Granulated anthelmintic preparations and delivery systems

Abstract

The present invention relates to anthelmintic compositions comprising two or more anthelmintic active agents selected from one or more of the following groups; imidazothiazoles such as levamisole, benzimidazoles such as oxfendazole, or fenbendazole, macrocylic lactones such as ivermectin or avermectin, salicylanilides, and praziquantel. The composition being in the form of stable granules that are readily dispersible in water so as to provide a homogenous mixture of the anthelmintic agents suitable for administration. Methods of preparing the composition are also described.

We claim: 
     
         1 . A method of manufacturing a granule by granulation comprising
 dry mixing a first beneficial agent with 0.1 to 20% by weight of a suspending agent on a fluidised bed,   spraying a first granulating solution onto the fluidised bed, the first granulating solution comprising 0.1 to 8% by weight of a surfactant, 0.1 to 10% by weight of a non-aqueous co-solvent,   spraying a second granulating solution onto the fluidised bed, the second granulating solution comprising a buffering agent,   to form the granules and drying the granules to achieve a moisture content of less than 5% by weight.   
     
     
         2 . A method of  claim 1  wherein the first beneficial agent is at least sparingly soluble in water. 
     
     
         3 . A method of  claim 1  wherein the first beneficial agent is selected from the group consisting of levamisole HCL, a benzimidazole, and a combination thereof. 
     
     
         4 . A method of  claim 1  wherein the first granulating solution comprises a particulate mineral source. 
     
     
         5 . A method of  claim 1  wherein the non-aqueous co-solvent is an alcohol. 
     
     
         6 . A method of  claim 5  wherein the alcohol is benzyl alcohol. 
     
     
         7 . A method of  claim 1  wherein the surfactant is selected from the group consisting of polysorbate 80, sodium lauryl sulphate, glycerol formal, propylene glycol, glycerine and a combination thereof. 
     
     
         8 . A method of  claim 1  wherein the first granulating solution comprises a beneficial agent soluble in the non-aqueous co-solvent. 
     
     
         9 . A method of  claim 8  wherein the beneficial agent soluble in the non-aqueous co-solvent is a macrocyclic lactone. 
     
     
         10 . A method of  claim 1  wherein the second granulating solution comprises a particulate mineral source. 
     
     
         11 . A method of  claim 10  wherein the particulate mineral source of the second granulating solution comprises selenium. 
     
     
         12 . A method of  claim 4  wherein the particulate mineral source of the first granulating solution comprises cobalt. 
     
     
         13 . A method of  claim 1  wherein the suspending agent is selected from the group consisting of a gum and colloidal silicon dioxide. 
     
     
         14 . A method of  claim 13  wherein the gum is xanthan gum. 
     
     
         15 . A method of  claim 1  wherein the granule remains stable for at least 2 to 6 months. 
     
     
         16 . A method of  claim 1  wherein the produced granule is dispersible in water. 
     
     
         17 . An anthelmintic composition in the form of a stable granule(s) comprising a gum and one or more anthelmintic actives comprising one or more macrocyclic lactones, the stable granule being readily dispersible in water to provide a homogenous mixture of the anthelmintic actives for administration to a non-human mammal, and the granule further comprising a wetting agent. 
     
     
         18 . A composition of  claim 17  further comprising a particulate source of one or more minerals or at least one further anthelmintic active selected from the group consisting of levamisole HCL, a benzimidazole, and/or praziquantel. 
     
     
         19 . A dosage system for orally dosing animals with an anthelmintic agent, the system comprising:
 (a) one or more packs of granules for addition into an aqueous liquid, the granules comprising at least one macrocyclic lactone and a gum and at least one further anthelmintic active selected from the group consisting of:
 i) a benzimidazole and a suspending agent for the benzimidazole; 
 ii) a salicylanilide and a wetting agent; 
 iii) praziquantel and a wetting agent; 
 iv) an imidazothiazole and one or more anthelmintic agents selected from benzimidazoles, salicylanilides, and praziquantel, and optionally a suspending agent, and; 
   (b) a suspending agent if (i) the granules do not comprise a suspending agent, or (ii) additional suspending agent is required to suspend the anthelmintic actives in the liquid.   
     
     
         20 . A dosage system of  claim 19  further comprising:
 (a) a drenching device and a mixing container, or 
 (b) a drenching device having a mixing reservoir, 
 when in use the one or more packs are used with a mixing container or mixing reservoir with water or an aqueous carrier or a drenching device for its fixed dosage amounts or a calibrated variable dosage amount to deliver an effective amount of the anthelmintic actives to an animal.