Sustained-release solid preparation for oral use

Inactive Publication Date: 2013-01-03
DAIICHI SANKYO CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Benefits of technology

[0021]The present invention can provide a sustained-release pharmaceutical composition for oral administration containing a pharmacologically active drug. Thus, the present invention provides, for example, an oral matrix preparation having a prolonged effect, which contains activated blood coagulation factor X (FXa) inhibitor compound (1) as a pharmaceutically active ingredient. The sustained-release pharmaceutical composition of th

Problems solved by technology

Meanwhile, since compounds exhibiting the main pharmacological effect have diverse chemical properties, some sustained release techniques, albeit still insufficient, adaptable to the diverse chemical properties of these compounds have been reported (see e.g., Patent Documents 1 and 2).
Low water-soluble compounds have many disadvantages in the design of preparations to improve dissolution properties.
Acidic drugs are disadvantageously low soluble in acidic solutions, for example, in the upper gastrointestinal tract such as the stomach.
A salt (alkali- or amine-adduct salt) of an acidic compound disadvantageously becomes a low soluble free acid in an acidic solution.
For example, a challenge for the design of sustained-release preparations for oral administration containing a basic drug is dose dumping of the drug when t

Method used

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  • Sustained-release solid preparation for oral use
  • Sustained-release solid preparation for oral use
  • Sustained-release solid preparation for oral use

Examples

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example 1

[0150]Tablets having formulations 1 and 1a shown in Table 1 were produced by mixing of each component using a mortar followed by the direct compression method and subjected to the dissolution test in an acidic or neutral solution. The results obtained from the acidic solution are shown in Table 2 and FIGS. 1 and 2. The results obtained from the neutral solution are shown in FIGS. 3 and 4.

TABLE 1Content (mg)Formulation 1Formulation 1aCompound (1a)36.436.4HPC-M fine60.060.0HPC-SL regular12.012.0HPMCAS-LF120.0—Mannitol59.6179.6Sodium stearyl fumarate12.012.0Total300.0300.0

TABLE 2Influence of paddle rotation rate in acidic test medium ontablets having formulations 1 and 1aFormulation 1Formulation 1aD2 h,200 rpm-D2 h,50 rpm3.6%30.6%D2 h,200 rpm / D2 h,50 rpm1.21.4

[0151]As is evident from FIGS. 3 and 4, both the tablets of formulations 1 and 1a exhibited prolonged dissolution properties in the neutral solution. On the other hand, it was demonstrated that the tablets of formulation 1a were l...

example 2

[0152]Tablets having formulations 1 and 2a shown in Table 3 were produced by mixing of each component using a mortar followed by the direct compression method and subjected to the dissolution test in an acidic solution. The results are shown in Table 4 and FIGS. 1 and 5.

TABLE 3Content (mg)Formulation 1Formulation 2aCompound (1a)36.436.4HPC-M fine60.060.0HPC-SL regular12.012.0HPMCAS-LF120.0—HPMCAS-LG—120.0Mannitol59.659.6Sodium stearyl fumarate12.012.0Total300.0300.0

TABLE 4Influence of paddle rotation rate in acidic test mediumon tablets having formulations 1 and 2aFormulation 1Formulation 2aD2 h,200 rpm-D2 h,50 rpm (%)4.315.0D2 h,200 rpm / D2 h,50 rpm1.21.6

[0153]The tablets of formulation 1 in which HPMCAS having a small particle size was used were less influenced by the paddle rotation rate in the acidic solution, than the tablets of formulation 2a in which HPMCAS having a large particle size was used. Thus, HPMCAS having a small particle size was effective for maintenance of tablet ...

example 3

[0154]Tablets having formulations 1 and 3a shown in Table 5 were produced by mixing of each component using a mortar followed by the direct compression method and subjected to the dissolution test in a neutral solution, a dissolution test using USP Apparatus 3, and in vivo absorption property evaluation using dogs. The results of the dissolution test in the neutral solution are shown in FIG. 6.

TABLE 5Content (mg)Formulation 1Formulation 3aCompound (1a)36.436.4HPC-M fine60.060.0HPC-SL regular12.012.0HPMCAS-LF120.0120.0Mannitol59.6—Microcrystalline cellulosea)—59.6Sodium stearyl fumarate12.012.0Total300.0300.0a)grade PH101

[0155]As shown in FIG. 6, the tablets obtained using mannitol or crystalline cellulose exhibited prolonged drug dissolution in the neutral solution. On the other hand, the dissolution test using USP Apparatus 3 showed that the tablets of formulation 1 in which mannitol was used exhibited prolonged drug dissolution, whereas the tablets of formulation 3a in which cryst...

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Abstract

It is intended to avoid dose dumping of a drug and improve the dissolution properties of the drug in the lower gastrointestinal tract, and thereby provide a sustained-release matrix preparation for oral administration that reliably exhibits its main pharmacological effect when orally administered once or twice a day. The present invention provides a sustained-release preparation obtained by mixing of (A) a pharmacologically active drug, (B) hydroxypropyl methylcellulose acetate succinate having a median size (D50) of 40 μm or smaller, (C) a cellulose derivative, and (D) a saccharide or a nonionic water-soluble polymer followed by molding.

Description

[0001]This application is a continuation of International Application No. PCT / JP2011 / 053642, filed on Feb. 21, 2011, entitled “SUSTAINED-RELEASE SOLID PREPARATION FOR ORAL USE”, which claims the benefit of Japanese Patent Application Number JP 2010-035882, filed on Feb. 22, 2010, all of which are hereby incorporated by reference.FIELD OF THE INVENTION[0002]The present invention relates to a sustained-release matrix preparation that reliably exhibits its main pharmacological effect when orally administered once or twice a day.BACKGROUND[0003]Sustained-release preparations for the adjustment of blood concentrations of drugs are highly useful in terms of separation between the main pharmacological effect and adverse reaction, improvement in compliance (e.g., the number of doses reduced by improvement in prolonged efficacy), medical economy, etc. In this regard, some techniques have been reported for sustained-release preparations. Meanwhile, since compounds exhibiting the main pharmaco...

Claims

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Application Information

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IPC IPC(8): A61K9/14A61K31/437A61K31/403
CPCA61K31/403A61K31/4745A61K9/2054A61K9/2027A61K9/2018A61K31/437A61K31/522A61P7/02A61P43/00A61K9/2077A61K9/5047A61K9/7007
Inventor KANAMARU, TAROTAJIRI, SHINICHIROFUKUI, SACHIKOYOSHIDA, KAZUHIRO
Owner DAIICHI SANKYO CO LTD
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