Transdermal dosage form for low-melting point active agent

1. A hydrophobic patch for transdermal administration of a hydrophobic drug, comprising:

a hydrophobic reservoir having a first surface and a second surface;

a backing layer overlying said first surface, said backing layer being impermeable to said hydrophobic drug; and

optionally a release sheet overlying said second surface;

said hydrophobic reservoir comprising a hydrophobic matrix and said hydrophobic drug, said hydrophobic drug being homogeneously dispersed through said hydrophobic matrix,

said hydrophobic matrix comprising:

from about 6% to about 30% by weight of said reservoir of hydrophobic colloidal silica dispersed through said hydrophobic matrix; and

a mixture of mineral oil and polyisobutylene in a weight ratio of said mineral oil to said polyisobutylene of between about 0.05:1 and about 1:1;

wherein said hydrophobic colloidal silica adsorbs at least a portion of said hydrophobic drug.

2. The hydrophobic patch of claim 1 , wherein said weight ratio of said mineral oil to said polyisobutylene is between about 0.087:1 and about 0.60:1.

3. The hydrophobic patch of claim 1 , wherein said weight ratio of said mineral oil to said polyisobutylene is between about 0.25:1 and about 0.60:1.

4. The hydrophobic patch of claim 1 , wherein said weight ratio of said mineral oil to said polyisobutylene is between about 0.30:1 and about 0.50:1.

5. The hydrophobic patch of claim 1 , further comprising a release-controlling adhesive layer in contact with said second surface,

with the proviso that if said release sheet is present, said release-controlling adhesive layer is between said hydrophobic reservoir and said release sheet.

6. The hydrophobic patch of claim 5 , wherein said release-controlling adhesive layer comprises:

from about 0.5% to about 5% by weight of said release-controlling adhesive layer of hydrophobic colloidal silica; and

a mixture of mineral oil and polyisobutylene in a weight ratio of said mineral oil to said polyisobutylene of between about 0.05:1 and about 0.50:1.

7. The hydrophobic patch of claim 6 , wherein said hydrophobic matrix in said hydrophobic reservoir comprises from about 8% to about 20% by weight of hydrophobic colloidal silica; and

said release-controlling adhesive layer comprises from about 0.5% to about 4% by weight of hydrophobic colloidal silica.

8. The hydrophobic patch of claim 1 , wherein said hydrophobic drug is a hydrophobic drug which is able to diffuse through said hydrophobic matrix.

9. The hydrophobic patch of claim 1 , wherein said hydrophobic drug has a melting point of between 20° C. and 150° C.

10. The hydrophobic patch of claim 9 , wherein said hydrophobic drug is methylphenidate, ibuprofen, clonidine, or scopalamine.

11. The hydrophobic patch of claim 9 , wherein said hydrophobic drug is methylphenidate.

12. The hydrophobic patch of claim 1 , wherein said hydrophobic colloidal silica has a mean particle size of between about 30 nm and about 150 nm.

13. The hydrophobic patch of claim 1 , wherein said hydrophobic colloidal silica is colloidal silica which has been treated with a silane of formula I:

R (4-n) SiX n   I

where R is a C1 to C20 alkyl or aromatic group, X is a hydrolysable group, and n is 1, 2, or 3.

14. The hydrophobic patch of claim 13 , wherein X is —OH, —O 2 CR 1 , —Cl, —Br, —I, —OR 1 , —COR 1 , —NHR 1 , or —NR 1 2 , where R 1 is a C1 to C20 alkyl group.

15. The hydrophobic patch of claim 1 , wherein the hydrophobic reservoir is a skin-contacting adhesive layer.

16. A hydrophobic patch for transdermal administration of a hydrophobic drug, wherein said hydrophobic drug is an oil or a drug having a melting point between about 20° C. and about 150° C., comprising:

a hydrophobic reservoir comprising said hydrophobic drug, said reservoir having a first surface and a second surface;

a backing layer overlying said first surface, said backing layer being impermeable to said hydrophobic drug; and optionally

a release sheet overlying said second surface;

said hydrophobic reservoir comprising said hydrophobic drug and a hydrophobic matrix, said hydrophobic matrix comprising:

a mixture of mineral oil and polyisobutylene in a weight ratio of said mineral oil to said polyisobutylene of between about 0.05:1 and about 0.50:1; and

an excipient or filler in an amount which is effective to adsorb said hydrophobic drug, thereby preventing said hydrophobic drug from forming a liquid or oily layer at the interface between said hydrophobic reservoir and said release sheet or said backing layer.

17. The hydrophobic patch of claim 16 , wherein said hydrophobic drug and said excipient or filler are present in a weight ratio of between about 2:1 and about 0.9:1.

18. The hydrophobic patch of claim 16 , wherein said excipient or filler is a hydrophobic filler.

19. The hydrophobic patch of claim 18 , wherein said hydrophobic filler is hydrophobic colloidal silica.

20. The hydrophobic patch of claim 16 , wherein said excipient or filler comprises at least one material selected from the group consisting of:

hydrophobic colloidal silica in an amount of about 8% to about 30%;

a combination of hydrophobic colloidal silica in an amount of about 1% to about 3% and titania in an amount of about 2%;

neusilin (magnesium aluminometasilicate) in an amount of about 2% to about 5%;

a combination of neusilin (magnesium aluminometasilicate) in an amount of about 2% to about 5% and at least one of magnesium stearate in an amount of about 2% to about 5% and polyethoxylated castor oil in an amount of about 2% to about 5%, and a mixture thereof;

colloidal silica or dried colloidal silica in an amount of about 1% to about 10%;

a combination of colloidal silica in an amount of about 1% to about 3% and at least one of neusilin in an amount of about 2%, magnesium stearate in an amount of about 1% to about 3%, disodium hydrogen phosphate in an amount of about 2% to about 5%, and polyethoxylated castor oil in an amount of about 2% to about 5%;

disodium hydrogen phosphate in an amount of about 2% to about 5%;

anhydrous calcium phosphate dibasic in an amount of from 5% to about 10%;

a combination of anhydrous calcium phosphate dibasic in an amount of from 5% to about 10% and polyethoxylated castor oil in an amount of about 2% to about 5%;

polyethoxylated castor oil in an amount of about 2% to about 5%;

magnesium stearate in an amount of about 2% to about 5%;

clays in an amount of about 5% by weight;

up to 1% by weight of alpha-tocopherol; and

from about 5% to about 20% of a cationic copolymer comprising dimethylaminoethyl methacrylate, butyl methacrylate, and methyl methacrylate;

wherein all percentages are based on the weight of the hydrophobic reservoir.

21. A hydrophobic patch for transdermal administration of a hydrophobic drug, comprising:

a skin-contacting adhesive layer;

a drug reservoir layer comprising said hydrophobic drug, said drug reservoir layer having a first surface and a second surface, said first surface of said drug reservoir layer contacting said skin-contacting adhesive layer; and

a backing layer overlying said second surface of said drug reservoir layer, said backing layer being impermeable to said hydrophobic drug;

said skin-contacting adhesive layer comprising an adhesive matrix, said adhesive matrix comprising from about 0.5% to about 5% by weight of hydrophobic colloidal silica, and a mixture of polyisobutylene and mineral oil;

wherein said hydrophobic colloidal silica prevents formation of a drug layer at the interface between said skin-contacting adhesive layer and said backing layer.

22. The hydrophobic patch of claim 21 , wherein said drug reservoir layer comprises a hydrophobic matrix and said hydrophobic drug;

said hydrophobic matrix comprising:

from about 6% to about 30% by weight of said reservoir of hydrophobic colloidal silica dispersed through said hydrophobic matrix; and

a mixture of mineral oil and polyisobutylene.

23. The hydrophobic patch of claim 1 , wherein said hydrophobic colloidal silica has a specific surface area of between 90 m 2 /g and 130 m 2 /g.

24. The hydrophobic patch of claim 16 , wherein said hydrophobic colloidal silica has a specific surface area of between 90 m 2 /g and 130 m 2 /g.

25. The hydrophobic patch of claim 21 , wherein said hydrophobic colloidal silica has a specific surface area of between 90 m 2 /g and 130 m 2 /g.