ALFUZOSIN FORMULATIONS, METHODS OF MAKING, AND METHODS OF USE
Alfuzosin compositions comprising alfuzosin and a release-retarding matrix comprising about 40 to about 80% (by weight) hydroxypropyl methyl cellulose with a maximum apparent viscosity of about 5600 cP, wherein the compositions are bioequivalent to the reference dosage form of NDA #021287 are disclosed. Alfuzosin compositions comprising alfuzosin and a release-retarding matrix comprising about 40 to about 80% (by weight) hydroxypropyl methyl cellulose (HPMC) with a maximum apparent viscosity of about 5600 cP, wherein the dissolution profile of the compositions are substantially identical to the dissolution profile of the reference dosage form of NDA #021287 are also disclosed. Methods of making and using the alfuzosin compositions are also disclosed.
1 . An alfuzosin composition comprising
alfuzosin; and
a release-retarding matrix comprising about 40 to about 80% (by weight, based on the total weight of the alfuzosin composition) hydroxypropyl methyl cellulose (HPMC) 2208 with a maximum apparent viscosity of about 5600 cP.
2 . The alfuzosin composition of claim 1 , wherein the release-retarding matrix comprises about 40 to about 70% HPMC 2208 with an apparent viscosity of about 3000 to about 5600 cP.
3 . The alfuzosin composition of claim 2 , wherein the release-retarding matrix comprises about 40% HPMC 2208 with an apparent viscosity of about 3000 to about 5600 cP.
4 . The alfuzosin composition of claim 2 , wherein the release-retarding matrix further comprises about 10 to about 40% HPMC 2208 with an apparent viscosity of about 80 to about 120 cP.
5 . The alfuzosin composition of claim 1 , wherein the composition comprises about 10 mg alfuzosin and after a single administration of the composition to a population of at least 12 individuals,
a geometric mean of logarithmic transformed AUC 0-t for alfuzosin is within about 70% to about 143% of about 213 hr*ng/ml under fed conditions or of about 136 hr*ng/ml under fasting conditions;
a geometric mean of logarithmic transformed AUC 0-∞ for alfuzosin is within about 70% to about 143% of about 228 hr*ng/ml under fed conditions or of about 149 hr*ng/ml under fasting conditions; and
a geometric mean of logarithmic transformed C max for alfuzosin is within about 70% to about 143% of about 15.8 ng/ml under fed conditions or of about 7.9 ng/ml under fasting conditions.
6 . The alfuzosin composition of claim 1 , wherein the composition comprises about 10 mg alfuzosin and after a single administration of the composition to a population of at least 12 individuals,
a geometric mean of logarithmic transformed AUC 0-t for alfuzosin is about 99 to about 512 hr*ng/ml under fed conditions or about 58 to about 379 hr*ng/ml under fasting conditions;
a geometric mean of logarithmic transformed AUC 0-∞ for alfuzosin is about 106 to about 554 hr*ng/ml under fed conditions or about 68 to about 438 hr*ng/ml under fasting conditions; and
a geometric mean of logarithmic transformed C max for alfuzosin is about 7.1 to about 33.2 ng/ml under fed conditions or about 3.7 to about 18.0 ng/ml under fasting conditions.
7 .- 9 . (canceled)
10 . The alfuzosin composition of claim 1 , wherein the composition further comprises up to about 30% ethyl cellulose with an ethoxyl substitution greater than about 49.5%.
11 . The alfuzosin composition of claim 1 , wherein the composition is a compressed tablet.
12 . The alfuzosin composition of claim 1 , wherein the composition further comprises microcrystalline cellulose, magnesium stearate, colloidal silicon dioxide, and optionally up to about 30% ethyl cellulose with an ethoxyl substitution greater than about 49.5%.
13 .- 21 . (canceled)
22 . A sustained release dosage form consisting of the alfuzosin composition of claim 1 compressed into a tablet, wherein the alfuzosin is about 10 mg alfuzosin HCl.
23 .- 26 . (canceled)
27 . An alfuzosin composition comprising
alfuzosin and
a release-retarding matrix comprising about 40 to about 80% (by weight, based on the total weight of the alfuzosin composition) hydroxypropyl methyl cellulose (HPMC) 2208 with a maximum apparent viscosity of about 5600 cP,
wherein the alfuzosin composition has a dissolution profile determined according to USP 28 <711> test apparatus 2 (paddle) in 500 mL 0.01 M HCl with a 100 rpm paddle speed at 37° C., wherein
about 10 to about 17% of the alfuzosin is dissolved in 1 hour;
about 20% to about 40% of the alfuzosin is dissolved in 3 hours;
about 45% to about 70% of the alfuzosin is dissolved in 8 hours;
and no less than about 80% of the alfuzosin is dissolved in 24 hours is.
28 . The alfuzosin composition of claim 27 , wherein the release-retarding matrix comprises about 40 to about 70% HPMC 2208 with an apparent viscosity of about 3000 to about 5600 cP.
29 . The alfuzosin composition of claim 28 , wherein the release-retarding matrix comprises about 40% HPMC 2208 with an apparent viscosity of about 3000 to about 5600 cP.
30 . The alfuzosin composition of claim 28 , wherein the release-retarding matrix further comprises about 10 to about 40% HPMC 2208 with an apparent viscosity of about 80 to about 120 cP.
31 . The alfuzosin composition of claim 27 , wherein the composition further comprises up to 30% ethyl cellulose with an ethoxyl substitution greater than about 49.5%.
32 . (canceled)
33 . The composition of claim 27 , wherein the composition further comprises microcrystalline cellulose, magnesium stearate, colloidal silicon dioxide, and optionally up to about 30% ethyl cellulose with an ethoxyl substitution greater than about 49.5%.
34 .- 44 . (canceled)
45 . A method of treatment, comprising
administering the composition of claim 1 to an individual in need of alfuzosin therapy.
46 .- 76 . (canceled)
77 . The method of claim 45 , wherein the individual has benign prostatic hyperplasia
78 . A method of treatment, comprising
administering the composition of claim 27 to an individual in need of alfuzosin therapy.
79 . The method of claim 78 , wherein the individual has benign prostatic hyperplasia.