Sustained release particle formulations
Particles for delivery of active ingredients formed from an active ingredient and a hydrophobic matrix, as well as methods for making such particles.
1. A sustained-release solid dosage form comprising particles, each particle comprising:
an active ingredient present in an amount from 20% to about 60% by weight of the particles;
a hydrophobic matrix present in an amount from about 30% to about 80% by weight of the particles; and
an optional release modifier, that when present is in an amount from about 0.5% to about 25% by weight of the particles,
wherein the particles are substantially spherical and have a mean particle size diameter of from about 50 μm to about 500 μm and particle size distribution within a 10% standard deviation from the mean particle size diameter, and wherein the particles release from 62% to 80% of the active ingredient in 6 hours as measured by the USP II dissolution test.
2. The solid dosage form of claim 1 , wherein the active ingredient is a hydrophilic active ingredient.
3. The solid dosage form of claim 1 , wherein the active ingredient is a hydrophobic active ingredient.
4. The solid dosage form of claim 1 , wherein the active ingredient is guaifenesin, metformin hydrochloride, ibuprofen, dextromethorphan HBr, pseudoephedrine HCl, carbinoxamine, clonidine, chlorpheniramine, hydrocodone, azithromycin, methylphenidate HCl, nystatin, ritonavir, prednisone, or a mixture thereof.
5. The solid dosage form of claim 1 , wherein the active ingredient is guaifenesin, dextromethorphan, or a mixture thereof.
6. The solid dosage form of claim 1 , wherein the active ingredient is ibuprofen.
7. The solid dosage form of claim 1 , wherein the active ingredient is present in an amount from about 30% to about 40% by weight of the particles.
8. The solid dosage form of claim 1 , wherein the release modifier is present in an amount from about 5% to about 20% by weight of the particles.
9. The solid dosage form of claim 1 , wherein the release modifier is selected from the group consisting of stearic acid, sodium stearate, magnesium stearate, glyceryl monostearate, polyoxyethylene glycol castor oil, oleic acid, sodium oleate, lauric acid, sodium laurate, myristic acid, sodium myristate, vegetable oils, coconut oil, mono-, di-, tri-glycerides, stearyl alcohol, sorbitan monolaurate, sorbitan monooleate, polyethylene glycol, and combinations thereof.
10. The solid dosage form of claim 1 , wherein the release modifier is selected from the group consisting of stearic acid, stearyl alcohol, glyceryl monostearate and combinations thereof.
11. The solid dosage form of claim 1 , wherein each particle further comprises a stabilizer, wherein the stabilizer is present in an amount from about 0.1% to about 5% by weight of the particles.
12. The solid dosage form of claim 11 , wherein the stabilizer is cellulose, ethyl cellulose, hydroxypropylmethyl cellulose, microcrystalline cellulose, cellulose acetate, cellulose phthalate, methyl cellulose, chitin, chitosan, pectin, polyacrylates, polymethacrylates, poly-vinyl acetate, ethyl vinyl acetate copolymer (EVA) resins, acetate phthalate, poly-anhydrides, polyvinylalcohols, silicone elastomers, poloxamers, or mixtures thereof.
13. The solid dosage form of claim 1 , wherein the hydrophobic matrix is present in an amount from about 50% to about 60% by weight of the particles.
14. The solid dosage form of claim 1 , wherein the hydrophobic matrix is present in an amount from about 60% to about 70% by weight of the particles.
15. The solid dosage form of claim 1 , wherein the hydrophobic matrix is a hydrophobic wax material, a lipid material, or a combination thereof.
16. The solid dosage form of claim 15 , wherein the hydrophobic wax matrix is selected from the group consisting of ceresine wax, beeswax, ozokerite, microcrystalline wax, candelilla wax, montan wax, carnauba wax, paraffin wax, cauassu wax, Japan wax, and Shellac wax.
17. The solid dosage form of claim 15 , wherein the lipid material is selected from the group consisting of glycerol fatty acid esters, hydrogenated fats, and ceramides.
18. The solid dosage form of claim 17 , wherein the glycerol fatty acid ester is a triacylglycerol selected from the group consisting of tripalmitin, tristearin, glyceryl trilaurate, and coconut oil.
19. The solid dosage form of claim 1 , wherein the particle size distribution is within a 5% standard deviation from the mean particle size diameter.
20. The solid dosage form of claim 1 , wherein the particles further comprise a layer disposed on the surface of the particle.
21. The solid dosage form of claim 1 , further comprising a liquid vehicle.
22. The solid dosage form of claim 21 , wherein the liquid vehicle comprises an additional active ingredient that is the same or different than the active ingredient in the particle.
23. The solid dosage form of claim 1 , wherein the particles, when loaded into a dissolution medium of 667 mL of 0.1N HCl with 0.025 M sodium dodecyl sulfate at 37±1° C. and subject to impeller rotation at 75 rpm followed by neutralization to pH 6.7 after 2 hours, provide sustained release of the active ingredient over a period of 8 hours or longer.
24. The solid dosage form of claim 1 , wherein the particles release about 40-55% of the active ingredient in 2 hours when tested for dissolution using the USP II dissolution test.
25. A sustained-release solid dosage form comprising particles, each particle comprising: (a) guaifenesin, dextromethorphan, ibuprofen, or a combination thereof in an amount from 20% to about 50% by weight of the particles, (b) a glycerol fatty acid in an amount from about 30% to about 80% by weight of the particles, and (3) stearic acid present in an amount from 0% to about 25% by weight of the particles, wherein the particles are substantially spherical and have a mean particle size diameter of from about 50 μm to about 500 μm and a particle size distribution within a 10% standard deviation from the mean particle size diameter, and wherein the particles release from 62% to 80% of the active ingredient in 6 hours as measured by the USP II dissolution test.
26. The solid dosage form of claim 25 , wherein the particles comprise 25-45% w/w guaifenesin, 35-70% w/w glycerol fatty acid ester, and 5-20% w/w stearic acid.
27. The solid dosage form of claim 25 , wherein the particles comprise 25-45% w/w guaifenesin, 1-5% w/w dextromethorphan, 30-70% w/w glycerol fatty acid ester, and 5-20% w/w stearic acid.
28. The solid dosage form of claim 25 wherein the particles comprise 20-50% w/w guaifenesin, 30-60% w/w glycerol fatty acid ester, and 0-20% w/w stearic acid.
29. The solid dosage form of claim 25 , wherein the particles comprise 20-50% w/w ibuprofen, 50-80% w/w glycerol fatty acid ester, and 0-20% w/w stearic acid.