Methods of treating nausea utilizing semi-solid delivery vehicle compositions comprising granisetron
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 the prophylactic treatment of nausea and vomiting 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 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 to 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 to 5 weight % of the composition.
2. The method of claim 1 , wherein the nausea and vomiting is associated with chemotherapy.
3. The method of claim 1 , wherein the nausea and vomiting is acute or delayed.
4. The method of claim 1 , wherein the composition is administered to the patient in combination with another antiemetic.
5. The method of claim 3 , wherein the composition is administered to the patient in combination with another antiemetic.
6. The method of claim 1 , wherein the administering is by injection.
7. The method of claim 1 , wherein the administering is by subcutaneous injection.
8. The method of claim 7 , wherein the administering is by a syringe with a 16 to 25 gauge needle.
9. The method of claim 1 , wherein the polyethylene glycol monomethyl ether has a molecular weight between 200 and 4000.
10. The method of claim 9 , wherein the total concentration of the polyethylene glycol monomethyl ether is 5 to 60 weight % of the composition.
11. The method of claim 1 , wherein the polyethylene glycol monomethyl ether is polyethylene glycol monomethyl ether 550.
12. The method of claim 9 , wherein the polyethylene glycol monomethyl ether is polyethylene glycol monomethyl ether 550.
13. The method of claim 1 , wherein the composition comprises 78.4 weight % polyorthoester, 19.6 weight % polyethylene glycol monomethyl ether and 2 weight % granisetron.
14. The method of claim 1 , wherein p is an integer of 1 to 7 in a portion of the units of formula I.
15. The method of claim 1 , wherein x is 2 in a portion of the units of formula I.
16. The method of claim 1 , wherein s is 2 in a portion of the units of formula I.
17. The method of claim 1 , wherein the total concentration of the polyethylene glycol monomethyl ether is 5% to 80% weight percent of the composition.
18. The method of claim 1 , wherein about 0.1 to 25 mol percent of the A units are of the formula R 1 .