COMPOSITIONS AND METHODS OF USE
Provided is a pharmaceutical composition comprising: (a) granules comprising an active pharmaceutical ingredient, and one or more intragranular excipients; and an extragranular portion comprising at least one release modifier. Also provided are process for the preparation and methods for the use of the pharmaceutical composition.
1 . A pharmaceutical composition comprising:
(a) granules comprising dichlorphenamide, and one or more intragranular excipients; and
(b) an extragranular portion comprising at least one release modifier; wherein the release modifier is a hydroxypropyl methylcellulose or a mixture thereof,
wherein the composition has a dissolution profile of at least about 80% mean drug release between about 6 hours and about 10 hours as measured using the paddle method (USP apparatus 2) with a stirring rate of 75 rotations per minute in 900 mL of phosphate buffer pH 8.0 with 0.5% hexadecyltrimethylammonium bromide at 37±0.5° C.
2 . The pharmaceutical composition of claim 1 , wherein the one or more intragranular excipients are chosen from fillers, binders, and glidants.
3 . The pharmaceutical composition of claim 2 , wherein the one or more fillers are chosen from dibasic calcium phosphate, tribasic calcium phosphate, carmellose, sugar alcohols, kaolin, lactose, sucrose, mannitol, cellulose, calcium carbonate, magnesium carbonate, starch, mixtures of isomaltulose derivatives, and mixtures thereof.
4 . The pharmaceutical composition of claim 2 , wherein the one or more fillers is present in the granules in an amount of between about 20 and about 40% w/w.
5 . The pharmaceutical composition of claim 2 , wherein the one or more binders are chosen from hydroxypropyl celluloses in various grades, hydroxypropyl methylcelluloses in various grades, polyvinylpyrrolidones in various grades, copovidones, powdered acacia, gelatin, guar gum, carbomers, methylcelluloses, polymethacrylates, starches, and mixtures thereof.
6 . The pharmaceutical composition of claim 2 , wherein the one or more binders is present in the granules in an amount of between about 5 and about 15% w/w.
7 . The pharmaceutical composition of claim 2 , wherein the one or more glidants are chosen from talc, colloidal silica (colloidal silicon dioxide), cornstarch, calcium silicate, magnesium silicate, colloidal silicon, silicon hydrogel, and mixtures thereof.
8 . The pharmaceutical composition of claim 2 , wherein the one or more glidants is present in the granules in an amount of between about 0% w/w and about 2% w/w.
9 . The pharmaceutical composition of claim 1 , wherein the release modifier is a hydroxypropyl methylcellulose or a mixture thereof chosen from low to medium viscosity hydroxypropyl methylcellulose and mixtures thereof.
10 . The pharmaceutical composition of claim 1 , wherein the release modifier is present in the pharmaceutical composition in an amount of between about 30% w/w and about 40% w/w.
11 . The pharmaceutical composition of claim 1 , wherein the extragranular portion further comprises one or more extragranular excipients.
12 . The pharmaceutical composition of claim 11 , wherein the one or more extragranular excipients comprises one or more lubricants.
13 . The pharmaceutical composition of claim 11 , wherein the one or more extragranular excipients comprises one or more fillers.
14 . A pharmaceutical composition of claim 1 , comprising: dichlorphenamide, lactose monohydrate, magnesium stearate, and pregelatinized starch.
15 . A method of treating primary hyperkalemic periodic paralysis or primary hypokalemic periodic paralysis in a patient in need thereof wherein the patient is being administered an organic anion transporter-1 (OAT1) substrate, wherein the OAT1 substrate is sensitive to OAT1 inhibition and is famotidine, comprising discontinuing administration of the OAT1 substrate famotidine, and subsequently administering to the patient, a pharmaceutical composition comprising dichlorphenamide.