Powder blend processability improvements through minimal amounts of synergistically selected surface coating agents
Inventors
Dave, Rajesh N. • Kim, Sangah • Lin, Zhixing
Assignees
New Jersey Institute of Technology
Publication Number
US-12076440-B2
Publication Date
2024-09-03
Expiration Date
2043-07-12
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Abstract
High (greater than 30%) and/or low (less than 10%) loaded multiple API powdered/nanoparticle were tabulated with increased flowability and physical properties. Properties include blend flowability and uniformity, bulk packing density, compactability, tensile strength, and dissolution. Blending is done through solventless dry mechanical coating of at least one minority API component defined as the API component with the least weight per volume surface coated with nano-sized powders in lesser amounts by wt % of the blend, and preferably less than 10% dry coated of the minority API. An excipient may be dry coated in the lesser amount wherein the excipient is a minority component. Both minority excipient and minority API may be dry coated. Using dry coating instead of dry granulation and/or wet granulation techniques in producing tablets saves manufacturing steps, costs, and produces higher quality tablets with surprisingly higher properties than expected for low flowability solid powdered ingredients.
Core Innovation
The invention provides a pharmaceutical composition and method that enhance critical properties of multi-component blends of fine powders, specifically by performing solventless dry mechanical coating on only a selected minor or minority component within the blend. This minority component, which can be an active pharmaceutical ingredient (API) or excipient, is surface-coated with nano-sized powders in exceedingly low amounts—preferably less than 10% by weight, and often between 0.1 wt % to less than 5 wt % of the blend. Once coated, the minority component is blended with the remaining constituents using conventional powder mixers, developing a synergistic enhancement in properties such as blend flowability, uniformity, bulk packing density, compactability, tensile strength, and dissolution.
The problem addressed is that achieving desired blend processability (e.g., sufficient flowability, bulk density, uniformity, and compaction strength) is difficult when using fine, micronized APIs, especially at very low or very high drug loadings and in multi-component systems. Prior techniques, such as dry or wet granulation, require additional steps, use higher amounts of additives, and may compromise product quality or process efficiency. Simply adding flow aids like silica during blending is inadequate, especially at low API loadings, while coating all API or excipients is resource-intensive.
The core innovation lies in dry coating only the fine minority component—rather than the whole blend—with a minimal amount of nano-sized flow aid, such as silica. This approach achieves unexpected synergistic improvements: flow function coefficient (FFC) values rise beyond those predicted by conventional weighted averages, and critical properties such as blend content uniformity, tablet tensile strength, and drug dissolution are greatly enhanced. The process reduces manufacturing steps, avoids the need for liquid-based granulation, lowers additive usage, and enables direct compression and encapsulation of challenging blends, including those with ultra-low or high API content.
Claims Coverage
The patent claims cover two main inventive features: one relating to a pharmaceutical composition with a specific dry coated minority component, and another to a method of preparing such a blend.
Pharmaceutical composition with only a dry coated minority component
A pharmaceutical composition comprising: - Multiple fine cohesive powder components (with particle size between 10–30 microns and flow function coefficient (FFC) under 4 before any modification), wherein at least one is an API. - Only a minority component (0.1 wt % to less than 5 wt % of total blend) is dry coated with a nano-sized flow aid powder (about 0.1 microns or less). - The minority component is the only component in the blend to receive any surface modification or treatment. - The resulting composition after blending achieves a flow aid concentration in the entire blend between 0.007 to 0.116 wt % and a surface area coverage (SAC) of about 0.1–9%. - The blend demonstrates an actual FFC greater than 4 that exceeds the expected/calculated FFC based on weighted averages of individual components (as specified in the claim), and this improvement arises specifically from including the dry coated minority component, not from the flow aid powder itself.
Method for preparing a pharmaceutical composition by dry coating only a minority component
A method including: 1. Providing a plurality of fine cohesive powder components (10–30 microns particle size, FFC < 4), with at least one as API. 2. Separating only a minority component (0.1 wt % to less than 5 wt % of the total) from these powders. 3. Dry coating only the minority component with nano-sized flow aid powder (about 0.1 microns or less), forming the only dry coated component. 4. Mixing this dry coated minority component back into the remainder of the powders to create the blend, achieving total flow aid content between 0.007—0.116 wt % and a SAC of 0.1—9%. 5. Yielding a blend wherein the actual FFC is greater than 4 and is greater than the expected/calculated (weighted average) FFC for the blend, and the improvement is due to the dry coated minority component rather than the direct effect of the flow aid powder.
The inventive features provide for the targeted dry coating of only a low-percentage minority component in a pharmaceutical blend, with specified characteristics and process steps, to achieve synergistic improvements in flowability and related properties—beyond what would be predicted by known approaches or simple addition of flow aids.
Stated Advantages
Significant synergistic enhancement of blend flowability, bulk packing density, uniformity, compactability, and drug dissolution with minimal use of flow aid additives.
Elimination of the need for wet or dry granulation processes, reducing manufacturing steps and costs.
Enables direct compaction, capsule filling, and sachet filling even for fine powders and low API loadings.
Dry coating process is environmentally benign, solvent-free, and avoids liquid-based processing issues.
Improvements are achieved even at ultra-low concentrations of flow aids, such as silica, saving on material usage.
Dry coating of only the minority component leads to unexpected enhancements in flow function coefficient, tensile strength, and dissolution versus calculated or expected values.
Simplifies manufacturing by reducing the need to dry coat or process the entire batch of pharmaceutical powders.
Dry coating does not adversely affect tablet strength or compaction properties.
Documented Applications
Formulation of pharmaceutical tablets by direct compression without the need for wet or dry granulation.
Preparation of pharmaceutical capsules filled using blends with enhanced flowability and uniformity.
Preparation of pharmaceutical sachets using powder blends with improved processability.
Application to multi-component blends of APIs, including cases with three to five API components or high API loadings.
Processing of both fine and coarse or weakly cohesive pharmaceutical powder blends.
Application to blends with ultra-low API loading (as low as 1 wt %) and high API loading (up to 95 wt %).
Industrial application in powder handling for pharmaceutical, nutraceutical, food, agrochemical, specialty chemical, energy, metal, and cement industries where improved flow and compaction are required.
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