IL32200A - Sustained release drug composition - Google Patents

Description

Sustained release drug compoGition Cj 305Q9 AHP-i*566/Cl/lsrael This invention relates to therapeutic composition for use in prepared tablets with delayed release action including the ability to release a drug, or the active ingredient, gradually over relatively long periods of time, to the tablets made therefrom and to methods for preparing and using such compositions,, More particularly, the invention relates to a sustained action dosage composition, containing a high molecular weight carboxy vinyl polymer and polyethylene glycol, and having a controlled rate of release of a contained drug, substantially independent of pH„ Various processes and compositions have been proposed which delay or prolong the release of medicaments in oral form. Some such compositions are disclosed in U.S. Patent Nos. 3107½1852, 3*330, 729 and 3,3^6, *9 and U.K. Patent No. 908, 016. The first three mentioned patents disclose the sustained release of a drug using a carboxy vinyl polymer, such as Carbopol 93^ * either alone as in U.S. Patent No. 3,0 ^,852, or with other excipients as in U.S. Patent Nos. 3»330,729 and 3,3^6,^9. U.K. Patent No. 9^8,016 discloses a sustained release drug composition containing a methylacrylate-raethylmethacrylate copolymer together with an excipient which may be a polyethylene glycol; copolymers of this type do not form complexes with polyethylene glycol. The prior art differs from the present invention in that nowhere is there disclosed a sustained release drug composition containing a carboxy vinyl copolymer, as hereinafter defined, together with a polyethylene glycol which has a controlled rate of drug release substantially independent of pH.

The slow release prior art compositions which contain a carboxy vinyl polymer^ such as Carbopol 93^, are pH dependent. That is, there is a delayed release of a drug in a medium having a pH from about pH i to about pH 11, but there is a rapid release of a drug in a medium of low pH where the polymeric material is not hydrated.

For example, sustained action formulations of oxazepam utilizing the prior art compositions of the preceding paragraph demonstrate a pH-dependent drug release. In an acidic solvent (O.IN HCl), representing gastric fluid, the polymer is not hydrated and consequently does not significantly retard the dissolution of the active component from the dosage unit, however, in a buffer solution (pH 7·5) representing the intestinal fluid, hydration of the polymer takes place with a resulting slowing of the release of the drug.

Because the acid content of the stomach varies considerably and the time interval during which a dosage composition remains in the 3 32200/2 stomach also varies, ideally, a sustained action system should he independent of pH so that the release of the dru would he independent of the foregoing factors.

Accordin to the present invention there is provided a tablet composition for sustained release of a drug opmprising a drug, a water-insoluble carboxy vinyl polymer and polyethylene glycol the ratio of carboxy vinyl polymer to polyethylene glycol being such as to provide a controlled rate of release of the drug which is substantially independent of. pH.

The carboxy vinyl polymer is in the form of a i copolymer of an. olefinically unsaturated carboxylic aoid monomer containing at least 1 carbon-to-carbon olefinic double bond and at least 1 carboxyl group combined with from 0·75 to 2% by weight of a polyalkenyl polyether as a cross-linking agent.

In one aspect the present invention provides a pharmaceutical composition which is capable of releasing drug immediately and the ■ uuii'prndy ov In another aspect this invention provides a pharmaceutical . · composition in which the rate of release of drugs of different solubilities may be controlled. , It has been found that the rate of release of a drug from a ■ therapeutic composition may be made substantially independent of pH . , where the composition includes a carboxy vinyl polymer and a polyethylene glycol. The drug preferabl is utilizable in powdered '. ■'.'·; ,' form. The drug desirably comprises about 1 to 0 percent by weight, '. preferably 5 to 20 percent by weight, of the tablet composition. .

The total of the carboxy vinyl polymer and polyethylene glycol preferably comprises about 10 to; 60. percent by weight, preferably about 20 to 50 percent by weight, of the composition. The remainder of the composition may be a fast release drug, extenders, lubricants, Advantageous results may be obtained when the carboxy vinyl polymer is present in the amount of about 15 to 25 percent by weight.

Similarly the polyethylene glycol is generally present in the amount of about * to 30 percent by weight, preferably about 10 to percent by weight0 Advantageous results may be obtained where glycol and a carboxy vinyl polymer in a therapeutic formulation resulted in a product demonstrating a significant decrease in the rate of drug release in an acidic medium, with substantially no effect on the rate of release in a pH 7«5 medium. Without wishing to be bound by a theory of operation, the probable mechanism by which this delayed release occurs in the acidic medium is through the formation of a molecular complex between the polyethylene glycol and the carboxy vinyl polymer,, The complex, however, is apparently not stable in a basic medium, and i the latter environment the normal hydration of the carboxy vinyl polymer acts as a delaying mechanism,. By varying the ratio of complexable to free polymeric substances in the dosage form, the release of drugs of varying solubilities may be controlled. The carboxy vinyl polymer is substantially insoluble in water and is preferably the acid form of a polymer prepared as described in United States Patent No, 2,798,053, granted July 2, 1957, selectively utilizing from about 0„75 to 2 percent by weight of poly- alkenyl polyether, for example, polyallyl sucrose as the cros'slinking material, the remainder being essentially acrylic acid or its equivalent and the polymerisation being carried out in a hydrocarbon diluent with a free radical catalyst, for example, benzoyl peroxide. The carboxy vinyl polymers employed in this invention are more AHP«4566/Cl/f specifically described in. United States Patent No0 209O9iA62 of particular interest being the preparation produced in acid form0 A particularly effective embodiment of the high molecular weight in carboxy vinyl polymer is a water soluble polymer of acrylic acid crosslinked with 1% of a pplyallyl ether of sucrose having an average of about 5< 8 allyl groups for each molecule of sucrose (Carbopol 93 (formerly known as "Good-rite I is to be understood that the carboxy vinyl polymer used in this invention is unsteamed as required by The polyethylene glycol employed in the present invention may have a molecular weight from about 1,000 to 20,000, preferably ,000 to 6 ,000ο The limiting factors are melting point at the lower molecular weights and solubility at the higher molecular weights, the determining factors being the dose form, storage conditions, and the like0 Advantageous results have been obtained with polyethylene glycol having a molecular weight of about 4,000 hereafter sometimes referred to as "PEG 4000"0 The use of the invention to control the release drugs from tablets containing a carboxy vinyl polymer-polyethylene glycol mixture has been demonstrated with a substantially insoluble drug, oxazepam, and with a quinine salt, a readily soluble drugo Oxazepam is the generic name for 7-chloro~l,3-dihydro~3=hydroxy~5-phenyl-2H-l,i-benzodiazepine-2-one0 The dosage and mode of administration of oxazepam and quinine are well known, see for instance, Physician's 1203-4 and 782 respectively Desk Reference, 22nd edition, 1967, /page-13 ~e*e-0 It is to be understood that the invention is applicable to other drugs as well, for example penicillins or derivatives thereof, as will be disclosed hereafter0 In one preferred embodiment the invention includes a sustained release tablet in which the components includes Oxazepam 15 to 60 milligrams Carboxy vinyl polymer 20 to 150 milligrams Polyethylene glycol 20 to 150 milligrams Extenders, lubricants, flavouring and the like 5 to ^ 0 milligrams.

In another preferred embodiment the invention provides a sustained release tablet in which the components include: Quinine salt 15 to 60 milligrams Carboxy vinyl polymer 20 to 150 milligrams Polyethylene glycol 20 to 150 milligrams Extenders, lubricants, flavouring and the like 5 to ^50 milligrams A further embodiment of the invention provides a sustained release tablet in which the components include: Percent by weight 6-(l-Aminocyclohexanecarboxamido) -3 » 3- dimethyl-y-oxo- -thio-l-azabicyclo [3«2.0]heptane-2-carboxylic acid 5-20 Carboxy vinyl polymer 15-25 Polyethylene glycol 15-25 Diluents, lubricants, flavouring and the- like 5-65 The invention is illustrated by the following examples and the accompanying drawings in which Figure 1 is a graph of the drug release characteristics of a ty ical pH-dependent drug release composition and of a composition of the present invention, both in an acidic medium and in an alkaline medium; Figure 2 is a graph of the phase solubility study of Carbopol 93^ and polyethylene glycol having a molecular weight of about ^000; and Figure 3 is graph of the drug release characteristics of drug-containing compositions at various ratios of carboxy vinyl polymer and polyethylene glycol.

EXAMPLE 1 The following example illustrates the effect on the dissolution rate of a relatively insoluble compound,.

Part 1 Tablets were prepared. from the . following control formula which does not- contain polyethylene glycolo Ingredient Weight percent Oxazepam 9o 7 Carbopol 93 »· (2 „ 5# Carbosil) 62 20 o 0 Lactose 211 68 o l Magnesium stearate 7 2 o 2 The ingredients were weighed, screened, and blended, then densified by compacting in a tableting machine0 Dissolution tests on the tablets were performed using a low agitation procedure„ In such a procedure one tablet is placed in a two litre, round bottom flask containing 1750 millilitres of a solvent, and agitated,, Agitation is accomplished by rotating a 7o 5 centimetre Teflon paddle located 2 „ 5 centimetres from the bottom of the flask at 50 revolutions per minute,.

One group of Formula A tablets were placed in one-tenth normal hydrochloric acid (0„1N HC1)„ The pH of 0.1N HC1 is about 1„ 5<, The amount of oxazepam in solution at various time intervals was recorded, A second group of Formula A tablets was placed in 0o 2 molar solution of disodium phosphate and monosodium phosphate buffered to a pH of 7<> 5 ° Samples were withdrawn at the -times indicated by the dots in Figure 1 , either 1, 2 , 3 , , or 6 hours0 The samples were filtered and assayed for drug contento The results are shown in Figure 1 where the percent of drug in solution is recorded,, Part 2 Tablets were prepared as in Part 1 in which the delayed release portion had the following formula which includes polyethylene glycolo Formula B 0 Ingredient Milligrams Weight percent Oxazepam 30 7<>8 Carbopol 93f (2„5% Carbosil) 93 2½02 Lactose l80 kSo ? Magnesium stearate 7 lo8 Following the procedure of Part 1„ one group of Formula B tablets was placed in 0»1N HCl and another group of Formula B tablets was placed in a phosphate solution buffered to a pH of 7 «5° The amount of oxazepam in solution was determined at various time intervals as indicated by the dots in Figure 10 The results are shown in Figure lo Curve A in Figure 1 shows the amount of oxazepam from Formula A in solution in a pH 105 medium at various times after immersion.

Curve B in Figure 1 shows the amount of oxazepam from Formula A in a pH 7o medium at various times after immersion,.

Curve C in Figure 1 shows the amount of oxazepam from Formula B in solution in a pH 10 medium at various times after immersion.

Curve D in Figure 1 shows the amount of oxazepam from Formula B in solution in a pH 7» 5 medium at various times after immersion,.

As may be seen from a comparison of Curves A and B with Curves C and D, the oxazepam in tablets containing both Carbopol 9 k and PEG 4000 was released at a rate substantially independent of pH.

The oxazepam in tablets without PEG 000 was released more quickly in a pH 1„5 solution than in a pH 7«5 solution. The oxazepam in tablets containing both Carbopol 934 and PEG 4000 was released at a rate that was substantially independent of pH„ Also, there is a substantially lower release rate in an acidic medium such as gastric juices, so that the oxazepam will not be totally released in the stomach, but will continue to be released in the intestines and at a substantially uniform rate.

Other tablets having sustained release characteristics may be prepared by the foregoing procedure but substituting other active ingredients for oxazepan Such active ingredients include: amphetamine sulphate acetyl salicylic acid aminophylline antazoline hydrochloride alkaloids of belladonna ampicillin ascorbic acid atropine sulphate aureomycin bethanecholchloride caffeine codeine sulphate colchicine cortisone dextroamphetamine sulphate digitoxin dihydrostreptomycin dienestrol diethyl carbamazine citrate diethylpropion doxylamine succinate d-methorphan hydrobromide erythrityltetranitrate ephedrine sulphate ergonovine maleate ethisterone hexocyclium methylsulphate isoniazid morphine sulphate meprobamate mercurophylline methyltestosterone methamphetamine hydrochloride neostigmine bromide nicotinic acid nicotinamide N-acetyl-p-aminophenol pentobarbital pyrilamine maleate. pilocarpine hydrochloride progestrone prednisone propylthiouracil piperazine tartrate phenobarbital sodium promazine hydrochloride potassium phenoxymethyl penicillin pheniramine maleate , ..;½·. piperazine tartrate quinidine sulphate quinine sulphate reserpine sodium penicillin sodium salicylate sulphadiazine sulphanilamide tolbutamide tolazoline hydrochloride and their pharmaceutically active acid-addition salts.

EXAMPLE 2 The following example illustrates the slow release of a readily water soluble compound.

Twenty tablets were prepared according to each of the following formulas where amounts are stated in grams.

Ingredient A B C D E F G Quinine hydrochloride 0.050 O0O50 0.050 0.050 0.050 0.050 0.050 Carbopol 9 0.050 0.050 0.050 O.O5O O.O5O 0.050 O.O5O Carbowax 4000 None . 0.010 O.O^O O.O5O 0.075 0.100 0.190 Tricalcium' phosphate 0.390 0.380 0.350 0.3^0 O.315 Ο.29Ο 0.200 Magnesium stearate 0.010 0,010 0.010 0.010 0.010 0.010 0.010 Total O.5OO O.5OO O.5OO O.5OO O.5OO O.5OO O.5OO The tricalcium phosphate acts as a diluent and the magnesium stearate as a lubricanto The ingredients were weighed, screened, and blended, then densified by compacting in a tableting machine,, The tablets were crushed and screened as necessary to obtain granules„ The granules were compacted in a tableting machine to form tablets for testing,, Dissolution tests on tablets of each formula were performed in a Stoll-Gershberg (U0S0P0) apparatus as follows,, Two tablets were placed in a beaker in a basket without discs, in 500 millilitres of OolN hydrochloric acido The basket was oscillated and samples withdrawn, with filtration, at intervals of 15 minutes, 30 minutes, 60 minutes, 90 minutes, 120 minutes and l80 minutes after tablet addition to the solution,, Each withdrawn sample was diluted with aqueous solution and assayed spectrophotometrically for drug contento The results are shown in Figure 3» The results show that with no polyethylene glycol present there was substantially no retardation of the dissolution of the quinine hydrochloride in the pH 1„5 medium,, Formulations B, C, D and E with progressively increasing quantities of PEG showed a stepwise decrease in the dissolution of the quinine hydrochloride reaching the slowest rate of dissolution in sample E„ In sample E the PEG content was 15 by weight and the ratio of Carbopol 93^ to PEG was Formulations F and G with further progessively increasing concentrations of PEG showed a stepwise increase in the dissolution rate of the quinine hydrochloride from the minimum rate reached with Formula E„ This is believed to be due to the presence of an excess of PEG in the presence of the Carbopol-PEG complex which functioned as a retarding mechanism0 The excess PEG acted as a solubilizing agent to increase the dissolution of the quinine hydrochlorideo ; 1 It may be inferred from the foregoing data that the rate of dissolution of an active ingredient may be readily controlled by varying the PEG content and the ratio of Garbopol to PEG in the system.

From the foregoing data it is apparent that the use of varying relative amounts of the carboxy vinyl polymer and polyethylene glycol will permit the formulation of a sustained action system giving a desired release rate of a drug, substantially independent of pH.

If desirable, an immediate-release portion of a drug may be included in one of several ways, such as in a separate layer of a double-layer tablet, or in the coating of a coated tablet.

EXAMPLE 3 The following example illustrates the preparation of a two-layered tablet embodiment of a composition of this invention.

Layer 1 - Sustained Action Portio Oxazepam 30 mg.

Carbopol 93^ 75 mg.

Avicel (Monocrystalline cellulose) 150 mg.

Carbowax kOOQ (PEG 4000) 75 mg.

Lactose, monohydrate, USP 162 mg.

Magnesium stearate USP 8 mg.

Total 500 mg.

Layer 2 - Fast Release Portion Oxazepam 15 mg.

Methylcellulose (* 00 CPS) 30 mg.

Amberlite IRPEA 3 mg.

FDA Yellow No. 5 lake 1.9 mg.

Magnesium stearate USP 1.5 mg.

Lactose, monohydrate, USP 138.6 mg.

Total I90.0 m . ' ■ . i Preparation of Layer 1 All of the ingredients were mixed and screened then slugged on a tableting machine., The slugs were comminuted to produce granules of predetermined size. The granules were then compressed as a first layer in a double-layer, tableting machine<, Preparation of Layer 2 All of the ingredients were mixed and screened then slugged on a tableting machine0 The slugs were reduced in particle size and the resulting granules were recorapressed as the second layer of the above tablets in a double-layer, tableting machine0 The dissolution rate of the drug contained in layer 1 is substantially similar to that shown in curve D of Figure 1, when tested by the procedure of Example 1« EXAMPLE k The following example illustrates the preparation of a tablet by a wet granulation methods The sustained release layer of the tablet was prepared with! Oxazepam 50 mg0 PEG 000 75 mg.

Carbopol 9 k 75 mg„ Avicel 150 mg„ Lactose hydrous USP Powder 162 mg0 Magnesium stearate USP 8 mg0 Total weight 500 mg„ All of the solid ingredients except magnesium stearate were wet granulated by mixing with ethyl ether, placed in trays and dried in an atmospheric oven at 135 degrees F0 The dried mixture was passed through a number 12 (U.S0 Standard Sieve Series) wire screen, and magnesium stearate was added through a number 30 screen,, The . ingredients were mixed thoroughly and pressed o a tablet press0 The fast release layer had the same formula as the fast release layer of Example 3 and was . prepared by dry granulation as in Example 3o A two-layer tablet was formed as described in Example 3» The dissolution of the active ingredient from the sustained release layer portion was - shown to .be substantially the same in a pH 7Λ phosphate buffer as that shown in' curve D of Figure 10 Tablets may also be prepared following the above procedure but substituting absolute . ethyl alcohol- for ethyl ether in the granulating solution or by substituting PEG 6000„ PEG 100000, or PEG 20,000 for the PEG * 000.

EXAMPLE ■ 5 ' " ' · ■' Sustained release tablets are prepared by the procedure of Example , but substituting the following formula per tablet for the sustained release layer: Mephentermine Sulphate Powder 1 0 mg„ Carbopol 93^ 1 0 mg0 Powdered sucrose t0 mgo Total 500 mg0 The fast release layer had the same formula as that of Example 3¾ except that the drug mephentermine sulphate was substituted for the oxazepamo EXAMPLE 6 Sustained release tablets are prepared by the procedure of Example 1, but substituting the following formula per tablet; Promazine Hydrochloride Powder Carbopol 93^ PEG 20 , 000 Calcium stearate USP Kaolin Total' EXAMPLE 7 Sustained release tablets are prepared by the procedure of Example 1 , but substituting the following formula per tablets EXAMPLE 8 Sustained release tablets are prepared by the procedure of Example 1 , but substituting the following formula per tablet: Crystalline acetylsalicylic acid Carbopol 93^ 75 mgo White mineral oil 10 mgo Dry starch O mgo Total 500 mgo EXAMPLE 9 Sustained release tablets are prepared by the procedure of Example 1 , but substituting the following formula per tablet? τ.

Potassium phenoxymethyl penicillin 250 mg0 Carbopol 93^ 75 mg° PEG iOOO 7 mgo Sodium benzoate 10 mg0 Lactose (Milk Sugar) 90 mg0 Total . . 500 rage The invention includes a process for preparing sustained action pharmaceutical tablets which comprises intimately mixing a powdered drug with a carboxy vinyl polymer and polyethylene glycol and then compressing the intimately mixed ingredients to form tablets for oral medicationo In a preferred process the powdered drug is intimately mixed with a carboxy vinyl polymer of acrylic acid copolymerised with about Oo 5 to 2 percent of polyalkenyl polyether, and polyethylene glycol hairing a molecular weight of about 1,000 to 20, 000 in which the drug comprises about 1 to 90 percent by weight of the mixture, and the carboxy vinyl polymer together with the polyethylene glycol comprises about 10 to 60 percent by weight of the composition, the latter being present in a ratio of about ls 0„ 5 to 1S3O8 , preferably I s 0o 5 to Is 3o 0 , to each other, and then compressing the intimately mixed ingredients to form tablets for oral medication,, The invention also provides a method of obtaining the sustained release of an orally effective drug in the gastrointestinal tract (excluding humans) which comprises administering to a host/a tablet as described herein,.

The existence of a carboxy vinyl polymer-polyethylene glycol complex may be demonstrated as follows,, A solution of polyethylene glycol is added to a solution of carboxy vinyl polymer at various pHSo A precipitate forms below about pH 0 No precipitate forms when the pH is about k or highe „ The results indicate the formation of an insoluble complex below about pH but not above about pH a s ■ Figure 2 is a graph of a phase solubility study of Carbopol 93^ and PEG O00a In carrying out the study known amounts of various concentrations by weight of PEG ^OOO were added to known amounts of an aqueous solution of 0o5 percent by weight of Carbopol 3½ο The amount of PEG.4000 remaining in solution was determined and subtracted from the total PEG ^000 added to determine the amount of PEG OOO in the complex. The slope of the curve of Figure 2 indicates that the interaction is about 1ί1„5 on a weight basis of the two polymers Carbopol The ratio may vary through a range of 1:0<>5 to 1ί30.

The terms and expressions which have been employed are used as terms of description and not of limitation, and there is no intention in the use of such terms and expressions of excluding any equivalents of the features shown and described or portions thereof5 but it is recognised that various modifications are possible within the scope of the invention claimed..

Claims (1)

1. AHP~ 566/Cl/fl WHAT WE CLAIM ISg le A tablet composition for sustained release of a drug comprising water-insoluble (as hereinbefore defined) a drug, a/carboxy vinyl polymer/and polyethylene glycol, the ratio of carboxy vinyl polymer to polyethylene glycol being such as to provide a controlled rate of release of the drug which is substantially independent of pH0 2 o A tablet composition ae claimed in claim 1, comprising from 1 to 90$ by weight of a drug, from to 3 $ by weight of a carboxy vinyl polymer and from to 30$ by weight of polyethylene glycolo 3 o A tablet composition as claimed in claim 1 or claim 2 , wherein the total of carboxy vinyl polymer and polyethylene glycol comprises from 10 to 60# by weight of the composition. *e A tablet composition as claimed in claim 3 » wherein the total of carboxy vinyl polymer and polyethylene glycol comprises from 20 to 50$ by weight of the composition,, 5 o A tablet composition as claimed in any one of the preceding claims wherein the polyethylene glycol has a molecular weight of from 1000 to 20 , 000„ 6 o A tablet composition as claimed in claim 5s wherein the polyethylene glycol .has a molecular weight of from 4 , 000 to 690O0 o 7 · A tablet composition as claimed in claim 5 wherein the polyethylene glycol has a molecular weight of about f,000«, 8 o A tablet composition as claimed in any one of the preceding claims in wherein the carboxy vinyl polymer is a watei soluble polymer of acrylic acid crosslinked with from about 0o 75 to 2 percent by weight of a polyallyl ether of sucrose having an average of about AHP=4566/Cl/fl o A tablet composition as claimed in claim 8 , wherein the water ^soluble polymer of acrylic acid is one crosslinked with about Vfo -? -by weight of said polyallyl ether0 10o A tablet composition as claimed in any one of the preceding claims wherein the drug comprises from 5 to 20$ by weight of the composition,, lie A tablet composition as claimed in any one of the preceding claims wherein the drug is oxazepam,, 12e A tablet composition as claimed in any one of claims 1 to 10 wherein the drug is a quinine salt0 13 o A tablet composition as claimed in any one of claims 1 to 10 wherein the drug is a penicillin or derivative thereof,, A tablet composition as claimed in claim 135 wherein the drug is 6·»(l^aminocyclohexanecarboxamido) ~3o 3-dimethyl'=7~oxo»it.=thio=>l~ azabicyclo [3 o 20OUheptane^^carboxylic acid„ 15o A tablet composition as claimed in claim 13 wherein the drug is potassium phenoxymethyl penicillin. 16. A tablet composition as claimed in any one of claims 1 to 10 „ wherein the drug is a mephentermine salt0 17o A tablet composition as claimed in any one of claims 1 to 10 „ wherein the drug is a promazine salto l8 o A tablet composition as claimed in any one of claims 1 to 105 wherein the drug is acetyl salicylic acid0 19o A tablet composition as claimed in any one of the preceding claims wherein the carboxy vinyl polymer is present in an amount from 0o A tablet composition as claimed in claim 19 <> wherein the carboxy vinyl polymer is present in an amount from 15 to 25% by weight of the compositiono 1o A tablet composition as claimed in any one of the precedin claims, wherein the polyethylene glycol is present in an amount from 10 to % by weight of the compositiono 2o A tablet composition as claimed in claim 21, wherein the polyethylene glycol is present in an amount from 15 to 25% by weight of the compositiono j5o A tablet composition as claimed in any one of the preceding claims wherein the ratio of carboxy vinyl polymer to polyethylene glycol k0 A tablet . composition as claimed in claim 23 wherein the ratio of carboxy vinyl polymer to polyethylene glycol is from ls008 to l oOo o A tablet composition as claimed in any one of claims 1 to 11 wherein the ratio of carboxy vinyl polymer to polyethylene glycol is from 6o A tablet formed from a composition as claimed in any one of claims 1 to 11 or 25 o 7o A tablet as claimed in claim 26 β which further comprises a ready release portion of a drugo 8o A tablet formed from a composition as claimed in any one of claims P A tablet formed from a composition as claimed in claim 28 which further comprises a ready release portion of a drugo AHP« 566/Cl/fl T 30o A sustained release tablet in which the components includes Oxazepam 15 to 60 milligrams Carboxy vinyl polymer 20 to 150 milligrams Polyethylene glycol 20 to 150 milligrams Extenders, lubricants, flavoring and the like to 50 milligrams 31e A sustained release tablet in which the components includes Quinine salt 15 to 60 milligrams Carboxy vinyl polymer 20 to 150 milligrams Polyethylene glycol 20 to 150 milligrams Extenders, lubricants, flavoring and the like 5 to 450 milligrams 32 o A sustained release tablet in which the components includes Percent by weigh Carboxy vinyl polymer 15-2 Polyethylene glycol 15-25 Diluents, lubricants, flavoring and the like 5-65 33 o A tablet composition for sustained release of a drug substantially as described in Example 1 , Formula B0 3 . A tablet composition for sustained release of a drug substantially as described in Example 2 , formula's C to Q0 35 » A sustained release tablet substantially as described in any one of examples 3 to 9o 36 e A process for preparing sustained action pharmaceutical tablets j a powdered drug with a carboxy vinyl polymer and polyethylene glycol and then compressing the intimately mixed ingredients to form tablets for oral medicationo 37o A process for preparing sustained action pharmaceutical tablets as claimed in claim 28 which process comprises intimately mixing a powdered drug with a carboxy vinyl polymer and polyethylene glycol and then compressing the intimately mixed ingredients to form tablets for oral medicationo as claimed in Claim 26 38. A process for making sustained action pharmaceutical tablets/ comprising intimately mixing a powdered drug with a carboxy vinyl polymer of acrylic acid copolymerized with about 0„ 75 to 2 percent of polyalkenyl polyether, and polyethylene glycol having a molecular weight of about 1 ,000 to 20 ,000 in which said drug comprises about 1 to 90 percent by weight of the mixture, and said carboxy vinyl polymer together with said polyethylene glycol comprises about 10 to 60 percent by weight of the composition, the latter being present in a ratio of about 1 § 005 to ls3<>0 to each other, and then compressing the intimately mixed ingredients to form tablets for oral medicationo 39o A process as claimed in any one of claims 36-38 , wherein the ingredients are mixed in a liquid0 0o A process as claimed in claim 38 , substantially as described in Example 1 » *lo A process as claimed in claim 38 substantially as described in any one of Examples 2 to » A method of obtaining the sustained release of an orally effective drug in the gastrointestinal tract which comprises administering (excluding humans) to a host/a tablet as claimed in claim 26 » jo A method of obtaining the sustained release of an. orally effective dru in the astrointestinal tract which com rises administerin