Delayed release softgel capsules
Delayed release softgel capsules comprise a fill material and a pH dependent shell composition, characterized in that the delayed release nature of the capsules may be achieved without a pH dependent coating or added conventional pH dependent polymers. The delayed release softgel capsules described herein are particularly suitable for initiating release of the active agent in a target location in the colon environment.
1 . A delayed release softgel capsule comprising:
(a) a fill material; and
(b) a shell derived from a pH dependent shell composition,
wherein the fill material comprises at least one pharmaceutically active ingredient,
wherein the pH dependent shell composition comprises gelatin, pectin, and dextrose,
wherein the shell ruptures in the colon environment, and
wherein the pH dependent shell composition has a viscosity ranging from about 60,000 cPs to about 150,000 cPs when measured using a rheometer at 60° C. at ambient conditions.
2 . The delayed release softgel capsule of claim 1 , wherein the pH dependent shell composition further comprises a plasticizer.
3 . The delayed release softgel capsule of claim 1 , wherein the pectin is low methoxyl pectin.
4 . The delayed release softgel capsule of claim 1 , wherein the pectin is selected from the group consisting of amidated pectin, non-amidated pectin and combinations thereof.
5 . The delayed release softgel capsule of claim 1 , wherein the pH dependent shell composition comprises about 40 wt % to about 80 wt % of a gelatin, based on the dry pH dependent shell composition weight.
6 . The delayed release softgel capsule of claim 1 , wherein the pH dependent shell composition comprises about 2 wt % to about 20 wt % of pectin, based on the dry pH dependent shell composition weight.
7 . The delayed release softgel capsule of claim 1 , wherein the pH dependent shell composition comprises about 0.01 wt % to about 4 wt % of dextrose, based on the dry pH dependent shell composition weight.
8 . The delayed release softgel capsule of claim 2 , wherein the plasticizer is selected from the group consisting of glycerin, sorbitol and combinations thereof.
9 . The delayed release softgel capsule of claim 1 , wherein the capsule dissolves/disintegrates after at least about 10 minutes, after at least about 15 minutes, after at least about 20 minutes, after at least about 25 minutes, after at least about 30 minutes, after at least about 35 minutes, after at least about 40 minutes, or from any of about 10 minutes, about 15 minutes, about 20 minutes, about 25 minutes or about 30 minutes up to any of about 35 minutes, about 40 minutes, about 45 minutes, about 50 minutes, about 55 minutes, about 60 minutes, about 75 minutes, or about 90 minutes in an intestinal environment based on a dissolution/disintegration test performed in a USP Apparatus II with paddles at a speed of 50 rpm in pH 6.8 phosphate buffer, optionally with pancreatin.
10 . The delayed release softgel capsule of claim 1 , wherein the capsule dissolves/disintegrates in at least about 15 minutes, at least about 30 minutes, at least about one hour, at least about two hours, at least about three hours, at least about four hours, or at least about five hours in an acidic medium based on a dissolution/disintegration test performed in a USP Apparatus II with paddles at a speed of 50 rpm in 0.1N HCl, optionally with pepsin.
11 . The delayed release softgel capsule of claim 1 that is free of additional pH dependent polymers.
12 . The delayed release softgel capsule of claim 1 , wherein the pH dependent shell composition has a gelatin to pectin w:w ratio ranging from about 2:1 to about 20:1 or from about 6:1 to about 18:1.
13 . The delayed release softgel capsule of claim 1 , wherein the pH dependent shell composition has a plasticizer to gelatin w:w ratio ranging from about 5:1 to about 1:5.
14 . A method for tuning the pH dependent dissolution profile of the delayed release softgel capsule of claim 1 , the method comprising adjusting an amount of pectin and dextrose in the pH dependent shell composition to attain a target pH dependent dissolution profile in acidic medium and/or in buffer medium.
15 . A method of treating a condition comprising, administering to a subject in need thereof the delayed release softgel capsule according to claim 1 .
16 . A method of reducing incidence of belching comprising, administering to a subject in need thereof the delayed release softgel capsule of claim 1 .
17 . A delayed release softgel capsule comprising:
(a) a fill material; and
(b) a shell derived from a pH dependent shell composition,
wherein the fill material comprises at least one pharmaceutically active ingredient,
wherein the pH dependent shell composition comprises gelatin, a pH dependent polymer, and dextrose,
wherein the pH dependent shell composition ruptures in the colon environment, and
wherein the pH dependent shell composition has a viscosity ranging from about 60,000 cPs to about 150,000 cPs when measured using a rheometer at 60° C. at ambient conditions.
18 . A method of delivering a drug to the colon of a patient comprising orally administering the delayed release softgel capsule of claim 1 .