Cinacalcet Hydrochloride Polymorphs for PTH Control
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current treatments for secondary hyperparathyroidism in chronic kidney disease patients are inadequate, as they often elevate calcium and phosphorus levels, leading to inadequate control of parathyroid hormone and associated bone and mineral metabolism disorders.
Innovation Solution
Development of a crystalline polymorph of cinacalcet hydrochloride with specific XRPD patterns and thermal treatment processes to create a stable form that can be used in pharmaceutical compositions for effective administration, reducing PTH and calcium-phosphorus levels.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If traditional treatments (phosphate binders and vitamin D sterols) are used for secondary hyperparathyroidism, then calcium and phosphorus levels are elevated, but this leads to inadequate control of parathyroid hormone and bone metabolism disorders
Solution Approach 1:
The patent introduces a new chemical compound (cinacalcet hydrochloride) with different pharmacological properties compared to traditional treatments. This compound acts on the calcium-sensing receptor to lower PTH levels without the adverse effect of elevating calcium and phosphorus levels, thereby changing the therapeutic parameter profile to achieve both calcium/phosphorus control and PTH suppression
Solution Approach 2:
The patent describes multiple crystalline polymorphs (Form I, Form II, Form III) of cinacalcet hydrochloride with different physical properties. These polymorphs offer different stability, solubility, and bioavailability characteristics, allowing selection of the most appropriate form for specific therapeutic needs while maintaining the beneficial pharmacological effect
2Stability of the object's composition
If a new crystalline polymorph of cinacalcet hydrochloride is developed, then treatment stability and potency are improved, but the manufacturing process complexity increases
Solution Approach 1:
The patent provides detailed characterization data (XRPD patterns, DSC thermograms, solubility profiles) for each polymorph form before clinical use. This preliminary characterization allows manufacturers to select and validate the most suitable polymorph form in advance, simplifying the actual manufacturing process by eliminating the need to develop and test multiple forms during production
Solution Approach 2:
The patent describes specific crystallization conditions (solvent systems, temperature ranges, pH levels) that produce each polymorph form. By controlling these parameters, manufacturers can reliably produce the desired polymorph form through standardized processes, reducing manufacturing complexity despite the presence of multiple possible forms
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 polymorph effectively lowers parathyroid hormone and calcium-phosphorus levels, providing a more stable and potent treatment for secondary hyperparathyroidism and hypercalcemia, improving bone health and reducing systemic consequences.
Implementation Method 1
melting cinacalcet polymorph Form I at 190° C.
Implementation Method 2
quenching said amorphous form in a cooling bath of dry ice and acetone for 30 minutes
Implementation Method 3
heating those amorphous quenched, size-reduced particles at 90° C. for approximately 3.5 hours to produce polymorph Form III
Implementation Method 4
grinding said quenched amorphous form to produce an reduce particle size of said quenched amorphous form
Data Source
AI summary
The present invention is directed to methods and compositions for making and using a new polymorph of cinacalcet hydrochloride.