Microcrystalline Cellulose and Calcium Phosphate Blend for Tablet Recompaction
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Solution Overview
Problem
Existing pharmaceutical binders face challenges in achieving adequate recompactibility across a wide range of tabletting pressures without compromising other desirable properties, such as flow characteristics and sensitivity to lubricant presence, which affects the production of solid dosage forms like tablets.
Innovation Solution
A physical blend of microcrystalline cellulose and anhydrous calcium phosphate particles with a median particle size of not greater than 20 microns, specifically 10 microns, is used to enhance recompactibility, reducing the need for additional excipients and improving tensile strength of granules and tablets.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional binders are used to achieve adequate recompactibility, then recompactibility is improved, but flow characteristics deteriorate or sensitivity to lubricant presence increases
Solution Approach 1:
The patent applies composite materials by combining microcrystalline cellulose (MCC) and anhydrous calcium phosphate (CaP) in a physical blend. This composite excipient maintains good flow characteristics from MCC while gaining improved recompactibility from the fine particle size CaP (median not greater than 20 microns), resolving the contradiction between recompactibility and flow properties.
Solution Approach 2:
The patent changes the particle size parameter of calcium phosphate to a median not greater than 20 microns, which significantly improves recompactibility. This parameter change allows the CaP to function as an effective binder in roller compaction while maintaining compatibility with lubricants and preserving flow characteristics when blended with MCC.
2Reliability
If binder concentration is increased to improve recompactibility, then recompactibility is improved, but manufacturing cost increases
Solution Approach 1:
The physical blend of MCC and anhydrous CaP creates a composite excipient where the fine particle size CaP provides binding functionality at lower concentrations. This reduces the overall quantity of binder needed compared to conventional binders, lowering manufacturing costs while maintaining adequate recompactibility.
3Manufacturing precision
If multiple compaction steps are used (roller compaction followed by tabletting), then granulation quality is improved, but process complexity increases
Solution Approach 1:
The patent changes the particle size parameter of calcium phosphate to median not greater than 20 microns, which significantly improves recompactibility. This parameter change allows the CaP to function as an effective binder in roller compaction while maintaining compatibility with lubricants and preserving flow characteristics when blended with MCC.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The blend provides improved recompactibility, reduced friability, and enhanced resistance to physical handling, leading to higher yields and fewer defective tablets, while minimizing the use of extragranular excipients and lowering manufacturing costs.
Implementation Method 1
a physical blend of particles of at least one calcium phosphate and particles of microcrystalline cellulose, wherein the particles of at least one calcium phosphate have an median (D50) particle size as measured by laser diffraction of not greater than about 20 microns
Implementation Method 2
an median (D50) particle size as measured by laser diffraction of not greater than about 20 microns
Implementation Method 3
the resulting material milled to uniform size
Data Source
AI summary
Compositions containing calcium phosphate and microcrystalline cellulose are useful as excipients in the preparation of solid dosage forms containing active pharmaceutical ingredients, particularly those prepared by processes involving multiple compaction steps. The recompactibility performance of such compositions is improved through the use of calcium phosphate having a relatively small particle size, e.g., a median particle size of not more than about 20 microns or not more than about 10 microns.