Stable Formulations of Linaclotide

a technology of linaclotide and stable formulation, which is applied in the field of stable pharmaceutical compositions of linaclotide, can solve problems such as exacerbated difficulties

Inactive Publication Date: 2014-12-25
FOREST LAB HLDG LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0008]In some embodiments of the present invention, a stable pharmaceutical composition is provided which comprises linaclotide, a cation or salt thereof, and a sterically hindered amine selected from meglumine, histidine or a mixture thereof, and, optionally, a polymer.
[0022]In some embodiments, a stable low-dose pharmaceutical composition of linaclotide is provided. In some embodiments, a stable pediatric pharmaceutical composition of linaclotide is provided.

Problems solved by technology

These difficulties may be exacerbated when producing pediatric formulations and other low-dose formulations of linaclotide, e.g., because the linaclotide is more dispersed and has greater surface area exposure to aqueous environments such as during preparation.

Method used

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  • Stable Formulations of Linaclotide
  • Stable Formulations of Linaclotide
  • Stable Formulations of Linaclotide

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0119]Linaclotide beads were prepared in the following manner using the components set forth in Table 1. First, a linaclotide solution was prepared by combining linaclotide, polyvinyl alcohol, calcium chloride, meglumine and water in the concentrations set forth in Table 1. The linaclotide solution was then pH-adjusted to about 2.5 and mixed until clear. Next, the linaclotide solution was layered onto isomalt beads by spraying the beads with the linaclotide solution using a Wurster process. The linaclotide-layered beads were then dried until the product loss on drying (LOD) was less than about 3%.

TABLE 1Linaclotide beads, 5 μg / 50 mgWeightComponents(g)Wt. %Linaclotide0.240.012Isomalt191595.8Meglumine2.60.1Calcium chloride dihydrate2.00.1PVA804HClQ.S.QSPurified water*1000QSTOTAL2000100.0*Water is removed during the manufacturing process

[0120]The stability performance of the linaclotide beads were assessed following storage of the beads for 1 month at 40° C. and 75% RH in 45 cc HDPE bo...

example 2

[0121]Linaclotide beads were prepared in the following manner using the components set forth in Table 3. First, a linaclotide solution was prepared by combining linaclotide, polyvinyl alcohol, calcium chloride, histidine and water in the concentrations set forth in Table 3. The linaclotide solution was then pH-adjusted to about 2.5 and mixed until clear. Next, the linaclotide solution was layered onto isomalt beads by spraying the beads with the linaclotide solution using a Wurster process. The linaclotide-layered beads were then dried until the product loss on drying (LOD) was less than about 3%.

TABLE 3Linaclotide beads, 5 μg / 50 mgWeightComponents(g)Wt. %Linaclotide0.240.012Isomalt191695.8Histidine20.1Calcium chloride dihydrate2.00.1PVA804HClQ.S.—Purified water*1000—TOTAL2000100.0*Water is removed during the manufacturing process

example 3

[0122]Linaclotide beads were prepared in the manner described in Example 2 using the components set forth in Table 4.

TABLE 4Linaclotide beads, 5 μg / 50 mgWeightComponents(g)Wt. %Linaclotide0.240.012Isomalt191695.8Leucine20.1Calcium chloride dihydrate2.00.1PVA804HClQ.S.—Purified water*1000—TOTAL2000100.0*Water is removed during the manufacturing process

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Abstract

The present invention relates to stable pharmaceutical compositions comprising linaclotide or pharmaceutically acceptable salts thereof, as well as to various methods and processes for the preparation and use of the compositions.

Description

CLAIM OF PRIORITY[0001]This application is a continuation of U.S. patent application Ser. No. 13 / 816,154 filed Feb. 8, 2013, which is the United States national phase application of PCT / US2011 / 047434, filed on Aug. 8, 2011. This application also claims priority to U.S. Provisional Patent Application Ser. No. 61 / 372,804 filed Aug. 8, 2010. The entire contents of the aforementioned applications are incorporated herein by reference.SEQUENCE LISTING[0002]This application incorporates by reference in its entirety the Sequence Listing entitled “IW099PCT1US1CON1_ST25.txt” which is 620 bytes in size and last modified on Sep. 11, 2014 and filed electronically herewith.FIELD OF THE INVENTION[0003]The present invention relates to stable pharmaceutical compositions of linaclotide and methods for treating gastrointestinal disorders (e.g., irritable bowel syndrome or chronic constipation) by administering the pharmaceutical compositions.BACKGROUND OF THE INVENTION[0004]Linaclotide is a peptide th...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K38/12A61K47/18
CPCA61K47/18A61K38/12A61K9/1611A61K9/1641A61K9/1676A61K38/10A61P1/00A61P1/04A61P1/10
Inventor MO, YUNFRETZEN, ANGELIKACALI, BRIANDEDHIYA, MAHENDRA
Owner FOREST LAB HLDG LTD
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