Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Capsules
Reexamination Certificate
2001-07-11
2004-05-11
Page, Thurman K. (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Capsules
C424S457000, C424S458000, C424S459000, C424S461000, C424S462000, C424S489000, C424S490000, C424S493000, C424S494000
Reexamination Certificate
active
06733778
ABSTRACT:
BACKGROUND OF THE INVENTION
The present invention relates to a stable formulation of omeprazole. It is well known that omeprazole is sensitive to acidic conditions and after contact with an acid, omeprazole will degrade and will not function in its intended manner. Initially, alkaline materials were added to a core of omeprazole and later an enteric coating was applied over the core to prevent the omeprazole from contacting the acidic pH conditions of the stomach. This approach is satisfactory if the product is administered within a short time after it is manufactured but if the product is stored under ambient conditions, the acidic residue of the enteric coating appears to degrade the omeprazole before it is administered to a patient. To solve this problem, the prior art has used a separate layer of a coating agent to coat a pellet core which contains omeprazole and an alkaline material which is thereafter coated with the enteric coating. This technique is described in U.S. Pat. No. 4,786,505. In addition WO 96/24338 discloses the use of an in situ formed interlayer that is based on the reaction of an aqueous enteric coating material with an alkaline material in the core.
This dual layer coating technique requires the application of two separate functional coating operations which increases the length of the manufacturing process and the cost of the product. The applicants have surprisingly discovered a coating system which avoids the need to use a coating layer to separate the omeprazole core from the enteric coating layer in an omeprazole dosage form. The separate coating system is based on the combined use of an enteric coating agent which is applied to a pelletized core or a granular core of omeprazole as a suspension in a suitable solvent.
The applicants have also surprisingly discovered that arginine or lysine can be used as a pH stabilizing agent
SUMMARY OF THE INVENTION
The present invention provides a novel stable pharmaceutical composition of omeprazole for oral administration which consists essentially of:
(a) a core of omeprazole or a pharmaceutically equivalent salt, a filler and an alkaline material selected from the group consisting of lysine and arginine; and
(b) a single layer of coating on said core which comprises a layer of an enteric coating agent applied from an organic based solvent coating system.
The core of the pharmaceutical composition can be in the form of a compressed tablet which is further comprised essentially of a surface active agent, and a binder. Alternatively, the pharmaceutical composition can have a pelleted core which is further comprised essentially of an inert core component, a surface active agent and a binder.
Accordingly, it is a primary object of this invention to provide a pharmaceutical dosage formulation of omeprazole which is stable upon prolonged storage, is stable when administered to a patient and is capable of providing the desired therapeutic effect.
It is also an object of this invention to provide a pharmaceutical dosage form of omeprazole which is bioequivalent to dosage forms of omeprazole which have an intermediate layer of an inert coating material.
It is also an object of this invention to provide a stable dosage form of omeprazole which may be produced without the need to provide an intermediate coating layer that separates the omeprazole containing core from the enteric coating layer.
These and other objects of the invention will become apparent from a review of the appended specification.
DETAILED DESCRIPTION OF THE INVENTION
The omeprazole formulation of the invention is preferably based on a core of omeprazole or pharmaceutically equivalent salt, a filler and an alkaline material selected from the group consisting of arginine or lysine; and a single layer of coating on said core which comprises a layer of an enteric coating agent applied from an organic solvent based system. The Omeprazole core can either be pelleted or tabletted as described herein.
In the case of both the pelleted form and the tabletted form of the core a filler is used. A filler is used as a granulation substrate. Sugars such as lactose, dextrose, sucrose, maltose, or microcrystalline cellulose and the like may be used as fillers in either the pellet or the granulation composition. In the case of the pelleted form the filler may comprise from 20 to 90 wt % and preferably 65-85 wt % based on the total weight of the drug layer composition. In the case of the tabletted form the filler may comprise from 20 to 60 wt % and preferably 20 to 40 wt % based on the total weight of the granulation. In the case of the tabletted form of the invention a tablet disintegrant may be added which comprises corn starch, potato starch, croscarmelose sodium, crospovidone and sodium starch glycolate in an effective amount. An effective amount which may be from 3 to 10 wt % based on the total weight of the granulation.
In the case of both the tabletted form and the pelleted form of the core an alkaline agent that is either lysine or arginine is used as a stabilizer. In the case of the tabletted form a level of from 20 to 60 wt % and preferably 30 to 55 wt % based on the weight of the granulation may be employed. In the case of the pelleted form a level of from 0.5 to 10 wt % and preferably 1 to 3 wt % based on the weight of the pellet may be employed.
In the case of the pelleted form and the tabletted form of the invention an enteric coating agent is placed over the core. In both cases the enteric coating may comprise an acid resisting material which resists acid up to a pH of above about 5.0 or higher which is selected from the group consisting of cellulose acetate phthalate, hydroxypropylmethyl cellulose phthalate, polyvinyl acetate phthalate, carboxymethylethylcellulose, Eudragit L (poly(methacrylic acid, methylmethacrylate), 1:1 ratio; MW (No. Av. 135,000—USP Type A) or Eudragit S (poly(methacrylic acid, methylmethacrylate, 1:2 ratio MW (No. Av. 135,000—USP Type B) and mixtures thereof.
The enteric coating agent may also include an inert processing aid in an amount in the case of the tabletted form from 15 to 55 wt % and preferably 20 to 45 wt % based on the total weight of the acid resisting component and the inert processing aid. In the case of the pelleted form the inert processing aid is preferably in an amount from 5 to 50 wt % and most preferably 10-20 wt %. The inert processing aids include finely divided forms of talc, silicon dioxide, magnesium stearate etc. Typical solvents which may be used to apply the acid resisting component-inert processing aid mixture include isopropyl alcohol, acetone, methylene chloride and the like. Generally the acid resistant component-inert processing aid mixture will be applied from a 5 to 20 wt % of acid resisting component-inert processing aid mixture based on the total weight of the solvent and the acid resistant component-inert processing aid.
In the case of both the tabletted form and the pelleted form of the invention omeprazole or a pharmaceutically equivalent salt is used in the core. In the tabletted formulation the omeprazole may comprise from 5 to 70 wt % and preferably 10 to 30 wt % of the granulation. In the pelleted form the Omeprazole may comprise from 10 to 50 wt % and preferably 10 to 20 wt % of the drug layer composition.
A surface active agent is used in both the tabletted and the pelleted form of the invention. The surface active agent may be any pharmaceutically acceptable, non-toxic surfactant. Suitable surface active agents include sodium lauryl sulfate, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80 and the like. The surface active agent may be present at a level of from 0.1 to 5 wt %. In the case of the tabletted form the surface active agent is preferably 0.20 to 2.0 wt % based on the total weight of the granulation. In the pelleted form the surface active agent is preferably 0.20 to 2.0 wt % of the total weight of the drug layer composition.
The binder is used in both the tabletted and the pelleted form of the invention. The binder may be any pharmaceutically acceptable, non-to
Chen Chih-Ming
Chou Joseph
Kositprapa Unchalee
Andrx Pharmaceuticals Inc.
Hedman & Costigan ,P.C.
Page Thurman K.
Tran S.
LandOfFree
Omeprazole formulation does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Omeprazole formulation, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Omeprazole formulation will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3213615