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Dosage forms comprising a cetp inhibitor and an HMG-CoA reductase inhibitor

A technology of reductase inhibitors and inhibitors, which can be used in medical preparations containing active ingredients, pill delivery, medical preparations with non-active ingredients, etc., and can solve problems such as loss of stability

Inactive Publication Date: 2006-02-01
PFIZER PRODS ETAT DE CONNECTICUT
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

When packaged as tablets, powders, granules, or in capsules, HMG-CoA reductase inhibitors may be further destabilized by contact with molecular entities of other components of the dosage form

Method used

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  • Dosage forms comprising a cetp inhibitor and an HMG-CoA reductase inhibitor
  • Dosage forms comprising a cetp inhibitor and an HMG-CoA reductase inhibitor
  • Dosage forms comprising a cetp inhibitor and an HMG-CoA reductase inhibitor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[1317] Granules of the HMG-CoA reductase inhibitor torvastatin and granules containing a solid amorphous dispersion of the CETP inhibitor and concentration-enhancing polymer were prepared separately. The two granules were combined and stored at 50°C and 75% relative humidity for 3 weeks. The stability of atorvastatin was measured and found to be increased relative to the control composition.

[1318] The following procedure was used to form a spray-dried product containing 25 wt% [2R,4S]-4-[(3,5-bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-2-ethyl- 6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester (torcetrapib) and 75 wt% hydroxypropylmethylcellulose acetate succinate (medium size fraction, available from Shin Etsu located in Japan) (herein referred to as "HPMCAS-MG"). First, a spray solution containing 25 g torcetrapib, 75 g HPMCAS-MG and 900 g acetone was prepared. The spray solution was pumped with a high-pressure pump (ZenithZ-Drive 2000 Hig...

Embodiment 2 and 3

[1337] To make Example 2, equal weights of the granulated CETP inhibitor composition of Example 1 and the granulated HMG-CoA reductase inhibitor composition of Example 1 were blended as described in Example 1, from the blend Made into 200mg tablets. The acidic polymer HPMCAS accounts for 22.5wt% of Example 2, atorvastatin calcium accounts for 6.95wt% of Example 2, and the ratio of HPMCAS to atorvastatin is 3.24.

Embodiment 3

[1338] To make Example 3, tablets were made containing separate layers of the CETP inhibitor composition of Example 1 and the HMG-CoA reductase inhibitor composition of Example 1. Each tablet of Example 3 contained 400 mg of the dispersion granules in one layer and 288 mg of torvastatin granules in the second layer. The acid concentration-enhancing polymer HPMCAS accounted for 26.2wt% of Example 3, atorvastatin calcium accounted for 5.82wt% of Example 3, and the ratio of HPMCAS to atorvastatin was 4.5.

[1339] Examples 2 and 3 were stored at 50°C and 75% relative humidity for 3 weeks and analyzed by HPLC as described above. The results are shown in Table 5.

[1340] sample

Degradation degree (wt%)

Example 2

0.09

Example 3

0.04

[1341] Example 2 shows that tablets prepared by first forming separate granules (one containing a solid amorphous dispersion and one containing torvastatin) and then blending the granules into tablet...

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Abstract

A dosage form comprises (1) a solid amorphous dispersion comprising a cholesteryl ester transfer protein inhibitor and an acidic concentrationenhancing polymer and (2), an HMG-CoA reductase inhibitor. The solid amorphous dispersion and the HMG-CoA reductase inhibitor are combined in the dosage form so that the solid amorphous dispersion and the HMG-CoA reductase inhibitor are substantially separate from one another in the dosage form.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to Provisional Patent Application No. 60 / 435,345, filed December 20, 2002, which is hereby incorporated by reference in its entirety. technical field [0003] The present invention relates to a dosage form comprising: (1) a solid amorphous dispersion comprising a cholesteryl ester transfer protein (CETP) inhibitor and an acid concentration-enhancing polymer; and (2) an acid-sensitive HMG-CoA reductase Inhibitors. Background technique [0004] As we all know, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) is an important enzyme that catalyzes the synthesis of cholesterol in cells, which will cause the decrease of blood cholesterol level, especially the low density of cholesterol lipoprotein form. Therefore, HMG-CoA reductase inhibitors are considered to be potentially useful as hypocholesterolemic or hypolipidemic agents. [0005] CETP inhibitors are another class...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/40A61K47/38A61K9/16A61K31/4706A61K9/14A61K9/20A61K9/24A61K31/00A61K45/06
CPCA61K9/1652A61K9/2054A61K45/06A61K31/00A61K9/2081A61K9/146A61K9/2077A61K9/209A61K31/4706A61K31/40A61P3/06A61P43/00A61P9/10A61K2300/00A61K9/16A61K47/38
Inventor D·T·弗里森D·A·洛伦茨D·K·莱昂B·C·汉考克T·J·麦克德莫特R·M·尚克
Owner PFIZER PRODS ETAT DE CONNECTICUT
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