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 treatment of nausea and vomiting in a patient in need thereof comprising administering to the patient a semi-solid pharmaceutical composition, wherein the semi-solid pharmaceutical composition comprises a polyorthoester, 10-50 weight percent polyethylene glycol monomethyl ether having a molecular weight in a range of 200 to 4,000, and 1-5 weight percent granisetron, the polyorthoester comprising subunits selected from:
where
x is an integer from 1-4,
the total amount of p is an integer from 1-20,
s is an integer from 1-4,
the mole percentage of α-hydroxyacid containing subunits in the polyorthoester is from about 0.1 to about 25 mole percent, and the polyorthoester has a molecular weight in a range of 1000 to 10,000.
2. The method of claim 1 , wherein the polyethylene glycol monomethyl ether has a molecular weight of about 550.
3. The method of claim 1 , wherein the semi-solid pharmaceutical composition comprises from 2-3 weight percent granisetron.
4. The method of claim 1 , wherein the semi-solid pharmaceutical composition comprises 78.4 weight percent polyorthoester, 19.6 weight percent polyethylene glycol monomethyl ether and about 2 weight percent granisetron.
5. The method of claim 1 , wherein the polyorthoester has a molecular weight of about 6,500.
6. The method of claim 1 , wherein the semi-solid pharmaceutical composition is stable upon irradiation.
7. The method of claim 1 , wherein the semi-solid pharmaceutical composition is stable upon sterilization.
8. The method of claim 1 , wherein the granisetron is in the form of a solid having a particle size of less than 100 microns.
9. The method of claim 1 , wherein the semi-solid pharmaceutical composition is capable of being dispensed from a 16-25 gauge needle.
10. The method of claim 1 , wherein the semi-solid pharmaceutical composition is effective to release the granisetron in a sustained and controlled manner after administration.
11. The method of claim 1 , wherein the nausea and vomiting is associated with chemotherapy.
12. The method of claim 1 , wherein the nausea and vomiting is acute or delayed.
13. The method of claim 1 , wherein the semi-solid pharmaceutical composition is administered to the patient in combination with another antiemetic.
14. The method of claim 12 , wherein the semi-solid pharmaceutical composition is administered to the patient in combination with another antiemetic.
15. The method of claim 1 , wherein the administering is by injection.
16. The method of claim 1 , wherein the administering is by subcutaneous injection.
17. The method of claim 16 , wherein the administering is by a syringe with a 16 to 25 gauge needle.