AU603098C - Formulation for preparing sustained released drugs - Google Patents

Formulation for preparing sustained released drugs

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Publication number
AU603098C
AU603098C AU72883/87A AU7288387A AU603098C AU 603098 C AU603098 C AU 603098C AU 72883/87 A AU72883/87 A AU 72883/87A AU 7288387 A AU7288387 A AU 7288387A AU 603098 C AU603098 C AU 603098C
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AU
Australia
Prior art keywords
xanthan gum
matrix
formulation according
tablets
formulation
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
AU72883/87A
Other versions
AU603098B2 (en
AU7288387A (en
Inventor
Massimo Calanchi
Leonardo Gentilini
Luigi Mapelli
Marco Marconi
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Adare Pharmaceuticals SRL
Original Assignee
Eurand International SpA
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from IT19675/86A external-priority patent/IT1191674B/en
Application filed by Eurand International SpA filed Critical Eurand International SpA
Publication of AU7288387A publication Critical patent/AU7288387A/en
Publication of AU603098B2 publication Critical patent/AU603098B2/en
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Assigned to EURAND INTERNATIONAL S.P.A. reassignment EURAND INTERNATIONAL S.P.A. Alteration of Name(s) in Register under S187 Assignors: EURAND ITALIA S.P.A.
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Description

"FORMULATION FOR PREPARING SUSTAINED RELEASE DRUGS FOR ORAL
ADMINISTRATION"
The present invention relates to pharmaceutical formulations adapted to
prepare solid oral dosage forms, such as capsules, tablets, lozenges and the like,
having a regular and sustained release after administration.
The advantages of the sustained release or retard drugs are well known
since a long time, because delaying the dissolution of the active substance, the
absorption time in the gastrointestinal tract is extended, thus prolonging the
therapeutic effect, at the same time avoiding or at least reducing the side effects.
For this purpose a retard formulation has to meet some criteria, namely
causing a uniform and constant dissolution and being effective for an extended
period of time. It is also important that such a formulation be simple to be made,
the manufacturing process be reproducible and may be used for a high number of
different substances. There are several known methods for preparing retard products in the form
of solid oral dosage such as tablets or capsules. Among these methods, delaying
hydrophilic matrices are often used because the manufacture of finished form is
simple and reproducible, it is possible to obtain a gradual and continuous release,
they can be applied to many drugs and are economically advantageous.
Hydrophilic matrix is defined a homogeneous mixture of substances,
substantially comprising polymers which are slowly dissolved in water and then
receiving a well defined form by compression or encapsulation. When the tablet is
contacted with water or aqueous based dissolution media as the gastro-intestiπal
juices, the hydrophilic polymers give rise to the formation of a gelatinous surface
layer, through which water slowly penetrates inside, hydrating and swelling the
polymer; then the polymer in the gel form, gradually goes in solution, first the
outermost layer and thereafter the inner layers until it is totally dissolved and
disappears.
In this way the active substance is totally and slowly released by two
contemporaneous mechanisms, namely diffusion through the gelatinous layer and
gel erosion.
While the first of these release mechanisms prevails in case of drugs very
solubnle in the dissolution medium, the second prevails in case of poorly soluble
drugs.
The polymers suitable for the preparation of hydrophilic retard matrices are
relatively few, but there are already patents and publications on this subject
matter.
U.S. patents N° 4,259,341 to Lowey, N°3,870,790 to Lowey et al,
N°4,226,849 to Schor and N° 4,357,469 to Schor relate to the preparation of tablets with a hydrophilic matrix comprising hydroxypropylmethylcellulose, alone or mixed
with other cellulose derivatives, having undergone particular treatment such as
high drying, humidification, hydrolysis, oxidation.
Also U.S. patents Nos. 4,369,172 and 4,389,393 to Schor et al relate to the
use of one or more types and well defined quantities of hydroxypropylmethyl¬
cellulose alone or mixed with methylcellulose and/or sodium carboxymethyl-
cellulose.
U.S. patents Nos. 4,167,448 and 4,126,672 to Sheth et al relate to the use of
hydroxypropylmethylcellulose for preparing tablets and more particularly capsules
with hydrophilic matrix having such a composition that they remain floating in the
gastric juices.
The article titled "A review of cellulose ethers in hydrophilic matrices for
oral controlled release dosage forms by D.A. Alderman, published on Int. Journal
Pharm. Techn. & Prod. Mfr. 5(3) 1-9, 1984, widely deals with the use of
hydroxypropylmethylcellulose for preparing retard hydrophilic matrices and studies
the influence on the drug release, of several parameters characteristic of hydroxy¬
propylmethylcellulose such as molecular weight, substitution degree, grain size
distribution, velocity of hydration.
The present invention relates to the use of hydrophilic polymers of natural
origin, more particularly polysaccharides as main constituents of formulations
adapted to prepare hydrophilic retard matrices for the administration of drugs in
the form of tablets, lozenges, capsules and so on. Among the polysaccharides of
natural origin, modified corn starch, modified corn flour and xanthan gum are
preferred. The main feature of this invention consists indeed in using polysac- attained up to now only using hydroxypropylmethylcellulose as single or main
hydrophilic polymer. In the relevant literature moreover these polysaccharides of
natural origin are generally used in water solution as thickeners to stabilize
emulsions, suspensions, creams, latices and the like, and their use as basic
excipients for preparing solid matrices is never cited.
According to the present invention it was indeed found that use of polysac¬
charides of natural origin allows to obtain matrices giving rise to a sustained and
gradual drug release; moreover by varying the quantity of the polysaccharide of
natural origin in the formulation according to the solubility and dosage of the drug,
it is possible to change the pattern of in vitro drug release. As a matter of fact
polysaccharides of natural origin, which are hydrophilic polymers of high molecular
weight, when they are contacted by water or gastrointestinal juices, give rapid rise
to the formulation of a gelatinous surface layer controlling the further diffusion of
water or gastrointestinal juices to the interior and consequently the drug release.
Water or juices penetrate inside the matrix in subsequent layers gradually
transforming the polymer into a gelatinous mass and then dissolving it while active
substance is at the same time released.
Another advantage of polysaccharides of natural origin is that they allow to
extend release of a great number of drugs, irrespective of their dosage and
solubility, by employing economical and reproducible manufacturing processes.
Still another advantage is given by the possibility of preparing formulations
giving rise to retard matrices releasing the drug even in very long times that may
even reach 24 hours so as to allow only one single administration per day.
Xanthan gum is a high molecular natural carbohydrate and more particularly
an exocellular biopolysaccharide produced by a fermentation process of the microorganism Xanthomonas campestris. Structure, molecular weight and
properties of dissolution of this natural polymer are constant and reproducible
under strictly controlled operative conditions. Xanthan gum, know also under the
R R registered names of Keltron and Kelzan , is used in many fields, such as the
food, drug and cosmetic field. In these cases the thickening and stabilizing property
of emulsions or suspensions given by xanthan gum in solution is used. Precooked
modified corn starch known under the trademark Instant Cleargel is used, like
generally all starches, as a thickening, binding, stabilizing or gelling agent,
especially in the food industry, for instance as a thickener for instance of deeply
10 frozen desserts, mayonnaise and sauces in general.
In the following description only xanthan gum is generally mentioned, but
the same arguments obviously apply also in case of Instant Cleargel , of other
starches and modified flours and generally of all hydrophilic polysaccharides of
natural origin.
15 With the present invention it was found that it is possible to utilize the
properties of xanthan gum even for solid formulations of drugs, using it for
preparing hydrophilic matrices in which xanthan gum has the effect of delaying the
drug dissolution.
Matrix may comprise either xanthan gum alone or a mixture of xanthan gum
20 with other natural or synthetic polymers, having the effect of varying the drug
release curve so as to obtain those more adapted to reach the maximum in vivo
bioavailability and efficiency thereof.
Therefore it is posssible to mix to xanthan gum the following:
1) polymers hydrating and dissolving in water such as methylcellulose, hydroxy-
25 ethylcellulosε, gum arabic, polyvinylpyrrolidoπe, gelatine; 2) polymers having a pH dependent solubility such as shellac, cellulose aceto-
phtalate, xydroxypropylmethylcellulose phtalate, polyvinylacetophtalate, polyacry-
lates;
3) polymers hydratiπg and dissolving slowly in water, such as xydroxypropyl-
methylcellulose, modified starch and rubber of natural origin.
Matrix is therefore comprising xanthan gum, in a percentage varying
between 31 and 100% and preferably between 50 and 100%, alone or mixed with
one or more polymers of one or more of the three above mentioned groups, in a
quantity between 0 and 69% and preferably between 0 and 50% .
The retarding matrix is mixed in a suitable apparatus with the drug or even
more drugs, which are intended to be administrated in a sustained release form.
Among the possible drugs, the following are cited as illustrative non limiting
examples only:
adrenergic amines (ethylephrine, phenylephrine, phenylpropanolamine', d-pseudo-
ephedrine), antispasmodics (scopolamine and other belladonna alkaloids, papaverine
and its derivatives), antihistaminics (bronchopheniramine, chloropheniramiπe,
dipheπylpyraline, dimenhydrinate), anorexics (norpseudoephedrine, phenermine,
diethylpropione, phenfluramine), antiasthmatics (theophylline, sulbutamol,
terbutaliπe), antiaπginics (isosorbide - 5 - mononitrate, isosorbide dinitrate, penta-
erythritol tetranitrate, nitroglycerin, nifedipine, dilthiazem), antiflammatories and
antipyretics (indomethacine, ibuprofen, ketoprofeπ, acetylsalicylic acid,
paracetamol, phenacetine), hypotensives (nifedipine, hydrolazine, prazosine, vera-
pamil), antidepressants (anitryptiline, lithium salt), aπtitussives (dextrome-
thorphane, noscapine, codeine), gastroenterics (cimetidine, ranitidine, methoclo-
pramide), antiarrhythmics (procainamide, lidocaine, flecainide, propophenone), analgesics (morphine), vitamins (ascorbic acid) and their salts used in the pharma- _
ceutical field.
In addition to polymers and drugs, in the formulation there may be also inert
excipients commonly used by men skilled in the art to improve the characteristics
of said formulation. Thus for instance, lubricants, dyestuffs, sweeteners, flavouring agents, inert
excipients and so forth may be added in the preparation of tablets in order to
improve flowance of powders, appearance, taste, dosage precision and the like.
The quantity of matrix used to delay drug release may therefore be varied in
a broad interval, depending whether the formulation comprises only drug and
matrix or other excipients are present in a more or less high amount according to
the high or low level of solubility and/or the high or low dosage of the active
substance.
Therefore said matrix may vary between 10 and 80% by weight of the
formulation and preferably between 20 and 6Q% by weight.
The following examples are intended to better clarify the invention and it is
to be understood that they are not limiting the scope of the invention, as many
variations may be readily apparent to a man skilled in the art.
EXAMPLE 1 - 3
Sustained release tablets of theophylline (dosage 350 mg) were prepared,
containing the" percentages of delaying substances set forth in the following table:
Example ND Xanthan gum % Hydroxypropylcellulose ?ό
1 27.2 9.0
2 19.8 9.9
3 10.1 10.1 Tablets of 350 mg each were prepared with the following excipients:
Ingredients Example 1 Examplf 3 2 Exam)pie 3
g mg/tablet g mg/tablet g mg/tablet
1) Theophylline 105.0 350.0 105.0 350.0 105,0 350.0
2) Xanthan gum 45.0 150.0 30.0 100,0 150 50.0
3) Hydroxypropyl- cellulose 15.0 50.0 15,0 50.0 15.0 50.0
4) Flame silica 0.6 2,0 0.6 2.0 0.6 2.0 5) Magnesium stearate 0.8 3.0 0.9 3.0 0.9 3.0
The ingredients 1, 2 and 3 were mixed for 15 minutes. Then ingredient 4 was
added and after further 15 minutes of mixing, also the ingredient 5 was added. The
mixture was agitated for 10 minutes and then subjected to compression in a
tabletting machine with punches of 15 x 6 mm (r = 5.0 mm)' to make about 250
candle shaped tablets with double fracture line.
Samples were obtained having the following characteristics:
Sample Average weight Thickness Harness I- riability mg/tablet mm Kg 10 x 4
1 555 5.88 13.1 0.26 2 505 5.33 . 13,4 0.20 3 455 4.85 13.7 0,22 - 9 -
Hardness of the tablets was determined with the apparatus Erweka TBH 28 .
and friability with the apparatus Roche Friabilator at 25 rpm checking the loss of
weight of 10 tablets after 4 minutes of rotation.
In vitro release of the tablets was determined with the rotary blade method
described in USP, XXI ed., page 1244, employing according to the kind of analysis,
the proper vessels containing 500 ml of artificial gastric juice (pH 1.2) or 500 ml of
artifical intestinal juice (pH 6.8) preheated at 37° C. The vessels were closed and
agitator was regulated at a speed of 150 rpm. In each vessel a tablet corresponding
to 350 mg of active substance was added. 0 At predetermined intervals of 1, 2 , 4, 8, 12 and 14 hours a sample of 5 ml
was taken and the vessel refilled with the same amount of juice or fluid. The
sample was suitably diluted and analyzed at the spectrophotometer at a wavelength
of 270 nm in 100 N HC1 against standard reference.
The. results- of the analysis, given in. the following table, show that the
5 release of theophylline occurs in 12 or more hours according to the matrix
composition.
Sample Buffer pH Cumulative release %
lh 2h 4h 8h 12h 14h
1 1.2 10.5 17.0 27.2 40.7 51.9 58.2
"20 6.8 7.8 12.8 22.4 47.8
2 1.2 11.8 18.8 30,3 49.8 61.4 66.3
6.8 9.1 15.7 24.9 48.1
3 1.2 17.2 25.6 39.7 71.4 93.8 100.0
6.8 15.6 25.6 42.5 70.6 EXAMPLES 4-5
Theophylline tablets (dosage 350 mg) were prepared, in which the delaying
substances are present in the amount given below:
Example N° Xanthan gum % Hydroxypropyl- Hydroxypropyl¬ methylcellulose % cellulose %
4 11.0 5.5 5.5
5 10.9 10.9
Tablets of 350 mg each were prepared with the followinq excipients: Excipients Example 4 Example 5 g mg/tablet g mg/tablet
Theophylline 105.0 350.0 105.0 350.0
1) Xanthan gum 15.0 50.0 15.0 50.0
2) Hydroxypropyl- cellulose 7.5 25.0 15.0 50.0
3) Hydroxypropyl methylcellulose 7.5 25.0 — —
4) Flame silica 0.6 2.0 0-6 2,0
5) Magnesium stearate 1.5 3.0 . 1.5 5.0
Mixing was effected in the manner described in Examples 1-3. The mixture
was subjected to compression in a tabletting machine with punches 15 x 6 mm (r =
5 mm) to make about 250 candle-shaped tablets with double fracture line. The
samples had the following characteristics: Sample ND Average Weight Thickness Hardness Friability mg/tablet mm Kg .0
4 457 4.87 13.4 0.1 5 457 4.85 13.7 0.1 Hardness and friability of the tablets were measured with the apparatus described
in Examples 1-3.
In order to check the in vitro release, the same method used for Example 1-
3 was employed and the results given in the following table were found, from which
one can see the delayed release of the drug due to the xanthan gum based matrix.
Sample N° Buffer pH Cumulative release % lh 2h 4h 8h 12h 14h
1.2 17.8 29.0 47,4 80t2 95.9
6.8 12.6 23.2 38.7 58.8 79.7
1.2 15.3 25, 1 40.5 65.5 88.7 100
6.8 12.3 21.0 34.2 55.1 81.4 100
-EXAMPLE 6
Theophylline tablets (dosage 350 mg) were prepared, containing as delaying
substance 22% xanthan gum. The tablets had the following composition:
Ingredients t-xainμ LC U g mg/tablet
105.0 350.0 Theophylline
Xanthan gum 30.0 100.0
Flame silica 0.6 2.0
Magnesium stearaite 0.9 3,0
Mixing was effected as in Examples 1-3. Mixture was subjected to compres-
sion in a tabletting machine with punches 15 x 6 mm (r = 5 mm) to make about 250 candle shaped tablets with double fracture line having the following
characteristics:
Sample N° Average weight Thickness Hardness Friability mg/tablet mm Kg %
6 455 4.85 13.76 0.2
and- the following in vitro release.:
Sample N° Buffer pH Cumulative release .0 lh 2h 4h 8h 12h 14h
6 1.2 12.5 20.2 31.2 45.9 58.1 63.8
6. S 7.6 13.8 25.4 45.9 88.9 100.0
EXAMPLE 7
Tablets of 50 mg of amitryptiline retard were prepared containing 16.6% of
xanthan gum and 16.6 % of hydroxypropylcellulose, as costituents of the delaying
matrix.
The tablets of 50 mg were prepared with the following excipients: Ingredients Example 7 g mg/tablet
Amitryptiline 25 50.0
Xanthan gum 10 20.0 Hydroxypropylcellulose 10 20.0
Lactose 13.75 27-5 Flame Silica 0.25 0.5 Magnesium stearate 1,00 2.0
Mixing was effected as in Examples 1-3. The mixture was subjected to compression in a tabletting machine with punches 4 x 9 mm to make about 350 flat candle tablets . The samples had the following characteristics : Sample N° Average weight Hardness Frability mg/tablet Kg %
1 120 7.06 0.1 Hardness and friability of the tablets were measured with the apparatus
described in Examples 1-3.
In order to check the in vitro release the same method used in Examples 1-3
was employed and the following results were obtained:
Sample N° Buffer pH Cumulative release %
Ih 2h 4h 8h 12h 14h
7 12.2 33.3 48.8 72.8 100
EXAMPLES 8-9
Retard tablets of methoclopramide chlorohydrate were prepared with a
dosage of 30 mg of methoclopramide, containing either 29.2 % xanthan gum, 14.6%
hydroxypropylcellulose and 14.6 % hydroxypropylmethylcellulose (Ex. 8) or 31.9%
xanthan gum and 31.9% hydroxypropylmethylcellulose (Ex. 9) as constituents of the
delaying matrix. The tablets of- 30 mg methoclopramide were prepared with the
following excipients:
Excipients Example 8 Example 9 g mg/tablet g mg/tablet
Methoclopramide HC1 16.8 33.7 16.8 33,7
Xanthan gum 17.5 35.0 17.5 35.0
Hydroxypropyl¬ cellulose 8.7 17.5
Hydroxypropylmethyl¬ cellulose 8 8..77 1 177..55 1 177..55 3 355..00
Spray Dry Lactose 5 5..11 1 100..33
Flame silica 1 1..00 2 2..00 1 1..00 2 2..00
Magnesium Stearate ? 2..n0 4 4..00 ? 2..n0 4 4,_n0 Mixing was effected in the same manner as in Examples 1-3. The mixture
was subjected to compression in a tabletting machine with punches 4 x mm to
make about 500 flat candle tablets having the following characteristics:
Sample N° Average weight Hardness . Friability mg/tablet Kg
8 123 9.8 0.2 114 11.6 0.2
Hardness and friability of the tablets were measured with the apparatus
described in Examples 1-3. In order to check the in vitro release the same method
of Examples 1-3 was used with the only change that the agitator was set at a speed 0 of 125 rpm instead of 150 rpm.
The methoclopramide tablets had the following in vitro release:
Sample Buffer pH Cumulative release %
lh 2h 4h 8h 12h 16h
8 1.2 41.2 59.5 82.8 96.3 100.0
•15
6.8 35.2 49,1 68c7 82.0 91-3 97.6
9 1.2 34.1 49.9 71.6 94-0 100.0
6.8 28,6 41.8 60.7 82.9 94.1 99.2
Retard tablets of methoclopramide chlorohydrate of 30 mg methoclo¬
20 pramide were prepared, containing 58.6 % xanthan gum as a delaying substance.
The 30 mg methoclopramide tablets were prepared with the following excipients: Ingredients E.sempio 10 g mg/tablet
Methoclopramide HC1 16.8 33.7
Xanthan gum 35.1 70.3
Spray Dry Lactose 5.0 10.0
Flame silica 1.0 2.0
Magnesium stearate 2.0 4.0
Mixing was effected in the same manner as in Examples 1-3. The mixture
was subjected to compression in a tabletting machine with punches 4 x 9 mm to
make about 500 flat candle tablets having the following characteristics: Sample N° A Avveerraaggee wweeiigghhtt H Haarrddnneessss F riability mg/tablet Kg
i n 126.4 7 .7 0.2
Hardness and friability of the tablets were measured with the apparatus
described in Examples 1-3. In order to check the in vitro release the same method
used for Examples 8 and 9 was employed. The tablets had the following in vitro
release:
Sample Nc Buffer pH Cumulative release % lh 2h 4h 8h 12h 16h
10 1. 2 43.8 61 .5 84.0 100
6. 8 27 .8 41 .8 61 .6 85.4 93. 5 98.6
EXAMPLES 11-13
Retard tablets of theophylline with a dosage of 350 mg were prepared, containing
the percentages of delaying substances indicated in the following table: Example N° Instant Cleargel Hydroxypropylcellulose % 11 26.9 9.0 12 19.7 9.0 13 10.9 10.9
The tablets of 350 mg were prepared with the following excipients:
Ingredients Example 11 Example 12 Exc imple 13
g mg/tablet mg/ tablet g g mg/ tab l et
Theophylline 105 350 105 350 105 350
Instant Cleargel 45 150 30 100 15 50
Hydroxypropyl¬ cellulose LF 15 50 15 50 — —
Hydroxypropyl¬ cellulose HF — — — ~ 15 50
Flame silica 0.6 2 0.6 2 0.6 2
Magnesium stearate 1.5 5 1.5 5 1.5 5
was compressed in a tabletting machine with punches 15 x 6 mm (r = 5 mm) to
make about 250 candle shaped tablets with double fracture line. The samples had
the following characteristics:
Sample NQ Average weight Thickness Hardness Friabilit mg/tablet mm 0'
Kg /O
11 557 5.00 13. 1 0. 1
12 507 5.56 13.7 0.1
13 457 5.12 15.6 0.1
Hardness and friability of the tablets were measured with the apparatus
described in Examples 1-3.
In order to check the in vitro release the same method used for Examples 1-
3 was employed and the results are given in the following table, where one can see the delaying effect of drug release due to the matrix based on Instant Cleargel : Sample N° Buffer pH Cumulative release % lh 2h 4h 8h 12h 14h
11 1.2 20.2 38.1 60.3 81.2
12 1.2 28.3 45.1 68.5 88,1
13 1.2 28.1 35.4 48.7 71.9 87.0 93,5
6.8 31.2 37.9 49.6 70.0 84,7 91.5
EXAMPLE 14
Theophylline tablets with a dosage of 350 mg were prepared, containing as
delaying substance 22% of Instant Cleargel . The tablets had the following
composition:
Ingredients Example 14 mg/ tablet
Theophylline 105 350
Instant Cleargel 30 100
Flame silica 0.6 2
Magnesium Stearate 1.5 5
Mixing was effected as in Examples 1-3. The mixture was subjected to
compression in a tabletting machine with punches 15 x 6 mm (r = 5 mm) to make
about 250 candle-shaped tablets with double fracture line having the following
characteristics:
Sample N° Average weight Thickness Hardness Friability mg/tablet mm Kg %
* 14 457 5.0Q 14.1 0.1
and the following in vitro release:
Sample N° Buffer pH Cumulative release % lh 2h 4h 8h
14 1.2 28.1 35.4 48.7 71.9 EXAMPLE 15
Hard gelatin capsule (size 1, transparent neutral colour) of theophylline
(dosage 100 mg) were prepared, containing as delaying substance 33.3 % of xanthan
gum with the followi ing composition:
Ingredients Example 15 g mg/tablet
Theophylline 30 100
Xanthan gum 60 200
The mixture was prepared as in the Examples 1-3.
The capsules were filled with a laboratory capsule filling machine of the
10 Zuma type in order to make 300 capsules.
For controllfrig the in vitro release the same method used for Examples 1-3
was employed, with the only variant that the agitator was set at a speed of 75 rpm
instead 150 rpm.
The theophylline release from the capsules is delayed by the Xanthan gum
-, c matrix as shown by the following values of in vitro release:
Sample N° Buffer pH Cumulative release % lh 2h 4h 8h
15 1.2 21.2 36.3 60.1 83.0
It is therefore clear, from the foregoing description and the illustrative
2Q examples, that the desired objects are fully attained, while it is also to be
understood that many variations, modifications, additions and/or substitutions of
elements may be resorted to the formulations according to the present invention,
without departing however from its spirit and objects and without falling outside
its scope of protection, as it is defined in the appended claims.

Claims (10)

.CLAIMS
1. Formulation for preparing solid dosage forms having a regular and
sustained release, characterized by the fact of comprising one or more active
« substances and a matrix, imparting the retard effect, consisting of polysaccharides
5 of natural origin.
2. Formulation according to Claim 1, wherein the natural polysaccharide is
xanthan gum.
3. Formulation for preparing solid dosage forms having a regular and
sustained release, characterized by the fact of comprising one or more active
j Q substances and a matrix, imparting the retard effect, consisting of xanthan gum
and one or more natural or synthetic polymers, hydrating and dissolving slowly
and/or quickly in water or in the gastrointestinal juices or the dissolution velocity
of which is a function of the pH value of the medium.
4. Formulation according to Claim 3, characterized in that the percentage
25 by weight of the matrix components is preferably 50-100% of xanthan gum and 0-
50% of one or more of said polymers.
5. Formulation according to Claim 3, characterized in that the matrix
comprises, in addition to xanthan gum, hydroxypropylcellulose or hydroxypropyl¬
methylcellulose or mixtures thereof.
,20 6. Formulation according to Claims 2, 3, 4 or 5 wherein precooked modified
corn starch (Instant Cleargel ) is used instead of xanthan gum.
7. Formulation according to one or more of the preceding claims, when used
for the preparation of sustained release pharmaceutical solid dosage forms, such as
tablets, capsules, lozenges and the like,
r
8. Formulation according to one or more of the preceding claims wherein, in addition to one or more active substances and the constituents of the delaying
matrix, there are inert excipient used for obtaining the desired dosage form, such
as lubricants, dyestuffs, diluents, sweeteners, flavouring agents.
9. Formulation according to one or more of the preceding claims,
characterized in that the matrix has such as composition as to prolong the drug
release up to 24 hours so as to allow one single administration per day.
10. Formulations for preparing sustained release drugs adapted for oral
administration, substantially as hereinbefore described and as illustrated in the
annexed examples, for the above mentioned objects.
AU72883/87A 1986-03-07 1987-03-02 Formulation for preparing sustained released drugs Ceased AU603098C (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IT19675/86 1986-03-07
IT19675/86A IT1191674B (en) 1986-03-07 1986-03-07 FORMULATIONS FOR THE PREPARATION OF PROLONGED-RELEASE DRUGS SUITABLE FOR ORAL ADMINISTRATION

Publications (3)

Publication Number Publication Date
AU7288387A AU7288387A (en) 1987-09-28
AU603098B2 AU603098B2 (en) 1990-11-08
AU603098C true AU603098C (en) 1995-09-21

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