Solid or semisolid lipid based dosage form stabilization through curing and addition of low HLB surfactant(s)

Patent metadata

Field	Value
Publication number	US-12544338-B2
Application number	US-201917273863-A
Country	US
Kind code	B2
Filing date	Sep 9, 2019
Priority date	Sep 7, 2018
Publication date	Feb 10, 2026
Grant date	Feb 10, 2026

Abstract

Disclosed herein are dosage forms comprise a solid or a semisolid lipid with immediate release properties and/or with extended release properties. The dosage forms disclosed herein may have their active pharmaceutical ingredient's (API's) release profile stabilized via curing and/or via the addition of a surfactant with an HLB value of less than 10.

First claim

What is claimed is:

1 . A method for stabilizing an active pharmaceutical ingredient release profile of a dosage form, the method comprising:
incorporating a surfactant having an HLB value of less than about 10 and at least one of a solid or a semisolid lipid into the dosage form, wherein the incorporating comprises forming a homogenous mixture of the surfactant and the at least one of the solid or the semisolid lipid, wherein the homogenous mixture forms a matrix, subsequently dissolving or suspending an active pharmaceutical ingredient in the matrix; and subsequently curing the dosage form comprising the active pharmaceutical ingredient, wherein the curing is performed at a temperature from about 30° C. to about 60° C. for a duration of about 3 hours to about 7 days, wherein the release profile of the active pharmaceutical ingredient from the dosage form after an accelerated stability study has a similarity factor (f2) no less than 50 as compared to the release profile of the same active pharmaceutical ingredient from the dosage form before the accelerated stability study, wherein the accelerated stability study is performed at a temperature of about 40° C. and at a humidity of about 75% for a duration of 1 month.

2 . The method of claim 1 , wherein the surfactant is selected from the group consisting ethylene oxide/propylene oxide (EO/PO) copolymers, glycerol monocaprylate, glycerol monocaprate, glycerol caprylate/caprate, glycerol monooleate, glycerol monostearate, glycerol laurate, glycerol monolinoleate, glycerol behenate, glycerol palmitostearate, petrolatum and lanolin alcohols, polyoxyethylene alkyl ethers, sorbitan fatty acid esters, sucrose esters, poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) copolymers, lecithin, phospholipids, steareth-2, oleth-2, ceteth-2, PEG-30 dipolyhydroxystearate, propylene glycol monocaprylate, propylene glycol dilaurate, propylene glycol monolaurate, propylene glycol monostearate, propylene glycol isostearate, alpha tocopherol, mixed tocopherols, tricaprylin, nonionic emulsifying waxes, anionic emulsifying waxes, sorbitan monooleate, sorbitan monostearate, sorbitan monopalmitate, sorbitan tristearate, sorbitan trioleate, and combinations thereof.

3 . The method of claim 1 , wherein the active pharmaceutical ingredient has a half-life of less than about 8 hours.

4 . The method of claim 1 , wherein the active pharmaceutical ingredient is selected from the group consisting of dabigatran, dronedarone, ticagrelor, iloperidone, ivacaftor, midostaurine, asimadoline, beclomethasone, apremilast, sapacitabine, linsitinib, abiraterone, vitamin D analogs, COX-2 inhibitors, tacrolimus, testosterone, lubiprostone, pharmaceutically acceptable salts thereof, and combinations thereof.

5 . The method of claim 1 , further comprising dosing the dissolved or suspended active pharmaceutical ingredient within the matrix into preformed blister cavities using a rotary die machine, cooling the dosed blister cavities, and sealing the blister cavities.

6 . The method of claim 1 , further comprising filling the dissolved or suspended active pharmaceutical ingredient within the matrix into a softshell capsule or into a hardshell capsule.

7 . The method of claim 1 , further comprising solidifying the dissolved or suspended active pharmaceutical ingredient within the matrix and compressing the solidified active pharmaceutical ingredient within the matrix into a tablet, wherein solidifying comprises drying in drying tunnels, freeze-drying, or cooling the dissolved or suspended active pharmaceutical ingredient within the matrix.

8 . The method of claim 1 , further comprising extruding the dissolved or suspended active pharmaceutical ingredient within the matrix.

9 . The method of claim 1 , wherein the dosage form has about 20 w/w % or less fillers, based on total weight of the dosage form.

10 . The method of claim 1 , wherein the dosage form further comprises excipients selected from the group consisting of high melting point fats, waxes, low melting point oils, surfactants with HLB values greater than 10, solvents, cosolvents, solid high molecular weight polyethylene glycol, liquid polyethylene glycol, lubricants, pore formers, dispersing agents, gelatin, gums, water-soluble polymers, water, glycerin, sorbitol, cyclodextrins, flavoring agents, disintegrants, and combinations thereof.

11 . The method of claim 1 , wherein the dosage form is suitable for administration via an oral route, sublingual route, buccal route, vaginal route, or rectal route.

12 . The method of claim 1 , wherein the dosage form demonstrates an extended release profile.

13 . A dosage form prepared by the method of claim 1 .

14 . A method for stabilizing an active pharmaceutical ingredient release profile of a dosage form, the method comprising:
incorporating a surfactant having an HLB value of less than about 10 and at least one of a solid or a semisolid lipid into the dosage form, wherein the incorporating comprises forming a homogenous mixture of the surfactant and the at least one of the solid or the semisolid lipid, wherein the homogenous mixture forms a matrix, subsequently dissolving or suspending an active pharmaceutical ingredient in the matrix; and subsequently curing the dosage form comprising the active pharmaceutical ingredient, wherein the curing is performed at a temperature from about 30° C. to about 60° C. for a duration of about 3 hours to about 7 days, wherein the release profile of the active pharmaceutical ingredient from the dosage form after an accelerated stability study has a similarity factor (f2) no less than 50 as compared to the release profile of the same active pharmaceutical ingredient from the dosage form before the accelerated stability study, wherein the accelerated stability study is performed at a temperature of about 40° C. and at a humidity of about 75% for a duration of 1 month, wherein the surfactant with an HLB value of less than 10 is selected from the group consisting of glycerol monocaprylate, glycerol monocaprate, glycerol caprylate/caprate, glycerol monooleate, glycerol monostearate, glycerol laurate, sorbitan fatty acid esters, sucrose esters, lecithin, phospholipids, propylene glycol dilaurate, propylene glycol monolaurate, propylene glycol monostearate, nonionic emulsifying waxes, anionic emulsifying waxes, sorbitan monooleate, sorbitan monostearate, sorbitan monopalmitate, sorbitan tristearate, sorbitan trioleate, and combinations thereof and the solid or the semisolid lipid is glyceryl distearate.

Assignees

• Scherer Technologies Llc R P

Inventors

• Lazaro Monica
• Mcguffy Irena
• Bush Derek
• Fonkwe Linus Gomsi

Classifications

• A61K31/167 Primary

  having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol · CPC title

• A61K9/4866 Primary

  Organic macromolecular compounds · CPC title

• A61K9/4816

  Wall or shell material · CPC title

• A61K9/2095

  Tabletting processes · CPC title

• A61K9/2077

  Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets · CPC title