IES950907A2 - "A process" - Google Patents
"A process"Info
- Publication number
- IES950907A2 IES950907A2 IE950907A IES950907A IES950907A2 IE S950907 A2 IES950907 A2 IE S950907A2 IE 950907 A IE950907 A IE 950907A IE S950907 A IES950907 A IE S950907A IE S950907 A2 IES950907 A2 IE S950907A2
- Authority
- IE
- Ireland
- Prior art keywords
- veterinary
- vessel
- excipients
- additive
- batch
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 14
- 239000000203 mixture Substances 0.000 claims abstract description 42
- 239000000654 additive Substances 0.000 claims abstract description 36
- 230000000996 additive effect Effects 0.000 claims abstract description 35
- 239000000546 pharmaceutical excipient Substances 0.000 claims abstract description 29
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 28
- 238000009472 formulation Methods 0.000 claims abstract description 23
- 239000004480 active ingredient Substances 0.000 claims abstract description 20
- 230000000507 anthelmentic effect Effects 0.000 claims abstract description 12
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 claims abstract description 5
- 239000007788 liquid Substances 0.000 claims description 17
- 239000004615 ingredient Substances 0.000 claims description 10
- 239000000375 suspending agent Substances 0.000 claims description 6
- 239000002518 antifoaming agent Substances 0.000 claims description 5
- 239000003755 preservative agent Substances 0.000 claims description 5
- 239000000080 wetting agent Substances 0.000 claims description 5
- 230000001804 emulsifying effect Effects 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 230000002335 preservative effect Effects 0.000 claims description 4
- 238000005303 weighing Methods 0.000 claims description 3
- 239000006172 buffering agent Substances 0.000 claims description 2
- 229940124339 anthelmintic agent Drugs 0.000 description 7
- 239000000921 anthelmintic agent Substances 0.000 description 7
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 239000000872 buffer Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- BEZZFPOZAYTVHN-UHFFFAOYSA-N oxfendazole Chemical compound C=1C=C2NC(NC(=O)OC)=NC2=CC=1S(=O)C1=CC=CC=C1 BEZZFPOZAYTVHN-UHFFFAOYSA-N 0.000 description 3
- 229960004454 oxfendazole Drugs 0.000 description 3
- 238000004806 packaging method and process Methods 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000008213 purified water Substances 0.000 description 2
- 239000001509 sodium citrate Substances 0.000 description 2
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 2
- YASYEJJMZJALEJ-UHFFFAOYSA-N Citric acid monohydrate Chemical compound O.OC(=O)CC(O)(C(O)=O)CC(O)=O YASYEJJMZJALEJ-UHFFFAOYSA-N 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 229960004106 citric acid Drugs 0.000 description 1
- 229960002303 citric acid monohydrate Drugs 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- AMTWCFIAVKBGOD-UHFFFAOYSA-N dioxosilane;methoxy-dimethyl-trimethylsilyloxysilane Chemical compound O=[Si]=O.CO[Si](C)(C)O[Si](C)(C)C AMTWCFIAVKBGOD-UHFFFAOYSA-N 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 229960005473 fenbendazole Drugs 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229950008882 polysorbate Drugs 0.000 description 1
- 229940068977 polysorbate 20 Drugs 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 238000005086 pumping Methods 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 229940083037 simethicone Drugs 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
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
- A61K9/10—Dispersions; Emulsions
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F23/00—Mixing according to the phases to be mixed, e.g. dispersing or emulsifying
- B01F23/50—Mixing liquids with solids
- B01F23/59—Mixing systems, i.e. flow charts or diagrams
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F25/00—Flow mixers; Mixers for falling materials, e.g. solid particles
- B01F25/50—Circulation mixers, e.g. wherein at least part of the mixture is discharged from and reintroduced into a receptacle
- B01F25/51—Circulation mixers, e.g. wherein at least part of the mixture is discharged from and reintroduced into a receptacle in which the mixture is circulated through a set of tubes, e.g. with gradual introduction of a component into the circulating flow
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Dispersion Chemistry (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
A batch vessel of typically 10,000 litres is filled with a predetermined quantity of water. Veterinary formulation excipients are added to an additive hopper and the excipients are emulsified in the water by circulation through a homogeniser and the batch vessel. A veterinary active ingredient, especially an anthelmintic such as a benzimidazole anthelmintic is added to the additive hopper and the active ingredient is emulsified in the mixture. Further water may be added to the vessel to bring the batch volume to a required concentration of veterinary active ingredient.
Description
A Process
Introduction
The invention relates to a process for preparing an aqueous based liquid veterinary formulation, particularly of water insoluble veterinary anthelmintics, especially benzimidazole anthelmintics.
There are considerable difficulties in formulating aqueous anthelmintic compositions, particularly of active anthelmintic agents which are not water soluble, on an industrial scale. The formulations must be readily and efficiently prepared, stable and effective in use.
Statements of Invention
According to the invention, there is provided a process for preparing an aqueous based liquid veterinary formulation in a batch apparatus comprising a batch vessel having a capacity of at least 3,000 litres, the vessel having a top liquid inlet and a bottom liquid outlet, an additive line leading from the bottom liquid outlet, an additive hopper for delivery of veterinary formulation ingredients into the additive line and a homogeniser including a pump for delivery of liquid from the additive line to the vessel inlet, the process comprising the steps of: filling a predetermined quantity of water into the batch vessel;
adding veterinary additive hopper;
formulation excipients to the ,w ?/qo
I-&AIE
OPEN TO PUBLIC INSPECTION
SECTION 28 AND RUt F >3 iNL No 1.7*° OF 2 Ή
- 2 95 0 3 0 7 emulsifying the excipients in the water by circulation through the homogeniser and batch vessel;
adding a veterinary active ingredient to the additive hopper to form a mixture;
emulsifying the veterinary active ingredient in the mixture; and, as required, adding further water to the vessel to bring the batch volume to a required concentration of veterinary active ingredient.
In a particularly preferred embodiment of the invention, there are a number of veterinary formulation excipients which are separately added to the additive hopper.
In one preferred aspect, the process includes the step of weighing the contents of the vessel after addition of each veterinary excipient and veterinary active ingredient.
In one embodiment of the invention, the veterinary formulation excipients include water soluble and water insoluble excipients and the water soluble excipients are added to the mixture through the additive hopper prior to addition of the water insoluble excipients.
The veterinary formulation ingredients typically include at least one wetting agent, at least one suspending agent, at least one buffering agent and at least one preservative.
In one preferred embodiment of the invention, the veterinary formulation ingredients include an antifoaming agent which is added to the mixture through the additive
950907 hopper before addition of the veterinary active ingredient.
The veterinary active ingredients are usually veterinary anthelmintics, especially benzimidazole anthelmintics.
The invention will be more clearly understood from the following description thereof, given by way of example only.
The process of the invention is performed using a batch apparatus comprising a batch vessel having a capacity of at least 3,000 litres, preferably at least 5,000 litres, in this case of 10,000 litres. The vessel has a top liquid inlet and a bottom liquid outlet to a delivery line. An additive line is also connected to the bottom liquid outlet and leads to a homogeniser including a pump for delivery of liquid from the additive line to the vessel inlet. An additive hopper is connected to the additive line for delivery of veterinary excipients into the additive line. Load cells are provided for measuring the weight of the contents of the vessel.
In the process of the invention, a predetermined quantity, such as 3,000 litres of water is first delivered into the batch vessel. The veterinary formulation excipients to be added generally comprise water soluble excipients and substantially water insoluble excipients. Each of the water soluble excipients is introduced separately by loading into the additive hopper, homogenising with water from the vessel and mixing by pumping around the circuit from the top inlet to the bottom outlet of the vessel. After mixing, the contents of the vessel are weighed using the load cells to provide a check weight of the amount of excipient added to the batch. The excipients are added separately in this way to form a liquid mixture that is
950907
- 4 ready to receive the veterinary active ingredient. The last excipient to be added in this way is preferably an anti-foaming agent which resists any tendency of the mixture to generate foam when the veterinary active ingredient is added. After addition of the veterinary active ingredient through the additive hopper, the mixture is homogenised and circulated using the pump. The weight of the contents of the tank are again measured to provide a check weight for the added veterinary active ingredient. The volume of the batch is then made up to a required volume by further addition of water, followed by homogenisation and circulation as described above. After the batch is prepared, valves are used to disconnect the additive line from the vessel outlet and the contents of the vessel are delivered to a packaging area where the liquid veterinary formulation is filled into containers.
By adding the veterinary excipients in this way, the batch preparation time is minimised as there is substantially no entrainment of air in the mixture. Thus, settlement time between additives is not required. The production process is optimised as the time required for batch preparation is minimised. By weighing the contents of the vessel during the formulation procedure, a check weight of all excipients and active ingredients added to the batch is provided. The process is particularly applicable to substantially water insoluble veterinary anthelmintics in general and benzimidazole anthelmintics in particular.
After a batch is complete, the additive line, hopper, and associated homogeniser and pump may be easily disconnected and cleaned in situ. If required, the unit may be readily moved to another batch vessel while the first vessel is being emptied and cleaned.
950907
- 5 EXAMPLE - FENBENDAZOLE FORMULATION
A formulation of oxfendazole was prepared from the following ingredients : -
Ingredient Percentage Function Active Ingredient: Oxfendazole 2.265% Anthelmintic Other Ingredients: Methyl Parahydroxybenzoate 0.2% Preservative Propyl Parahydroxybenzoate 0.02% Preservative Citric Acid Monohydrate 0.868% Buffer Component Sodium Citrate 1.215% Buffer Component Colloidal Silica Anhydrous 0.55% Suspending Agent Xanthan Gum 0.3% Suspending Agent Povidone 90 1.0% Suspending Agent Polysorbate 20 0.5% Wetting Agent Propylene Glycol 5.0% Wetting Agent Simethicone Emulsion 0.025% Antifoaming Agent
3,000 litres of purified water were added into a 10,000 litre batch vessel and the weight of the vessel is measured and recorded. The citric acid and sodium citrate buffer components are added separately to the additive hopper and the mixture is mixed for 10 minutes. The suspending agents are separately added to the additive hopper and the mixture is mixed for 40 minutes to ensure complete dissolution. The polysorbate and propylene glycol wetting agents are then added separately to the additive hopper and the mixture is mixed for a further 10 minutes. The preservatives are added separately to the
950907
- 6 additive hopper and the mixture is again mixed for 10 minutes. The antifoaming agent is added to the additive hopper and mixing is continued for a further 5 minutes. Oxfendazole is added in stages to the additive hopper and the mixture is thoroughly mixed for 70 minutes in total. The batch is then adjusted to desired batch volume with purified water. After sampling and analysis, the prepared formulation is transferred to packaging where it is filled into containers .
After each addition, the weight of the vessel is measured and recorded as a further check weight of the added ingredients.
The invention is not limited to the embodiments hereinbefore described which may be varied in detail.
Claims (6)
1. A process for preparing an aqueous based liquid veterinary formulation in a batch apparatus comprising a batch vessel having a capacity of at least 3,000 litres, the vessel having a top liquid inlet and a bottom liquid outlet, an additive line leading from the bottom liquid outlet, an additive hopper for delivery of veterinary formulation ingredients into the additive line and a homogeniser including a pump for delivery of liquid from the additive line to the vessel inlet, the process comprising the steps of:filling a predetermined quantity of water into the batch vessel; adding veterinary formulation excipients to the additive hopper; emulsifying the excipients in the water by circulation through the homogeniser and the batch vessel; adding a veterinary active ingredient to the additive hopper to form a mixture; emulsifying the veterinary active ingredient in the mixture; and, as required, adding further water to the vessel to bring the batch volume to a required concentration of veterinary active ingredient.
2. A process as claimed in claim 1 wherein there are a number of veterinary formulation excipients which are 950907 - 8 separately added to the additive hopper, preferably the process includes the step of weighing the contents of the vessel after addition of each veterinary excipient and veterinary active
3. 5 ingredient, preferably the veterinary formulation excipients include water soluble and water insoluble excipients and the water soluble excipients are added to the mixture through the additive hopper prior to addition of the water insoluble excipients.
4. 10 3. A process as claimed in any preceding claim wherein the veterinary formulation excipients include at least one suspending agent and/or at least one wetting agent and/or at least one buffering agent and/or at least one preservative.
5. 15 4 . A process as claimed in any preceding claim wherein the veterinary formulation ingredients include an antifoaming agent which is added to the mixture through the additive hopper before addition of the veterinary active ingredient.
6. 20 5. A process as claimed in any preceding claim wherein the veterinary active ingredient is a veterinary anthelmintic, preferably a benzimidazole anthelmintic.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IE950907A IES950907A2 (en) | 1995-12-01 | 1995-12-01 | "A process" |
| GB9525073A GB2307871B (en) | 1995-12-01 | 1995-12-06 | A process for preparing an aqueous based liquid veterinary formulation |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IE950907A IES950907A2 (en) | 1995-12-01 | 1995-12-01 | "A process" |
| GB9525073A GB2307871B (en) | 1995-12-01 | 1995-12-06 | A process for preparing an aqueous based liquid veterinary formulation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IES66993B2 IES66993B2 (en) | 1996-02-21 |
| IES950907A2 true IES950907A2 (en) | 1996-02-21 |
Family
ID=26308248
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IE950907A IES950907A2 (en) | 1995-12-01 | 1995-12-01 | "A process" |
Country Status (2)
| Country | Link |
|---|---|
| GB (1) | GB2307871B (en) |
| IE (1) | IES950907A2 (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PL2037914T3 (en) * | 2006-06-14 | 2014-04-30 | Intervet Int Bv | A suspension comprising benzimidazole carbamate and a polysorbate |
| TW200815001A (en) * | 2006-06-14 | 2008-04-01 | Intervet Int Bv | Benzimidazole carbamate composition |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1982001478A1 (en) * | 1980-10-31 | 1982-05-13 | Goeran Bernhardsson | A method and a device for mixing and homogenization of a main substance with at least one additive substance,liquids in particular |
| US5538989A (en) * | 1993-11-10 | 1996-07-23 | Hoechst-Roussel Agri-Vet Company | Fenbendazole formulations |
-
1995
- 1995-12-01 IE IE950907A patent/IES950907A2/en not_active IP Right Cessation
- 1995-12-06 GB GB9525073A patent/GB2307871B/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| IES66993B2 (en) | 1996-02-21 |
| GB9525073D0 (en) | 1996-02-07 |
| GB2307871A (en) | 1997-06-11 |
| GB2307871B (en) | 1999-04-07 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FD4E | Short term patents deemed void under section 64 |