Enteric coated multiparticulate composition with proteinaceous coating for improved storage stability
A storage stable L-menthol composition includes a tablet, caplet, capsule, or sachet dosage form. The dosage form has (a) a plurality of individual cores containing an L-menthol source and at least one pharmaceutical excipient and (b) a proteinaceous coating of a continuous film of proteinaceous material over the individual cores forming a plurality of proteinaceous coated individual cores. The film is effective to substantially prevent L-menthol in the L-menthol source from leaving the individual cores when stored at a temperature of 40 degrees C. and 75% relative humidity for at least 1 day. The dosage form contains an effective amount of the L-menthol source for treating a gastrointestinal disorder.
1. A storage stable L-menthol composition comprising:
a tablet, caplet, capsule, or sachet dosage form comprising:
(a) a plurality of individual cores containing an L-menthol source and at least one pharmaceutical excipient; and
(b) a proteinaceous coating of a continuous film of proteinaceous material over the individual cores forming a plurality of proteinaceous coated individual cores, the film being effective to substantially prevent L-menthol in the L-menthol source from leaving the individual cores when stored at a temperature of 40 degrees C. and 75% relative humidity for at least 1 day;
wherein the dosage form contains an effective amount of the L-menthol source for treating a gastrointestinal disorder;
wherein the dosage form includes an enteric coating over the proteinaceous coated individual cores and the proteinaceous coating is 3.5% w/w to 35% w/w of the individual enteric coated cores.
2. The storage stable L-menthol composition of claim 1 , wherein the film is effective to substantially prevent L-menthol in the L-menthol source from leaving the cores when the proteinaceous coated individual cores are stored at 40 degrees C. and 75% relative for at least up to 30 days.
3. The storage stable L-menthol composition of claim 1 , wherein the L-menthol in the L-menthol source is in crystalline form.
4. The storage stable L-menthol composition of claim 1 , wherein the L-menthol in the L-menthol source is in polycrystalline powder form.
5. The storage stable L-menthol composition of claim 1 , wherein the L-menthol in the L-menthol source is in an essential oil.
6. The storage stable L-menthol composition of claim 1 , wherein the L-menthol source is peppermint oil.
7. The storage stable L-menthol composition of claim 1 , wherein the proteinaceous material includes gelatin.
8. The storage stable L-menthol composition of claim 1 , wherein the proteinaceous material includes acid bone gelatin.
9. The storage stable L-menthol composition of claim 1 , wherein the dosage form also has an enteric coating over the proteinaceous coated individual cores.
10. The storage stable L-menthol composition of claim 9 , wherein the enteric coating comprises a methacrylic acid based material.
11. The storage stable L-menthol composition of claim 1 , wherein the at least one pharmaceutical excipient includes both of methylcellulose and microcrystalline cellulose.
12. The storage stable L-menthol composition of claim 1 , wherein:
the L-menthol in the L-menthol source is in polycrystalline powder form;
the at least one pharmaceutical excipient includes both of methylcellulose and microcrystalline cellulose; and
the proteinaceous material includes acid bone gelatin.
13. The storage stable L-menthol composition of claim 1 , wherein:
the L-menthol source is peppermint oil;
the at least one pharmaceutical excipient includes both of methylcellulose and microcrystalline cellulose; and
the proteinaceous material includes acid bone gelatin.
14. The storage stable L-menthol composition of claim 1 , wherein proteinaceous coated individual cores are spheroidal and have a diameter of 0.1 mm to 3 mm.
15. The storage stable L-menthol composition of claim 1 , wherein the effective amount is 80 to 100 mg of the L-menthol source.
16. A method of improving the storage stability of the L-menthol dosage form of claim 1 , the method comprising preparing the composition of claim 1 by:
forming a solid core by combining an L-menthol source and at least one pharmaceutical excipient;
spraying a liquid proteinaceous material over the solid core to form a film of a proteinaceous material over the solid core; and
drying the film of proteinaceous material over the solid core to form a proteinaceous material coated core.
17. The method of claim 16 , wherein the dried film is effective to substantially prevent L-menthol in the L-menthol source from leaving the core when the proteinaceous material coated core is stored at 40 degrees C. and 75% relative humidity for between 1 day to 30 days.
18. The method of claim 16 , further comprising loading a plurality of proteinaceous material coated cores into a tablet, caplet, capsule, or sachet dosage form.
19. The method of claim 18 , wherein the tablet, caplet, capsule, or sachet dosage form includes a plurality of the proteinaceous material coated cores, the proteinaceous material coated cores are spheroidal, and the proteinaceous material coated cores have a diameter of 0.1 mm to 3 mm.
20. The method of claim 16 , wherein the L-menthol source is L-menthol crystals and the method further comprises, prior to forming the solid core, micronizing the L-menthol crystals by jet milling.
21. The method of claim 16 , wherein the L-menthol source is L-menthol in polycrystalline powder form.
22. The method of claim 16 , wherein the L-menthol source is L-menthol in an essential oil.
23. The method of claim 16 , wherein the L-menthol source is peppermint oil.
24. The method of claim 16 , wherein the liquid proteinaceous material includes gelatin and water.
25. The method of claim 16 , wherein the liquid proteinaceous material is a solution containing at least about 35% gelatin.
26. The method of claim 16 , wherein the liquid proteinaceous material is a solution containing at least about 50% gelatin.
27. The method of claim 16 , wherein the liquid proteinaceous material includes acid bone gelatin.
28. The method of claim 16 , further comprising a step of applying an enteric coating over the proteinaceous material coated core.
29. The method of claim 28 , wherein the enteric coating includes a methacrylic acid based material.
30. The method of claim 16 , wherein:
the L-menthol source is L-menthol in polycrystalline powder form;
the at least one pharmaceutical excipient includes both of methylcellulose and microcrystalline cellulose; and
the liquid proteinaceous material is a solution containing at least about 35% acid bone gelatin.
31. The method of claim 16 , wherein:
the L-menthol source is peppermint oil;
the at least one pharmaceutical excipient includes both of methylcellulose and microcrystalline cellulose; and
the liquid proteinaceous material is a solution containing at least about 35% acid bone gelatin.
32. The method of claim 16 , wherein the at least one pharmaceutical excipient includes both of methylcellulose and microcrystalline cellulose.