EP0358665A1 - Pharmaceutical compositions having spasmolytic activity - Google Patents
Pharmaceutical compositions having spasmolytic activityInfo
- Publication number
- EP0358665A1 EP0358665A1 EP88903795A EP88903795A EP0358665A1 EP 0358665 A1 EP0358665 A1 EP 0358665A1 EP 88903795 A EP88903795 A EP 88903795A EP 88903795 A EP88903795 A EP 88903795A EP 0358665 A1 EP0358665 A1 EP 0358665A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- pharmaceutical compositions
- idanpramine
- sulfate
- compositions according
- granules
- 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.)
- Withdrawn
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/72—Two oxygen atoms, e.g. hydantoin
- C07D233/76—Two oxygen atoms, e.g. hydantoin with substituted hydrocarbon radicals attached to the third ring carbon atom
- C07D233/78—Radicals substituted by oxygen atoms
Definitions
- the present invention relates to pharmaceutical compositions containing as the active ingredient (1-(2-piperidinoethyl)-4 ,4-bis-(4-methoxyphenyl)-2,5-imi- dazolidinedione (i.e. idanpramine) sulfate, and to the use thereof in human therapy.
- hydrochloride salt which is easy and economic to prepare, has been hitherto used for the preparation of suitable pharmaceutical formulation; however, the cha ⁇ racteristics of said salts are not perfectly suited for the envisaged pharmaceutical uses.
- a particularly preferred object of the invention is provided by capsules or tablets in which the active ingredient is slowly and gradually released during time.
- idanpramine sulfate can be prepared by means of per se known methods.
- idanpramine sulfate can be obtained by trea ⁇ ting an aqueous or aqueous-alcoholic solution or suspen ⁇ sion of idanpramine base with sulfuric acid, recovering the salt by precipitation with a non-solvent, by lyophi- lization or similar techniques.
- the techniques and the excipients used for the pre ⁇ paration of- the pharmaceutical compositions are those described, for instance, in "Remington's Pharmaceutical Sciences Handbook",hack Pub. Co., New York, USA.
- examples of formulations comprise capsule, sugar-coated pills, drops, solutions, syrups, vials, suppositories, rectal capsules, granulates, lozenges.
- compositions of the invention will possibly contain other active ingredients having complementary, synergic or anyhow useful activities.
- Unitary dosages will usually contain 50 to 200 mg of idanpramine sulfate, and will be administered 1 to 3 times a day, depending on the conditions of the patient and the severity of the disease. The following non-limiting examples further illu ⁇ strate the invention.
- Each rectal capsule contains:
- Each vial contains
- Each 10 ml ampoule contains Active ingredient:
- a mixture comprising 75% saccharose and 25% maize starch was placed into a stainless steel rotary pan; while the rotary pan rotated, water was sprayed on the mixture, in an amount of 15% w/w based on the total mass, thus obtaining spherical granules of different sizes.
- a predetermined amount of spherical nuclei was placed into a special rotary stainless steel pan rotating at moderate speed.
- the drug was distributed on the granules by means of a suited binding solution.
- the whole operation was carried out slowly so as to avoid as much as possible the formation of clots; when the predetermined amount of active principle has been applied, the granules were sieved through a 1340.u sieve and then dried at 35°C with forced ventilation.
- d) Application of the delaying membrane on the granules The granules obtained in c) were placed again in rotary pan. The delaying membrane was applied on them, slowly, keeping the pan at moderate speed and portion- wise, so as to obtain a uniform distribution of the coating on the granules surface; the product was dried with talc portions between each application.
- the application of the membrane was normally carried out in more than a phase, up to the obtainment of the desired i ⁇ vitro release values.
- the granules were dried by insufflating air at 35 ⁇ C into the rotating pan, till the content of the residual solvents is within the predetermined limits.
Abstract
Le sulfate d'idanpramine permet la préparation de compositions pharmaceutiques possèdant des propriétés de biodisponibilité.Idanpramine sulfate allows the preparation of pharmaceutical compositions with bioavailability properties.
Description
"PHARMACEUTICAL COMPOSITIONS HAVING SPASMOLYTIC ACTIVITY"
The present invention relates to pharmaceutical compositions containing as the active ingredient (1-(2-piperidinoethyl)-4 ,4-bis-(4-methoxyphenyl)-2,5-imi- dazolidinedione (i.e. idanpramine) sulfate, and to the use thereof in human therapy.
Idanpramine of formula I
is a well-known therapeutical agent used as a spasmolytic agent [II Farmaco (Ed. Sci.) I960, 150:809; Arzn. Forsch. 1970, 20:277].
The hydrochloride salt, which is easy and economic to prepare, has been hitherto used for the preparation of suitable pharmaceutical formulation; however, the cha¬ racteristics of said salts are not perfectly suited for the envisaged pharmaceutical uses.
Now it has been found that idanpramine sulfate al¬ lows to attain the following advantages, in comparison with the use of the free base or of the hydrochloride:
1) easier preparation of the pharmaceutical formula¬ tions;
2) better bioavailability of the active ingredient;
3) better hydrosolubility;
4) possibility of preparing sustained-release formu¬ lations having improved release characteristics of the active ingredient. A particularly preferred object of the invention is provided by capsules or tablets in which the active ingredient is slowly and gradually released during time.
The active ingredient, idanpramine sulfate, as well as the pharmaceutical compositions of the invention, can be prepared by means of per se known methods. Thus, idanpramine sulfate can be obtained by trea¬ ting an aqueous or aqueous-alcoholic solution or suspen¬ sion of idanpramine base with sulfuric acid, recovering the salt by precipitation with a non-solvent, by lyophi- lization or similar techniques. The techniques and the excipients used for the pre¬ paration of- the pharmaceutical compositions are those described, for instance, in "Remington's Pharmaceutical Sciences Handbook", Hack Pub. Co., New York, USA.
Besides the oral administration route, also the pa- renteral and rectal route may be envisaged: examples of formulations comprise capsule, sugar-coated pills, drops, solutions, syrups, vials, suppositories, rectal capsules, granulates, lozenges.
The compositions of the invention will possibly contain other active ingredients having complementary, synergic or anyhow useful activities. Unitary dosages will usually contain 50 to 200 mg of idanpramine sulfate, and will be administered 1 to 3 times a day, depending on the conditions of the patient and the severity of the disease.
The following non-limiting examples further illu¬ strate the invention.
EXAMPLE 1
Rectal σapules
Each rectal capsule contains:
Active ingredient
Idanpramine sulfate mg 180
Excicipients:
Liquid paraffin mg 220
Solid paraffin mg 10
Gelatin mg 80
Glycerine mg 30
Ethyl p-hydroxybenzoate mg 0.33
Propyl " mg 0.2
Polyethylenglycol mg 5.6
Titanium dioxide mg 5.5
Glyceryl-mono-dioleate mg 4
Polyvinylacetate mg 0. , 2
EXAMPLE 2
Vials
Each vial contains
Active ingredient:
Idanpramine sulfate mg 180
Excipients:
Bidistilled water for injectable preparation q.s.
EXAMPLE 3 Sugar-coated pills Each sugar-coated pill contains:
Active ingredient:
Idanpramine sulfate mg 60
Excipients:
Dextrose mg 100 Talc mg 7 Maize starch mg 40 Gum arabic mg 3
Sodium stear te mg 10 Saccharose q.s. a mg 375
EXAMPLE 4
Drops
Each 10 ml ampoule contains Active ingredient:
Idanpramine sulfate mg 800
Exci ients:
Sweeteners water q.s. a 10 ml
Natural flavor q.s. EXAMPLE 5
"Retard" sugar-coated pills a) Composition for sugar-coated pill Active ingredient: Idanpramine sulfate mg 180 Excipients-
Inert granules mg 76
PEG 4000 mg 7.71
Ethylcellulose mg 14.0
Stearic acid mg 1.40 Polymethacrylate mg 5.58
Talc mg 15.31 b) Preparation of inert granules
A mixture comprising 75% saccharose and 25% maize starch was placed into a stainless steel rotary pan; while the rotary pan rotated, water was sprayed on the
mixture, in an amount of 15% w/w based on the total mass, thus obtaining spherical granules of different sizes.
The obtained granules were dried in thermostatic oven at 40°C, under forced ventilation. After drying, residual water must not be higher than 2%. Granules were sieved to separate those having the desired size from the ones having higher or lower diameter. c) Application of the medicament on the spherical granules ,
A predetermined amount of spherical nuclei was placed into a special rotary stainless steel pan rotating at moderate speed. The drug was distributed on the granules by means of a suited binding solution. The whole operation was carried out slowly so as to avoid as much as possible the formation of clots; when the predetermined amount of active principle has been applied, the granules were sieved through a 1340.u sieve and then dried at 35°C with forced ventilation. d) Application of the delaying membrane on the granules The granules obtained in c) were placed again in rotary pan. The delaying membrane was applied on them, slowly, keeping the pan at moderate speed and portion- wise, so as to obtain a uniform distribution of the coating on the granules surface; the product was dried with talc portions between each application.
The application of the membrane was normally carried out in more than a phase, up to the obtainment of the desired i^ vitro release values. The granules were dried by insufflating air at 35βC into
the rotating pan, till the content of the residual solvents is within the predetermined limits.
At the end of drying the granules, sieved so as to obtain a particle size ranging from 707 to 1340.U, are distributed in capsules size "1" by means of a suited incapsulating machine.
Claims
1. Idanpramine sulfate as therapeutic agent.
2. Pharmaceutical compositions containing as an active principle idanpramine sulfate in admixture with acceptable excipients and optionally with other active principles.
3. Pharmaceutical compositions according to claim 2 for oral, parenteral or rectal administration.
4. Pharmaceutical compositions according to claim 3 in form of capsules, tablets, sugar-coated tablets, drops, suppositories, vials.
5. Pharmaceuticals compositions according to claim 2 in form of sustained release capsules.
6. Pharmaceutical compositions according to claim 5 wherein the active principle is coated with a membrane consisting of polymethaacrylate, ethylcellulose, polyethylenglycol.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IT8720229A IT1215441B (en) | 1987-04-23 | 1987-04-23 | PHARMACEUTICAL COMPOSITIONS SPASMOLITHIC ADAPTITY CONTAINING AS A PRINCIPLE ACTIO IDANPRAMINA |
IT2022987 | 1987-04-23 |
Publications (1)
Publication Number | Publication Date |
---|---|
EP0358665A1 true EP0358665A1 (en) | 1990-03-21 |
Family
ID=11164959
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP88903795A Withdrawn EP0358665A1 (en) | 1987-04-23 | 1988-04-15 | Pharmaceutical compositions having spasmolytic activity |
Country Status (6)
Country | Link |
---|---|
EP (1) | EP0358665A1 (en) |
JP (1) | JPH03500163A (en) |
KR (1) | KR890700580A (en) |
AU (1) | AU1685088A (en) |
IT (1) | IT1215441B (en) |
WO (1) | WO1988008421A1 (en) |
-
1987
- 1987-04-23 IT IT8720229A patent/IT1215441B/en active
-
1988
- 1988-04-15 AU AU16850/88A patent/AU1685088A/en not_active Abandoned
- 1988-04-15 KR KR1019880701708A patent/KR890700580A/en not_active Application Discontinuation
- 1988-04-15 JP JP63503658A patent/JPH03500163A/en active Pending
- 1988-04-15 WO PCT/EP1988/000318 patent/WO1988008421A1/en not_active Application Discontinuation
- 1988-04-15 EP EP88903795A patent/EP0358665A1/en not_active Withdrawn
Non-Patent Citations (1)
Title |
---|
See references of WO8808421A1 * |
Also Published As
Publication number | Publication date |
---|---|
WO1988008421A1 (en) | 1988-11-03 |
KR890700580A (en) | 1989-04-25 |
IT8720229A0 (en) | 1987-04-23 |
JPH03500163A (en) | 1991-01-17 |
AU1685088A (en) | 1988-12-02 |
IT1215441B (en) | 1990-02-14 |
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Legal Events
Date | Code | Title | Description |
---|---|---|---|
PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): AT BE CH DE FR GB IT LI LU NL SE |
|
17P | Request for examination filed |
Effective date: 19891018 |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN |
|
18D | Application deemed to be withdrawn |
Effective date: 19921105 |