Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Tablets – lozenges – or pills
Patent
1994-09-27
1997-11-25
Page, Thurman K.
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Tablets, lozenges, or pills
424474, 424482, 424494, 424497, A61K 932, A61K 936
Patent
active
056909608
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/SE 94/00681 filed Jul. 8, 1994.
FIELD OF THE INVENTION
The present invention is related to a new pharmaceutical formulation containing a novel physical form of a magnesium salt of omeprazole, to a method for the manufacture of such a formulation, and to the use of such a formulation in medicine.
BACKGROUND OF THE INVENTION
The compound known under the generic name omeprazole, 5-methoxy-2(((4-methoxy-3,5-dimethyl-2-pyridinyl)methyl)sulfinyl)-1H-benzi midazole, is described i.a. in EP-A 0 005 129.
Omeprazole is useful for inhibiting gastric acid secretion and has gastric mucosa protective activity. In a more general sense, omeprazole may be used for prevention and treatment of gastric acid related disorders in mammals and man, including e.g. gastroesofageal reflux disease, gastritis, gastric ulcer and duodenal ulcer. Omeprazole is susceptible to degradation/transformation in acid reacting and neutral media. The half-life of degradation of omeprazole in water solutions at pH-values less than four is shorter than ten minutes. Also at neutral pH-values degradation proceeds rapidly, e.g. at pH=7 the half-life of omeprazole is about 14 hours, while at higher pH-values the stability in solution is much better (Pilbrant and Cederberg, Scand. J. Gastroenterology 1985; 20 (suppl. 108) p. 113-120). Omeprazole also in the solid state is susceptible to degradation and is stabilized in mixtures with alkaline reacting compounds. The stability of omeprazole is also affected by moisture, heat, organic solvents and to some degree by light.
From what is said about the stability properties of omeprazole, it is obvious that an oral dosage form of omeprazole must be protected from contact with the acid reacting gastric juice and the active substance must be transferred in intact form to that part of the gastrointestinal tract where pH is near neutral and where rapid absorption of omeprazole can occur.
A pharmaceutical oral solid dosage form of omeprazole must be protected from contact with acidic gastric juice by an enteric coating. In U.S. Pat. No. 4,786,505 is described an enteric coated omeprazole preparation containing a separating subcoat between the core material and the enteric coating. Said preparation contains an alkaline core comprising omeprazole, a subcoating and an enteric coating.
Certain salts of omeprazole including alkaline reacting salts of omeprazole are described in EP-A 0 124 495. In said patent specification the requirements and importance regarding storage stability of omeprazole for incorporation in pharmaceutical preparations are emphasized.
There is however, a demand for the development of new enteric preparations of omeprazole with enhanced stability and for environmental aspects there is also a strong desire for the use of water based processes in production of pharmaceutical products.
The isolation and purification in full manufacturing scale of the magnesium omeprazole salts described in EP-A 0 124 495 presents one major problem in that the magnesium omeprazole salt particles are very fragile making pharmaceutical manufacturing processes utilising this product less attractive in full scale production. Performing the process without crystallization of the magnesium omeprazole gives a product which is less suitable as a pharmaceutical substance.
In order to use the magnesium salt of omeprazole, in this specification denoted magnesium omeprazole, in full manufacturing scale in preparing pharmaceutical formulations primarily for oral administration, such as tablets, it is necessary that said magnesium omeprazole possesses a combination of properties which makes such full scale manufacturing feasible.
The combination of physical properties of the novel magnesium omeprazole product described in the present specification with respect to the degree of crystallinity, particle diameter, density, hygroscopicity, low water content and low content of other solvents is favorable and permits the manufacture of magnesium omeprazole in a form which is useful for the manufacture
REFERENCES:
patent: 4738974 (1988-04-01), Brandstrom
patent: 4786505 (1988-11-01), Lovgren et al.
Pilbrant et al., "Development of an oral formulation of omeprazole," Scand J Gastroenterol 1985; vol. 20 (Suppl 108) : 113-120.
Bengtsson Inga Siv
Lovgren Kurt Ingmar
Astra Aktiebolag
Page Thurman K.
Spear James M.
LandOfFree
Pharmaceutical formulation of omeprazole does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Pharmaceutical formulation of omeprazole, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Pharmaceutical formulation of omeprazole will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2104564