Efavirenz tablet formulation having unique biopharmaceutical characteristics

1 . An efavirenz tablet dosage form, said efavirenz tablet dosage form providing, when administered as a single dose to a subject,

a mean maximum plasma concentration (Cmax) of about 4 μM to about 14 μM;

a mean time of maximum plasma concentration (Tmax) of about 2 hours to about 5 hours; and

a mean area under the plasma concentration versus time curve from time zero to time infinity (AUC) of about 190 μM hour to about 470 μM hour.

2 . A tablet dosage form of claim 1 further having a mean area under the plasma concentration versus time curve from time zero to the last quantifiable concentration-time point (AUCT) of about 180 μM hour to about 430 μM hour.

3 . A tablet dosage form of claim 2 wherein the mean AUCT is about 270 μM hour to about 350 μM hour.

4 . A tablet dosage form of claim 1 further having a mean terminal disposition half-life (T 1/2 ) of about 30 hours to about 140 hours.

5 . A tablet dosage form of claim 4 wherein the mean T 1/2 is about 70 hours to about 100 hours.

6 . An efavirenz tablet dosage form, said efavirenz tablet dosage form providing, when administered as a single dose to a subject,

a mean maximum plasma concentration (Cmax) of about 7 μM to about 9 μM;

a mean time of maximum plasma concentration (Tmax) of about 2 hours to about 5 hours; and

a mean area under the plasma concentration versus time curve from time zero to time infinity (AUC) of about 250 μM hour to about 400 μM hour.

7 . A tablet dosage form of claim 1 comprising a therapeutically effective amount of efavirenz and about 4% by weight of a disintegrant relative to the total dry weight of the tablet dosage form.

8 . A kit comprising packaging including one or more efavirenz tablet of claim 1 and a package insert or label indicating to a user that the efavirenz tablet may be suitable for the treatment of human immunodeficiency virus Type 1 (HIV-1) infection.

9 . A tablet dosage form of claims 1 , 2 , 3 , 4 , 5 , 6 or 7 comprising 300 mg of efavirenz per tablet.

10 . A tablet dosage form of claims 1 , 2 , 3 , 4 , 5 , 6 or 7 comprising 600 mg of efavirenz per tablet.

11 . A kit comprising at least one efavirenz tablet of claim 1 and a package insert or label instructing the user on dosage and administration of the tablet dosage form.

12 . A kit comprising at least one efavirenz tablet of claim 1 and a package insert or label warning the user of potential side effects, adverse reactions or drug interactions.

13 . A method of treating human immunodeficiency virus Type 1 (HIV-1) infection comprising administering to a mammal the efavirenz tablet formulation of claim 1 .

14 . A method of treating human immunodeficiency virus Type 1 (HIV-1) infection comprising administering to a mammal an efavirenz tablet dosage form, said efavirenz tablet dosage form providing, when administered as a single dose to a subject,

a mean maximum plasma concentration (Cmax) of about 4 μM to about 14 μM;

a mean time of maximum plasma concentration (Tmax) of about 2 hours to about 5 hours; and

a mean area under the plasma concentration versus time curve from time zero to time infinity (AUC) of about 190 μM hour to about 470 μM hour.

15 . A 300 mg efavirenz tablet dosage form suitable for use in treating human immunodeficiency virus Type 1 (HIV-1) infection, said 300 mg efavirenz tablet dosage form providing,

an in vitro dissolution profile, when measured in a type II dissolution apparatus, according to U.S. Pharmacopeia XXIV, at about 37° C. in 2% (w/v) aqueous sodium lauryl sulfate at about 50 rpm, as follows:

(a) between about 62% and about 75% of the efavirenz tablet dosage form is dissolved after about 10 minutes in the type II dissolution apparatus,

(b) between about 90% and about 95% of the efavirenz tablet dosage form is dissolved after about 20 minutes in the type II dissolution apparatus,

(c) between about 96% and about 98% of the efavirenz tablet dosage form is dissolved after about 30 minutes in the type II dissolution apparatus, and

(d) between about 99% and about 100% of the efavirenz tablet dosage form is dissolved after about 45 minutes in the type II dissolution apparatus.

16 . The 300 mg efavirenz tablet dosage form of claim 15 wherein 100% of the 300 mg efavirenz tablet dosage form is dissolved after about 45 minutes.

17 . A 300 mg efavirenz tablet dosage form suitable for use in treating human immunodeficiency virus Type 1 (HIV-1) infection, said 300 mg efavirenz tablet dosage form providing,

an in vitro dissolution profile, when measured in a type II dissolution apparatus, according to U.S. Pharmacopeia XXIV, at about 37° C. in 2% (w/v) aqueous sodium lauryl sulfate at about 50 rpm, as follows:

(a) between about 62% and about 75% of the efavirenz tablet dosage form is dissolved after about 10 minutes in the type II dissolution apparatus,

(b) between about 89% and about 95% of the efavirenz tablet dosage form is dissolved after about 20 minutes in the type II dissolution apparatus,

(c) between about 94% and about 98% of the efavirenz tablet dosage form is dissolved after about 30 minutes in the type II dissolution apparatus, and

(d) between about 97% and about 100% of the efavirenz tablet dosage form is dissolved after about 45 minutes in the type II dissolution apparatus.

18 . The 300 mg efavirenz tablet dosage form of claim 17 wherein 100% of the 300 mg efavirenz tablet dosage form is dissolved after about 45 minutes.

19 . A 600 mg efavirenz tablet dosage form suitable for use in treating human immunodeficiency virus Type 1 (HIV-1) infection, said 600 mg efavirenz tablet dosage form providing,

an in vitro dissolution profile, when measured in a type II dissolution apparatus, according to U.S. Pharmacopeia XXIV, at about 37° C. in 2% (w/v) aqueous sodium lauryl sulfate at about 50 rpm, as follows:

(a) between about 49% and about 71% of the efavirenz tablet dosage form is dissolved after about 10 minutes in the type II dissolution apparatus,

(b) between about 87% and about 95% of the efavirenz tablet dosage form is dissolved after about 20 minutes in the type II dissolution apparatus,

(c) between about 97% and about 99% of the efavirenz tablet dosage form is dissolved after about 30 minutes in the type II dissolution apparatus, and

(d) between about 99% and about 100% of the efavirenz tablet dosage form is dissolved after about 45 minutes in the type II dissolution apparatus.

20 . The 600 mg efavirenz tablet dosage form of claim 19 wherein 100% of the 600 mg efavirenz tablet dosage form is dissolved after about 45 minutes.

21 . A 600 mg efavirenz tablet dosage form suitable for use in treating human immunodeficiency virus Type 1 (HIV-1) infection, said 600 mg efavirenz tablet dosage form providing,

an in vitro dissolution profile, when measured in a type II dissolution apparatus, according to U.S. Pharmacopeia XXIV, at about 37° C. in 2% (w/v) aqueous sodium lauryl sulfate at about 50 rpm, as follows:

(a) between about 49% and about 71% of the efavirenz tablet dosage form is dissolved after about 10 minutes in the type II dissolution apparatus,

(b) between about 86% and about 95% of the efavirenz tablet dosage form is dissolved after about 20 minutes in the type II dissolution apparatus,

(c) between about 94% and about 99% of the efavirenz tablet dosage form is dissolved after about 30 minutes in the type II dissolution apparatus, and

(d) between about 97% and about 100% of the efavirenz tablet dosage form is dissolved after about 45 minutes in the type II dissolution apparatus.

22 . The 600 mg efavirenz tablet dosage form of claim 21 wherein 100% of the 600 mg efavirenz tablet dosage form is dissolved after about 45 minutes.

23 . A method of treating human immunodeficiency virus Type 1 (HIV-1) infection comprising administering to a mammal a 300 mg efavirenz tablet dosage form, said 300 mg efavirenz tablet dosage form providing,

an in vitro dissolution profile, when measured in a type II dissolution apparatus, according to U.S. Pharmacopeia XXIV, at about 37° C. in 2% (w/v) aqueous sodium lauryl sulfate at about 50 rpm, as follows:

(a) between about 62% and about 75% of the efavirenz tablet dosage form is dissolved after about 10 minutes in the type II dissolution apparatus,

(b) between about 90% and about 95% of the efavirenz tablet dosage form is dissolved after about 20 minutes in the type II dissolution apparatus,

(c) between about 96% and about 98% of the efavirenz tablet dosage form is dissolved after about 30 minutes in the type II dissolution apparatus, and

(d) between about 99% and about 100% of the efavirenz tablet dosage form is dissolved after about 45 minutes in the type II dissolution apparatus.

24 . The method of claim 23 wherein 100% of the 300 mg efavirenz tablet dosage form is dissolved after about 45 minutes.

25 . A method of treating human immunodeficiency virus Type 1 (HIV-1) infection comprising administering to a mammal a 300 mg efavirenz tablet dosage form, said 300 mg efavirenz tablet dosage form providing,

an in vitro dissolution profile, when measured in a type II dissolution apparatus, according to U.S. Pharmacopeia XXIV, at about 37° C. in 2% (w/v) aqueous sodium lauryl sulfate at about 50 rpm, as follows:

(a) between about 62% and about 75% of the efavirenz tablet dosage form is dissolved after about 10 minutes in the type II dissolution apparatus,

(b) between about 89% and about 95% of the efavirenz tablet dosage form is dissolved after about 20 minutes in the type II dissolution apparatus,

(c) between about 94% and about 98% of the efavirenz tablet dosage form is dissolved after about 30 minutes in the type II dissolution apparatus, and

(d) between about 97% and about 100% of the efavirenz tablet dosage form is dissolved after about 45 minutes in the type II dissolution apparatus.

26 . The method of claim 25 wherein 100% of the 300 mg efavirenz tablet dosage form is dissolved after about 45 minutes.

27 . A method of treating human immunodeficiency virus Type 1 (HIV-1) infection comprising administering to a mammal a 600 mg efavirenz tablet dosage form, said 600 mg efavirenz tablet dosage form providing,

an in vitro dissolution profile, when measured in a type II dissolution apparatus, according to U.S. Pharmacopeia XXIV, at about 37° C. in 2% (w/v) aqueous sodium lauryl sulfate at about 50 rpm, as follows:

(a) between about 49% and about 71% of the efavirenz tablet dosage form is dissolved after about 10 minutes in the type II dissolution apparatus,

(b) between about 87% and about 95% of the efavirenz tablet dosage form is dissolved after about 20 minutes in the type II dissolution apparatus,

(c) between about 97% and about 99% of the efavirenz tablet dosage form is dissolved after about 30 minutes in the type II dissolution apparatus, and

(d) between about 99% and about 100% of the efavirenz tablet dosage form is dissolved after about 45 minutes in the type II dissolution apparatus.

28 . The method of claim 27 wherein 100% of the 600 mg efavirenz tablet dosage form is dissolved after about 45 minutes.

29 . A method of treating human immunodeficiency virus Type 1 (HIV-1) infection comprising administering to a mammal a 600 mg efavirenz tablet dosage form, said 600 mg efavirenz tablet dosage form providing,

an in vitro dissolution profile, when measured in a type II dissolution apparatus, according to U.S. Pharmacopeia XXIV, at about 37° C. in 2% (w/v) aqueous sodium lauryl sulfate at about 50 rpm, as follows:

(a) between about 49% and about 71% of the efavirenz tablet dosage form is dissolved after about 10 minutes in the type II dissolution apparatus,

(b) between about 86% and about 95% of the efavirenz tablet dosage form is dissolved after about 20 minutes in the type II dissolution apparatus,

(c) between about 94% and about 99% of the efavirenz tablet dosage form is dissolved after about 30 minutes in the type II dissolution apparatus, and

(d) between about 97% and about 100% of the efavirenz tablet dosage form is dissolved after about 45 minutes in the type II dissolution apparatus.

30 . The method of claim 29 wherein 100% of the 600 mg efavirenz tablet dosage form is dissolved after about 45 minutes.