Elagolix Sodium Formulation Dissolution and Stability
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Solution Overview
Problem
Elagolix sodium-based pharmaceutical formulations face challenges with instability during long-term storage and slow dissolution rates, leading to unacceptably slow release of the active ingredient, despite previous attempts to address these issues with anti-gelling agents and solid dispersions.
Innovation Solution
A pharmaceutical formulation comprising elagolix sodium, magnesium oxide, and at least one disintegrating agent, such as crospovidone, croscarmellose sodium, and pregelatinized starch, which improves dissolution rates and storage stability by optimizing the composition and preparation methods, including direct compression and granulation techniques.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If elagolix sodium is formulated in conventional dosage forms, then the active ingredient can be delivered to patients, but the dissolution rate is slow leading to unacceptably slow release
Solution Approach 1:
The patent uses a composite formulation combining elagolix sodium with magnesium oxide and specific disintegrating agents (crospovidone, croscarmellose sodium, or pregelatinized starch). This composite material system achieves rapid dissolution by leveraging the synergistic effects of the excipients, particularly the disintegrating agents that facilitate rapid tablet breakdown and drug release, resolving the contradiction between maintaining drug delivery and achieving acceptable release rates.
2Duration of action of stationary object
If elagolix sodium is stored during long term storage, then the pharmaceutical product can be distributed and used over time, but the compound degrades forming lactam impurity
Solution Approach 1:
The patent employs magnesium oxide as a stabilizing excipient that provides protection against degradation during storage. This approach allows the formulation to maintain stability over the intended storage period without requiring complex stabilization systems, enabling long-term storage while preventing lactam impurity formation through the protective effect of the magnesium oxide-containing matrix.
3Ease of manufacture
If conventional excipients are used in elagolix formulation, then the formulation can be manufactured using standard processes, but the dissolution rate remains slow and stability is poor
Solution Approach 1:
The patent specifies precise compositional parameters: elagolix sodium (20-50% w/w), magnesium oxide (10-30% w/w), and disintegrating agents (15-40% w/w). By optimizing these parameter ranges, the formulation achieves both manufacturability using conventional tabletting processes and superior performance in terms of rapid dissolution and enhanced stability, resolving the contradiction between ease of manufacture and reliability of performance.
Data Source
AI summary
A pharmaceutical formulation is disclosed which includes at least: (1) elagolix sodium, (2) magnesium oxide, and (3) at least one disintegrating agent, such as crospovidone, croscarmellose sodium, sodium starch glycolate, pregelatinized and mixtures thereof. A tablet is also disclosed which includes a tablet core formed from the pharmaceutical formulation. The elagolix sodium tablets of the present disclosure display improved dissolution rates when tested using for example the Tablet Sink Time test. The tablets also exhibit improved storage stability of the elagolix sodium, with a reduction in degradation products during storage.