Patent Application: US-55448309-A

Abstract:
according to the present invention there is provided a pharmaceutical product for retention in the stomach . the product is produced by extrusion . the use of extrusion enables the product to take many useful forms . the product may comprise a sheet of hydratable polymer , the hydrated sheet being of a size which will not pass out of the stomach , for example a shaped sheet or a roll . the product may also comprise a scaled hollow tubular extrudate , for example a tube scaled at both ends . the product may comprise a filled capsule .

Description:
in one embodiment , the product of this invention comprises a sheet of hydratable polymer , the hydrated sheet being of a size which will not pass out of the stomach . typically the hydrated sheet is at least 8 mm by 8 mm , perhaps at least 12 mm by 12 mm . the sheet is made by extrusion of a mix of active ingredient and polymer , along with other optional ingredients . the mix is preferably extruded as a shaped sheet , and for example takes the form of a roll . as it is extruded , the roll is cut to size . the cut roll may then be filled in a capsule . upon swallowing , the capsule dissolves and the roll rehydrates and unrolls . other configurations may be employed for the sheet of hydratable polymer , and for example it can be a folded sheet , or otherwise compacted . the sheets of this invention can be made by melt extrusion . redesigning only the extrusion mold can produce a pre - folded sheet which can either be taken orally directly or after filling into capsules . the opened flat sheet may benefits from both the size enlargement , preventing it from passing through the pyloric sphincter and from the non - disintegrating low density polymer which should aid the floating of the devise . with a range of gel forming polymers , each individual characteristic of buoyancy ( high - density differential ) and size ( larger than 8 mm ) can be varied . the opened sheet could combine both the large area and the floating characteristics required for prolonging the residency time in the stomach . as mentioned earlier , the folded sheet could be filled into capsules using a tablet filling mechanism . the folded sheet dimensions could be varied from 5 . 0 - 9 . 0 mm diameter and 14 . 2 - 24 . 4 mm in length to either match the dimensions for direct delivery or for filling into size 4 - 0 elongated capsules . a preferred system comprises of a single folded sheet opened flat upon hydration by the gastric media . the medium to low density polymer and the geometrical size and shape of the sheet grants prolonged residency in the stomach . the presence of water and food in the stomach could be a vital factor in maintaining the buoyancy of both systems necessary for preventing an early transit of the system out of the stomach . the sheet may include acid or enzyme degradable materials , for example polymers , which will eventually be digested and thus change the physica structure , for example by fragmentation of the sheet , and make it susceptible for evacuation with the stomach contents . in another embodiment , the product of this invention comprises a sealed hollow tubular extrudate . a mix of suitable ingredients including the active ingredient is extruded as a tube , and is cut when still pliable to seal the cut ends , resulting in a hollow particle with active ingredient in the walls . the specific gravity of the particle is such that it floats on gastric juices , and gradually releases the active agent . this product can be made by melt extrusion . the melt extrusion head can simply be modified to extrude hollow tubes rather than solid strand . these tubes can be made with different inner and outer diameters and can also be cut to any predetermined lengths . the method of executing cutting while the extrudates ( solid strands or hollow tubes ) are hot and flexible is called surface cutting . the cutting blades are mounted on the die plate to provide an immediate cut that blinds the cutting edge of the tube while it is still in a semi - melted condition . the produced hollow extrudate tubes provides a low density product with significant buoyancy power . in this dosage form the drug can either be loaded in the tube wall within the protective modified release polymer or can be loosely packed within the tube void using a second single screw extruder mounted on the side of the extrusion head . it is believed that the hollow tube extrudates with two sealed ends will remain buoyant over the stomach contents until the differential density between the dosage form and the content is diminished . this will occur after the drug and other water - soluble components are released from the dosage form . this elimination from the tube wall will create pores allowing water penetration into the tube voids . this will balance the density differential and hence the multiparticulates sink down and are transported with other gastric contents . hollow tubes can be heat sealed at both ends . the trapped air within the void provides floating properties to the device . the final density of the proposed solid dosage form will be much lower than the gastric contents . low glass transition tg polymers with or without plasticizer ( eg : eudragit rspo , ethyl cellulose , polyvinyl acetate phthalate and other ) can be loaded with the drug and extruded as a hollow tubes . pelletisation by surface cutting will boost sealing of the two ends of the tubes . a multi - 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