Oral formulation of creatine derivatives and method of manufacturing same
Oral formulation of creatine derivative and in particular creatine esters and more particularly ethyl esters of creatine are described. The formulations comprise a phosphate such as dicalcium phosphate, a biodegradable polymer such as a polyvinyl pyrrolidine and a starch. The formulation may further comprise other excipients such as metal salt of a stearate, e.g. magnesium stearates. The formulation is produced as flowable particles with a sieve size of about 20 to 60 which particles are coated with a shellac to mask taste, avoid moisture uptake, and extend shelf life.
1 . An oral formulation, comprising:
a creatine derivative present in a therapeutically effective amount;
a phosphate; and
a biodegradable polymer.
2 . The oral formulation of claim 1 , further comprising:
a starch.
3 . The oral formulation of claim 1 , further comprising:
a metal salt of a stearate.
4 . The oral formulation of claim 1 , wherein the creatine derivative is an ester.
5 . The oral formulation of claim 4 , wherein the ester group is —COOR where R is a lower alkyl.
6 . The oral formulation of claim 5 , wherein R is methyl, ethyl, butyl, isobutyl, or tertiary butyl.
7 . A controlled release oral dosage formulation, comprising:
a therapeutically effective amount of a creatine derivative; and
an excipient material; wherein the formulation is characterized by releasing the creatine derivative in a manner so as to increase a period of time over which a therapeutic level of creatine derivative is maintained as compared to a quick release formulation.
8 . The formulation of claim 7 , wherein the releasing is in a manner which maintains the therapeutic level of creatine in blood for a period of time which is 10% or more longer as compared to a quick release formulation.
9 . The formulation of claim 7 , wherein the releasing is in a manner which maintains the therapeutic level of creatine in blood for a period of time which is 50% or more longer as compared to a quick release formulation.
10 . The formulation of claim 7 , wherein the releasing is in a manner which maintains the therapeutic level of creatine in blood for a period of time which is 100% or more longer as compared to a quick release formulation.
11 . The formulation of claim 7 , wherein the releasing is in a manner which maintains the therapeutic level of creatine in blood for a period of time which is 200% or more longer as compared to a quick release formulation.
12 . The formulation of claim 7 , wherein the releasing is sufficiently slow that a maximum level of creatine in blood obtained is less as compared to a maximum level obtained with a quick release formulation.
13 . The formulation of claim 7 , wherein the releasing is sufficiently slow that a maximum level of creatine in blood obtained is 50% or more, less as compared to a maximum level obtained with a quick release formulation.
14 . The formulation of claim 7 , wherein the releasing of creatine derivative is at a rate of about 25% or less per hour after an initial release rate within 30 minutes following administration as compared to a quick release formulation.
15 . The formulation of claim 7 , wherein the releasing of creatine derivative is at a rate of about 50% or less per hour after an initial release rate within 30 minutes following administration as compared to a quick release formulation.
16 . A method of treating a human patient, comprising:
administering to a human patient a controlled release formulation of creatine derivative which formulation is characterized by maintaining a therapeutic level of creatine in the patient's circulatory system over a period of time greater than that obtained with a quick release formulation; and
repeating the administering on three or more consecutive days thereby maintaining a therapeutic level of creatine in the patient's circulatory system over a therapeutically effective period of time on three or more consecutive days.
17 . The method of claim 16 , wherein the therapeutic level is maintained over a period of time which is 10% or more than that obtained with a quick release formulation and further wherein the repeating is over thirty or more consecutive days.
18 . The method of claim 16 , wherein the therapeutic level is maintained over a period of time which is 100% or more than that obtained with a quick release formulation and further wherein the repeating is over thirty or more consecutive days.
19 . The method of claim 18 , wherein the therapeutic level is a level sufficient to obtain measurable increase in muscle endurance in a human patient.
20 . The method of claim 18 , wherein the therapeutic level is a level sufficient to enhance muscle performance.
21 . An oral formulation, comprising:
a creatine ethyl ester;
a phosphate a biodegradable polymer;
a starch; and
a metal salt of a stearate.
22 . The formulation of claim 21 , wherein the phosphate is dicalcium phosphate.
23 . The formulation of claim 21 , wherein the biodegradable polymer is polyvinyl pyrrolidine.
24 . The formulation of claim 21 , wherein the stearate is magnesium stearates.
25 . The formulation of claim 21 , wherein the creatine ethyl ester is present in the formulation in an amount in a range of about 83%+10% by weight based of the total weight of the formulation.
26 . The formulation of claim 22 , wherein the dicalcium phosphate is present in an amount in a range of about 9% to about 11% by weight based on the total weight of the formulation.
27 . The formulation of claim 23 , wherein the polyvinyl pyrrolidone is present in an amount in a range of about 2% to about 4% by weight based on the total weight of the formulation.
28 . The formulation of claim 24 , wherein the starch is present in an amount in a range of about 2% to about 4% by weight based on the total weight of the formulation.
29 . The formulation of claim 25 , wherein the magnesium stearate is present in an amount in a range of about 2% to about 4% by weight based on the total weight of the formulation.
30 . The formulation of claim 21 , in a form chosen from a tablet, a capsule, and a caplet.
31 . The formulation of claim 21 , comprised of particles where 60% to 40% by weight of the particles have a sieve size of about 20 and 20% to 40% by weight of the particles have a sieve size of about 40.
32 . The formulation of claim 31 , wherein the formulation of particles is flowable.
33 . The formulation of claim 31 , wherein 10% or less of the particles have a sieve size of 80 or more.
34 . The formulation of claim 33 , wherein 10% or less of the particles have a sieve size of 18 or less.
35 . The formulation of claim 21 , comprised of particles wherein 50% or the particle±5% have a sieve size of 20 and 20% of the particles±5% have a sieve size of 40 and 10% of the particles±5% have a sieve size of 60.
36 . A method of treating muscle tissue of a human patient, comprising:
orally administering to a human patient a controlled release formulation of creatine derivative which formulation is comprised of:
a creatine derivative present in a therapeutically effective amount; and
a biodegradable polymer.