PROPRANOLOL FORMULATIONS
Controlled-release propranolol formulations comprise a core comprising a pharmaceutically acceptable propranolol salt and an inert core; and a coating disposed on the core, the coating comprising about 70:30 to about 85:15 of ethylcellulose:polyvinylpyrrolidone or about 60:40 to about 75:25 of ethylcellulose:hydroxypropylmethylcellulose.
1 . A composition comprising:
a core comprising a pharmaceutically acceptable propranolol salt disposed on a sugar sphere; and
a coating disposed on the core, the coating comprising about 70:30 to about 85:15 of ethylcellulose:polyvinylpyrrolidone.
2 . The composition of claim 1 , wherein the sugar sphere has a diameter of about 500 to about 710 micrometers.
3 . The composition of claim 1 , wherein the coating comprises 10 wt % to about 17 wt % of the total weight of the coated cores.
4 . The composition of claim 1 , wherein the coating comprises about 12 wt % to about 15 wt % of the total weight of the coated cores.
5 . The composition of claim 1 , wherein the coating comprises ethylcellulose having a viscosity of 5 to about 20 cps at 20° C. and polyvinylpyrrolidone having a viscosity of about 5.5 to 8.5 cps at 20° C.
6 . The composition of claim 1 , exhibiting a dissolution profile in a pH 6.8 medium such that:
less than 10 wt % of the propranolol is released at 1 hour;
44 wt % to 64 wt % of the propranolol is released at 6 hours; and
greater than 80 wt % of the propranolol is released at 15 hours.
7 . The composition of claim 1 , exhibiting a dissolution profile in 0.1 M HCl such that:
less than 10 wt % of the propranolol is released at 1 hour;
40 wt % to 60 wt % of the propranolol is released at 6 hours; and
greater than 80 wt % of the propranolol is released at 15 hours.
8 . The composition of claim 1 , wherein the coated core comprises no added organic acid.
9 . A dosage form comprising:
a core comprising a pharmaceutically acceptable propranolol salt disposed on a sugar sphere; and
a coating disposed on the core, the coating comprising polyvinylpyrrolidone and ethylcellulose;
wherein the dosage form comprises one type of controlled-release coated core; and
wherein the average C max of the dosage form is about 105 ng/mL to about 270 ng/mL and the average AUCO 0-∞ of the dosage form is about 2100 ng hr/mL to about 5400 ng hr/mL when measured under fasting conditions.
10 . The dosage form of claim 9 , wherein the coating comprises about 70:30 to about 85:15 of ethylcellulose:polyvinylpyrrolidone.
11 . The dosage form of claim 9 , wherein the coating comprises about 75:25 to about 80:20 of ethylcellulose:polyvinylpyrrolidone.
12 . The dosage form of claim 9 , wherein the ethylcellulose has a viscosity of 5 cps to about 20 cps at 20° C. and the polyvinylpyrrolidone has a viscosity of about 5.5 to 8.5 cps at 20° C.
13 . The dosage form of claim 9 , exhibiting a dissolution profile in a pH 6.8 medium such that:
less than 10 wt % of the propranolol is released at 1 hour;
44 wt % to 64 wt % of the propranolol is released at 6 hours; and
greater than 80 wt % of the propranolol is released at 15 hours.
14 . The dosage form of claim 9 , exhibiting a dissolution profile in 0.1 M HCl such that:
less than 10 wt % of the propranolol is released at 1 hour;
40 wt % to 60 wt % of the propranolol is released at 6 hours; and
greater than 80 wt % of the propranolol is released at 15 hours.
15 . The dosage form of claim 9 , wherein the coated core comprises no added organic acid.
16 . The dosage form of claim 9 , wherein the dosage form comprises a capsule.
17 . A method of treating a human, comprising administering a pharmaceutically effective amount of the dosage forms of claim 9 to a human in need of treatment for angina, cardiac arrhythmia, or hypertension.
18 . The method of claim 17 , wherein the coating comprises about 70:30 to about 85:15 of ethylcellulose:polyvinylpyrrolidone.
19 . The method of claim 17 , wherein the coated core comprises no added organic acid.
20 . The method of claim 17 , wherein the dosage form comprises a capsule.