IE55139B1 - Compositions containing salbutamol - Google Patents
Compositions containing salbutamolInfo
- Publication number
- IE55139B1 IE55139B1 IE1267/83A IE126783A IE55139B1 IE 55139 B1 IE55139 B1 IE 55139B1 IE 1267/83 A IE1267/83 A IE 1267/83A IE 126783 A IE126783 A IE 126783A IE 55139 B1 IE55139 B1 IE 55139B1
- Authority
- IE
- Ireland
- Prior art keywords
- cellulose
- pharmaceutical composition
- composition according
- salbutamol
- hydroxyethyl
- Prior art date
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
New medicaments are aq. dispersions of one or more cellulose derivs. contg. salbutanol and/or one or more physiologically acceptable salts of salbutanol. Suitable cellulose derivs. are those which form an optically transparent or opalescent dispersion in water. Particularly pref. are ethylcellulose, methylcellulose, ethylmethylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxyethyl methylcellulose, hydroxypropylmethylcellulose, hydroxyethyl-ethyl cellulose and carboxymethyl cellulose and its salts. The cellulose deriv. is pref. used in a total amt. of at least 0.1% w/v. For oral formulations, the cellulose deriv. is pref. present in an amt. such as to give a viscosity of 5-10000 (esp. 10-100) cPs. Salbutanol or its salt is pref. present in an amt. of 1-4 (esp.2) mg. per 5 ml., expressed as salbutanol free base. The prepn. pref. has a pH of 3.5. Salbutanol is a beta-stimulant with improved stability.
[FR2527442A1]
Description
2 2 55139 The present invention relates to a pharmaceutical composition containing as active ingredient the β-stimulant salbutamol.
Salbutamol [(a^-tert-butylaminomethyl)-4-hydroxy-5 m-xylene-α ,ct -diol)] and its physiologically acceptable salts are described in British Patent Specification No. 1200886. In that specification there is reference to pharmaceutical compositions containing salbutamol and there is a description of solid and liquid 10 preparations for oral and intravenous use.
Liquid preparations of salbutamol and/or a physiologically acceptable salt thereof are conveniently water based and for oral use the preparations contain sucrose or sorbitol which acts both as a sweetener and 15 thickening agent.
Such pharmaceutical compositions have been successfully marketed. However, it is known that the presence of a substance such as sucrose, or sorbitol or glycerol in aqueous compositions of 20 salbutamol or a physiologically acceptable salt thereof is associated with an accelerated deterioration in the stability of the salbutamol in the composition.
We have now surprisingly found that the stability 3 3 55139 of salbutamol in aqueous formulations may be significantly enhanced by the presence of a cellulose derivative which forms a colloidal dispersion in water.
Thus, the present invention provides an improved pharmaceutical composition which comprises an aqueous dispersion of one or more cellulose derivatives containing salbutamol and/or one or more of its physiologically acceptable salts.
According to a preferred embodiment of the invention, the pharmaceutical composition is formulated as a liquid preparation suitable for oral administration in which the cellulose derivative is advantageously used as thickening agent.
Suitable cellulose derivatives are those which form an optically transparent or opalescent dispersion in water, preferably an optically transparent colloidal dispersion.
Preferred cellulose derivatives include non-ionic derivatives such as alkyl and/or hydroxyalkyl ethers of cellulose, particularly C^_4 alkyl and/or hydroxy C^_4 alkylethers of cellulose for example, ethyl cellulose, methyl cellulose, ethylmethyl cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxyethyl methylcellulose, hydroxypropyl methylcellulose and hydroxyethyl ethylcellulose. 55139 Suitable ionic cellulose derivatives include carboxyraethylcellulose and salts thereof such as the calcium or sodium salts.
Particularly preferred cellulose derivatives 5 are hydroxyethyl cellulose and more especially hydroxypropyl methylcellulose.
A preferred salt of salbutamol for use in the pharmaceutical composition according to the invention is the sulphate.
The total amount of dispersible cellulose derivatives present in the pharmaceutical composition according to the invention is such that the resulting colloidal dispersion has the desired enhanced stability and has a viscosity suitable for its 15 proposed mode of administration. Preferably, the pharmaceutical composition contains at least 0.1% w/v of the cellulose derivatives.
For liquid preparations suitable for oral administration the total amount of cellulose 20 derivatives will be determined primarily by the requirement to obtain a solution with a viscosity suitable for oral administration, preferably within the range 5 to 10,000 centipoises, more preferably from 10 to 100 centipoises.
The concentration of the salbutamol or its gaits in the formulation may be adjusted to suit the use 25 5 55139 for which the formulation is required and/or the patient's requirements. For example, for oral use the concentration is conveniently equivalent to lmg to 4mg, preferably 2mg, of salbutamol, 5 expressed as salbutamol free base, per 5 ml of the liquid.
Preferably the pH of the pharmaceutical composition Is in the range of from 2.5 to 7, more particularly 3.5 and this is conveniently achieved 10 by the use of a buffer. For oral compositions, suitable buffers include a sodium citrate/citric acid buffer; The pharmaceutical composition according to the invention may also contain an antimicrobial preservative, such as benzoic acid or a salt thereof 15 which generates the acid in situ, or a methyl, ethyl, propyl or butyl hydroxybenzoate. For oral use the composition preferably also contains a flavouring, a sweetening agent such as saccharin sodium or sodium cyclamate and/or a colouring.
The pharmaceutical composition according to the invention may be prepared by dispersing one or more cellulose derivatives in water, and then adding or mixing with the salbutamol or physiologically acceptable salts thereof, conveniently dissolved in 25 water, together with any optional components of the composition. 6 6 SS139 Illustrative examples of formulations (expressed as a 5 ml dose for oral administration according to the invention are as follows:-.
Example 1 5 Salbutamol sulphate 2.40 mg Hydroxyethyl cellulose (Natrosol (Trade Mark) 250H) 22.5 mg Distilled water to 5 ml To prepare the formulation the hydroxyethyl 10 -cellulose is dispersed in water and then mixed with a solution of salbutamol sulphate in water.
Example 2 Salbutamol sulphate 2. ,40 mg Sodium citrate dihydrate 9. .60 mg Citric acid monohydrate 15, ,15 mg Natrosol 250H 15. .0 mg Distilled water to 5, .0 ml To prepare the formulation the hydroxyethyl cellulose is dispersed in water, and then mixed with a solution of salbutamol and the buffers salts in water. 7 5 5 1 3 9 Example 3 Salbutamol sulphate 2.40 mg Sodium citrate dihydrate 9.60 mg Citric acid monohydrate 15.25 mg 5 Hydroxypropyl methylcellulose viscosity type 4000 22.5 mg Distilled water to 5 ml Example 4 2.40 mg 7.5 mg 25.0 mg 22.5 mg 10.0 mg 2.5 mg qS 5 ml Salbutamol sulphate B.P.
Sodium citrate B.P.
Citric acid monohydrate B.P.
Hydroxypropyl methylcellulose (viscosity type 4000) Sodium benzoate B.P.
Saccharin sodium B.P.
Flavouring Purified water to To prepare the formulations of Examples 3 and 4 20 the hydroxypropyl methylcellulose is dispersed in hot water, cooled and then mixed with an aqueous solution containing the salbutamol sulphate and the other components of the formulation.
Claims (15)
1. A pharmaceutical composition comprising an aqueous dispersion of one or more cellulose derivatives containing salbutamol and/or one or more of its physiologically acceptable salts. 5
2. ' 2. A pharmaceutical composition according to claim 1, which comprises the one or more cellulose derivatives in a total amount of at least 0.1 w/v.
3. A pharmaceutical composition according to claim 1 or 2» wherein the cellulose derivative is an alkyl 10 and/or hydroxyalkyl ether.
4. A pharmaceutical composition according to claim 3, wherein the cellulose derivative is a alkyl and/or hydroxy Cj_4 alkyl ether.
5. A pharmaceutical composition according to 15 any of claims 1 or 2, in which the cellulose derivative is selected from ethyl cellulose, methyl cellulose, ethylmethyl cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxyethyl methylcellulose, hydroxypropyl methyl-20 cellulose, hydroxyethyl ethycellulose, carboxymethyl-cellulose and salts of carboxymethylcellulose.
6. , 6. A pharamceutical composition according to claim 5, wherein the cellulose derivative is hydroxypropyl methylcellulose. 25
7. A pharmaceutical composition according to claim 5, wherein the cellulose derivative is hydroxyethyl cellulose. 9 SS139
8. A pharmaceutical composition according to any of claims 1 to 7, which is formulated as a liquid preparation suitable for oral administration. 5 8 8 5S139
9. A pharmaceutical composition according to claim 8r which contains the one or more cellulose derivatives in a total amount such as to provide the liquid preparation with a viscosity in the range of from 5 to 10,000 centipoises. 10
10. A pharmaceutical composition according to claim 9, wherein the viscosity is in the range of from 10 to 100 centipoises.
11. A pharmaceutical composition according to any of claims 8 to 10, which contains salbutamol and/or one or more of its physiologically acceptable salts 15 in a concentration of lmg to 4mg, expressed as salbutamol free base per 5 ml of liquid.
12. A pharmaceutical composition according to claim 11, wherein the concentration is 2mg expressed as salbutamol free base per 5 ml of liquid. 20
13. A pharmaceutical composition according to any of claims 1 to 12, having a pH in the range of from 2.5 to 7.
14. A pharmaceutical composition according to claim 13, having a pH of 3.5.
15. A pharmaceutical composition according to claim 1, substantially as herein described with reference to any of the specific Examples. F. R. KELLY & CO. AGENTS FOR THE APPLICANTS. 25
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8215502 | 1982-05-27 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IE831267L IE831267L (en) | 1983-11-27 |
| IE55139B1 true IE55139B1 (en) | 1990-06-06 |
Family
ID=10530673
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IE1267/83A IE55139B1 (en) | 1982-05-27 | 1983-05-27 | Compositions containing salbutamol |
Country Status (25)
| Country | Link |
|---|---|
| JP (1) | JPH0629181B2 (en) |
| AT (1) | AT390191B (en) |
| AU (1) | AU567675B2 (en) |
| BE (1) | BE896870A (en) |
| CA (1) | CA1203176A (en) |
| CH (1) | CH656308A5 (en) |
| DE (1) | DE3319356C2 (en) |
| DK (1) | DK167558B1 (en) |
| ES (1) | ES8502336A1 (en) |
| FI (1) | FI81257C (en) |
| FR (1) | FR2527442B1 (en) |
| GR (1) | GR82681B (en) |
| IE (1) | IE55139B1 (en) |
| IL (1) | IL68805A0 (en) |
| IT (1) | IT1174759B (en) |
| LU (1) | LU84828A1 (en) |
| MY (1) | MY8700275A (en) |
| NL (1) | NL192663C (en) |
| NO (1) | NO163166C (en) |
| NZ (1) | NZ204385A (en) |
| PH (1) | PH19601A (en) |
| PT (1) | PT76773B (en) |
| SE (1) | SE454946B (en) |
| ZA (1) | ZA833854B (en) |
| ZW (1) | ZW11883A1 (en) |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3624213A (en) * | 1963-10-30 | 1971-11-30 | Merck & Co Inc | Method of sterilizing aqueous pharmaceutical solutions employing propylene oxide and entrained air |
| GB1200886A (en) * | 1966-09-23 | 1970-08-05 | Allen & Hanburys Ltd | Phenylaminoethanol derivatives |
| GB1453034A (en) * | 1972-12-15 | 1976-10-20 | Boehringer Sohn Ingelheim | Pharmaceutical composition for treating spasticity |
| JPS5831210B2 (en) * | 1973-04-09 | 1983-07-05 | 武田薬品工業株式会社 | antennae |
| DE2714065A1 (en) * | 1977-03-30 | 1978-10-12 | Boehringer Mannheim Gmbh | INSTILLATION PREPARATION |
-
1983
- 1983-05-20 CH CH2779/83A patent/CH656308A5/en not_active IP Right Cessation
- 1983-05-24 GR GR71454A patent/GR82681B/el unknown
- 1983-05-26 NO NO831875A patent/NO163166C/en not_active IP Right Cessation
- 1983-05-26 FR FR8308722A patent/FR2527442B1/en not_active Expired
- 1983-05-27 PT PT76773A patent/PT76773B/en unknown
- 1983-05-27 CA CA000429095A patent/CA1203176A/en not_active Expired
- 1983-05-27 PH PH28974A patent/PH19601A/en unknown
- 1983-05-27 DK DK241783A patent/DK167558B1/en not_active IP Right Cessation
- 1983-05-27 LU LU84828A patent/LU84828A1/en unknown
- 1983-05-27 IE IE1267/83A patent/IE55139B1/en not_active IP Right Cessation
- 1983-05-27 SE SE8303012A patent/SE454946B/en not_active IP Right Cessation
- 1983-05-27 JP JP58093896A patent/JPH0629181B2/en not_active Expired - Lifetime
- 1983-05-27 IT IT48384/83A patent/IT1174759B/en active Protection Beyond IP Right Term
- 1983-05-27 IL IL68805A patent/IL68805A0/en not_active IP Right Cessation
- 1983-05-27 AU AU15039/83A patent/AU567675B2/en not_active Expired
- 1983-05-27 DE DE3319356A patent/DE3319356C2/en not_active Expired - Lifetime
- 1983-05-27 NL NL8301900A patent/NL192663C/en not_active IP Right Cessation
- 1983-05-27 NZ NZ204385A patent/NZ204385A/en unknown
- 1983-05-27 BE BE0/210866A patent/BE896870A/en not_active IP Right Cessation
- 1983-05-27 ZA ZA833854A patent/ZA833854B/en unknown
- 1983-05-27 ZW ZW118/83A patent/ZW11883A1/en unknown
- 1983-05-27 ES ES522752A patent/ES8502336A1/en not_active Expired
- 1983-05-27 AT AT0195283A patent/AT390191B/en not_active IP Right Cessation
- 1983-05-27 FI FI831893A patent/FI81257C/en not_active IP Right Cessation
-
1987
- 1987-12-30 MY MY275/87A patent/MY8700275A/en unknown
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK9A | Patent expired |