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Orally disintegrating pharmaceutical composition

IP.com Disclosure Number: IPCOM000200137D
Publication Date: 2010-Sep-30
Document File: 4 page(s) / 558K

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Orally disintegrating pharmaceutical composition

The issue is addressed to the development of orally disintegrating dosage forms of 1-[[3-(4,7-Dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-ethoxyphenyl]sulfonyl]-4-methylpiperazine - also known as sildenafil - that disintegrate or dissolve in the mouth and are swallowed with or without small amount of water. Besides improving acceptability and compliance of patients sildenafil orally disintegrating tablets (ODT) have been investigated for their potential to increase the bioavailability through the enhancement of the dissolution rate.

Commercially, drug comprising sildenafil citrate is available in 25 mg, 50 mg and 100 mg immediate release tablets useful for the treatment of sexual dysfunction.

Different orally disintegrating formulations with sildenafil and its pharmaceutically available salts as active ingredient are known from the literature (EP 960 621, WO 00/07597, WO 00/54777, WO 02/05820, WO 03/072084, WO 2004/017976, EP 1 658 053, US 2009/0047330, CN 1586483, JP 10298062). Many technologists have been confronted with problems such as unpleasant bitter taste of citrate salt and/or with extremely low solubility of corresponding free base in water, as well as with further limitations related to different ODT manufacturing processes.

Disclosed is a method as well as compositions for preparing sildenafil ODT that comprises the active substance in the form of free base or its pharmaceutically acceptable salts, preferentially citrate.

Sildenafil or sildenafil citrate as prepared by any of the known prior art may be used in the below described ODT preparation process.

Sildenafil citrate or its free form used for the production of  sildenafil ODT  has an average particle size of less than about 200 microns, more preferably less than about 100 microns more preferably less than 20 microns. Sildenafil citrate or its free form may be milled to reduce the size of particles as required.

The average diameter refferes to the volume mean diameter measured by laser diffraction method.

volume average diameter

16µm

61µm

175µm

4µm

d10

4.9µm

14.3µm

49.2µm

1.4µm

d50

12.6µm

51.1µm

141.6µm

3.7µm

d90

29.7µm

122.4µm

349.7µm

8.5µm

Preparation of granules:

Granules were prepared using wet granulation. Preferred principles are high-shear granulation and fluid bed granulation. Granules were prepared by mixing sildenafil citrate or sildenafil with a suitable filler and additional excipients such as stabilizers, sweeteners, flavours, colours, taste masking agents and taste correction agents in a high shear mixer of fluid bed granulator, and granulating with a granulation liquid. Purified water or aqueous binder solution were used as granulation liquid. Other solvents that can be used include methanol, ethanol, 1-propanol, 2-propranol and acetone. Wet granules were dried in a fluid bed drier to desired LOD. Dry granules were sieved. Alternatively direct compression can be used.

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