MULTIPARTICULATE 5-HTP COMPOSITIONS AND RELATED METHODS
Enteric coated multiparticulate compositions that use 5-HTP as an active ingredient are disclosed. The multiparticulates have a spheroidal core comprising 5-HTP, microcrystalline cellulose, and hydroxypropyl methylcellulose; a sub-coat comprising hydroxypropyl methylcellulose 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 5-Hydroxytryptophan, 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 spheroidal core further comprises about 0.005% to 1.5% w/w melatonin.
3 . The composition of claim 2 , wherein the spheroidal core further comprises about 2.0% to 7.0% w/w of PEG8000 and about 3.0% to 40% w/w of citric acid.
4 . The composition of claim 1 , wherein the spheroidal core further comprises an outer coating having about 0.005% to 1.5% w/w melatonin.
5 . 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.
6 . 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.
7 . The composition of claim 6 , wherein the polymeric material is ethyl cellulose and the pore former material is sodium alginate.
8 . The composition of claim 1 , further comprising a 5-Hydroxytryptophan permeation enhancer adapted to assist 5-Hydroxytryptophan in permeating biological tissue.
9 . The composition of claim 8 , wherein the 5-Hydroxytryptophan permeation enhancer is a p-glycoprotein efflux pump inhibitor.
10 . The composition of claim 9 , wherein the p-glycoprotein efflux pump inhibitor is polysorbate 80.
11 . The composition of claim 1 , wherein the core further comprises a pellet and wherein the 5-Hydroxytryptophan is located on an outer surface of the pellet.
12 . The composition of claim 11 , wherein the pellet is a non-pareil or microcrystalline cellulose pellet.
13 . The composition of claim 1 , wherein the multiparticulate composition is present in a pharmaceutically acceptable dosage form.
14 . A method of treating a physiological condition in a patient, the method comprising administering the composition of claim 1 to the patient.
15 . The method of claim 14 , wherein the physiological condition is selected from serotonin deficiency, depression, weight loss, headaches, fibromyalgia, cerebellar ataxia, insomnia, or a combination thereof.
16 . The method of claim 14 , wherein administering the composition of claim 1 to the patient comprises administering a capsule having the independently dispersible particulates therein.
17 . The method of claim 14 , wherein administering the composition of claim 1 to the patient comprises combining the composition of claim 1 with a semi-solid acidic food.
18 . The method of claim 14 , wherein administering the composition of claim 1 to the patient comprises combining the composition of claim 1 with a semi-solid acidic food and delivering the composition and semi-solid acidic food to a patient through a feeding tube.
19 . A method of making a controlled-release multiparticulate composition of 5-Hydroxytryptophan, the method comprising:
producing a spheroidal core comprising about 70%-90% w/w 5-Hydroxytryptophan, 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.
20 . The method of claim 19 , wherein the spheroidal core is produced by extrusion and spheronization.
21 . The method of claim 19 , wherein the spheroidal core is produced by blending the 5-Hydroxytryptophan, 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.
22 . The method of claim 21 , wherein the spheronized pieces are dried at a temperature of about 50° C.-60° C.
23 . The method of claim 19 , wherein the spheroidal core is produced by coating a non-pareil or microcrystalline cellulose pellet with the 5-Hydroxytryptophan, microcrystalline cellulose, and hydroxypropyl methylcellulose.
24 . The method of claim 19 , wherein the spheroidal core further comprises about 0.005% to 1.5% w/w melatonin.
25 . The method of claim 24 , wherein the spheroidal core further comprises about 2.0% to 7.0% w/w of PEG8000 and about 3.0% to 40% w/w of citric acid.
26 . The method of claim 19 , wherein the spheroidal core is coated with an outer coating having about 0.005% to 1.5% w/w melatonin.