Mosapride sustained-release formulation providing pharmacological and clinical effects with once-daily administration
Inventors
Kim, Byung Jin • CHOI, Youn Woong • Song, Hee Yong • Kim, Jong-Il • Kim, Yong Hee • Lim, Myoung-Hwa • Kim, Min Soo • Ha, Dae-Chul
Assignees
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Publication Number
US-9962390-B2
Publication Date
2018-05-08
Expiration Date
Abstract
The formulation for oral administration of the present invention containing Mosapride or its salt is a double layer formulation consisting of a fast-release layer for rapid release of a drug and a sustained-release layer for slow release in order to simultaneously satisfy the rapid exhibition of pharmacological activities and sustained maintenance of pharmacological activities for 24 hours, wherein the high-viscosity hydroxypropyl methylcellulose (HPMC) and the low-viscosity HPMC are used in mixture such that the content of a high viscosity HPMC as a controlled-release matrix within the sustained-release layer has a higher content, thereby capable of controlling the dissolution rate in the regions having different pH values within the gastrointestinal tract and/or the retention time in the gastrointestinal tract. Additionally, the formulation of the present invention is a small-sized preparation with a total weight of 200 mg or less, preferably from 150 mg to 160 mg, thus capable of improving drug compliance of patients.
Core Innovation
The invention relates to a sustained-release formulation for once-daily oral administration containing Mosapride or its salt as an active ingredient. The formulation includes a fast-release layer comprising the active ingredient, a filler, a disintegrating agent, and a binder, and a sustained-release layer comprising the active ingredient, a filler, low substituted hydroxypropylcellulose (L-HPC), a controlled-release matrix, and a binder.
The formulation has a gastrointestinal retention time of from 18 hours to 24 hours. It specifies release of from 20% to 50% of Mosapride or its salt in the stomach and from 50% to 80% of Mosapride or its salt in the intestinal tract during gastrointestinal transit.
The formulation complies with a dissolution profile measured by the paddle method of the Korean Pharmacopoeia at 37°C in dissolution media of pH 4.0, 6.8, 1.2 and water. The dissolution profile includes releasing 25% to 45% in 1 hour, 60% to 80% in 8 hours, at least 85% in 24 hours, and 45% or less in 16 hours in the dissolution medium of pH 6.8.
The sustained-release matrix is a mixture of high-viscosity hydroxypropyl methylcellulose (HPMC) and low-viscosity HPMC. The high-viscosity HPMC has a viscosity of from 80,000 cps to 120,000 cps and the low-viscosity HPMC has a viscosity of 2,000 cps to 20,000 cps, with a weight ratio between high-viscosity HPMC and low-viscosity HPMC in the range of from 2.6:1 to 1:1, and the total amount of the high-viscosity HPMC and the low-viscosity HPMC is from 5 to 20 wt% relative to the total weight of the formulation.
Claims Coverage
Two independent claims are provided. They center on a once-daily oral sustained-release Mosapride formulation with a two-layer design, defined gastrointestinal retention and regional release, dissolution profile compliance across multiple pH media, and a controlled-release matrix defined by HPMC viscosity-mixture ratio and loading.
Two-layer once-daily oral sustained-release Mosapride formulation with defined retention and regional release
A sustained-release formulation for once-daily oral administration containing Mosapride or its salt, comprising a fast-release layer and a sustained-release layer, having a gastrointestinal retention time of from 18 hours to 24 hours, with release from 20% to 50% in the stomach and from 50% to 80% in the intestinal tract during transit.
Dissolution-profile compliance across pH media with staged release targets
The formulation complies with a dissolution profile measured by the paddle method of the Korean Pharmacopoeia at 37°C in dissolution media of pH 4.0, 6.8, 1.2 and water, with releasing 25% to 45% in 1 hour, 60% to 80% in 8 hours, at least 85% in 24 hours, and 45% or less in 16 hours in the dissolution medium of pH 6.8.
HPMC controlled-release matrix defined by viscosity grades and weight ratio
The controlled-release matrix is a mixture of high-viscosity HPMC and low-viscosity HPMC, with the high-viscosity HPMC at 80,000 cps to 120,000 cps, the low-viscosity HPMC at 2,000 cps to 20,000 cps, a weight ratio of 2.6:1 to 1:1, and a total amount of 5 to 20 wt% relative to the total weight of the formulation.
Two-layer excipient-defined composition with lactose hydrate, L-HPC, and polyvinyl pyrrolidone
A sustained-release formulation comprising a fast-release layer and a sustained-release layer with lactose hydrate, L-HPC, and polyvinyl pyrrolidone.
The claimed coverage is directed to a once-daily oral Mosapride sustained-release formulation with two layers, specified gastrointestinal retention time and stomach-versus-intestine release distribution, dissolution profile targets across multiple pH media, and an HPMC controlled-release matrix defined by viscosity grade ranges, HPMC weight ratio, and total HPMC loading. One independent claim additionally specifies lactose hydrate, L-HPC, and polyvinyl pyrrolidone in the layer compositions.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Once-daily oral administration of Mosapride or its salt in a sustained-release formulation.
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