IES66993B2

IES66993B2 - A process

Info

Publication number: IES66993B2
Authority: IE
Inventors: Michael Hilary Burke
Original assignee: Chanelle Chemicals Ltd
Priority date: 1995-12-01
Filing date: 1995-12-01
Publication date: 1996-02-21
Also published as: GB2307871A; GB9525073D0; GB2307871B; IES950907A2

Abstract

A process for formulating aqueous anthelmintic compositions, particularly of active anthelmintic agents which are not water soluble, on the industrial scale is disclosed. A batch vessel of at least 3,000 litres - typically 10,000 litres - is first filled with a predetermined quantity of water. Veterinary formulation excipients are then added to an additive hopper and the excipients emulsified in the water by circulation through a homogeniser and the batch vessel. A veterinary active ingredient, such as a benzimidazole anthelmintic, is then added to the additive hopper and emulsified in the mixture. Further water may be added to the vessel to bring the batch volume to a required concentration. A fenbendazole or an oxfendazole formulation may be prepared in this way.

Description

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.

Stateaaeafcs off 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; ’· «t adding veterinary formulation excipients to the *· additive hopper; 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 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 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.

EXAMPLE - FSNBSNP&ZOLE FORMULATION A formulation of oxfendazole was prepared from the following ingredients: - Ingredient Percentage Function Active Ingredients 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% Anti foaming 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 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

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 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.