United States Patent:  6,013,282

Assignee:  Bpsi Holdings, Inc. (Wilmington, DE)

Filed:  November 26, 1997

A non-toxic edible enteric film coating dry powder composition for use in making an aqueous enteric coating suspension which may be used in coating pharmaceutical tablets and the like comprises an enteric film forming polymer, a detackifier, a viscosity modifier, and an alkalizing/anti-coagulating agent. Advantageously, the inventive dry powder compositions may include a solid plasticizer, a lubricant, an anti-caking agent, a liquid plasticizer, and a pigment.

DETAILED DESCRIPTION OF THE INVENTION

A non-toxic edible enteric film coating dry powder composition for use in making an aqueous enteric coating suspension which may be used in coating pharmaceutical tablets and the like comprises an enteric film forming polymer, a detackifier, a viscosity modifier, and an alkalizing/anti-coagulating agent. In a particularly preferred embodiment, the inventive non-toxic edible enteric film coating dry powder composition also includes a solid plasticizer.

Advantageously, the inventive dry powder compositions may include a lubricant, an anti-caking agent, a liquid plasticizer, and a pigment.

A method of making the inventive non-toxic edible film coating dry powder composition comprises the steps of mixing an enteric film forming polymer with a detackifier, a viscosity modifier, and an anti-coagulating/alkalizing agent, and optionally with one or more of the following components, until a dry homogeneous powder mixture is produced: a solid plasticizer, a lubricant, an anti-caking agent, a liquid plasticizer, and a pigment. The resulting enteric film coating dry powder composition is readily dispersible in deionized water to form a liquid enteric coating suspension and is ready to use in 30 to 45 minutes.

The invention also includes an aqueous enteric coating suspension for making an enteric coating for pharmaceutical tablets and the like which comprises an enteric film forming polymer, a detackifier, a viscosity modifier, an alkalizing agent, a plasticizer, and an antifoaming agent mixed into water. Advantageously, the inventive suspension may include an optional lubricant, an optional anti-caking agent, and/or an optional pigment.

A method of making the aqueous enteric coating suspension of the invention comprises mixing the anti-foaming agent into water, mixing the inventive enteric dry powder composition, or the individual ingredients of the inventive enteric dry powder composition separately, into the water, and stirring until a homogeneous suspension is produced. When using an embodiment of the inventive enteric dry powder composition that does not have a plasticizer mixed into it, a plasticizer, preferably a liquid plasticizer, is mixed into the water, preferably after the step of mixing the anti-foam into the water.

The inventive suspension may include a solid plasticizer in combination with a liquid plasticizer. In such a suspension, the liquid plasticizer may be mixed into the enteric dry powder coating composition to become part of the enteric dry powder coating composition of the invention, or the liquid plasticizer may be added separately to the water when preparing the inventive suspension.

The invention also includes a method of coating substrates such as pharmaceutical dosage forms like tablets and the like with a non-toxic edible enteric film coating, which comprises the steps of forming the inventive aqueous enteric coating suspension as discussed above, applying the inventive aqueous coating suspension onto the substrates to form a film coating on the substrates, and drying the film coating on said substrates.

The enteric film forming polymer is PVAP-T (titanized polyvinyl acetate phthalate), PVAP-J (polyvinyl acetate phthalate which has been jet milled), HPMCP (hydroxypropyl methylcellulose phthalate), HPMCAS (hydroxypropyl methylcellulose acetate succinate), or CAP (cellulose acetate phthalate). The titanized polyvinyl acetate phthalate (PVAP-T), comprises about 10% titanium dioxide mixed into polyvinyl acetate phthalate (PVAP), while it is being made. A preferred enteric polymer is PVAP-T.

Preferably, the enteric polymer has a particle size such that 90% of the polymer particles are under 25 microns, and more preferably, under 13 microns.

The enteric polymer is about 65-85% by weight of the dry powder composition, and is preferably in the range of about 65-81% by weight of the dry powder composition.

The detackifier is talc, aluminum hydrate, or mixtures thereof. The detackifier is about 5-15% by weight of the dry powder composition, and is preferably in the range of about 6-12% by weight of the dry powder composition.

The viscosity modifier is sodium alginate, hydroxypropyl methylcellulose (HPMC), hydroxyethylcellulose (HEC), sodium carboxymethycellulose (sodium CMC), polyvinylpyrrolidone (PVP), Konjac flour, carrageenan, xanthan gum, other hydrophilic polymers, or mixtures thereof. The viscosity modifier is present in the dry powder composition to assist in the forming of a film on the tablets and to act as a suspending agent for the insoluble components in the coating suspension, as well as adding viscosity to the coating suspension. The viscosity modifier helps the coating to adhere to the tablet surface while the enteric polymer particles are fusing to form a film. In other words, the viscosity modifier makes the coating suspension thicker and thereby inhibits settlement and acts as a suspending agent, and also acts as a film former. A preferred viscosity modifier is a medium viscosity grade of sodium alginate (e.g., Kelco Manugel A3B812 sodium alginate).

The viscosity modifier is about 0.5 to 7% by weight of the dry powder composition, and is preferably in the range of about 1-6% by weight of the dry powder composition.

The alkalizing agent is a bicarbonate, a carbonate, a phosphate, or a hydroxide of sodium or potassium, magnesium carbonate, magnesium hydroxide, ammonium carbonate, ammonium bicarbonate, magnesium oxide, calcium hydroxide, or mixtures thereof.

The alkalizing agent is about 1-15% by weight of the dry powder composition, and is preferably in the range of about 1.5-12% by weight of the dry powder composition. Sodium bicarbonate and/or sodium carbonate as the alkalizing agent are preferably used in a range of about 2.0% to about 6% by weight of the dry power composition, and more preferably used in a range of about 2.0% to about 4.5% since above 6% may lead to tackiness problems. When using tri-sodium phosphate as the alkalizing agent, a range of 4.5% to 7% by weight of the dry power composition is preferred for tri-sodium phosphate (anhydrous) and a range of 8% to 12% by weight of A the dry power composition is preferred for tri-sodium phosphate (hydrated).

The alkalizing agent acts as an anti-coalescing or stabilizing agent to raise the agglomeration or gel temperature of the coating suspension to prevent coalescing or blockage of the spray lines and guns. The alkalizing agent also reduces the tackiness of the coating.

The solid plasticizer is polyethylene glycol having a molecular weight of 1500 to 8000, or Pluronic F86 (a block co-polymer of ethylene oxide and propylene oxide (EO/PO)), or mixtures thereof. The preferred solid plasticizer is polyethylene glycol 3350 (PEG 3350) or polyethylene glycol 4000 (PEG 4000).

The solid plasticizer when included in the inventive enteric dry powder composition is about 1-20% by weight of the dry coating composition, and is preferably about 1-18% by weight of the dry coating composition.

The liquid plasticizer may be triethylcitrate, glyceryl triacetate, acetyltriethylcitrate, dibutyl sebacate, diethyl phthalate, polyethylene glycol 400, glycerol, castor oil, or mixtures thereof.

When the liquid plasticizer is included in the dry powder composition of the invention, the liquid plasticizer is in a range of greater than 0% to about 6% by weight of the dry powder composition. The dry powder composition of the invention is still dry even though it may contain about 4-6% liquid plasticizer by weight of the dry powder composition.

When no plasticizer is included in the dry powder coating composition of the invention or when no liquid plasticizer is included in the dry powder coating composition of the invention, about 5% to about 20% of liquid plasticizer by weight of the dry solid ingredients of the coating suspension of the invention is mixed separately into the coating suspension of the invention.

The inventive coating suspension has about 5% to about 20% of solid plasticizer, liquid plasticizer, or a combination of solid plasticizer and liquid plasticizer by weight of the non-water ingredients of the inventive coating suspension.

The lubricant is stearic acid, which is in a range from 0% to about 3% by weight of the dry coating composition.

The anti-caking agent may be Cabosil, fumed silica made by Cabot, Inc., which is present in a range from 0% to about 2% by weight of the dry powder composition, and preferably is present in a range from 0% to 1.5% by weight of the dry powder coating composition. The anti-caking agent acts as a processing aid and also keeps the dry powder from lumping up while in storage. Use of this anti-caking agent is optional because any lumps that are formed are screened out as part of the preparation of the dispersion.

The pigment may be any of the pigments used in making coating dispersions for pharmaceutical tablets and the like. For example, the pigments may be FD&C and D&C lakes, titanium dioxide, magnesium carbonate, talc, pyrogenic silica, iron oxides, channel black, and insoluble dyes. Also, natural pigments such as riboflavin, carmine 40, curcumin, and annatto. Other examples of suitable pigments are listed in Jeffries U.S. Pat. No. 3,149,040; Butler et al. U.S. Pat. No.3,297,535; and Colorcon U.S. Pat. No. 3,981,984; all of which are incorporated herein by reference.

The pigment may also include lake blends, which contain a plasticizer, and OPADRY pigmented coating compositions, some of which are disclosed in Colorcon U.S. Pat. No. 4,543,370 issued on Sept. 24, 1985, which is incorporated herein by reference.

The pigment, in addition to adding color to the coating of the invention, also acts as an anti-gelling agent.

The pigment is in a range from 0% to about 25% by weight of the dry coating composition, and preferably is in a range from 0% to about 15% by weight of the dry powder composition.

The antifoaming agent is a silicone based antifoam, such as Antifoam FG-10 made by Dow Corning. The antifoaming agent is in a range from about 0.1% to about 5% by weight of the dry powder composition, and is preferably about 0.5% to about 5% by weight of the dry powder composition.

The inventive dry powder non-toxic enteric coating composition is to be made and sold by Colorcon, West Point, Pa. 19486, under the trademark SURETERIC.

Claim 1 of 5 Claims

1. A method of coating substrates such as pharmaceutical tablets with an enteric film coating, comprising

mixing an antifoaming agent into water,

mixing an enteric film forming polymer, a detackifier, a viscosity modifier, an alkalizing agent, and a plasticizer into the water to form an aqueous enteric coating suspension,

applying the aqueous enteric coating suspension onto the substrates to form an enteric film coating on the substrates, and

drying the enteric film coating on said substrates.

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