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"Solid Particulate Tadalafil Having A Bimodal Particle Size Distribution"

Abstract: Provided is a solid particulate tadalafil having a bimodal particle size distribution.

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Patent Information

Application #
Filing Date
28 December 2007
Publication Number
25/2008
Publication Type
INA
Invention Field
PHARMACEUTICALS
Status
Email
Parent Application

Applicants

TEVA PHARMACEUTICAL INDUSTRIES LTD.
5 BASEL STREET, P.O.BOX 3190, PETAH TIQVA 49131, ISRAEL.

Inventors

1. JUDITH ARONHIME
5A HARAV MAOR YOSEF STREET, REHOVOT, 76217, ISRAEL.
2. GUY SAMBURSKI
HAIRUSIM 19, GANOT-HADAR, 42930, ISRAEL.
3. YHOSHOA OVADYA
38/6 NACHAL HATZVI ST., MIGDAL HAEMEK, ISRAEL

Specification

SOLID PARTICULATE TADALAFIL HAVING A BIMODAL PARTICLE SIZE DISTRIBUTION RELATED APPLICATION This application claims the benefit of provisional application Serial Number 60/712,589, filed August 29,2005, which is incorporated herein by reference. FIELD OF THE INVENTION The field of the invention relates to solid particulate tadalafil having a bimodal particle size distribution. BACKGROUND OF THE INVENTION Tadalafil is a potent and selective inhibitor of the cyclic guanosine monophosphate (cGMP) - specific phosphodiesterase enzyme, PDE5. The inhibition of PDE5 increases the amount of cGMP, resulting in smooth muscle relaxation and increased blood flow. Tadalafil is therefore currently used in the treatment of male erectile dysfunction. Tadalafil is reported in the PDR to be a crystalline solid that is practically insoluble in water. The particle size of a poorly water soluble drug is reportedly influenced by the size of the particle of the drug. United States Patent No. 6,821,975 claims a free drug particulate form of a compound having a formula (Formula Removed) comprising particles of the compound wherein at least 90% of the particles have a particle size of less than about 40 microns (40µ). Particle size distribution ('TSD") of a poorly water soluble drug such as tadalafil may greatly affect its bioavailability. Yet, when a active pharmaceutical ingredient is obtained with a relatively low particle size, the process of reducing particle size, such as milling, adversely affects the properties of the powder. For example, a great amount of highly fine solids can be produced by milling which may adversely affect the flow properties of the powder. There is a need in the art for tadalafil with a desirable PSD, which has otherwise good properties (such as flow properties). SUMMARY OF THE INVENTION In one embodiment, the present invention provides solid particulate tadalafil having a bimodal size distribution. In one embodiment, the present invention provides solid particulate tadalafil having at least one of the following particle size distribution as determined by volume by laser-diffraction method: a) 41µ41µ), such as 41µ41 µ), such as 41 µ < d(0.9) <81 µ and/or 45µ < d(0.9) <70µ. The pharmaceutical compositions can be prepared by combining tadalafil having a bimodal PSD with a pharmaceutically acceptable excipient. In one embodiment, large particle size solid particulate tadalafil, wherein d(O.l) ~ lOµ. and d(0.9) ~ 120µ, is combined with a second, small particle size solid particulate tadalafil, wherein at least about 98 volume-% of the particles of the second, small particle size tadalafil have a nominal particle size of about 15µ or less; this mixture is admixed with at least one pharmaceutically acceptable excipient. hi one embodiment, the small particle size solid particulate tadalafil is d(0.9) < 10µ. and the large particle size solid particulate tadalafil is d(0.9)=150µ and lOµ

Documents

Application Documents

# Name Date
1 10162-DELNP-2007-Pre-Grant-Opposition-(18-02-2011).pdf 2011-02-18
1 10162-DELNP-2007_EXAMREPORT.pdf 2016-06-30
2 10162-delnp-2007-abstract.pdf 2011-08-21
2 10162-delnp-2007-pct-308.pdf 2011-08-21
3 10162-delnp-2007-pct-306.pdf 2011-08-21
3 10162-delnp-2007-claims.pdf 2011-08-21
4 10162-delnp-2007-pct-304.pdf 2011-08-21
4 10162-delnp-2007-correspondence-others 1.pdf 2011-08-21
5 10162-delnp-2007-pct-237.pdf 2011-08-21
5 10162-delnp-2007-correspondence-others.pdf 2011-08-21
6 10162-delnp-2007-pct-210.pdf 2011-08-21
6 10162-delnp-2007-description (complete).pdf 2011-08-21
7 10162-delnp-2007-gpa.pdf 2011-08-21
7 10162-delnp-2007-drawings.pdf 2011-08-21
8 10162-delnp-2007-form-5.pdf 2011-08-21
8 10162-delnp-2007-form-1.pdf 2011-08-21
9 10162-delnp-2007-form-18.pdf 2011-08-21
9 10162-delnp-2007-form-3.pdf 2011-08-21
10 10162-delnp-2007-form-2.pdf 2011-08-21
11 10162-delnp-2007-form-18.pdf 2011-08-21
11 10162-delnp-2007-form-3.pdf 2011-08-21
12 10162-delnp-2007-form-1.pdf 2011-08-21
12 10162-delnp-2007-form-5.pdf 2011-08-21
13 10162-delnp-2007-drawings.pdf 2011-08-21
13 10162-delnp-2007-gpa.pdf 2011-08-21
14 10162-delnp-2007-description (complete).pdf 2011-08-21
14 10162-delnp-2007-pct-210.pdf 2011-08-21
15 10162-delnp-2007-correspondence-others.pdf 2011-08-21
15 10162-delnp-2007-pct-237.pdf 2011-08-21
16 10162-delnp-2007-correspondence-others 1.pdf 2011-08-21
16 10162-delnp-2007-pct-304.pdf 2011-08-21
17 10162-delnp-2007-claims.pdf 2011-08-21
17 10162-delnp-2007-pct-306.pdf 2011-08-21
18 10162-delnp-2007-abstract.pdf 2011-08-21
18 10162-delnp-2007-pct-308.pdf 2011-08-21
19 10162-DELNP-2007_EXAMREPORT.pdf 2016-06-30
19 10162-DELNP-2007-Pre-Grant-Opposition-(18-02-2011).pdf 2011-02-18