Controlled release tablet formulation

The present invention is directed to a controlled release dosage form which may be made using an osmotic core which contains a drug containing phase which includes a water swellable component and a continuous coating which comprises a major amount of a water resistant polymer and a minor amount of a non-toxic, water soluble, pharmaceutically acceptable compound.

BACKGROUND OF THE INVENTION 
The present invention is concerned with a controlled release tablet dosage 
formulation that is based on the use of a tablet core which has a coating 
which contains a major amount of a water insoluble polymer and a minor 
amount of a water soluble compound. 
In order to provide a controlled release product, a water insoluble 
material such as a resin or a wax has been used to coat discrete drug 
containing units in order to resist the action of the fluids in the 
gastrointestinal tract. These coatings have resulted in the production of 
satisfactory pellets or granules that would usually be placed in a gelatin 
capsule because if a tablet was made from the resin or wax coated pellets, 
the coating would either rupture or become so deformed that the uniformity 
of any wax coating would be adversely affected. 
U.S. Pat. No. 3,977,404 discloses that in the prior art, attempts were made 
to make sustained release devices by placing a water soluble drug in a 
polymer film and allowing the drug to be leached out. Another attempt was 
based on the use of a drug that was coated with a film of water insoluble 
plastic containing a modifying agent which was soluble at a certain pH. 
This device would form a porous film under the proper pH conditions which 
would allow gastrointestinal fluid to dissolve the drug and leach it 
outwards through the pores in the film. The pH dependent nature of the 
film made it difficult to control the rate and site of release because of 
variations in the pH of the gastrointestinal tract. 
Osmotic tablets are described in U.S. Pat. No. 3,977,404 which are based on 
the use of a microporous core which is coated with a material that does 
not allow for the passage of a drug. These tablets are provided with a pre 
formed osmotic delivery orifice which allows gastrointestinal fluid to 
flow into the osmotic core and cause the osmotic core to deliver the 
contents of the core over an extended period of time. Other variations on 
this concept are described in U.S. Pat. No. 4,687,660 which describes the 
use of a polymer coating having a water soluble pore forming material 
therein which surrounds a core which contains a water soluble enhancing 
agent. 
SUMMARY OF THE INVENTION 
The present invention is directed to a controlled release dosage form which 
may be made using an osmotic core which contains a drug containing phase 
which includes a water swellable component and a continuous coating which 
comprises a major amount of a water resistant polymer and a minor amount 
of a non-toxic, water soluble, pharmaceutically acceptable compound. 
Accordingly it is a primary object of this invention to provide a novel 
controlled release dosage formulation. 
It is also an object of this invention to provide a novel tabletted 
formulation which is made by forming a core which contains a drug and a 
water swellable agent and coating said core with a continuous coating 
which comprises a polymer and a water soluble compound. 
It is also an object of this invention to provide an osmotic tablet which 
does not require a pre-formed osmotic delivery orifice which exposes the 
osmotic core to the action of gastrointestinal fluid. 
It is also an object of this invention to provide a novel osmotic tablet in 
which the osmotic core is sealed against the ambient atmosphere. 
These and other objects of the invention will become apparent from a review 
of the appended specification.

DETAILED DESCRIPTION OF THE INVENTION 
The present invention is directed to a controlled release dosage form which 
may be made using an osmotic core which contains a drug containing phase 
and a swelling agent and optionally an osmotic flow agent. The swelling 
agent is a water insoluble hydrophilic material which may be 
hydroxypropylmethyl cellulose or polyethylene oxide. The purpose of the 
swelling agent is to expand the core and provide a drug rich surface in 
contact with the internal end of the microporous channels that are formed 
when the non-toxic, water soluble, pharmaceutically acceptable compound 
dissolves in the gastrointestinal fluid. The presence of a drug rich 
surface in contact with the interior of the water insoluble polymer 
provides for a substantially continuous availability of drug which is 
transported through the microporous channels of the water insoluble 
polymer. 
The osmotic agent which is optionally placed in the tablet core is an agent 
which is water soluble and will provide an osmotic pressure in the tablet 
which is greater than the osmotic pressure in the gastrointestinal fluid. 
The presence of the osmotic agent will enhance the delivery of the drug 
from the core of the coated tablet of the invention. Suitable osmotic 
agents include magnesium sulfate, magnesium chloride, sodium chloride, 
lithium chloride, potassium sulfate, sodium carbonate, lithium sulfate, 
potassium chloride, calcium bicarbonate, sodium sulfate, calcium lactate, 
potassium acid phosphate, urea, magnesium succinate, sucrose, citric acid, 
or mixtures thereof and the like. The swelling agent is used in an amount 
which will result in the expansion of the tablet core without causing the 
tablet to rupture as the swelling agent becomes wet with gastrointestinal 
fluid. The osmotic agent is used in an amount which will result in an 
increased osmotic pressure between the core of the tablet and the 
gastrointestinal fluid which contacts the tablet in vivo. The tablet core 
may comprise from 40 to 90 wt % and preferably 65 to 85 wt % of the drug; 
from 0.5 to 15 wt % and preferably 2 to 8 wt % of the swelling agent and 
optionally from 0.5 to 15 wt % and preferrably 2 to 8% of the osmotic 
agent. The wt % is computed based on the total weight of the drug, 
swelling agent and osmotic agent. 
The water resistant polymer may be any polymer which forms a semi-permeable 
membrane that has a water sorptivity of 5 to 50% by weight. The materials 
from which the water resistant polymer may be made include cellulose 
acetate, cellulose triacetate, agar acetate, amylose triacetate, beta 
glucan acetate, acetaldehyde dimethyl acetate, cellulose acetate methyl 
carbamate, cellulose acetate phthalate, cellulose acetate succinate, 
cellulose acetate dimethylamino acetate, cellulose acetate ethyl 
carbonate, cellulose acetate chloroacetate, cellulose acetate ethyl 
oxalate, cellulose acetate propionate, poly(vinylmethylether) copolymers, 
cellulose acetate butyl sulfonate, cellulose acetate octate, cellulose 
acetate laurate, cellulose acetate p-toluene sulfonate, triacetate of 
locust gum bean, hydroxylated ethylene-vinyl acetate, cellulose acetate 
butyrate, ethyl cellulose and the like. Other useful membrane forming 
materials are disclosed in U.S. Pat. No. 3,977,404, which is incorporated 
by reference. 
The non-toxic, water soluble, pharmaceutically acceptable material may be 
selected from magnesium sulfate, magnesium chloride, sodium chloride, 
lithium chloride, potassium sulfate, sodium carbonate, lithium sulfate, 
potassium chloride, calcium bicarbonate, sodium sulfate, calcium lactate, 
potassium acid phosphate, urea, magnesium succinate, sucrose, citric acid, 
or mixtures thereof and the like. 
Generally, the ratio of the water resistant polymer to the non-toxic, water 
soluble, pharmaceutically acceptable material will be 20:1 to 2:1, and 
preferably about 8:1 to 4:1. 
The drug that may be formulated according to the method of the present 
invention may be any inorganic or organic medicinal including but not 
limited to antibiotics, tranquilizers, agents which act on the heart, 
liver, kidneys, central nervous system, muscles, contraceptives, hormonal 
agents, antineoplastic agents or combinations of therapeutically 
complimentary drugs. These drugs are described in the Physicians Desk 
Reference, 1993 Ed., and U.S. Pat. No. 3,977,404 which are incorporated by 
reference. The preferred drugs are water soluble drugs. 
The amount of the drug is that amount which is sufficient to deliver a 
therapeutic plasma level which is sufficient to provide the desired 
therapeutic result. The dosages for the drugs which are usable according 
to the present invention are described in the literature and one who is 
skilled in the art can readily determine the amount of any particular drug 
which is to be used by routine experimentation. 
The following Example is merely added to illustrate the invention and is 
not to be considered as limiting the scope of the invention in any way. 
EXAMPLE 
A core tablet was prepared which had the following formulation: 
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Pseudoephedrine HC1, U.S.P. 
79.34 wt % 
Povidone, U.S.P. (Kollidon K30) 
9.4 wt % 
Polyethylene oxide 5.24 wt % 
Sodium Chloride, U.S.P. 3.00 wt % 
Myvatex, Eastman Kodak (lubricant) 
3.00 wt % 
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The pseudoephedrine HCl is granulated in the solution of povidone in a 
fluid bed processor. The granulated product is is combined with the 
polyethylene oxide and the sodium chloride in a Patterson Kelly blender at 
25 rpm for 10 minutes. The Myvatex is passed through a #40 US Standard 
mesh screen and added to the blender. The combined ingredients are blended 
for an additional 3 minutes. The powder blend is compressed into tablets 
using a punch tip size of 0.375" in diameter; a weight of 242 mg (230-254 
mg.) and a hardness of 10-20 kp. 
A sustained release coating composition is prepared using the following 
formulation: 
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Cellulose Acetate (Wt Av MW 30,000) 
7.35 wt % 
Sodium Chloride 1.47 wt % 
Triacetin 2.12 wt % 
Acetone 40.0 wt % 
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The cellulose acetate is dissolved in the acetone in a stainless steel tank 
using a propeller shaped stirring device. The triacetin is then added and 
the sodium chloride is then dispersed in the solution. The previously 
prepared pseudoephedrine tablets are spray coated in a fluidized bed 
coater with the coating suspension to provide coated tablets which have a 
coating which is 11% by weight of the total weight of the uncoated tablets 
and the coating. These tablets release the pseudoephedrine HCl over a 
period of 24 hours when 500 ml of purified water was used as the 
dissolution medium and the USP XXII paddle method at 100 rpm.