oral ribavirin composition according to claim 1 or 2, including a therapeutically effective amount of at least an interferon.

4- Oral ribavirin composition according to claim 2, comprising a modified release form of ribavirin wherein the modified release form of ribavirin is a sustained release form with a release profile at pH 6.8 such that 70% of the ribavirin is released over a period of time, designed as t(70%), of between 1.5 and 15 h, preferably 2 and 10 h and even more preferably between 3 and 8 h.

5- Oral ribavirin composition according to claim 4, wherein the modified release form of ribavirin has an in vitro release profile, in 0.05M potassium dihydrogeno phosphate/sodium hydroxide buffer medium at pH 6.8, such that, for any value of time t of between 2 h and t(70%), preferably for any value of time t of between 1 h and t(70%), the % of dissolved (released) ribavirin is greater or equal to 35×t/t(70%).

6- Oral ribavirin composition according to claim 2, wherein the modified release form of ribavirin is a sustained release form with an in vitro dissolution behaviour such that:

• the release of ribavirin is controlled by means of two distinct triggering mechanisms, one being based on a variation in pH and the other allowing the release of the active principle(s) after a predetermined period of residence in the stomach;
• at constant pH 1.4, the dissolution profile comprises a lag phase of less than or equal to 7 h, preferably less than or equal to 5 h, and even more preferably of between 1 and 5 h;
• and the change from pH 1.4 to pH 7.0 results in a release phase that begins without any lag time.

7- Oral ribavirin composition according to claim 6, wherein the modified release form of ribavirin has an in vitro dissolution behaviour, measured in an in vitro dissolution test, such that:

• less than 20% of the ribavirin is released after 2 h at pH 1.4;
• at least 50% by weight of the ribavirin is released after 16 h at pH 1.4.

8- Oral ribavirin composition according to claim 1 or 2, wherein the modified release form is a reservoir type form.

9- Oral ribavirin composition according to claim 1 or 2, wherein the modified release dosage form is a matrix type form.

10- Oral ribavirin composition according to claim 8 or 9, wherein the modified release form is a gastric retentive system.

11- Oral ribavirin composition according to claim 8 or 9, wherein the modified release form is a multiparticulate form.

12- Oral ribavirin composition according to claim 4 or 5, wherein the microparticles have a mean diameter less or equal to 1000 μm, preferably comprised between 20 and 800 μm and more preferably comprised between 50 and 600 μm.

13- Oral ribavirin composition according to claim 6, wherein the microparticles have a mean diameter less than 2000 μm, and preferably between 50 and 800 μm, and even more preferably between 100 and 600 μm.

14- Oral ribavirin composition according to claim 11, wherein the modified release form is a reservoir type form comprising a plurality of microcapsules with modified release of ribavirin, these microcapsules individually consisting of a microparticle including some ribavirin and coated with at least one coating for modified release of the ribavirin.

19- Oral ribavirin composition, according to claim 17, wherein the composite material A″B″ for the coating for modified release of the active principle with low solubility is such that:

• the B″/A″ weight ratio is between 0.2 and 1.5, preferably between 0.5 and 1.0,
• and the hydrophobic compound B″ is selected from products that are crystalline in the solid state and that have a melting point MpB≧40° C., preferably MpB≧50° C., and even more preferably 40° C.≦MpB≦90° C.

20- Oral ribavirin composition according to claim 18, wherein the hydrophilic polymer A″ is chosen from:

• A″.a copolymers of (meth)acrylic acid and of (meth)acrylic acid alkyl ester, and mixtures thereof;
• A″.b cellulose derivatives, preferably cellulose acetates, cellulose phthalates, cellulose succinates and mixtures thereof, and even more preferably hydroxypropylmethylcellulose phthalates, hydroxypropylmethylcellulose acetates, hydroxypropylmethylcellulose succinates and mixtures thereof;
• and mixtures thereof.

22- Oral ribavirin composition according to claim 21, wherein the compound B″ is chosen from the group of following products:

• hydrogenated cottonseed oil, hydrogenated soybean seed oil, hydrogenated palm oil, glyceryl behenate, hydrogenated castor oil, tristearin, tripalmitin, trimyristin, yellow wax, hard fat or fat that is useful as suppository bases, anhydrous dairy fats, lanolin, glyceryl palmitostearate, glyceryl stearate, lauryl macrogolglycerides, cetyl alcohol, polyglyceryl diisostearate, diethylene glycol monostearate, ethylene glycol monostearate, omega 3 and any mixture thereof,
• preferably from the subgroup of following products:
• hydrogenated cottonseed oil, hydrogenated soybean seed oil, hydrogenated palm oil, glyceryl behenate, hydrogenated castor oil, tristearin, tripalmitin, trimyristin and any mixture thereof.

25- Oral ribavirin composition according to claim 24, provided in the form of a unit dosage adapted for a single or a twice daily oral administration.

26- Oral ribavirin composition according to claim 1 or 2, provided in the form of a sachet of powder, of a powder for multidose suspension to be reconstituted in liquid suspension, of a tablet or of a gelatin capsule.

27- A method of treating viral infections in a patient comprising administering to said patient a therapeutic amount of the oral ribavirin composition according to claim 1 or 2.

28- A method according to claim 27, further comprising co-administering to the patient a therapeutically effective amount of at least an interferon.

29- A method according to claim 28, wherein the viral infection is hepatitis C.

30- Use of the oral ribavirin composition according to claim 1 or 2 for preparing pharmaceutical or dietetic, (e.g. microparticulate), oral galenical forms, preferably in the form of tablets, of powders for oral suspension, of stable liquid suspensions or of gelatin capsules.

An oral pharmaceutical formulation that comprises at least one antiviral drug that has an in vivo bio-absorption time between about 2 and 15 h, and said bio-absorption time is greater than the bio-absorption time of a reference immediate release form of the antiviral drug administered at the same dose.

The oral pharmaceutical formulation that comprises at least one antiviral drug having an in vitro release profile such that about 70% of the antiviral drug is released over a period of time of between about 1.5 and 16 h when the pH is maintained at about pH 1.4 for 1.5 h and then increased to about pH 6.8.

An oral pharmaceutical formulation that comprises at least one antiviral drug in a sustained release form, said antiviral drug having a mean diameter of about 20 to 1000 μM.

An oral pharmaceutical formulation comprising at least one antiviral drug, wherein said antiviral drug is released by at least two mechanisms, wherein first said mechanism is antiviral drug release after a predetermined period of residence in the stomach.