Robust pellet
Inventors
Cao, Bruce X. • Burnside, Beth A. • Wassink, Sandra E. • Baker, Matt R.
Assignees
Publication Number
US-8758820-B2
Publication Date
2014-06-24
Expiration Date
2024-08-11
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Abstract
Compositions and methods for making robust pellets that contain a high percentage, by weight, of active drug agent, and which also contain additional components that enhance the absorption and solubility of the active drug agent within the gastrointestinal tract (GI tract) without diminishing the robust nature of the pellet, are disclosed.
Core Innovation
The invention provides robust pharmaceutical pellets containing a high percentage by weight of an active drug agent, combined with additional components that enhance the absorption and solubility of the active drug agent within the gastrointestinal (GI) tract. This is accomplished without diminishing the physical integrity and robustness of the pellet during and after processing, including coating and other manufacturing operations. The robust pellets permit compounding and processing into finished pharmaceutical products with modified or controlled release profiles.
The problem addressed by this invention is the difficulty in formulating solid oral dosage forms that include high levels of absorption-enhancing and solubility-enhancing agents. Traditional formulations often result in pellets that are too brittle, sticky, or light, impeding downstream processing and coating. This is particularly challenging for drugs requiring targeted GI tract delivery or modified release, especially for drugs that are sensitive to stomach acid and not suitable for gelatin capsule delivery.
The core innovation lies in the combination of a high dosage of an active drug agent with both a pharmaceutically acceptable absorption enhancing surfactant and a pharmaceutically acceptable solubilizing agent that acts as a solvent for the drug component. This combination, contrary to expectations, yields pellets that are neither brittle nor sticky, but robust and capable of withstanding multiple downstream manufacturing processes such as extrusion, spheronization, fluid-bed drying, and coating, facilitating the production of finished pharmaceutical products with efficient, targeted drug delivery.
Claims Coverage
There are two independent claims in this patent, each defining a composition with specific inventive features regarding the pellet composition and its component selection.
Pharmaceutical pellet with high drug load, surfactant-type absorption enhancer, and solubility enhancer as solvent
The pharmaceutical pellet comprises a granulated mixture with: - At least one active ingredient drug component, constituting at least 50% by weight (W/W) of the pellet and being at least one beta lactam penicillin. - At least one pharmaceutically acceptable absorption enhancing agent, chosen from the group consisting of non-ionic surfactants, hydrophilic surfactants, hydrophobic surfactants, short chain fatty acids, long chain fatty acids, short chain triglycerides, and long chain triglycerides, present at 2–10% W/W. - At least one pharmaceutically acceptable solubility enhancing agent, selected from the group consisting of Methyl-2 Pyrrolidone, diethylene glycol monoethyl ether, and pharmaceutically accepted alcohols, where the solubility enhancer is a solvent for the drug component. The composition achieves a robust pellet that combines the high drug load with both types of enhancers.
Pharmaceutical pellet with surfactant triglyceride as absorption enhancer and solubility enhancer as solvent
The pharmaceutical pellet includes: - At least one active drug component being a beta lactam penicillin and constituting at least 50% W/W of the pellet. - At least one pharmaceutically acceptable absorption enhancing agent which is a surfactant triglyceride, present at 2–10% W/W. - At least one pharmaceutically acceptable solubility enhancing agent selected from the group consisting of Methyl-2 Pyrrolidone, diethylene glycol monoethyl ether, and pharmaceutically accepted alcohols, with the agent being a solvent for the active drug component, and present at 2–10% W/W. This combination creates a pellet of high drug content which remains robust due to the specified component selection.
Both independent claims focus on pharmaceutical pellets with a high content of a beta lactam penicillin, combined with a specific ratio of surfactant-type absorption enhancer and a solubility enhancer that acts as a solvent for the active drug. The inventive features specify unique, robust compositions enabling efficient downstream pharmaceutical processing.
Stated Advantages
The robust pellets can withstand downstream pharmaceutical processes, such as coating, extrusion, spheronization, and tablet manufacturing, without becoming brittle or sticky.
The invention allows for high dosage incorporation of active drug agents with absorption and solubility enhancers, overcoming traditional limitations that led to pellets being too brittle or soft and tacky.
Use of the robust pellets improves efficiencies and effectiveness in downstream processing operations, resulting in increased total product yield.
The pellets permit the production of finished pharmaceutical products with modified or targeted release, including delivery systems like the Pulsys™ system.
Documented Applications
Production of oral solid dosage forms using robust pellets for modified or targeted drug delivery, particularly for pharmaceuticals that require protection from stomach acid or controlled release patterns.
Inclusion in the Pulsys™ dosage form system, providing pulsatile drug delivery across multiple sites in the GI tract.
Use in forming finished pharmaceutical products, such as matrix tablets and other modified or sustained release formulations.
Processing methods such as wet granulation, fluid bed drying, extrusion, spheronization, fluid bed coating, roller compaction, and tablet coating employing robust pellets as intermediates.
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