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Patent 1067407 Summary

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(12) Patent: (11) CA 1067407
(21) Application Number: 230802
(54) English Title: PHARMACEUTICAL PREPARATION IN THE FORM OF A FOIL HAVING AN ACTIVE SUBSTANCE INCORPORATED THEREIN
(54) French Title: PREPARATION PHARMACEUTIQUE FORMEE D'UNE PELLICULE CONTENANT UNE SUBSTANCE ACTIVE
Status: Expired
Bibliographic Data
(52) Canadian Patent Classification (CPC):
  • 167/153
  • 167/156
(51) International Patent Classification (IPC):
  • A61K 47/00 (2006.01)
  • A61K 9/70 (2006.01)
(72) Inventors :
  • FUCHS, PETER (Not Available)
  • HILMANN, JURGEN (Not Available)
(73) Owners :
  • SCHERING AKTIENGESELLSCHAFT (Not Available)
(71) Applicants :
(74) Agent:
(74) Associate agent:
(45) Issued: 1979-12-04
(22) Filed Date:
Availability of licence: N/A
(25) Language of filing: English

Patent Cooperation Treaty (PCT): No

(30) Application Priority Data: None

Abstracts

English Abstract


ABSTRACT OF THE DISCLOSURE
A pharmaceutical preparation for internal or external
use includes a foil incorporating one or more pharmacologically
active ingredients, the material forming the foil being soluble
in water or organic solvents. The foil forming material may
be poly-N-vinyl-pyrrolidone, vinylpyrrolidone-vinyl acetate,
methyl- and ethyl-cellulose, hydroxypropyl-cellulose, hydroxyethyl-
cellulose or methylhydroxypropyl-cellulose. The active ingredient
may be a gestagen, oestrogen, mixture of a gestagen and an
oestrogen, a tranquillizer, an anti-diabetic, sulphonamide,
antibiotic, a trichomonal agent or an inflammation inhibitor.


Claims

Note: Claims are shown in the official language in which they were submitted.


THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. In a pharmaceutical composition in unit dosage form
for enteral or topical administration and comprising a safe and
effective amount of a pharmaceutically active medicament compound
and a flexible, water soluble film carrier therefore, the improve-
ment wherein the medicament is dissolved or uniformly suspended,
together with about 0.01 - 2% by weight of a pharmaceutically
acceptable release agent in a film carrier consisting essentially
of a non-ionic, water soluble methyl ether or hydroxyalkyl ether
of cellulose and the pharmaceutical composition is in the form of
a tissue-like sheet, having a uniform dry film thickness of about
0.05 - 1 mm, drawn from a solution of the film carrier containing
0.01 - 2% by weight of a pharmaceutically acceptable release agent,
0 - 30% by weight of a filler and up to 60% by weight of the film
carrier of the medicament.
2. A composition according to claim 1, wherein the film
carrier is hydroxypropyl-cellulose, hydroxyethyl-cellulose, methyl-
hydroxypropylcellulose and mixtures thereof.
3. A composition according to claim 1, wherein the
medicament is an estrogen, gestagen or admixture thereof.
4. A composition according to claim 1, wherein the
release agent is a polyoxethylene-polyoxypropylene copolymer(s),
a polyoxylstearate or an alkyl- or alkanoyl-substituted poly-
addition product of ethylene oxide.
5. A composition according to claim 1 wherein the medi-
cament or concentration thereof differs in areas thereof defined
by strips adjacent to one another along the width of the sheet.
6. A composition according to claim 5, wherein the
strips are identified by different dyestuffs.
7. A composition according to claim 1, wherein the
sheet is perforated to provide a plurality of single-unit dosages.

23

8. A composition according to claim 1, wherein the
sheet is a transparent and smooth film.
9. A composition according to claim 1 containing a
water-insoluble filler uniformly suspended in the film carrier
and the film is paper-like.
10. A composition according to claim 9, wherein the
filler is cellulose.
11. A composition according to claim 1, wherein the
film carrier is methyl cellulose.
12. A composition according to claim 1, wherein the
sheet has a thickness of 0.07 - 0.3 mm.
13. A composition according to claim 1, wherein the
film carrier is hydroxypropyl-cellulose, hydroxyethyl-cellulose,
methylhydroxypropyl-cellulose or a mixture thereof; the medica-
ment is an estrogen, gestagen or admixture thereof; the release
agent is a polyoxyethylene-polyoxypropylene copolymer, a polyoxyl
stearate or an alkyl- or alkanoyl-substituted poly- addition
product of ethylene oxide; and the sheet has a thickness of 0.07 -
0.3 mm.
14. A process for the production of a pharmaceutical
composition in unit dosage form for enteral or topical adminis-
tration and comprising a safe and effective amount of a pharma-
ceutically active medicament compound and a flexible, water sol-
uble film carrier therefore, which process comprises: (a) draw-
ing into a sheet having a uniform layer thickness of about 0.1 -
2 mm and a dry thickness of about 0.05 - 1 mm, a homogeneous solu-
tion or suspension consisting essentially of (1) up to 60% by
weight, based on the film carrier, of the medicament, (2) 0 - 30
by weight of a pharmaceutically acceptable filler, (3) a film-
forming amount of a water-soluble film-forming polymer, and (4)
as solvent or suspending medium, one or both of water and an
organic volatile solvent system comprising an organic polar sol-

24

vent miscible in water; and (b) drying the thus-formed sheet to
remove the solvent or suspending medium therefrom.


Description

Note: Descriptions are shown in the official language in which they were submitted.


o~

This invention relates to a pharmaceutical prepaxation
in the form of a foil having an active substance incorporated
the~ein, for internal and external use.
Belgian Patent No. 637,363 describes paper foils coated
with active substances suitabLe for oral use. The foils consist
of cellulose fibres insoluble in water and a water-soluble binding
agent. The water-soluble binding agent i9 preferably sodium carb-
oxymethyl-cellulose. The active substance may be applied to the
paper foil by dropping a solution of the active substance onto
the foil, by spreading the solid active substance on the foil or
by drawing the foil through a solution of the active substance.
The discontinuous process of separately making the foil and apply-
ing the active substance has the disadvantage that the accuracy
of the dosage is not very good which is of great importance because
acti~e substances are generally used in small doses at the present
time. Inaccuracies arise not only in applying the active substance,
but also in the manufacture and pretreatment of the foil and
because of variations during storage of the foil material. Thus,
for example, it has been found that in using foil drawing machines
as prescribed in Belgian Patent No. 637,363, non-uniform layers
of foil are formed, and that the foil shrinks during drying.
However, it is easy to understand that with non-uniform ma~erial
the take-up of active substance is also not uniform. Moreover,
an active substance bound only on the surface can be partially
removed during handling of the foils, for example, during packing.
The sodium carboxymethyl-ceIlulose used as binding agent becomes
detached in the stomach and there is liberated carbo~ymethyl-
cellulose, which includes some of the active substance and liber-
ates it only slowly or not at all.
The present invention is based on the observation that
foils having a constant thickness and a uniform distribution of
active substance can be obtained by making foils having the active

- 1 - ~

~7

substance inco~porated therein and using foil formers that are
soluble in water or or~anic solvents.
The present invention provides a pharmaceut~cal
preparation in the form of a foil, wherein the foil incorporates
one or more pharmacologicall~ active ingredi.en-ts and is obtained
from a foil forming material or materials soluble in water or
organic sol~ents. Especially suitable are foil forming materials
soluble both in water and organic solYents.
Suitable foil formers there include poly-N-vinyl-
pyrrolidone, vinylpyrrolidone-vinyl acetate, methyl- and ethyl-
cellulose, but preferably non-ionic water-soluble hydroxyalkyl
ethers of cellulose such as, ~or example, hydroxypropyl-cellulose,
hydroxyethyl-cellulose and methylhydroxypropyl-cellulose.
In addition to the active substance or substances, the
foil may contain fillers and advantageously a small amount of
a release agent.
Suitable release agents are, polyoxyethylene-polyoxy-
propylene polymer (PLURaNIC F 68 ~?, polyoxyl stearates, alkyl-
or acyl-substituted polyaddition product~ of ethylene oxide, for
example, CR~MOPHOR EL ~ , silicones and silicone parting emulsions,
glycerine, propylene glycol and metal soaps.
The fillers include cellulose, sugars, for example,
lactose, dextrose and cane sugar, starches, polyhydric alc.ohols,
for example, m-nnitol, calcium carbonate, calcium phosphate,
talcum and dyestuffs in soluble form or as pigments. When soluble
fillers and soluble active substances are used, a transparent
smooth foil is formed, and when insoluble flllers or insoluble
active substances are used a white or coloured paper-like foil
is formed.
A11 acti~e substances used in human and veterinary
medicine can be used in accordance with the invention. ~or
internal use there comes into consideration especially oral

administration. As external use there is to be understood, more
especially, topical administration on the sk:in and in body cavi-
ties such, for example, as the nose, ears and vagina. The active
substances may be, for example, gestayens, oestrogens, mixtures
of gestagens and oestrogens, tranqui:llizers, anti.-diabetics,
sulphonamides, antibioticsl trichomonal agents and inflammation
inhibitors, for example,: corticoids.
The medicaments may be present in the car~ier materials
in a dissol~ed or uniformly .suspended state. The proportion of
acti.ve substance in the foil may be from 0 to 60 per cent. The
suraces may be cut or perforated to form single doses (units),
which contain quantities o~ active substance such as are usually
present in tablets, dragées, salves and suppositories. Thus, the
quantity of active substance per single dose may be as high as
desired depending on the mode of; use and between about 1 ~g
and 0.5 g, and the lower and upper dose may easily be smaller or
greater. It is, of course, possible also to make carriers free
from active substance (placebos).
For the production of the medicinal preparations in foil
form of the invention the active substance and/or parting compound
is disso.lved or suspended, the foil former and optionally the
filler is introduced, optionally homogenized, and the solution or
suspension is drawn out on a foil drawing machine to a sheet.
The foil obtained by drying the sheet is divided into sections
(units).
Into the solution or suspension are introduced the foil
former in a proportion by weight of about 6 to 7.0 per cent, the
filler in a proportion by weight of up to 30 per cent and the
release agent preferably in a proportion by weight of 0.01 to
per cent are introduced into the solution or suspension.
The content of solvent or suspension medium is about
~8 to 8~ per cent by weight and consists of water and/or one or


1~i7~0~

moxe organic solvents. The organic solvents are physiologically
tolerable solvents or solvents that are removed except for a
physiologically unobjectionable residue. ~uch solvents axe, for
example, ethyl alcohol, isopropanol and methylene chIoride, and
mixtures thereof. Water and ethyl alcohol or mixtures of water
and ethyl alcohol are preferably used.
The layer thickness of the wet sheet is about 0.1 to
2 mm and that of the dry foil is about 0.05 to 1 mm, and prefer-
ably 0.07 to 0.3 mm.
The process of making the medicinal preparation in foil
form in one operation (a continuous process) has the advantage
that the active substance is homogeneously and uniformly distri-
buted in the medicament carrier. By varying the concentration of
the~active substance in the carrier, the thickness of the foil
and the area of the foil the unit dose can be varied in a very
simple manner.
Foils can also be made with a sheet in which different
active substances and/or varying concentrations of active substance
are incorpoxated side by side over the width of the web of foil.
Zo ` By means of a special doctor, which consists of two or more
compartments, different solutions or suspensions can be drawn out
without mixing to form a coherent sheet. The width and thickness
of the sheet is separateIy adjustable for each compartment. If
desired, zones (strips) having different active substances or
different concentrations are made visible by different dyestuffs.
By drying the wet sheet there is obtained a foil, which by being
divided in an appropriate manner, for example, by perforation,
yields units containing different active substances and/or
concentrations of active substance or units containing no active
substance. Foils containing different active substances and/or
different concentrations of active substance are required for

making multi-phase preparations, for example, for making


~L~7~(37
contraceptive preparations~ The possibility o;E the spatial
separation of active substances that are incompatible with one
another i~ one foil unit improves the stability oE the individ-
ual active substances. ~oils for intravaginal application
may, for example, also be rolled round an ordinary commercial
tampon.
The following examples illustrate the invention; with
the exception of Examples 5 and 16, the preparations described
in the examples are primarily suitable for oral administration.
Example 1
Preparation for 1000 units:
0.25 g of d-norgestrel,
0.05 g of ethinyl-oestradiol and
0.84 g of polyoxyethylene-polyoxypropylene polymer
are dissolved in
95.00 g of ethyl alcohol while stirring, and into this
is introduced a powdered mixture of
16.93 g of hydroxypropyl-ceIlulose and
16.93 g of cellulose.
The suspension thus obtained is drawn on a suitable foil
drawing apparatus to a sheet having a thickness of 500 ~m, and
is then dried.
The composition of one unit:
0.25 mg of d-norgestrel
0.05 mg of ethinyl-oestradiol
0.84 mg of polyoxyethylene-polyoxypropylene polymer
16.93 mg of hydroxypropyl-cellulose
16.93 mg of cellulose
_. .
35.00 mg
One unit corresponds to an area of about 3 cm2.
~ppearance of the foil: white, paper-like.
The dry foil has a thickness of about 170 ~m.

~0~7~

Exam~le 2
A preparation for 1000 units:
1.10 g of Cremophor EL ~ are dissol~ed in
152.00 g of water. In this solution are suspended
0.25 g of micronized d-norgestrel and
0.05 g of micronized ethinyl-oestradiol and if necessary
homogenizea. Into the suspension are
introduced
22.10 g of hydroxypropyl-ceIlulose and
16.50 g of cellulose.
The suspension thus obtained is drawn on a suitable
foil drawing apparatus to a sheet having a thickness of 500 ~m,
and is then dried.
The com,position for one unit:
0.25 mg of d-norgestrel
0.05 mg of ethinyl-oestradiol
1.10 mg of Cremophor EL ~
22.10 mg of hydroxypropyl-cellulose
16.50 mg of cellulose
40.00 mg
One unit corresponds to an area of about 3 cm .
Appearance of the foil: white, paper-like.
The dry foil has a thickness of about 170 ~m.
'Ex'ample 3
A preparation for 1000 units:
0.03 ~ of d-norgestrel and
0.84 g of polyoxyl-40-stearate are dissolved, while
stirring, in
95.00 g of ethyl alcohol. Into this solution is
introduced a powdered mixture of
16.93 ~ of hydroxypropyl-ceIlulose and

17.20 g of cellulose.

~ ~7~q

The suspension thus obtained .is drawn on a sultable ~oil
drawing apparatus to a sheet having a thickness of 500 ~m, and
is then dried~
The composition of one.unit:
0.03 mg o~ d-norgestrel
0.84 mg of polyoxyl-40-stearate
16.93 mg of hydroxypropyl-ceIlulose
17.20 mg of cell.ulose
..35.00 mg
One unit corresponds to an area of about 3 cm2.
Appearance of the foil: ~hi.tel paper-like.
The dry foil has a thickness of about 170 ~m.
Example 4
A preparation for 1000 units:
1.10 g of polyoxyethylene-polyoxypropylene polymer
are dissolved in
152.00 g of demineralized water. In this solution is
suspended
0.03 g of microized d-norgestrel, and if necessary
homogenized. Into the suspension are
introduced.
22..10 g of hydroxypropyl-cellulose and
16.77 g of cellulose.
The suspension thus obtained is drawn on a suitable
foil drawing apparatus to a sheet having a thickness of.500 ~m,
and is then dried.
The composition for one unit:
0O03 mg of d-norgestrel
1.10 mg of polyoxyethylene-polyoxypropylene polymer
22.10 mg of hydroxypropyl-cellulose
16.77 mg of cellulose
-
40.00 mg



One unit corxesponds to an area of about 3 cm2.
Appearance of the.foil: white, paper-like.
The dry foil has a thickness of about 170 ~m,
Exam_le.5
A preparation for 1000..units
0~025 g of fluocortolone trimethylacetate and
0.183 ~ of gylcerine are dissolved in
.30.000 g of ethy.l alcohol. Into this solution are
introduced
7.292 g of hydroxypropyl-cellulose~
The solution thus obtained is draw on a suitable foil
drawing apparatus to a sheet having a thickness to.500 ~m, and
is then dried.
The composition of one unit:
0.025 mg fluocortolone trimethylacetate
0..183 mg of glycerine
- 7:.292 mg of hydroxypropyl-cellulose
7.500 mg
One unit corresponds to an area of about 1 cm2.
Appearance of the foil: transparent.
The dry foil has a thickness of about 70 ~m.
The foil is suitable for topical use.
Examp:le 6
A preparation for 1000 units:
10.00 g of 7-chloro,2-methylamino-5-phenyl-3~-1,4-
benzo-diazepine-4-oxide and
0.84 g of polyoxyethylene-polyoxypropylene polymer
are dissolved in
95.00 g of ethyl alcohol. Into this solution is
introduced a powdered mixture of
16.93 g of hydroxypropyl-cellulose and

7.23 g of cellulose.

~6'74t~~

The suspension thus o~tained is drawn on a suitable foil
dra~ing appaxatus to a sheet having a thickness o~ 500 ~m, and
is then dried.
The composition of one unit:
10.00 mg of 7-chloro-2-meth~lamino-5-phenyl-3H-1,4-
benzo-diazepine-~-oxide
0.84 mg of polyoxyethylene-polyoxypropylene polymer
16.93 mg of hydroxypropyl-cellulose
7.23 mg of cellulose
35.00 mg
One unit corresponds to an area of about 3 cm2.
Appearance of the foil: yello~, paper-like.
The dry foil has a thickness of about 170 ~m.
Example 7
A preparation for 1000 units:
1.00 g of norethisterone acetate,
0.03 g of ethinyl-oestradiol and
0.84 g of polyoxyethylene-polyoxypropylene polymer
and dissolved in
95.00 g of ethyl alcohol. Into this solution is introduced
a powdered mixture of
16.93 g of hydroxypropyl-cellulose and
16.20 g of cellulose.
The suspension thus obtained is drawn on a suitable foil
drawing apparatus to a sheet having a thickness of 500 ~m, and
is then dried.
The composition for one unit:
1.00 mg of norethisterone acetate
0.03 mg of ethinyl-oestradiol
0.84 mg of polyoxyethylene-polyoxypropylene polymer
16.93 mg of hydroxypropyl-cellulose
16.20 mg of cellulose
35.00 mg

4~

One unit corresponds to an area of about 3 cm2.
~ppearance of the ~oil: white, paper-like.
The dry foil has a thickness of about 170 ~m.
Example 8
A preparation for 1000units:
1.00 g of norethisterone acetate
0.03 g of ethinyl-oestradiol and
0.84 g of propylene glycol are dissolved in~.a mixture of
101.60 g of methylene chloride and
26.40 g of ethyl alcohol, Into this so}ution is
introduced a powdered mixture of
8.47 g of hydroxypropyl-ceIlulose,
8.47 g of hydroxyethyl-ceIlulose and
16.19 g of cellulose.
The suspension thus obtained is drawn on a suitable fo'il
drawing apparatus to a sheet having a thickness of 500 ~m, and
is then dried.
The composition fox one unit:
1.00 mg of norethistèrone acetate
0.03 mg of ethinyl-oestradiol
0.84 mg of propylene glycol
8.47 mg of hydroxypropyl-cellulose
8.47 mg of hydroxyethyl-cellulose
16.19 mg of cellulose
35.00 ~g
One unit corresponds to an area of about 3 cm2O
Appearance of the foil: white, paper-like.
The dry foil has a thickness of about 170 ~m.
Example 9
A preparation for 1000 units:
1.00 g of norethisterone aceta-te,
0.03 g of ethinyl-oestradiol and

-- 10 --

7~

0.84 g of polyoxyethylene-polyoxypropylene polymer
are dissolved in
101.60 g of methylene chloride and
25.40 ~ of ethyl alcohol. Into this solution is
introduced a powdered mixture o~
16~93 g o:E hydroxyethyl-cellulose and
16.20 g of starch.
The suspension thus obtained is drawn on a suitable foil
drawing apparatus to a sheet having a~hickness of 500 ~m, and
is then dried.
The composition for one unit:
1.00 mg o norethisterone acetate
0.03 mg of ethinyl-oestradiol
0.84 mg of polyoxyethylene-polyoxypropylene polymer
15.93 mg of hydroxyethyl-cellulose and
16.20 mg of starch
35.00 mg
One unit corresponds to an area of about 3 cm2.
Appearance of the foil: white, paper-like.
The dry foil has a thickness of about 170 ~m.
Example 10
A preparation for 1000 units:
1.00 g of norethisterone acetate
0.03 g of ethinyl-oestradiol and
0.84 g of polyoxyl-40-stearate
are dissol~ed in
95.00 g of ethyl alcohol. Into this solution is
introduced a powdered mixture of
16.93 g of hydroxypropyl-cellulose
8.10 g of lactose and
8.10 g of maize starch.
The suspension thus obtained is drawn on a suitable

-- 11 --

~ ~ t7~ ~ ~

foil drawing apparatus to a sheet ha~ing a thickness of 500 ~m,
and is then dried.
The composition ~or one unit:
1.00 mg of norethisterone acetate
0.03 mg of ethinyl-oestradiol
0.84 mg of polyoxyl-40-stearate
16.93 mg of hydroxypropyl-cellulose
8.10 mg of lactose
8.10 mg of maize starch
35.00 mg
One unit corresponds to an area of about 3 cm2.
Appearance of the foil: ~hite, paper-like.
The dry foil has a thickness of about 170 ~m.
Example ll
A preparation for 1000 units:
1.00 g of norethisterone~(l7~-ethinyl-19-nor-testosterone)
0.03 g of ethinyl-oestradiol and
0.22 g of polyoxyethylene-polyoxypropylene polymer
are dissolved in a mixture of
84.75 g of ethyl alcohol and
4.00 g of water. Into this solution is introduced a
powdered mixture of
16.00 g of hydroxypropyl-cellulose and
16.00 g of cellulose.
The suspension thus obtained is drawn on a suitable
foil drawing apparatus to a sheet having a thickness of 600 ~m
and then dried.
The composition for one unit:
1.00 mg of noxethisterone ~17~-ethinyl-l9-nor-testosterone)
0.03 mg o~ ethinyl-oestradiol
0.22 mg of polyoxyethylene-polyoxypropylene polymer
16.00 mg of hydroxypropyl-cellulose

- 12 -

~7~

16.00 mg of cellulose
.
33.25 mg
One unit corresponds to an area of about 3 çm2.
Appear~nce o~ the ~oil: white, paper~like.
The dry foil has a thickness of approx. 230 ~m.
Example 12
A preparation for 1000 uni*s:
4.0 g of glisoxepide.* in micronised form are suspended in
0..9 g of polyoxyl-40-stearate dissolved in
.152.0 g of water, and:if necessary homogenized. Into
the suspension are introduced
15.0 g of hydxoxyethyl-ceIlulose and
15.1 g of calcium carbonate.
The suspension thus obtained is drawn on a suitable foil
drawing appara*us to a sheet having a thickness of.500 ~m and
dried.
The composition for one unit:
4.00 mg of glisoxepide.*
0090 mg of polyoxyl-40 stearate
15.00 mg of hydroxyethyl-cellulose
15.10 mg of calc.ium carbonate
-
.35.00 mg
One unit corresponds.to an area of about 3 cm2.
Appearance of the foil: white, paper-like.
The dry foil has a thickness of about 170 ~m.
4-{~-[~-(5-methyl-isoxazol-3-carboxamido~-ethyl~-benzolsulphonyl}-
l,l-hexamethylene-semicarbazide.
Example 13
A preparation for lOOO.units:
0.030 g of d norgestreI are dissolved in

40.000 g of methylene chloride and
55.000 g of ethanol. Into this solution are introduced

0.840 g of silicone oil
6.930 g of methyl-cellulo:se and
10.000 g of poly-N.-vinyl-pyrrolidone and
17.200 g of starch~,and i~ necessary homoyenlzed.
The suspension thus obta:ined is drawn on a :suitable
foil drawing apparatus to a sheet having a t:hickness of;500 ~m
and dried.
The composition of one~.unit:
Ø.030 mg of d-norgestrel
0.840 mg of silicone oil
6.930 mg of methyl-cellulose
10.000 mg of poly-N-~inyl-pyrrolidone
17:.200 mg of starch
.35.000 mg
One unit corresponds to an area of about.3 cm .
Appearance of the foil: white, paper-like.
The dry foil has a thickness of about 170 ~m.
Ex'ampl'e''14
A preparation for 1000. units:
0.84 g of polyoxyethylene-polyoxypropylene polymer
are dissolved in
95.00 g of ethyl alcohol while stirring, and into this
solution is introduced a powdered
mixture of
17.08 g of hydroxypropyl-ceIlulose and
17.08 g of cellulose.
The suspension thus obtained is drawn on a suitahle foil
dra~ing app~ratus to a sheet having a thickness of 500 ~m and
then dried~



- 14 -

~)t;i7~0P7

The compositi.on ~or one unit:
0.84 mg of polyoxyethylene-polyoxypropylene polymer
17.08 mg of hydroxypropyI-ceIlulsoe
17.08 mg of cellulose
..35.00 mg
Exampl:e :15`
A preparati.on for 1000 units:
0.04 g of saccharin
0.04 g of cream essence and
0.40 g of polyoxyethylene-polyoxypropyl.ene:polymer are
dissolved in a mixture of
79.00 g of ethyl alcohol and
4.00 g of water. Into this solution are introduced
.30:.00 g of iron (II? .umarate,
.15.00 g of hydroxypropyl-cellulose,
5..52 g of cocoa and
4:.00 g of ceI.lulose, and if necessaxy homogenized.
The suspension thus obtained is drawn on a suitable foil
drawing apparatus to a sheet having a thickness of 0.5 mm, and
then dried.
The composition for one unit:
30.00 mg of iron (II) :fumarate
15.00 mg of hydroxypropyl-cellulose
4.00 mg of cellulose
0.40 mg of polyoxyethylene-polyoxypropylene polymer
5..52 mg of co.coa
0.04 mg of saccharin
0.04 mg of cream ess~ence
55.00 mg. Weight per unit.
One unit corresponds to an ar~a of about 3 cm2.
Appearance o the foil: pale red-brown.

~;7~

Example 16
Foils for intravaginal application;
The foil is prepared in accordance with Example ll.
The co~position of one unit
100.0 mg of S-morpholinomethyl-3-(5-nitro-1-methyl-2-
imidazolyl)-methyleneamino-2-oxazoli-
done.HCl
8.4 mg of Cremopho~ EL ~
169.2 mg of methylhydroxypropyl-cellulose
72.4 mg of cellulose
350.0 mg. Weight of one unit.
One unit corresponds to an area of about 8 x 4 cm.
Appearance of the foil: pale yellow.
The $oil (1 unit~ is either rolled round an ordinary
commercial tampon or is itself rolled to form a naErow tube.
EXample 17
A two phase preparation
Part 1: 21 units containing active substance.
Part 2: 7 units without active substance.
A preparation for 3000 units. Part 1.
0.75 g of d-norgestrel
0.15 g of ethinyl-oestradiol and
0.54 g of polyoxethylene-polyoxypropylene polymer
are dissol~ed in a mixture of
237.00 g of ethyl alcohol and
12.00 g of water. Into this solution are introduced
44.28 g of hydroxypropyl-cellulose and
44.28 g of cellulose, and if necessary homogenized.
A preparation for 1000 units, Part 2.
0.18 g of polyoxyethylene-polyoxypropylene polymer
is dissolved in a mixture of
79.00 g of ethyl alcohol and

- 16 -


4.00 g of water. Into this solution are introduced
14~.91 g of h~droxypropyl-ceIlulose and
14.91 g of cellulose,~ and if necessary homogenized.
The suspensions thus :obtained are drawn on a suitable
foil drawing apparatus having a two compartment s~ecial doctor
(widths of the compartments: 1 =.54 mmi 2 = 18 mm) to form a
sheet of 0..5 mm and then dried. By appropriate division into
units measuring 18 x 18 mm, for example, by perforation, the
foil can be divided over its width into three units containing
active substance and one unit free from active substance. There
may be produced in the web of foil any desired number of sections
having a ratio of three units containing active substance to one
unit containing no active .substance.
The composition of each unit:

Part 1 (containing active :substance) Part 2 (free from
. ..... = . . active.. su~stance~

0.25 mg of d-norgestrel
0.05 mg of ethinyl-oestradiol
14.76 mg of hydroxypropyl-cellulose 14.91 mg
2014~76 mg of cellulose 14.91 mg

0.18 mg of polyoxyethylene-polyoxypropylene0.18 mg
polymer
30.00 mg weight per unit 30.00 mg
Area per unit: about 3 cm .
Appearance: white.
Example 18
Three phase preparation (two acti~e substance stage
preparation)
Part 1: 11 Units containing 0.05 mg of d-norgestrel



diol.
Part 2: 10 Units containing 0.125 mg of d-n~rgestrel

0.050 mg of ethinyl-oestra-
diol.
- 17 -


~67~

Part 3: 7 UnitS without active substance.preparation for 1100 units, Part 1:
0.055 g of d-noxgestre~ r
0.055 g of ethinyl-oestradiol and
0.198 g of polyoxyethylene-polyoxypropylene polymer
are dissolved in a mixture of
86.900 g of ethyl alcohol and
4.400 g of water. Into this solution are introduced
16.346 g of hydroxypropyl-ceIlulose and
16.346 g of cellulsoe, and if necessary homogenized.
A preparation for 1000 units t Part 2.
0.125 g of d-norgestreI
0.050 g of ethinyl-oestradiol and
0.180 g of polyoxyethylene-polyoxypropylene polymer
are dissolved in a mixture of
79.000 g of ethyl alcoho~ and
4.000 g of water. Into this solution are introduced
14.823 g of hydroxypropyl-ceIlulose and
14.822 g of cellulose, and if necessary homogenized.
A preparation for 700 units. Part 3:
0.189 g of polyoxyethylene-polyoxypropylene polymer
is dissolved in a mixture of
82.950 g of ethyl alcohol and
4.200 g of water. Into this solution are introduced
15.656 g of hydroxypropyl-cellulose and
15.655 g of ceIlulose, and if necessary homogenized.
The suspensions thus obtained are drawn on a suitable
foil drawing apparatus having a three compartment special doctor
(width per compartment 18 mm~ to a sheet and dried. By appropriate
division, or example, by perforationl there can be distributed
over the width of the foil three units of 18 x 18 mm for Part 1,
of 18 x 19.8 mm for Part 2 and of 18 x 28 for Part 3, having




- 18 -

-

~(~674~97

different contents of active substance. There can be separated
from the foil web preparations having 11 units of Part 1, 10
units of Part 2 and 7 units of Part.3.
The composition per:unit:
Part 1 Part 2. Part.3. . In~redients

O.OS0 mg 0.125 mg - d-norgestrel
0.050 m~ O.OS0 mg - ethinyl-oestradiol

0.180 mg 0.180 mg0.270 mg polyoxyethylene-
polyoxypropylene
polymer

1014.860 mg 14.823 mg23.366 mg hydroxypropyl-
cellulose
1-4.860 mg 14.822 mg22.3-64 mg cellulose
30.000 mg 30.000 mg45.000 mg weight per unit
about about about
3 cm2 3'5 cm25 cm area per unit
~hite ~hite white appearance
. .

:
Example 19
Three phase preparation:
Part 1: 11 Units containing 0.05 mg of d-norgestrel
0..05 mg of ethinyl-oestradiol
Part 2: 10 Units containing 0.125 mg of d-norgestrel
0.050 ~g of ethinyl-oestradiol
Part 3: 7 Units containing50.00 mg of iron (II) :fumarate.
A preparation for 1100 units. Part 1:
0.066 g of food colour yeIlow No. 2 (tartrazine; E 102)

is dissolved in
4.400 g of water, and then introduced into
86.900 g of ethyl alcohol. In this solution axe dissolved
0.055 g of d-norgestrel
0.055 g of ethinyl-oestradiol and
0.198 g of polyoxyethylene-polyoxypropylene polymer.

-- 19 --

Into this solution are in-troduced
16.313 g of hydroxypropyl.-cellulose and
16..313 g of cellulose, and if necessary homogenized.
preparation for lOOO.units. Part 2:
0.065 g of food..colour orange No. 2 (Sunset ~ellow;
E 110~ is disso:lved in
4.000 g o~ water, and then introduced into
79.000 g of ethyl alcohol. In this solution are
dissolved
0.125 g of d-norgestr~el
0..050 g of ethinyl-oestradiol and
0.18 g of polyoxyethylene-polyoxypropylene polymer.
Into this solution are:introduced
14.790 ~ of hydroxypropyl-.cellulose and
14.790 g of cellulose, and if necessaxy homo~enized.
A preparation for 700 units. Part.3:
0.042 g of saccharin
0.042 g of cream essence and
0.406 g of polyoxyethylene-polyoxypropylene polymer
are dissolved in a mixture of
55.300 g of ethyl alcohol and
2.800 g of water. Into this solution are introduced
.35.000 g of iron (II) .fumarate
17.500 g of hydroxypropyl-.cellulose
5.950 g of cocoa and
4.060 g of cellulose, and if necessary ho~ogenized.
The suspensions so prepared are drawn on a suitable
foil drawing apparatus having a three compartment special doctor
(width per compartment 18 mm) to a sheet and dried. By appropri-
ate division, for example, by perforation, there can be distribu-
ted over the width of the foil three units of 18 x 18 mm for
Part 1, of 18 x 19.8 mm for Part 2 and of 18 x 28 mm for Part 3,




- 20 -

7~

having different contents of acti.ve substance. r~here can be
separated from the ~oil web preparations having ll..unit o~
Part 1, 10 units of Part.2 and 7 units oE ~art 3.
The composition per.unit:
Part 1 P~rt 2Part 3 In~redients
0.050 mg 0.125 mg - 'd-norgestrel
O... OS0 mg 0.050 mg - ethinyl-oestradiol
- - 50.000 mg iron ~II) fumarate
0~180 mg a .180 mg 0.580 mg polyoxyethylene-
polyoxypropylene
polymer
0.060 mg - - food colour yellow
No. 2
- 0.065 mg - food colour orange
No. 2
14.830 mg 14.790 mg25'.000 mg hydroxypropyl-
cellulose
14.830 mg 14.790 mg5.800 mg cellulose
- - 8.500 mg cocoa
- - 0.060 mg saccharin
.. . - - . .. 0.. 06Ømg cream essence
.
20 30.000 mg 30.000 mg 90.000 mg weight per unit
about about about
3 cm2 3.5 cm2 5 cm2 area per unit
yel.low . orange br.own . . .... a.ppe:a.rance
.
Exa~ple 20
Preparation for 1000 units
0.15 g of d-norgestreI
0.03 g of ethinyl-oestradiol and
0.84 g of polyoxethylene-polyoxypropylene polymer are
dissol~ed in
95.00 g of ethyl alcohol while stirring and a powdered
mixture o~
16.99 g of hydroxypropyl-cellulose and

- 21 -

16.99 g of cellulose is introduced into this solution.
The suspension obt~ined is drawn out on a suitable foil
drawing apparatus to ~ very thin foil having a thi.ckness of
500 ~m, and is then dried.
The composition of one unit:
0.15 mg of d-norgestrel
0.03 mg of ethinyl-oestradiol
0.84 mg of polyoxyethylene-polyoxypropylene polymer
16.99 mg of hydroxypropyl-cellulose
16.99 mg of cellulose
35.00
One unit corresponds to.an area of approxO 3 cm2
Appearance of the: foil: white, paper-like.
The dry foil has a thickness of approx. 170 ~m.




- 22 -

Representative Drawing

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Administrative Status

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Administrative Status

Title Date
Forecasted Issue Date 1979-12-04
(45) Issued 1979-12-04
Expired 1996-12-04

Abandonment History

There is no abandonment history.

Owners on Record

Note: Records showing the ownership history in alphabetical order.

Current Owners on Record
SCHERING AKTIENGESELLSCHAFT
Past Owners on Record
None
Past Owners that do not appear in the "Owners on Record" listing will appear in other documentation within the application.
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Document
Description 
Date
(yyyy-mm-dd) 
Number of pages   Size of Image (KB) 
Description 1994-05-03 22 784
Drawings 1994-05-03 1 11
Claims 1994-05-03 3 106
Abstract 1994-05-03 1 19
Cover Page 1994-05-03 1 29