United States Patent:  6,077,541

Assignee:  Andrx Pharmaceuticals, Inc. (Fort Lauderdale, FL)

Filed:  June 18, 1999

A pharmaceutical composition of omeprazole for oral administration is described which consists essentially of: (a) a pellet comprising an inert core component, a therapeutically effective amount of omeprazole, a surface active agent, a filler, a pharmaceutically acceptable alkaline agent and a binder; and (b) a single layer of coating on said pellet which comprises a layer of an enteric coating agent.

DETAILED DESCRIPTION OF THE INVENTION

The omeprazole formulation of the invention is preferably based on pellets having a core forming inert component which may comprise a starch or sugar sphere such as non-pareil sugar seeds having an average size of from 14 to 35 mesh, preferably about 18 to 20 mesh. The core forming inert component is coated with a formulation which comprises omeprazole, a surface active agent, a filler, an alkaline material and a binder, which are collectively referred to hereafter as the drug layer composition. The core forming inert component is employed at 1:1 to 5:1 and preferably from 2:1 to 3:1 weight ratio to the drug layer composition.

The omeprazole may comprise from 20 to 70 wt % and preferably 40 to 50 wt % of the drug layer composition.

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 % and preferably 0.25 to 2.5 wt % based on the total weight of the drug layer composition.

The alkaline material is selected from the group consisting of the sodium, potassium, calcium, magnesium and aluminum salts of phosphoric acid, carbonic acid, citric acid and aluminum/magnesium compounds such as Al₂ O₃.6MgO.CO₂.12H₂ O, (Mg₆ Al₂ (OH₁-6 CO₃.4H₂ O), MgO.Al₂ O₃.2SiO₂.nH₂ O where n is a whole integer of 2 or more. In addition the alkaline material may be selected from the group consisting of antacid materials such as aluminum hydroxides, calcium hydroxides, magnesium hydroxides and magnesium oxide. The alkaline agent may be present at a level of 1 to 20 wt % based on the total weight of the coating composition, depending on the relative strength of the alkaline material. If the preferred disodium phosphate alkaline agent is employed, a level of from 1 to 10 wt % and preferably 4 to 7 wt % based on the weight of the drug layer composition may be employed.

The binder may be any pharmaceutically acceptable, non-toxic pharmaceutically acceptable binder.

The binder is preferably a water soluble polymer of the group consisting of polyvinyl alcohol, polyvinylpyrrolidone, methylcellulose, hydroxypropyl cellulose, hydroxymethyl cellulose and the like. A water soluble binder is preferred which is applied from an aqueous medium such as water at a level of from 0.1 to 5 wt % and preferably from 0.25 to 3 wt % of binder based on the total weight of the drug layer composition.

A filler is added to the drug layer. Sugars such as lactose, dextrose, sucrose, maltose, microcrystalline cellulose and the like may be used as fillers in the pellet coating composition. The filler may comprise from 20 to 70 wt % and preferably 40 to 50 wt % based on the total weight of the drug layer composition.

The enteric coating agent may comprise a 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 from 10 to 80 wt % and preferably 30 to 50 wt % based on the total weight of the acid resisting component and the inert processing aid. 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 processsing aid mixture based on the total weight of the solvent and the acid resistant component-inert processing aid.

The cores are formed by spraying the non-pareil seeds with an aqueous or non-aqueous suspension which contains the alkaline agent, the omeprazole, the surface active agent and the binder. The suspension medium may comprise any low viscosity solvent such as water, isopropyl alcohol, acetone, ethanol or the like. When fluids such as water are employed, this will usually require a weight of fluid which is about seven times the weight of the dry components of the coating composition.

After the cores are dried, the cores are coated with the enteric coating agent. A color imparting agent may be added to the enteric coating agent mixture or a rapidly dissolving seal coat containing color may be coated over the enteric coating agent layer provided that the seal coat is compatible with and does not affect the dissolution of the enteric coating layer.

Claim 1 of 14 Claims

1. A pharmaceutical capsule for oral administration of omeprazole that consists essentially of a capsule and more than one pellet wherein the pellet consists of:

(a) an inert core;

(b) a drug layer surrounding the inert core consisting of 20-70 wt % of omeprazole, 0.1-5 wt % of a surface active agent, 20-70 wt % of a filler, 1-20 wt % of a pharmaceutically acceptable alkaline agent and 0.1-5 wt % of a binder; and

(c) a coating layer surrounding the drug layer that consists essentially of an enteric coating agent and an inert processing aid wherein the coating layer is applied directly to the omeprazole containing drug layer without a separating layer between the omeprazole containing drug layer and the coating layer.

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