IE920484A1 - Pharmaceutical Formulations - Google Patents
Pharmaceutical FormulationsInfo
- Publication number
- IE920484A1 IE920484A1 IE048492A IE920484A IE920484A1 IE 920484 A1 IE920484 A1 IE 920484A1 IE 048492 A IE048492 A IE 048492A IE 920484 A IE920484 A IE 920484A IE 920484 A1 IE920484 A1 IE 920484A1
- Authority
- IE
- Ireland
- Prior art keywords
- formulation
- antitussive
- dextromethorphan
- active
- component
- Prior art date
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
- A61K9/0078—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions
-
- 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
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/05—Phenols
-
- 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
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/05—Phenols
- A61K31/055—Phenols the aromatic ring being substituted by halogen
-
- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/235—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group
- A61K31/24—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group having an amino or nitro group
- A61K31/245—Amino benzoic acid types, e.g. procaine, novocaine
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/485—Morphinan derivatives, e.g. morphine, codeine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
- A61K9/0075—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
- A61K9/008—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy comprising drug dissolved or suspended in liquid propellant for inhalation via a pressurized metered dose inhaler [MDI]
Abstract
Pharmaceutical formulations for antitussive treatment adapted for delivery to the lung via the throat inhalation through the mouth.
Description
PHARMACEUTICAL FORMULATIONS This invention relates to pharmaceutical formulations, in particular pharmaceutical formulations for delivery to the lung and bronchial tract by inhalation via the throat for the treatment of coughs.
It is known to deliver drugs and other medications directly to the lung and bronchial tract by inhalation for the treatment of various diseases or the symptoms thereof, for example Thorax (1984) 39 1-7 gives a brief review of such treatments .
In the field of antitussive treatment, French Patent FR 260/246 and European Patent Application EP-A-0 0 21986 respectively describe the nasal administration of dextromethorphan [ ( + )-cis-1,3,4,9,10,10a-hexahydro-6methoxy-ll-methyl-2H-10,4a iminoethanophenanthrene] and the principal metabolite of dextromethorpahn i.e. dextrorphan [(+)-cis-1,3,4,9,10,10a-hexahydro-ll-methyl-llmethyl-2H-10,4a iminoethanophenanthrene-6-ol]. Here nasal administration with absorption by the nasal mucosa is used to reduce first pass losses that might occur on oral administration .
It is also known, in the field of suppression of lung spasm and/or cough resulting from fairly severe stimulus to the lung, e.g. lung surgery, bronchoscopy, major lung disease or serious lung damage, to administer lignocaine directly to the lung in quite high dosage rates using an aerosol spray. Such work is for example described in Br. J. Dis. Chest (1977) 77., 19 and Br. J. Anaesth. (1976) 48 899.
It has now been found that antitussive formulations administered by throat inhalation via the mouth are effective in the suppression of trivial coughs i.e. coughs C70002 -2resulting from minor and/or common diseases of the lung and bronchial tract, such as the common cold, etc.
The invention therefore provides an antitussive pharmaceutical formulation adapted for delivery to the lung via throat inhalation through the mouth, containing an active antitussive component which is a non-narcotic antitussive or local anaesthetic, the active component being present in the formulation in a form suitable for unit dose delivery.
A principal advantage of the formulation of the invention is that in many cases it allows delivery of the active antitussive component in a dosage which is substantially lower than would normally be used if the active component were administered orally or nasally. This is believed to be a consequence of a number of effects, for example the direct delivery of the active component to receptor sites in the lung, and in the case of compounds which are metabolised to active components, a reduced degree of metabolic degradation before the active component can have its effect on these receptor sites. Non-narcotic antitussive agents such as dextromethorphan and narcotic opioid antitussive agents such as codeine are generally believed to inhibit cough centrally by the action of active metabolites on the cough centre in the CNS.
A further advantage of the formulation of the invention is the rate of onset of antitussive effect which is more rapid than that observed after oral dosing. This is a further indication of direct delivery of active component to lung receptor sites.
Preferred active components are dextromethorphan and metabolities thereof such as dextrorphan, 3-methoxymorphinan and morphinan-3-ol, lignocaine, benzocaine, xylocaine, C70002 -3amethocaine, chlorinated phenols and hexylresorcinol, including derivatives thereof, for example pharmaceutically acceptable salts thereof. When used as the active antitussive component, dextromethorphan is preferably present as the hydrobromide salt (Dex HBr) or as the free base, and lignocaine is preferably present as the hydrochloride salt.
The formulation may in some cases comprise the active component in a pharmaceutically acceptable degree of purity, the physical form in which it is presented, e.g. a fine powder in an appropriate unit dose quantity, rendering it suitable for unit dose delivery. Alternatively, the active component may be present in the formulation together with a pharmaceutically acceptable carrier such as a liquid in which it is dissolved or suspended as fine particles, or a bulking agent. The formulation may also contain preservatives, surfactants, buffers and flavouring agents, and other conventional excipients.
Whatever form the formulation takes, it will normally be administered as a fine aerosol of solid particles or liquid droplets drown the throat. There are 3 main known methods of administering the formulation as an aerosol in this way which are convenient for use with formulations primarily intended for over the counter treatments for trivial coughs, i.e. which impose minimum cost upon the consumer and minimum manufacturing effort on the producer. These methods are metered dose inhalation, aqueous pump, and dry powder inhalation.
In metered dose inhalation, the formulation comprises a solution or suspension of the active component in a carrier which is a volatile propellant such as the known CFC class of propellants, or preferably of a class which is considered to be less environmentally harmful. This formulation is C70002 -4contained within a small aerosol spray dispenser having a metering outlet valve, e.g. of known type, so that each operation of the valve releases a predetermined volume of spray of liquid propellant and active component, from which the propellant almost immediately vapourises to form a cloud of particles of the active component for inhalation. Such a formulation may also include a surfactant material such as for example span 85 (Trade Mark), to assist in dispersion of the active component.
Typically a formulation for metered dose inhalation contains 0.05 to 10 weight %, for example 0.1-1 weight % of active antitussive component, and 0.05-0.5 weight % of surfactant, made up to 100% with propellant.
In aqueous pumps, the formulation comprises a solution or suspension of the active component in a carrier which is water, optionally also containing a surfactant such as a benzalkonium salt, a preservative such as sodium benzoate, a pH buffer, flavouring agents etc. In some cases it may be necessary to include an organic solvent, for example some ethanol in the solution to improve solubility of the active component but the amount should be small in view of the sensitivity of the lung. This formulation is contained within a dispenser in the form of a small container fitted with a spray pump, e.g. of known type, each operation of which ejects a predetermined volume of the formulation as fine droplets for inhalation.
Typically a formulation for aqueous pump delivery contains 0.05-10 weight %, for example 0.1-10 weight % of active component (the aqueous maximum solubility of Dex HBr is 2.5 wt %), 0.05-1.0 weight % of an inorganic salt containing chloride ions such as sodium chloride, 0.05-0.5 weight % of preservatives and optionally 0.05-0.5 weight % of C70002 -5surfactant. If pH buffers are used they may ideally maintain the pH of lung mucous, i.e. around pH 6-8, but in practice the pH will depend on the solubility of the active component, and the optimum value for adequate antimicrobial preservation.
In dry powder inhalation the formulation may comprise simply the active component, present in a pharmaceutially pure state and in a suitable particle size range. Alternatively the formulation may comprise a mixture of the active antitussive component with a pharmaceutically acceptable carrier, e.g. a bulking agent such as lactose. Various methods of dry powder inhalation are known, but in a common one, the formulation is contained within a fragile capsule which is inserted into a dispenser such as an inhaler, ruptured by an operation of the inhaler, and sucked as an aerosol from the capsule down the throat via the mouth.
However the aerosol of particles or droplets is produced, for example using the 3 methods suggested above, it is important that the dispensing method generates an aerosol of the active antitussive component having a particle or droplet (i.e. of solution or suspension of active component) size range such that the active component is deposited at suitable positions in the lung and/or tracheal airway so that the active component can act upon suitable receptor sites and have an optimum antitussive effect.
An example of a particle/droplet size distribution of the active component aerosol is: Size typical ranqe preferred distribution (by weight) (± 5%) (by weight) < 3μ 30 - 40% 35% 35 3-5μ 20 - 30% 25% 5-10μ 15 - 25 20% > ιομ 15 - 25% 20% C70002 -6A further example of a particle/droplet size distribution of the active component aerosol is: Size typical range preferred distribution (by weight) (± 5%) (by weight) 3μ 30 - 50% 40% 3-5μ 35 - 55% 45% 5-10μ 5 - 20 10% ΐθμ 2 - 15% 5% Preferably the majority of particles/droplets of active component, for example greater than 50% by weight have a size of 5μ or less. More preferably at least 80% by weight have a size of 5μ of less. The particle size of a bulking agent, e.g. lactose, when present in a formulation of the invention for dry powder inhalation is suitably in the range 30-120μπι by weight median diameter.
The dispenser, e.g. metered dose dispenser, aqeuous pump 20 dispenser or dry powder dispenser should preferably be adapted to produce aerosols having these size ranges, for example by suitable nozzles or powder size ranges in capsules or metered dose dispenser formulations.
However the formulation is dispersed, e.g. using the 3 types of dispensing system described above, it is preferred that the dispenser is adapted to dispense unit doses which are a fraction of the maximum recommended daily dose, preferably with instructions recommending the maximum number of unit doses per day.
In the case of dextromethorphan it is preferred that this is present as the free base or as the hydrobromide salt, for example in a solution or suspension. The maximum C70002 -7recommended daily oral dose of dextromethorphan free base, is in the region of 75mg/day. Dispensers for inhalation of formulations of the invention are preferably adapted to dispense unit doses of 0.05-5, suitably 0.1-2, e.g. ca. 0.15 lmg of dextromethorphan (calculated as the HBr salt) on each operation of the dispenser, e.g. in each dry powder capsule or puff of metered dose or aqueous pump.
Another aspect of this invention is a dispenser, e.g. of the io types described above, adapted to dispense the formulations described above in a form suitable for delivery to the lung for antitussive treatment via throat inhalation; and containing such a formulation.
Another aspect of this invention is a method of antitussive treatment, comprising delivering to the lung via throat inhalation through the mouth a formulation as desribed above .
Another aspect of this invention is a method of preparation of a pharmaceutical formulation for delivery to the lung for antitussive treatment via throat inhalation through the mouth which includes the step of mixing an active antitussive component which is a non-narcotic antitussive or local anaesthetic, preferably selected from dextromethorphan and metabolities thereof such as dextrorphan, 3-methoxymorphinan and morphinan-3-ol, lignocaine, benzocaine, xylocaine, amethocaine, chlorinated phenols and hexylresorcinol or derivatives thereof with a pharmaceutically acceptable carrier component and/or preparing the components in a particle size range adapted for such delivery.
The invention will now be described by way of example only.
C70002 -8Example 1 Formulation for Metered Dose Inhalation of Dextromethorphan Dex HBr was processed using a 2 pancake microniser to obtain a micronised powder having a particle size distribution: < 3μ ca. 35%, 3- 5μ ca. 25%, 5-10μ ca. 20%, > 10μ ca. 20%. This powder was made up into a formulation having the composition below: Dex HBr Span 85 Propellant 11 (known propellant) 5 0.2 24.8 wt % wt wt % % 15 Propellant 12 (known propellant) 70.0 wt Q, O Total 100 wt O. O The formulation was made up by suspending the Dex HBr and Span 85 in the propellant 11, introducing this suspension into a suitable commercially available aerosol container, adding propellant 12, then fitting the container with a commercially available metered dose valve. A suitable unit of this formulation was 100 μΐ, containing 5mg of Dex HBr per puff.
Example 2 Formulation for Metered Dose Inhalation of Dextromethorphan Dex HBr was processed as described in Example 1 to obtain a micronised powder having a particle size distribution: < 3μ £3· 40%, 3- 5μ ca. 40%, 5-10μ ca. 10%, > 10μ ca. 10%. This powder was made up into a formulation having the composition below: C70002 Dex HBr 0.5 wt Span 85 0.2 wt % Propellant 11 (known propellant) 25.8 wt % Propellant 12 (known propellant) 73.5 wt % 5 Total 100 wt % The formulation was made up by suspending the Dex HBr and Span 85 in the propellant 11, introducing this suspension into a suitable commercially available aerosol container, adding propellant 12, then fitting the container with a commercially available metered dose valve. A suitable unit of this formulation was 100 μΐ, containing 0.5mg of Dex HBr per puff.
Example 3 Formulation for Metered dose Inhalation of Lignocaine Lignocaine was processed as described in Example 1 to obtain 20 a micronised powder having the same size distribution as in Example 1. This powder was made up into a formulation having the composition below in exactly the same way as the formulation of Example 1.
Lignocaine Hydrochloride 5 wt . % Span 85 0.2 wt % Propellant 11 (known propellant) 24.8 wt % Propellant 12 (known propellant) 70.0 wt % Total 100 wt % A suitable unit dose of this formulation was again ΙΟΟμΙ, containing 5mg Lignocaine per puff.
C70002 -10Example 4 Formulation for Aqueous Pump Dispenser for Dextromethorphan Solution was made up having the Dex HBr Benzalkonium Chloride Sodium Benzoate Sodium Chloride Water Total following composition: 2 % w/v 0.1 % w/v 0.1 % w/v 0.9 % w/v 96.9 % w/v 100 % The solution was made up simply by dissolving the solids in 15 the water, and the solution was then introduced into a container fitted with a suitable pump, capable of producing an aqueous spray with an MMAD of ca. 5gm of this solution.
A suitable volume of this solution for a unit dose was 150μ1, containing 3mg of Dex HBr per puff.
Example 5 Formulation for Aqueous Pump Dispenser for Dextromethorphan Solution was made up having the following composition: Dex HBr Benzalkonium Chloride Sodium Benzoate Sodium Chloride Water Total 0.2 % w/v 0.1 % w/V 0.1 % w/v 0.9 % W / V 98.7 % w/V 100 % C70002 -11The solution was made up as described in Example 4. The solution was introduced into a container fitted with a suitable pump, capable of producing an aqueous spray with an MMAD of ca. 5μπι of this solution. A suitable volume of this solution for a unit dose was 150μ1, containing 0.3mg of Dex HBr per puff.
Example 6 Formulation for Aqueous Pump Dispenser for Lignocaine Solution was made up having the following composition: Lignocaine hydrochloride 15 Benzalkonium Chloride Sodium Benzoate Sodium Chloride Water Total 2 % w/v 0.1 % w/v 0.1 % w/v 0.9 % w/V 96.9 % w/v 100 % The solution was made up and introduced into a container fitted with a pump, as described for example 4, ΙΟΟμΙ being a suitable unit dose, containing 2mg of lignocaine per puff.
Example 7 Formulation for Dry Powder Inhalation of Dextromethorphan A dry powder mixture was prepared having the following 30 composition: Dex HBr (processed to size range 50 wt % of Example 1) Lactose Powder 50 wt % C70002 -12This powder mixture was filled into fragile gelatine capsules each containing lOmg of powder, i.e. a 5mg unit dose of Dex HBr.
Example 8 Formulation for Dry Powder Inhalation of Dextromethorphan A dry powder mixture was prepared having the following 10 composition: Dex HBr (processed to size range 5 wt % of Example 2) Lactose Powder 95 wt % This powder mixture was filled into fragile gelatine capsules each containing lOmg of powder, a i.e. 0.5mg unit dose of Dex HBr.
Example 9 Formulation for Dry Powder Inhalation of Dextromethorphan A dry powder mixture was prepared having the following 25 composition: Dex HBr (processed to size range 10 wt % of Example 1) Lactose Powder 90 wt % This powder mixture was filled into fragile gelatine capsules each containing lOmg of powder, i.e. a lmg unit dose of Dex HBr.
C70002 -13Example 10 Formulation for Dry Powder Inhalation of Dextromethorphan A dry powder mixture was prepared having the following composition : Dex HBr lOwt % Lactose Powder 90 wt % The Dex HBr was processed to size range: <3μ ca. 40%, 3-5μ ca. 45%, 5-10μ ca. 10%, >10μ ca. 5%.
This powder mixture was filled into fragile gelatine capsules each containing lOmg of powder, i.e. a lmg unit dose of Dex HBr.
Example 11 Formulation for Dry Powder Inhalation of Lignocaine A dry powder mixture was prepared having the following composition: Lignocaine hydrochloride 50 wt % (processed to size range of example 1) Lactose Powder 50 wt % This powder mixture was filled into fragile gelatine capsules each containing lOmg of powder, i.e. a 5mg unit dose of Lignocaine hydrochloride.
C70002 -14Example 12 Formulation for Dry Powder Inhalation of Lignocaine A dry powder mixture was prepared having the following composition: Lignocaine hydrochloride 25 wt % (processed to size range of example 2) Lactose Powder 75 wt % This powder mixture was filled into fragile gelatine capsules each containing 20mg of powder, i.e. a 5mg unit dose of Lignocaine hydrochloride.
Example 13 Antitiussive effect of dextromethorphan hydrobromide in conscious guinea pigs Male Dunkin Hartley guinea-pigs, (weight range 340-400g) were deprived of food but not water for 18 hours prior to the experiment. Each animal (group size 8) was placed in a plethysmometer and exposed to an aerosolised solution of vehicle (NaCl) or test material for 5 minutes. The aerosol was generated by compressed air at a constant pressure of 1.2kg/cm using a Wright nebuliser. The particle size generated was below 8μπι.
Five minutes post vehicle/test material exposure, the animals were exposed to 7.5% aqueous citric acid aerosol, similarly generated by a Wright nebuliser, for 10 minutes. The number of coughs elicited within the exposure period was counted.
C70002 -15Results Treatment Saline Dex. HBr Dex. HBr Concentration (mg/ml) 3.0 Inhaled Dose (mg/kg) 0.06 0.20 Mean No. of Coughs 19.3 17.1 8.9 An inhaled dose of Dex. HBr of 0.13 mg/kg gave a 54% cough reduction. This compares with a reported 44% cough reduction from a 56mg/kg oral dose and a 54% cough reduction from a lOmg/kg iv dose in SC^-induced cough in guinea-pigs.
Claims (13)
1. An antitussive pharmaceutical formulation adapted for delivery to the lung via throat inhalation through the
2. 5 mouth, comprising an active antitussive component which is a non-narcotic antitussive or a local anaesthetic and wherein the active component is present in the formulation in a form suitable for unit dose delivery. 10 2. A formulation as claimed in claim 1 wherein the nonnarcotic antitussive is dextromethorphan or a metabolite thereof, and pharmaceutically acceptable derivatives thereof. 15 3. A formulation as claimed in claim 2 wherein the nonnarcotic antitussive is dextromethorphan, dextromethorphan hydrobromide, dextrorphan, 3-methoxymorphinan or morphinan3-ol, or a pharmaceutically acceptable derivative thereof. 20 4. A formulation as claimed in claim 1 wherein the local anaesthetic is lignocaine, benzocaine, xylocaine, amethocaine, a chlorinated phenol or hexylresorcinol, or a pharmaceutically acceptable derivative thereof. 25 5. A formulation as claimed in any one of claims 1 to 4 further comprising a pharmaceutically acceptable carrier.
3. 6. A formulation as claimed in claim 5 comprising 0.05 to 10 weight % of the active antitussive component.
4. 7. A formulation as claimed in any one of claims 1 to 6 adapted for metered dose, aqueous pump or dry powder inhalation in aerosol form. 35
5. 8. A formulation as claimed in claim 7 wherein at least 80% by weight of the active component aerosol has a particle/droplet size below 10gm. C70002/C1 - 17 IE 920484
6. 9. A formulation as claimed in claim 8 wherein at least 80% by weight of the active component aerosol has a particle/droplet size at or below 5μιη.
7. 10. A formulation as claimed in any one of claims 2 to 9 comprising a unit dose of dextromethorphan in the range 0.05 to 5mg. 10
8. 11. A formulation as claimed in any one of claims 4 to 9 comprising a unit dose of lignocaine in the range 1 to 5mg.
9. 12. A pharmaceutical formulation substantially as hereinbefore described in the accompanying Examples.
10. 13. A dispenser adapted to dispense a unit dose of a formulation as defined in any one of claims 1 to 12 and containing such a formulation. 20
11. 14. A method of preparation of a pharmaceutical formulation as defined in any one of claims 1 to 12 comprising mixing the active antitussive component with a pharmaceutically acceptable carrier component and/or preparing the components in a particle size range adapted 25 for such delivery.
12. 15. A method of antitussive treatment comprising delivering to the lung via throat inhalation through the mouth an effective antitussive amount of a formulation as 30 defined in any one of claims 1 to 12.
13. 16. Use of a pharmaceutical formulation as defined in any one of claims 1 to 12 for the manufacture of a medicament for antitussive treatment.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB919103302A GB9103302D0 (en) | 1991-02-16 | 1991-02-16 | Pharmaceutical formulations |
Publications (1)
Publication Number | Publication Date |
---|---|
IE920484A1 true IE920484A1 (en) | 1992-08-26 |
Family
ID=10690127
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
IE048492A IE920484A1 (en) | 1991-02-16 | 1992-02-14 | Pharmaceutical Formulations |
Country Status (5)
Country | Link |
---|---|
AU (1) | AU1227292A (en) |
GB (1) | GB9103302D0 (en) |
IE (1) | IE920484A1 (en) |
WO (1) | WO1992014466A1 (en) |
ZA (1) | ZA921093B (en) |
Families Citing this family (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5593661A (en) * | 1993-03-29 | 1997-01-14 | Henry; Richard A. | Lidocaine aerosol anaesthetic |
CA2156821C (en) * | 1993-03-29 | 2005-02-15 | Richard A. Henry | Lidocaine aerosol anaesthetic |
US5589156A (en) * | 1994-05-02 | 1996-12-31 | Henry; Richard A. | Prilocaine and hydrofluourocarbon aerosol preparations |
SE9601528D0 (en) * | 1996-04-23 | 1996-04-23 | Pharmacia Ab | Transdermally administered dextromethorphan as an antitissue agent |
JP2002517438A (en) * | 1998-06-09 | 2002-06-18 | ノートラン・ファーマシューティカルズ・インコーポレーテッド | Compositions and methods for treating cough |
EP1137398B1 (en) * | 1998-12-11 | 2003-10-08 | Pharmachemie B.V. | Pharmaceutical preparation for inhalation of an opioid |
AU2001271386B2 (en) | 2000-06-23 | 2005-04-07 | Mayo Foundation For Medical Education And Research | Methods of treating neutrophil-related diseases with topical anesthetics |
MXPA04011327A (en) * | 2002-05-17 | 2005-08-15 | Jenken Biosciences Inc | Opioid and opioid-like compounds and uses thereof. |
EP2218448B1 (en) | 2002-12-13 | 2015-09-23 | Durect Corporation | Oral drug delivery system comprising high viscosity liquid carrier materials |
CA2959274C (en) * | 2007-12-06 | 2019-07-09 | Pain Therapeutics, Inc. | Micronized opioid compositions, formulations and dosage forms and methods of making same |
JP2011506319A (en) | 2007-12-06 | 2011-03-03 | デュレクト コーポレーション | Useful methods for the treatment of pain, joint inflammation symptoms, or inflammation associated with chronic diseases |
US20100260844A1 (en) | 2008-11-03 | 2010-10-14 | Scicinski Jan J | Oral pharmaceutical dosage forms |
US9572885B2 (en) | 2013-03-15 | 2017-02-21 | Durect Corporation | Compositions with a rheological modifier to reduce dissolution variability |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA1136547A (en) * | 1979-03-08 | 1982-11-30 | Song-Ling Lin | Aerosol anesthetic compositions |
US4241048A (en) * | 1979-05-01 | 1980-12-23 | Bristol-Myers Company | Suspension composition of benzocaine |
US4454140A (en) * | 1982-09-07 | 1984-06-12 | Hoffmann-La Roche Inc. | Nasal administration of dextromethorphan |
IT1187743B (en) * | 1985-09-26 | 1987-12-23 | Prodotti Formenti Srl | DESTRORPHANE BASED PHARMACEUTICAL COMPOSITIONS FOR INSTRANASAL APPLICATION |
FR2601246B1 (en) * | 1986-07-11 | 1990-01-05 | Bouchara Sa | NOVEL DEXTROMETHORPHANE-BASED ANTI-TUSSIVE COMPOSITIONS AND THEIR PROCESS FOR OBTAINING SAME. |
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1991
- 1991-02-16 GB GB919103302A patent/GB9103302D0/en active Pending
-
1992
- 1992-02-13 AU AU12272/92A patent/AU1227292A/en not_active Abandoned
- 1992-02-13 WO PCT/GB1992/000257 patent/WO1992014466A1/en active Application Filing
- 1992-02-14 ZA ZA921093A patent/ZA921093B/en unknown
- 1992-02-14 IE IE048492A patent/IE920484A1/en unknown
Also Published As
Publication number | Publication date |
---|---|
AU1227292A (en) | 1992-09-15 |
GB9103302D0 (en) | 1991-04-03 |
WO1992014466A1 (en) | 1992-09-03 |
ZA921093B (en) | 1993-01-27 |
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