Compositions for drug administration
View Patent ↗The present invention provides compositions and methods and for increasing the bioavailability of therapeutic agents in a subject. The compositions include at least one alkyl glycoside and at least one therapeutic agent, wherein the alkylglycoside has an alkyl chain length from about 10 to about 16 carbon atoms.
1. A method of increasing bioavailability and absorption of an opioid compound in a subject comprising administering a composition, the composition comprising:
a) an opioid compound; and
b) an alkylsaccharide, wherein the alkylsaccharide is dodecyl-beta-D-maltoside, wherein the composition has a pH of 5.5 or greater, wherein the composition is formulated for, and administered intranasally, thereby increasing bioavailability and absorption of the opioid compound in the subject, wherein the opioid compound is nalmefene or a compound of structural Formula I, or a pharmaceutically acceptable salt thereof:
wherein:
is a single or double bond;
R 1 is selected from the group consisting of hydrogen;
R 2 is alkyl or null;
R 3 is selected from the group consisting of substituted or unsubstituted alkyl, cycloalkylalkyl and alkenylalkyl;
R 4 is hydrogen or hydroxyl or R 4 is taken together with R 7 to form a carbocycle;
R 5 is selected from the group consisting of hydrogen, substituted or unsubstituted alkyl and substituted or unsubstituted hydroxyalkyl;
R 6 is hydrogen or —OR 8 ;
R 7 is hydrogen or R 7 and R 6 are taken together to form a carbonyl group; and
R 8 is selected from the group consisting of hydrogen, substituted or unsubstituted alkyl and acyl.
2. The method of claim 1 , wherein the opioid compound is a compound selected from the group consisting of morphine, oripavine, naltrexone, naloxone, buprenorphine, nalbuphine, methyl naltrexone, and salt thereof.
3. The method of claim 1 , wherein the composition further comprises ethylenediaminetetraacetic acid (EDTA) or a salt thereof.
4. The method of claim 1 , wherein the composition has a pH of about 7.0.
5. The method of claim 1 , wherein the composition exhibits a Tmax of about 30, 20, 15, 10 minutes or less in the subject.
6. The method of claim 1 , wherein the bioavailability of the opioid compound is increased in the cerebral spinal fluid.
7. A method of providing rapid onset of pain relief in a subject comprising administering a composition, the composition comprising:
a) an opioid compound; and
b) an alkylsaccharide, wherein the alkylsaccharide is dodecyl-beta-D-maltoside, wherein the composition has a pH of 5.5 or greater, wherein the composition is formulated for, and administered intranasally, wherein the composition exhibits a Tmax of less than about 20 minutes, thereby providing rapid onset of pain relief in the subject, and wherein the opioid compound is nalmefene or a compound of structural Formula I, or a pharmaceutically acceptable salt thereof:
wherein:
is a single or double bond;
R 1 is selected from the group consisting of hydrogen;
R 2 is alkyl or null;
R 3 is selected from the group consisting of substituted or unsubstituted alkyl, cycloalkylalkyl and alkenylalkyl;
R 4 is hydrogen or hydroxyl or R 4 is taken together with R 7 to form a carbocycle;
R 5 is selected from the group consisting of hydrogen, substituted or unsubstituted alkyl and substituted or unsubstituted hydroxyalkyl;
R 6 is hydrogen or —OR 8 ;
R 7 is hydrogen or R 7 and R 6 are taken together to form a carbonyl group; and
R 8 is selected from the group consisting of hydrogen, substituted or unsubstituted alkyl and acyl.
8. The method of claim 7 , wherein the opioid compound is a compound selected from the group consisting of morphine, oripavine, naltrexone, naloxone, buprenorphine, nalbuphine, methyl naltrexone, and salt thereof.
9. The method of claim 7 , wherein the composition further comprises ethylenediaminetetraacetic acid (EDTA) or a salt thereof.
10. The method of claim 7 , wherein the composition has a pH of about 7.0.
11. The method of claim 7 , wherein the composition exhibits a Tmax of about 15, 10 minutes or less in the subject.
12. The method of claim 7 , wherein the bioavailability of the opioid compound is increased in the cerebral spinal fluid.
13. A composition comprising:
a) an opioid compound; and
b) an alkylsaccharide, wherein the alkylsaccharide is dodecyl-beta-D-maltoside, wherein the composition has a pH of 5.5 or greater, wherein the composition is formulated for intranasal delivery, and wherein the opioid compound is nalmefene or a compound of structural Formula I, or a pharmaceutically acceptable salt thereof:
wherein:
is a single or double bond;
R 1 is selected from the group consisting of hydrogen;
R 2 is alkyl or null;
R 3 is selected from the group consisting of substituted or unsubstituted alkyl, cycloalkylalkyl and alkenylalkyl;
R 4 is hydrogen or hydroxyl or R 4 is taken together with R 7 to form a carbocycle;
R 5 is selected from the group consisting of hydrogen, substituted or unsubstituted alkyl and substituted or unsubstituted hydroxyalkyl;
R 6 is hydrogen or —OR 8 ;
R 7 is hydrogen or R 7 and R 6 are taken together to form a carbonyl group; and
R 8 is selected from the group consisting of hydrogen, substituted or unsubstituted alkyl and acyl.
14. The composition of claim 13 , wherein the opioid compound is a compound selected from the group consisting of morphine, oripavine, naltrexone, naloxone, buprenorphine, nalbuphine, methyl naltrexone, and salt thereof.
15. The composition of claim 13 , wherein the alkylsaccharide concentration is about 0.05% to 2% by weight.
16. The composition of claim 13 , further comprising ethylenediaminetetraacetic acid (EDTA) or a salt thereof.
17. The composition of claim 13 , wherein the composition has a pH of about 7.0.
18. The composition of claim 13 , wherein the composition provides a Tmax for the opioid compound of about 30, 20, 10 minutes or less in a human.