Multiparticulate L-carnitine compositions and related methods
Enteric coated multiparticulate compositions that use a L-carnitine compound an active ingredient are disclosed. The multiparticulates have spheroidal core comprising a L-carnitine, microcrystalline cellulose, and hydroxypropyl methylcellulose; a sub-coat comprising hydroxypropyl methyl cellulose on the spheroidal core; and an enteric coat on the sub-coated spheroidal core. The average diameter of the particulates is about 0.1-3 mm. Other aspects of the invention include methods of making and methods of using the multiparticulate compositions.
1. A composition comprising a plurality of independently dispersible particulates, the independently dispersible particulates comprising:
a spheroidal core comprising about 30%-90% w/w of an L-carnitine, about 15%-70% w/w microcrystalline cellulose, and about 0.5%-1.5% w/w hydroxypropyl methylcellulose;
a sub-coat on the spheroidal core, the subcoat comprising hydroxypropyl methyl cellulose present in an amount of about 2%-4% w/w of the independently dispersible particulates; and
an enteric coat on the sub-coated spheroidal core, the enteric coat being about 5%-15% w/w of the independently dispersible particulates;
wherein the average diameter of the independently dispersible particulates is about 0.1-3 mm.
2. The composition of claim 1 , wherein the L-carnitine is at least one of L-carnitine, acetyl-L-carnitine, propionyl-L-carnitine, or a combination thereof.
3. The composition of claim 1 , wherein the enteric coat is selected from methacrylic acid co-polymer, cellulose acetate phthalate, polyvinyl acetate phthalate, or a combination thereof.
4. The composition of claim 1 , wherein the enteric coat comprises a polymeric material that forms a film around the core and a pore former material that generates pores in the film under intestinal pH conditions.
5. The composition of claim 4 , wherein the polymeric material is ethyl cellulose and the pore former material is sodium alginate.
6. The composition of claim 1 , further comprising a L-carnitine permeation enhancer adapted to assist L-carnitine in permeating biological tissue.
7. The composition of claim 6 , wherein the carnitine permeation enhancer is a p-glycoprotein efflux pump inhibitor.
8. The composition of claim 7 , wherein the p-glycoprotein efflux pump inhibitor is polysorbate 80.
9. The composition of claim 1 , wherein the core further comprises a pellet and wherein the L-carnitine is located on an outer surface of the pellet.
10. The composition of claim 9 , wherein the pellet is a non-pareil or microcrystalline cellulose pellet.
11. The composition of claim 1 , wherein the multiparticulate composition is present in a pharmaceutically acceptable dosage form.
12. A method of treating a physiological condition in a patient, the method comprising administering the composition of claim 1 to the patient.
13. The method of claim 12 , wherein the physiological condition is selected from carnitine deficiency, age related decline in mitochondrial function, cardiovascular disease, myocardial infarction, heart failure, angina pectoris, intermittent claudication, end-stage renal failure, Alzheimer's disease, HIV/AIDS, decreased sperm motility or a combination thereof.
14. The method of claim 12 , wherein administering the composition of claim 1 to the patient comprises administering a capsule having the independently dispersible particulates therein.
15. The method of claim 12 , wherein administering the composition of claim 1 to the patient comprises combining the composition of claim 1 with an acidic food vehicle.
16. The method of claim 12 , wherein administering the composition of claim 1 to the patient comprises providing a blend of the composition and an acidic food vehicle to the patient through a feeding tube.
17. A method of making a controlled-release multiparticulate composition of carnitine, the method comprising:
producing a spheroidal core comprising about 30%-90% w/w of a L-carnitine, about 15%-70% w/w microcrystalline cellulose, and about 0.5%-1.5% w/w hydroxypropyl methylcellulose;
coating the spheroidal core with a sub-coat comprising hydroxypropropyl methyl cellulose, the sub-coat being about 2%-4% w/w of the particulates in the multiparticulate composition;
applying an enteric coat to the sub-coated spheroidal core, the enteric coat being about 5%-15% w/w of the particulates in the multiparticulate composition; and
wherein the average diameter of particulates in the multiparticulate composition is about 0.1-3 mm.
18. The method of claim 17 , wherein the spheroidal core is produced by extrusion and spheronization.
19. The method of claim 17 , wherein the spheroidal core is produced by blending the carnitine, microcrystalline cellulose, and hydroxypropyl methylcellulose with water to form a met mass, extruding the wet mass, cutting the extruded wet mass into pieces, spheronizing the pieces, and drying the spheronized pieces.
20. The method of claim 19 , wherein the spheronized pieces are dried at a temperature of about 50° C.-60° C.
21. The method of claim 17 , wherein the spheroidal core is produced by coating a non-pareil or microcrystalline cellulose pellet with the carnitine, microcrystalline cellulose, and hydroxypropyl methylcellulose.
22. The method of claim 17 , wherein the L-carnitine is at least one of L-carnitine, acetyl-L-carnitine, propionyl-L-carnitine, or a combination thereof.