MULTIPARTICULATE S-ADENOSYLMETHIONINE COMPOSITIONS AND RELATED METHODS
Multiparticulate compositions having S-adenosylmethionine an active ingredient are disclosed. The multiparticulates have spheroidal core comprising S-adenosylmethionine, 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, each independently dispersible particulate comprising:
a spheroidal core comprising about 70%-90% w/w S-adenosylmethionine, about 15%-25% 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 enteric coat is selected from methacrylic acid co-polymer, cellulose acetate phthalate, polyvinyl acetate phthalate, or a combination thereof.
3 . 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.
4 . The composition of claim 3 , wherein the polymeric material is ethyl cellulose and the pore former material is sodium alginate.
5 . The composition of claim 1 , further comprising a S-adenosylmethionine permeation enhancer adapted to assist S-adenosylmethionine in permeating biological tissue.
6 . The composition of claim 5 , wherein the S-adenosylmethionine permeation enhancer is a p-glycoprotein efflux pump inhibitor.
7 . The composition of claim 6 , wherein the p-glycoprotein efflux pump inhibitor is polysorbate 80.
8 . The composition of claim 1 , wherein the core further comprises a pellet and wherein the S-adenosylmethionine is located on an outer surface of the pellet.
9 . The composition of claim 8 , wherein the pellet is a non-pareil or microcrystalline cellulose pellet.
10 . The composition of claim 1 , wherein the multiparticulate composition is present in a pharmaceutically acceptable dosage form.
11 . A method of treating a physiological condition in a patient, the method comprising administering the composition of claim 1 to the patient.
12 . The method of claim 11 , wherein the physiological condition is selected from depression, fibromyalgia, osteoarthritis, headache, liver malfunction, or a combination thereof.
13 . The method of claim 11 , wherein administering the composition of claim 1 to the patient comprises administering a capsule having the independently dispersible particulates therein.
14 . The method of claim 11 , wherein administering the composition of claim 1 to the patient comprises combining the composition of claim 1 with an acidic food vehicle.
15 . The method of claim 11 , 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.
16 . A method of making a controlled-release multiparticulate composition of S-adenosylmethionine, the method comprising:
producing a spheroidal core comprising about 70%-90% w/w S-adenosylmethionine, about 15%-25% 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.
17 . The method of claim 16 , wherein the spheroidal core is produced by extrusion and spheronization.
18 . The method of claim 16 , wherein the spheroidal core is produced by blending the S-adenosylmethionine, 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.
19 . The method of claim 18 , wherein the spheronized pieces are dried at a temperature of about 50° C.-60° C.
20 . The method of claim 16 , wherein the spheroidal core is produced by coating a non-pareil or microcrystalline cellulose pellet with the S-adenosylmethionine, microcrystalline cellulose, and hydroxypropyl methylcellulose.