MCC and DCPA Tablet Formulations for Immediate Drug Release
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Solution Overview
Problem
Current SERD therapies like fulvestrant have limited efficacy due to pharmacological properties that result in less than 50% receptor turnover in patients, failing to achieve complete down-regulation of estrogen receptor alpha (ERα) in breast cancer cells, especially in the presence of ER mutations.
Innovation Solution
Formulations comprising N-(1-(3-fluoropropyl)azetidin-3-yl)-6-((6S,8R)-8-methyl-7-(2,2,2-trifluoroethyl)-6,7,8,9-tetrahydro-3H-pyrazolo[4,3-f]isoquinolin-6-yl)pyridin-3-amine (Compound (I)) with microcrystalline cellulose (MCC) and dicalcium phosphate anhydrous (DCPA) for oral solid dosage forms, allowing efficient processing and immediate release with high tensile strength and stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional SERD therapies like fulvestrant are used, then the drug can be administered orally, but the receptor turnover is limited to less than 50%, failing to achieve complete down-regulation of ERα
Solution Approach 1:
The patent modifies the pharmacological parameters of the SERD therapy by combining Compound (I) with specific excipients (MCC and DCPA) in optimized ratios to enhance the drug's ability to down-regulate ERα. This formulation approach changes the delivery parameters to achieve complete receptor turnover, overcoming the limitation of conventional therapies that only achieve less than 50% down-regulation.
2Speed
If formulations are designed for immediate release with rapid release properties, then the drug delivery speed is improved, but the manufacturing precision and stability become more challenging
Solution Approach 1:
The patent employs a composite formulation system combining Compound (I) with microcrystalline cellulose (MCC) and dicalcium phosphate anhydrous (DCPA) in specific ratios. This composite material approach enables immediate release properties while maintaining manufacturing precision and stability, as the combination of excipients provides both rapid disintegration and consistent formulation characteristics.
Solution Approach 2:
The patent optimizes the formulation parameters by controlling the ratios of MCC and DCPA to achieve the desired balance between rapid release and manufacturing consistency. By adjusting these parameters, the formulation achieves immediate release properties while maintaining tensile strength and storage stability.
3Reliability
If the formulation achieves complete ERα down-regulation, then the efficacy in ER-positive breast cancers is improved, but the formulation complexity increases
Solution Approach 1:
The patent applies local quality by targeting the specific formulation components (MCC and DCPA) with optimized local ratios to achieve complete ERα down-regulation. This approach focuses the formulation complexity only where needed to achieve the therapeutic effect, rather than increasing overall formulation complexity.
Data Source
AI summary
The present specification relates to pharmaceutical formulations comprising N-(1-(3-fluoropropyl)azetidin-3-yl)-6-((6S,8R)-8-methyl-7-(2,2,2-trifluoroethyl)-6,7,8,9-tetrahydro-3H-pyrazolo[4,3-f]isoquinolin-6-yl)pyridin-3-amine, microcrystalline cellulose (MCC) and dicalcium phosphate anhydrous (DCPA), for example tablets with immediate release properties.