Atorvastatin Salt Forms for Stability and Solubility
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Solution Overview
Problem
Current atorvastatin calcium formulations have limitations in terms of stability and formulation properties, necessitating the development of novel salt forms with improved characteristics for effective use in treating hyperlipidemia, hypercholesterolemia, osteoporosis, benign prostatic hyperplasia, and Alzheimer's disease.
Innovation Solution
The development of novel salt forms of atorvastatin, including ammonium, benethamine, benzathine, dibenzylamine, diethylamine, erbumine, L-lysine, morpholine, olamine, piperazine, sodium, and 2-amino-2-methylpropan-1-ol salts, characterized by specific x-ray powder diffraction patterns and solid-state nuclear magnetic resonance spectra, which offer enhanced stability and formulation advantages.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If atorvastatin calcium formulations are used, then the drug can be conveniently formulated in tablets, capsules, and other dosage forms, but the stability and formulation properties are limited
Solution Approach 1:
The patent applies parameter changes by converting atorvastatin calcium into different salt forms (such as atorvastatin magnesium, atorvastatin potassium, atorvastatin sodium) with varying solubility and stability characteristics. This allows optimization of both formulation convenience and stability by selecting appropriate salt forms based on specific pharmaceutical requirements.
2Reliability
If novel salt forms of atorvastatin are developed, then stability and aqueous solubility are improved, but the complexity of salt selection and characterization increases
Solution Approach 1:
The patent segments the atorvastatin drug substance into multiple distinct salt forms, each with characterized properties. By dividing the single calcium salt into various magnesium, potassium, sodium, and other salt forms with specific solubility and stability profiles, the patent enables selection of optimal forms for different pharmaceutical applications while maintaining manageable complexity through systematic characterization.
Data Source
AI summary
Novel salt forms of [R—(R*,R*)]-2-(4-fluorophenyl)-β,δ-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid characterized by their X-ray powder diffraction pattern and solid-state NMR spectra are described, as well as methods for the preparation and pharmaceutical composition of the same, which are useful as agents for treating hyperlipidemia, hypercholesterolemia, osteoporosis, benign prostatic hyperplasia, and Alzheimer's Disease.