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Sustained release beadlets conty. stavudine

A technology of stavudine and microspheres, applied in the field of sustained release microspheres containing stavudine

Inactive Publication Date: 2003-05-28
BRISTOL MYERS SQUIBB CO
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But traditional sustained-release dosage forms require a combination of steps of different approaches, typically including a granulation step involving an aqueous medium
Moisture-sensitive drugs such as stavudine therefore present great challenges when attempting to formulate them

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0016] Sustained release microspheres were prepared from the following formulations

[0017] Ingredients Mg\Capsules

[0018] nucleus

[0019] Stavudine 37.5

[0020] Lactose hydrate, NF 8.8

[0021] Microcrystalline Cellulose, NF 5.6

[0022] Magnesium stearate 0.6

[0023] seal coat

[0024] Hydroxypropylmethylcellulose, USP 1.9

[0025] Talc powder, USP 0.9

[0026] Modified Release Coating

[0027] Aqueous dispersion of ethyl cellulose, NF (dry weight) 2.2

[0028] Distilled acetylated monoglycerides 0.9

[0029] capsule

[0030] Hard Gelatin Capsules—Fill Weight 68.4

[0031] Aqueous ethylcellulose dispersion NF under the tradename Aquacoat ECD, available from FMC Corporation, contains ethylcellulose, cetyl alcohol, sodium lauryl sulfate and water. Distilled acetylated monoglycerides is manufactured by Eastman Chemical Company and it contains distilled acetylated monoglycerides, propylene glycol, propyl gallate and citric acid.

[0032] After the core constit...

Embodiment 2

[0034] Sustained release microspheres are prepared according to the method of Example 1, and the formula is as follows:

[0035] Ingredients Mg\Capsules

[0036] nucleus

[0037] Stavudine 100.0

[0038] Lactose hydrate, NF 23.3

[0039] Microcrystalline Cellulose, NF 41.7

[0040] Magnesium stearate 1.7

[0041] seal coat

[0042] Hydroxypropyl Methyl Cellulose, USP 5.0

[0043] Talc powder, USP 2.5

[0044] Modified Release Coating

[0045] Aqueous dispersion of ethyl cellulose, NF (dry weight) 5.8

[0046] Distilled acetylated monoglycerides 2.3

[0047] capsule

[0048] Hard Gelatin Capsules - Fill Weight 182.3

[0049] The analysis of the microspheres showed that the efficacy of stavudine was not significantly lost by this preparation method.

Embodiment 3

[0051] The stavudine microspheres prepared by the steps described in Example 1 and Example 2 were mixed with similar antiretroviral drug dideoxyinosine (2', 3'-dideoxyinosine) and [3S-( 3R*, 8R*, 9R*, 12R*)]-3,12-bis(1,1-dimethylethyl)-8-hydroxy-4,11-dioxo-9-(phenylmethyl) -Microspheres of 6{[4-(2-pyridyl)phenyl]methyl}}-2,3,6,10,13-pentaazaditetradecanedioic acid dimethyl ester mixed into hard in gelatin capsules. The formula and preparation method of the latter microspheres are generally as described in Example 1 and Example 2. See Table 1 for the microspheres and their content. The values ​​in each column represent the fill weight of the corresponding microspheres, and the drug amounts are given in parentheses. Thus, the first value given for stavudine microspheres indicates that the fill weight is 61 mg, of which 33 mg is stavudine and the remainder is excipients. The right column indicates the total fill weight of drug and excipients.

[0052] capsule size ...

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PUM

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Abstract

Extended dosage forms of stavudine are provided comprising beadlets formed by extrusion-spheronization and coated with a seal coating. The beadlets are also coated with a modified release coating such that a hard gelatin capsule containing such beadlets will provide blood levels of stavudine over approximately 24 hours. The beadlets are prepared from a dry blend of stavudine, a spheronizing agent, a suitable diluent and a stabilizing amount of magnesium stearate. The magnesium stearate, in contrast to other similar pharmaceutical adjuncts, has been found to stabilize stavudine against degradation due to hydrolysis in the presence of the limited amount of water necessary for the extrusion-spheronization process. Also included in the scope of the invention are hard gelatin capsules containing, in addition to the stavudine beadlets, similar beadlets containing other therapeutic agents utilized to treat retroviral infections.

Description

Background of the invention [0001] Stavudine (3'-deoxythymidine-2'-ene (3'-deoxy-2',3'-didehydrothymidine) is approved by the US Food and Drug Administration for the treatment of reverse transcription Virus-infected patients. This compound is a nucleic acid reverse transcriptase inhibitor, the preparation of which is disclosed, for example, in U.S. Patent 4,978,655 issued December 18, 1990. It is known that stavudine reverses the effect of treatment It is effective for infection caused by recorded viruses, such as murine leukemia virus and human immunodeficiency virus, namely HIV; HTLVIII / LAV virus (AIDS virus). Stavudine has achieved considerable commercial success as soon as it came out. [0002] In the treatment of HIV infection, a common approach is for the patient to take a combination of drugs. As a result, patients often suffer from a large daily drug burden, and reducing even one pill from the daily drug burden may be very welcome for these patient groups. Ultimately...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61J3/07A61K9/16A61K9/48A61K9/50A61K9/52A61K31/4402A61K31/4965A61K31/513A61K31/522A61K31/7072A61K31/7076A61K45/00A61K47/04A61K47/10A61K47/12A61K47/14A61K47/26A61K47/32A61K47/36A61K47/38A61P31/12A61P31/18
CPCA61K31/7076A61K9/1617A61K31/7072A61K9/5073A61P31/12A61P31/14A61P31/18A61K2300/00A61K9/14
Inventor R·阿布拉默维茨D·M·奥当诺胡伊N·B·贾恩
Owner BRISTOL MYERS SQUIBB CO
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