Methods of treating emesis utilizing semi-solid delivery pharmaceutical compositions comprising granisetron
View Patent ↗A semi-solid delivery vehicle contains a polyorthoester and an excipient, and a semi-solid pharmaceutical composition contains an active agent and the delivery vehicle. The pharmaceutical composition may be a topical, syringable, or injectable formulation; and is suitable for local delivery of the active agent. Methods of treatment are also disclosed.
1. A method for treating emesis in a patient in need thereof comprising administering to the patient a pharmaceutical composition comprising:
(A) a semi-solid delivery vehicle, comprising:
(i) a polyorthoester consisting of formula I
where:
R* is ethyl;
n is an integer of 5 to 1000; and
A is R 1 or R 3 where
R 1 is:
where:
p is an integer of 1 to 20;
R 5 is hydrogen; and
R 6 is:
where:
s is an integer of 0 to 10;
R 3 is:
where:
x is an integer of 0 to 30;
in which about 0.05-30 mol percent of the A units are of the formula R 1 ; and
(ii) polyethylene glycol monomethyl ether; and
(B) granisetron in an amount of 1-5 weight % of the composition.
2. The method of claim 1 , wherein the emesis is induced by a chemotherapeutic agent.
3. The method of claim 2 , wherein the administration is by injection.
4. The method of claim 3 , wherein the administration is by subcutaneous injection.
5. The method of claim 3 , wherein the administration is by a syringe with a 16-25 gauge needle.
6. The method of claim 1 , wherein the polyethylene glycol monomethyl ether has a molecular weight between 200 and 4000.
7. The method of claim 6 , comprising polyethylene glycol monomethyl ether 550.
8. The method of claim 6 , wherein the total concentration of the polyethylene glycol monomethyl ether is 5-60 weight % of the composition.
9. The method of claim 1 , wherein the polyorthoester is a reaction product of 3,9-di(ethylidene)-2,4,8,10-tetraoxaspiro[5.5]undecane (DETOSU), triethylene glycol (TEG) and triethylene glycol diglycolide (TEG-diGL).
10. The method of claim 1 , wherein the composition comprises 78.4 weight % polyorthoester, 19.6 weight % polyethylene glycol monomethyl ether and 2 weight % granisetron.
11. The method of claim 1 , wherein p is an integer of 1 to 7 in a portion of the units of formula I.
12. The method of claim 1 , wherein x is 2 in a portion of the units of formula I.
13. The method of claim 1 , wherein s is 2 in a portion of the units of formula I.
14. The method of claim 1 , wherein the total concentration of the polyethylene glycol monomethyl ether is 5% to 80% weight percent of the composition.
15. The method of claim 1 , wherein:
the polyorthoester is a reaction product of 3,9-di(ethylidene)-2,4,8,10-tetraoxaspiro[5.5]undecane (DETOSU), triethylene glycol (TEG) and triethylene glycol diglycolide (TEG-diGL); and
the polyethylene glycol monomethyl ether has a molecular weight between 200 and 4000.
16. The method of claim 1 , wherein about 0.1-25 mol percent of the A units are of the formula R 1 .