Effervescent formulations

Details Effervescent formulations Effervescent formulations

1999-03-26

2001-06-05

Spear, James M. (Department: 1615)

Drug, bio-affecting and body treating compositions

Preparations characterized by special physical form

Tablets, lozenges, or pills

C424S435000, C424S465000, C424S489000, C514S770000, C514S777000, C514S778000, C514S784000, C514S781000

Reexamination Certificate

active

06242002

ABSTRACT:

FIELD OF THE INVENTION
The invention relates to solid, rapidly disintegrating oral dosage forms for pharmaceutical administration as effervescent formulations for alkali-sensitive active ingredients, such as selegiline, and to a process for their preparation.
BACKGROUND
The (−) form of deprenyl, also known as selegiline (phenylisopropyl-methylpropynylamine) or its pharmaceutically acceptable salts, are used in the form of tablets as an antiparkinsonian drug.
A large number of forms for administration of selegiline have been described in the patent literature. Transdermal administration forms including, for example, patches, are disclosed in European patents Nos. 404 807; 406 488; 509 761; 591 432; 593 807; 617 515; 647 137; 683 668; 655 900; WO 96/02239; WO 95/18603; and WO 94/23707.
Drug forms for the controlled release of selegiline, for example in the form of tablets, are described in European patent No. 582 186; in WO 96/01612; and in U.S. Pat. No. 5,484,608, and osmotically acting release systems are described in U.S. Pat. No. 5,128,145; and normal-release oral formulations are described in WO 96/22435.
Patent application WO 96/12472 discloses a liposomal composition which comprises the active ingredient selegiline.
Buccal and sublingual forms of administration are disclosed in WO 97/-17067. WO 95/07070 describes effervescent formulations which, to avoid the insoluble residues of tricalcium citrate which can be formed when effervescent formulations are dissolved, comprise at least two different edible acids.
WO 93/00886 describes effervescent tablets having good storage stability, for example alkali-sensitive active ingredients such as acetylcysteine, captopril and minoxidil. The tablets comprise an effervescent base containing a solid edible organic acid as carrier crystals, an alkali metal carbonate or bicarbonate and an alkali metal salt of the acid. Two layers are applied onto the carrier crystals. The first layer contains a different acid than the carrier crystals, and the second layer contains the alkali metal salt of one of the two acids.
Selegiline is unstable in alkali-containing effervescent formulations. Even a multilayer construction is not sufficient for stabilization. Alkali carbonates and bicarbonates are more basic than alkaline earth carbonates, such as calcium carbonate. There are no suitable effervescent formulations known for selegiline, which is an alkali-sensitive active ingredient. This may partly be due to the fact that such formulations were so far not successful due to the instability of selegiline, as also shown in FIG.
1
.
The therapeutic treatment of various disorders requires, in particular in elderly people, a very frequent and in many cases even the permanent taking of pharmaceuticals.
Parkinson patients usually have problems due to strong tremor when swallowing tablets with liquids. Likewise, taking of tablets is very difficult for patients that have difficulties swallowing.
Therefore there is a need for novel solid, rapidly disintegrating oral dosage forms of administration, particularly effervescent formulations in the form of soluble tablets, buccal tablets or soluble granules which ensure easy administration, even for example, for elderly patients.
BRIEF DESCRIPTION OF THE INVENTION
It is an object of the present invention to provide novel and therapeutically advantageous effervescent formulations for selegiline as well as for other alkali-sensitive active ingredients.
The soluble-tablet-formulations of the present invention are also suitable in the combined use with other soluble tablets, such as with L-dopa, and benzerazide as described in European patent No. 521 388.
This object is achieved by the present invention which provides rapidly disintegrating oral dosage forms with or without water as an effervescent formulation comprising an alkali-sensitive active ingredient and an effervescent base of at least one of (i) an alkaline earth metal carbonate, (ii) an organic edible acid, and (iii) an alkali metal salt of citric acid and, optionally, pharmaceutically acceptable auxiliary ingredient.
The present invention provides effervescent formulations in the form of granules, tablets or sachets. The tablets can also be buccal tablets.
A suitable embodiment of the invention involves effervescent formulations of selegiline or its pharmaceutically acceptable salts.
By addition of water to, or contacting such effervescent formulations with saliva, a suspension or solution is formed with CO
2
evolution, and the suspension or solution develops a pleasant taste during taking. Here, a rapid release of the active ingredient is of particular importance to ensure a rapid onset of action. This applies particularly to buccal tablets.


REFERENCES:
patent: 5128145 (1992-07-01), Edgren et al.
patent: 5415870 (1995-05-01), Gergely et al.
patent: 5484608 (1996-01-01), Rudnic et al.
patent: 34 40 288 A1 (1986-05-01), None
patent: 0 396 335 A1 (1990-11-01), None
patent: 0 406 488 A1 (1991-01-01), None
patent: 593807A1 (1992-10-01), None
patent: 0 509 761 A1 (1992-10-01), None
patent: 0 521 388 A1 (1993-01-01), None
patent: 0 582 186 A1 (1994-02-01), None
patent: 0 617 515 A2 (1994-09-01), None
patent: 89/09051 (1989-10-01), None
patent: 93/00058 (1993-01-01), None
patent: 93/00886 (1993-01-01), None
patent: 94/00124 (1994-01-01), None
patent: 94/17792 (1994-08-01), None
patent: 94/23707 (1994-10-01), None
patent: 9612472A1 (1994-10-01), None
patent: 94/22435 (1994-10-01), None
patent: 94/26218 (1994-11-01), None
patent: 95/07070 (1995-03-01), None
patent: 95/13130 (1995-05-01), None
patent: 95/18603 (1995-07-01), None
patent: 95/34283 (1995-12-01), None
patent: 96/01612 (1996-01-01), None
patent: 96/02239 (1996-02-01), None
patent: 97/17067 (1997-05-01), None

Affiliated with

Also associated with

Rating

Effervescent formulations does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Effervescent formulations, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Effervescent formulations will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2513826