Oral taxane compositions and methods
A pharmaceutical composition comprises a taxane (e.g., paclitaxel, docetaxel, cabazitaxel, larotaxel, ortataxel, and/or tesetaxel) in a mixture of first and second surfactants. The absorption of the taxane is increased from the pharmaceutical composition is greater than the sum of the absorption of docetaxel from either the first or the second surfactant. The increase in absorption is especially enhanced when the ratio of the first surfactant to the second surfactant in the pharmaceutical composition is between 60:40 and 85:15 by weight, and the total surfactant weight does not exceed 98% of the total weight. Polysorbate 80, polysorbate 20, and caprylocaproyl polyoxylglycerides serve as suitable first surfactants, and polysorbate 80 or polyethyoxylated castor oil serve as suitable second surfactants. The stability of the pharmaceutical composition may be enhanced by further including a stabilizer (e.g., citric acid and/or ascorbic acid).
1. A pharmaceutical composition comprising:
a taxane; and
a surfactant mixture consisting of a first surfactant comprising a polysorbate and a second surfactant comprising a polyoxyl hydrogenated castor oil, wherein the first surfactant and the second surfactant are provided in a weight ratio of from 60:40 to 85:15, and wherein the first surfactant and the second surfactant comprise at least 90% of the pharmaceutical composition by weight,
wherein the pharmaceutical composition does not include an oil and is formulated for oral administration, and
wherein the pharmaceutical composition enhances at least one of taxane solubility and absorption of the taxane in a synergistic manner.
2. A pharmaceutical composition comprising:
a taxane; and
a surfactant mixture consisting of a first surfactant comprising a first polysorbate and a second surfactant comprising a second polysorbate or a polyoxyol hydrogenated castor oil, wherein the ratio of the first surfactant to the second surfactant in the pharmaceutical composition is between 60:40 and 85:15 by weight, and wherein the first surfactant and the second surfactant comprise at least 90% of the pharmaceutical composition by weights;
wherein the first and second surfactants comprise no more than 98% of total weight of the pharmaceutical composition and enhance at least one of taxane solubility and absorption of the taxane in a synergistic manner, and wherein the pharmaceutical composition does not include an oil and is formulated for oral administration.
3. The pharmaceutical composition of claim 2 , wherein the taxane is selected from the group consisting of paclitaxel, docetaxel, cabazitaxel, larotaxel, ortataxel, and tesetaxel.
4. The pharmaceutical composition of claim 2 , wherein the first surfactant comprises polysorbate 80 or polysorbate 20.
5. The pharmaceutical composition of claim 4 , wherein the second surfactant is polyoxyl 35 hydrogenated castor oil.
6. The pharmaceutical composition of claim 2 , further comprising a stabilizer.
7. The pharmaceutical composition of claim 6 , wherein the stabilizer comprises at least one of citric acid and ascorbic acid.
8. The pharmaceutical composition of claim 1 or claim 2 , wherein the first surfactant, the second surfactant, and the weight ratio are selected to form micelles on dilution of the pharmaceutical composition by stomach or intestinal fluids.
9. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition forms a micellar solution following ingestion.
10. The pharmaceutical composition of claim 1 , wherein the first surfactant is polysorbate 80 and the second surfactant is polyoxyl 35 hydrogenated castor oil.
11. The pharmaceutical composition of claim 1 , further comprising a P-glycoprotein inhibitor.
12. The pharmaceutical composition of claim 11 , wherein the P-glycoprotein inhibitor is HM30181A.
13. A pharmaceutical composition comprising:
a taxane; and
a surfactant mixture consisting of a first surfactant comprising a first polysorbate and a second surfactant comprising a second polysorbate; and
a P-glycoprotein inhibitor,
wherein the first surfactant and the second surfactant are provided in an 80:20 ratio by weight, and wherein the first surfactant and the second surfactant comprise at least 90, of the pharmaceutical composition by weight,
wherein the pharmaceutical composition does not include an oil, and
wherein the pharmaceutical composition enhances at least one of taxane solubility and absorption of the taxane in a synergistic manner and is formulated for oral administration.
14. The pharmaceutical composition of claim 13 , wherein the pharmaceutical composition forms a micellar solution following ingestion.
15. The pharmaceutical composition of claim 13 , wherein the first surfactant is polysorbate 80 and the second surfactant is polysorbate 20.
16. The pharmaceutical composition of claim 11 , wherein the P-glycoprotein inhibitor is HM30181A.
17. The pharmaceutical composition of claim 1 , wherein the taxane is dissolved in the surfactant mixture, and wherein the taxane is present in a concentration of at least 30 mg/mL to 70 mg/mL in the pharmaceutical composition.
18. The pharmaceutical composition of claim 2 , wherein the taxane is dissolved in the surfactant mixture, and wherein the taxane is present in a concentration of at least 30 mg/mL to 70 mg/mL in the pharmaceutical composition.
19. The pharmaceutical composition of claim 13 , wherein the taxane is dissolved in the surfactant mixture, and wherein the taxane is present in a concentration of at least 30 mg/mL to 70 mg/mL in the pharmaceutical composition.