L-menthol dosage forms having a proteinaceous coating for enhanced storage stability
A storage stable L-menthol composition including a tablet, caplet, capsule, or sachet dosage form has therein a core containing crystalline L-menthol and at least one pharmaceutical excipient. A proteinaceous coating of a continuous film of proteinaceous material is over the core. The film is effective to substantially prevent the crystalline L-menthol from volatilizing and leaving the core when stored at a temperature of 40 degrees C. and 75% relative humidity from between 1 day to 30 days. The dosage form contains an effective amount of the crystalline L-menthol for treating a gastrointestinal disorder.
1. A storage stable L-menthol composition comprising a multiparticulate dosage form having:
a plurality of individual cores containing crystalline L-menthol and at least one pharmaceutical excipient; and
a proteinaceous coating of a continuous film of proteinaceous material over the cores forming a plurality of proteinaceous coated individual cores, the film being effective to substantially prevent the crystalline L-menthol from volatilizing and leaving the proteinaceous coated individual cores when stored at a temperature of 40 degrees C. and 75% relative humidity from between 1 day to 30 days;
wherein the dosage form contains an effective amount of the crystalline L-menthol for treating a gastrointestinal disorder;
wherein an enteric coating over the proteinaceous coated individual cores prevents the L-menthol from releasing into the stomach and allows the L-menthol to release into the intestines; and
wherein the proteinaceous coating is 3.5% to 35% w/w of the individual enteric coated cores.
2. The storage stable L-menthol composition of claim 1 , wherein the crystalline L-menthol is in the form of a polycrystalline powder.
3. The storage stable L-menthol composition of claim 1 , wherein the proteinaceous material includes gelatin.
4. The storage stable L-menthol composition of claim 1 , wherein the proteinaceous material includes acid bone gelatin.
5. The storage stable L-menthol composition of claim 1 , wherein the enteric coating comprises a methacrylic acid based material.
6. The storage stable L-menthol composition of claim 1 , wherein the at least one pharmaceutical excipient includes each of methylcellulose and microcrystalline cellulose.
7. The storage stable L-menthol composition of claim 1 , wherein:
the crystalline L-menthol is in the form of a polycrystalline powder;
the at least one pharmaceutical excipient includes each of methylcellulose and microcrystalline cellulose; and
the proteinaceous material includes acid bone gelatin.
8. The storage stable L-menthol composition of claim 1 , wherein:
the crystalline L-menthol is in the form of a polycrystalline powder;
the at least one pharmaceutical excipient includes each of methylcellulose and microcrystalline cellulose;
the proteinaceous material includes acid bone gelatin; and
the enteric coating is methacrylic acid based.
9. The storage stable L-menthol composition of claim 1 , wherein the enteric coated cores are spheroidal and have a diameter of 0.1 mm to 3 mm.
10. The storage stable L-menthol composition of claim 1 , wherein the effective amount is 80 to 100 mg of crystalline L-menthol per dosage form.
11. A method of making a storage stable L-menthol composition, the method comprising preparing the composition of claim 1 by:
forming the plurality of individual cores by combining the crystalline L-menthol and at the least one pharmaceutical excipient;
applying the continuous film of the liquid proteinaceous material over the individual cores;
drying the liquid proteinaceous material over the individual cores to form the proteinaceous coated individual cores; and applying the enteric coating over the proteinaceous coated individual cores.
12. The method of claim 11 , further comprising preparing a tablet, caplet, capsule, or sachet dosage form having the individual enteric coated cores therein.
13. The method of claim 12 , wherein the individual enteric coated cores are spheroidal and have a diameter of 0.1 mm to 3 mm.
14. The method of claim 11 , further comprising, prior to forming the individual cores, micronizing L-menthol crystals by jet milling.
15. The method of claim 11 , wherein the crystalline L-menthol is in the form of a polycrystalline powder.
16. The method of claim 11 , wherein the liquid proteinaceous material includes gelatin and water.
17. The method of claim 11 , wherein the liquid proteinaceous material is a solution containing at least about 35% gelatin.
18. The method of claim 11 , wherein the liquid proteinaceous material is a solution containing at least about 50% gelatin.
19. The method of claim 11 , wherein the liquid proteinaceous material includes acid bone gelatin.
20. The method of claim 11 , wherein the enteric coating includes a methacrylic acid based material.
21. The method of claim 11 , wherein the at least one pharmaceutical excipient includes each of methylcellulose and microcrystalline cellulose.
22. The method of claim 11 , wherein the liquid proteinaceous material is applied by spraying it over the core.
23. The method of claim 11 , wherein:
the crystalline L-menthol is in the form of a polycrystalline powder;
the at least one pharmaceutical excipient includes each of methylcellulose and microcrystalline cellulose; and
the liquid proteinaceous material is a solution containing at least about 35% acid bone gelatin.
24. A method of treating a gastrointestinal disorder, the method comprising:
administering to a patient in need thereof an effective amount of the composition of claim 1 .
25. The method of claim 24 , wherein the crystalline L-menthol is in the form of a polycrystalline powder.
26. The method of claim 24 , wherein the proteinaceous material includes gelatin.
27. The method of claim 26 , wherein the proteinaceous material includes acid bone gelatin.
28. The method of claim 24 , wherein the enteric coating includes a methacrylic acid based material.
29. The method of claim 24 , wherein the at least one pharmaceutical excipient includes each of methylcellulose and microcrystalline cellulose.
30. The method of claim 24 , wherein:
the crystalline L-menthol is in the form of a polycrystalline powder;
the at least one pharmaceutical excipient includes each of methylcellulose and microcrystalline cellulose; and
the proteinaceous material includes acid bone gelatin.
31. The method of claim 24 , wherein:
the crystalline L-menthol is in the form of a polycrystalline powder;
the at least one pharmaceutical excipient includes each of methylcellulose and microcrystalline cellulose;
the proteinaceous material includes acid bone gelatin; and
the enteric coating is methacrylic acid based.
32. The method of claim 24 , wherein the enteric coated cores are spheroidal and have a diameter of 0.1 mm to 3 mm.
33. The method of claim 24 , wherein the effective amount is 80 to 100 mg of L-menthol per tablet, caplet, capsule, or sachet dosage form.