Simultaneous encapsulation technique for use in pharmaceutical compositions - Patents

Simultaneous encapsulation technique for use in pharmaceutical compositions

Agent: Wyeth Patent Law Group - Madison, NJ, US
Inventor: Nkere Kanu Ebube
Class: 424472000 (USPTO), (Intl Class)
#20060068011
03/30/06
Multiple active pharmaceutical ingredients may be simultaneously encapsulated into pellets using the melt pelletization technique. The resulting pellets exhibit high active ingredient content and good handling characteristics, such as flowability, lubrication, compression, and size distribution, for production of a solid dosage form of a pharmaceutical composition. A method for preparing pellets is also disclosed.
BACKGROUND OF THE INVENTION
[0001] The invention relates generally to a technique for the simultaneous encapsulation of multiple active ingredients into pellets for use in pharmaceutical compositions, and methods for use of the-pharmaceutical compositions. Multiple active ingredients may be simultaneously encapsulated into pellets using the melt pelletization technique resulting in uniform active ingredient distribution throughout the pellets for use in the preparation of solid dosage forms of pharmaceutical compositions, where the pellets exhibit desirable handling properties aiding in solid dosage form preparation. The melt pelletization technique is less expensive than other known techniques for the encapsulation of multiple active ingredients as used in solid dosage forms of pharmaceutical compositions.
SUMMARY OF THE INVENTION
[0020] It is an object of the invention to produce pellets including a mixture of multiple active pharmaceutical ingredients with optional inactive additives that can be formed into a solid dosage form.
[0021] It is also an object of the invention to produce pellets including a mixture of multiple active pharmaceutical ingredients with optional inactive additives that display a uniform distribution of the multiple active ingredients within each pellet that can be formed into a solid dosage form.
[0022] It is also an object of the invention to produce pellets of a mixture including multiple active pharmaceutical ingredients with optional inactive additives of a substantially uniform size that can be formed into a solid dosage form.
[0023] It is also an object of the invention to produce pelletized beads including a mixture of multiple active pharmaceutical ingredients with optional inactive additives having high concentrations of the active ingredients that can be formed into a solid dosage form.
[0024] It is further an object of the invention to produce pellets from a sparingly water-soluble or water-insoluble mixture including multiple active pharmaceutical ingredients with optional inactive additives that can be formed into a solid dosage form.
[0025] It is also an object of the invention to produce pellets including a mixture of multiple active pharmaceutical ingredients having optional inactive additives that exhibit desirable handling properties that can be formed into a solid dosage form.
[0026] Finally, it is an object of the invention to provide a method of preparing such pellets, and solid dosage forms of pharmaceutical compositions from such pellets.
[0027] In accordance with these and other features of the invention, there are provided pellets produced from a mixture including multiple active pharmaceutical ingredients with optional inactive additives produced by the melt pelletization process. According to one embodiment of the invention, the pellets have substantially uniform particle size distribution with a median particle size range of about 170 .mu.m-245 .mu.m. The pellets may be formed by subjecting a mix of multiple active pharmaceutical ingredients with at least one inactive additive, such as a binder, in a mixing device, imparting mechanical and thermal energy to the mixture until the binder has melted and pellets have formed. The pellets may then be cooled. In one embodiment of the invention, the pellets may be formed into a solid dosage form, such as for example a tablet or a capsule. The formation of solid dosage forms from pellets is well known to those skilled in the art, as described in U.S. Pat. No. 5,807,583 issued to Kristensen et. al., discussed infra. The pellets exhibit good uniformity of concentration of the multiple active pharmaceutical ingredients, substantially uniform particle size, good flowability, compression and lubrication, and other desirable handling characteristics for solid dosage formation.
[0028] In another embodiment of the invention, a more economical process than wet granulation for producing pellets including multiple active pharmaceutical ingredients is disclosed which produces a substantially uniformly sized pellet for the preparation of a solid dosage form of a pharmaceutical composition. The process comprises adding multiple active pharmaceutical ingredients along with at least one inactive additive, such as a binder, to a mixing device, adding thermal, and optionally mechanical energy, to the mixture, and mixing the multiple active pharmaceutical ingredients and binder until the pellets are formed, e.g., when the melting point of the binder is reached. The pellets formed by this process may then be cooled, and may be separated by size before being used to produce the solid dosage form.
[0029] In still another embodiment of the invention, pellets including multiple active pharmaceutical ingredients that are sparingly soluble or insoluble in water may be produced and subsequently used to prepare a solid dosage form.
[0030] In another embodiment, there is provided a method of preparing a solid dosage form of a pharmaceutical composition including multiple active pharmaceutical ingredients. The method comprises adding multiple active pharmaceutical ingredients to a mixing device; adding at least one inactive additive, such as a binder, to the mixing device; adding thermal energy to the mixing device; and mixing the multiple active ingredients and the binder until pellets are formed. A solid dosage form pharmaceutical composition is then formed from the pellets in any conventional manner known in the art.
[0031] In yet another embodiment of the invention, a process for treating cold and cough involves preparing a solid dosage form of a pharmaceutical composition from pellets including multiple active pharmaceutical ingredients and at least one optional inactive additive produced according to the invention, and administering the pharmaceutical composition to a recipient. In one embodiment, the pharmaceutical composition includes an expectorant, a cough suppressant and a nasal decongestant.
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