Tablet comprising a fibrate
Stable tablets and pharmaceutical compositions in particulate form comprising a fibrate, for example fenofibrate, dissolved or dispersed in an non-aqueous vehicle with improved bioavailability, thereby eliminating the food effect so that the tablet or composition can be administered to a patient irrespective of being in fed or fasted state.
1. A tablet comprising 33, 37, 40, 43, 48, 87, 100, 110, 120, 130, 145, or 160 mg fenofibrate in a hydrophilic vehicle, the vehicle comprising an effective amount of poloxamer and a hydrophilic polymer such that the tablet, upon oral administration to a patient in need thereof, results in a value of AUC fasted relative to a value of AUC fed of at least about 0.85 with a lower 90% confidence limit of at least 0.75.
2. The tablet according to claim 1 , wherein the fenofibrate is present in an amount of 145 mg.
3. The tablet according to claim 1 , wherein the fenofibrate is present in an amount of 130 mg.
4. The tablet according to claim 1 , wherein the fenofibrate is present in an amount of 120 mg.
5. The tablet according to claim 1 , wherein the fenofibrate is present in an amount of 110 mg.
6. The tablet according to claim 1 , wherein the fenofibrate is present in an amount of 100 mg.
7. The tablet according to claim 1 , which upon oral administration to a patient in need thereof results in a value of AUC fasted relative to a value of AUC fed of at least about 0.9.
8. The tablet according to claim 1 , which upon oral administration to a fasting patient in need thereof results in a bioavailability less than about 15% below the bioavailability after administration to the patient in fed state.
9. The tablet according to claim 1 , wherein the vehicle further comprises a polyethylene glycol (PEG) having an average molecular weight of at least 3000.
10. The tablet according to claim 9 , wherein the vehicle consists of a mixture of polyethylene glycol and poloxamer in a weight proportion of between 1:3 and 10:1.
11. The tablet according to claim 10 , wherein the poloxamer is poloxamer 188.
12. The tablet according to claim 10 , wherein the polyethylene glycol has an average molecular weight of about 6000 (PEG6000).
13. The tablet according to claim 1 , wherein at least 90% w/w of the fenofibrate is dissolved in the vehicle.
14. The tablet according to claim 1 , which further comprises one or more pharmaceutically acceptable excipients selected from the group consisting of fillers, diluents, disintegrants, binders, glidants and lubricants.
15. The tablet according to claim 1 , which is coated with a coating selected from the group consisting of film coatings, modified release coatings, enteric coatings, protective coatings and anti-adhesive coatings.
16. The tablet according to claim 1 , which is bioequivalent with any Orange Book listed commercially available drug product comprising fenofibrate as the active ingredient in the same amount as the solid dosage form.
17. The tablet according to claim 1 , which comprises 120 mg of fenofibrate and provides, in fasted state, an AUC value relative to that of commercially available Antara™ 130 mg capsules of at least about 1.1, the AUC values being determined under similar conditions.
18. A tablet comprising a solid dispersion or solid solution of fenofibrate in a vehicle, the vehicle comprising (i) polyethylene glycol having an average molecular weight of 3000 daltons to 35000 daltons and (ii) poloxamer in a weight proportion of between 1:3 and 10:1, wherein the tablet upon oral administration to a patient in need thereof results in a value of AUC fasted relative to a value of AUC fed of at least about 0.85 with a lower 90% confidence limit of at least 0.75.
19. The tablet solid dosage according to claim 1 , wherein the fenofibrate is present in an amount of 40 mg.
20. A tablet comprising 40 or 120 mg fenofibrate in a hydrophilic vehicle, wherein the fenofibrate and hydrophilic vehicle are on a solid carrier, and the vehicle comprises an effective amount of poloxamer and a hydrophilic polymer such that the tablet, upon oral administration to a patient in need thereof, results in a value of AUC fasted relative to a value of AUC fed of at least about 0.85 with a lower 90% confidence limit of at least 0.75.
21. The tablet according to claim 20 , wherein the weight ratio of fenofibrate to polymer in the hydrophilic vehicle ranges from about 1:1 to about 1:3.