Rosuvastatin Multiparticulate Pellets for Stable, Rapid Release
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Solution Overview
Problem
Solid oral dosage forms of rosuvastatin pose challenges for patients with dysphagia due to size, stickiness, taste, aftertaste, and frequency of administration, necessitating a more patient-compliant and chemically stable formulation.
Innovation Solution
A multi-particulate pharmaceutical composition with high rosuvastatin calcium loading, osmotic release modifiers, and stabilizers, allowing administration by sprinkling on food or via nasogastric tubing, ensuring chemical stability and rapid drug release.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Volume of moving object
If solid unit oral dosage forms are designed with sufficient drug loading, then the dosage form becomes compact, but it becomes difficult to swallow for patients with dysphagia
Solution Approach 1:
The patent divides the single solid unit dosage form into multiple smaller particulate forms (pellets or particles). Each particle contains a high percentage of rosuvastatin calcium (at least 5% by weight), allowing the total dose to be distributed across multiple small particles that are easier to swallow. The particles can be administered by sprinkling on soft food or via nasogastric tubing, thereby resolving the contradiction between compact dosage form and swallowability.
2Ease of operation
If the dosage form is made smaller to improve swallowability, then it becomes easier to swallow, but the drug loading percentage decreases
Solution Approach 1:
By segmenting the dosage into multiple particles, each particle can maintain high drug loading (at least 5% rosuvastatin calcium by weight) while the individual particle size remains small for easy administration. The cumulative effect of multiple high-loading particles delivers the required total dose.
Solution Approach 2:
The patent optimizes particle size parameters to fall within a specific range that balances swallowability with drug loading capacity. The multiparticulate system allows adjustment of particle number, size distribution, and individual particle drug content to achieve both ease of administration and sufficient drug delivery.
3Volume of moving object
If excipients are reduced to increase drug loading, then the dosage form becomes more compact, but chemical stability decreases
Solution Approach 1:
The patent employs a composite multiparticulate system where particles consist of rosuvastatin calcium combined with carefully selected excipients including osmotic release modifiers and stabilizers. This composite structure enables high drug loading while maintaining chemical stability through the protective and functional properties of the integrated excipient system.
Solution Approach 2:
The patent optimizes the quantity and type of excipients at controlled levels rather than complete elimination. By precisely controlling excipient parameters (types, amounts, and distributions), the formulation achieves high drug loading percentages while maintaining adequate chemical stability throughout shelf life.
4Speed
If the dosage form is designed for rapid drug release, then patient compliance improves, but chemical stability during shelf life may be compromised
Solution Approach 1:
The multiparticulate system provides a large total surface area for rapid drug release while each individual particle maintains a stable internal structure. The segmented design allows the outer surface to facilitate quick dissolution and release, while the internal composition remains protected and stable during storage.
Solution Approach 2:
The composite particle structure incorporates osmotic release modifiers that facilitate rapid drug release when exposed to gastrointestinal fluids, while stabilizers within the composite maintain chemical stability during shelf life. The multi-component composite enables simultaneous optimization of release rate and storage stability.
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 is patient-friendly, chemically stable, and provides rapid drug release, overcoming swallowing difficulties and maintaining impurity levels below 1.5% under accelerated conditions.
Implementation Method 1
The present inventors have discovered that the osmotic release modifiers are critical to accelerate release of rosuvastatin from the pellets
Implementation Method 2
The multiparticulate composition has been found to be not only patient compliant but also chemically stable throughout the shelf life of the product
Data Source
AI summary
The invention relates to a stable multi-particulate pharmaceutical composition comprising pellets, the pellets comprising a mixture of rosuvastatin or its pharmaceutically acceptable salts as a sole active ingredient, one or more osmotic release modifiers and one or more stabilizers.