Cinacalcet Hydrochloride Tablet Composition Dissolution
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Solution Overview
Problem
The existing formulations of cinacalcet hydrochloride tablets face challenges with poor solubility, large tablet size due to high excipient content, content uniformity issues, and stability problems, which affect bioavailability and patient compliance.
Innovation Solution
A tablet composition with a high drug load of cinacalcet hydrochloride having a particle size distribution D90 ≤ 30 µm, incorporating hydrophilic diluents like pregelatinized starch, binders, disintegrants, and lubricants, prepared through a wet-granulation process, to enhance bioavailability and dissolution profile.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a high amount of excipients (e.g., diluents and disintegrants) is incorporated into the formulation, then the dissolution rate of cinacalcet is improved, but the tablet size increases significantly causing patient compliance problems
Solution Approach 1:
The patent changes the particle size parameter of cinacalcet hydrochloride to D90 ≤ 30 µm (significantly finer than conventional formulations), which improves dissolution rate without requiring high excipient content. This parameter change allows achieving good dissolution with only 30-50% diluent content, reducing tablet size while maintaining bioavailability
Solution Approach 2:
The patent uses a composite approach by combining finely ground cinacalcet hydrochloride (D90 ≤ 30 µm) with specific excipients (pregelatinized starch, microcrystalline cellulose, crospovidone, magnesium stearate) in optimized proportions. This composite formulation achieves enhanced dissolution and bioavailability with reduced tablet size compared to conventional formulations
2Reliability
If a high amount of excipients is incorporated into the formulation, then the dissolution rate of cinacalcet is improved, but content uniformity becomes problematic
Solution Approach 1:
By changing the particle size parameter of cinacalcet hydrochloride to D90 ≤ 30 µm, the patent improves dissolution characteristics without relying on high excipient content. This reduces the total formulation mass and minimizes variability in content uniformity that would otherwise result from incorporating large amounts of excipients
3Reliability
If a high amount of excipients is incorporated into the formulation, then the dissolution rate of cinacalcet is improved, but stability problems occur related to interaction of the active pharmaceutical ingredient with excipients
Solution Approach 1:
The patent changes the particle size of cinacalcet hydrochloride to D90 ≤ 30 µm, which improves dissolution without requiring high excipient content. This reduction in excipient quantity minimizes potential interaction sites between excipients and the active pharmaceutical ingredient, thereby improving formulation stability
Solution Approach 2:
The patent employs pregelatinized starch and microcrystalline cellulose as intermediary excipients that are compatible with cinacalcet hydrochloride. These excipients serve as buffers that reduce direct interaction between the API and other formulation components, enhancing stability while maintaining dissolution performance
4Reliability
If the particle size of cinacalcet hydrochloride is reduced to D90 ≤ 30 µm, then bioavailability is improved, but manufacturing complexity increases
Solution Approach 1:
The patent performs preliminary size reduction of cinacalcet hydrochloride to D90 ≤ 30 µm before formulation development. This pre-processing step simplifies subsequent manufacturing by ensuring consistent particle size distribution from the outset, reducing the need for complex size control measures during tablet production
Solution Approach 2:
By establishing a specific particle size parameter (D90 ≤ 30 µm) for cinacalcet hydrochloride, the patent creates a well-defined starting material that simplifies formulation development and manufacturing. This parameter specification enables consistent processing and reduces manufacturing complexity compared to working with broader particle size distributions
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 composition achieves improved bioavailability and bioequivalence with a smaller tablet size, enhanced dissolution profile, and stability, releasing at least 75% of cinacalcet within thirty minutes, addressing the limitations of current formulations.
Implementation Method 1
The incorporation of a relatively high amount of excipients (e.g., diluents and disintegrants) into the formulation of a solid oral dosage form can improve the dissolution rate of active pharmaceutical ingredients, especially those that are relatively hydrophobic and poorly soluble in water like cinacalcet
Implementation Method 2
incorporating hydrophilic diluents like pregelatinized starch, binders, disintegrants, and lubricants, prepared through a wet-granulation process, to enhance bioavailability and dissolution profile
Data Source
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AI summary
The present invention relates to a tablet composition comprising a therapeutically effective dose of cinacalcet hydrochloride having a particle size distribution D90 equal to or less than 30 µm in an amount of from 40% to 60% by weight based on the total weight of the composition, and one or more pharmaceutically acceptable excipients.