Co-dissolution Process for API Suspension Uniformity
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Solution Overview
Problem
Formulating drug suspensions with low-dose active pharmaceutical ingredients (APIs) and high-dose APIs or excipients poses challenges in content uniformity, particularly at small volumes, leading to unreliable dosage delivery.
Innovation Solution
A method involving co-dissolving the APIs or API and excipient in a common solvent, followed by solvent removal and recovery, then forming a suspension in a liquid carrier, which includes options for particle size reduction through dry or wet milling, ensuring stable and uniform delivery of low-dose APIs and high-dose APIs or excipients.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If separate milling of solid APIs is performed and then combination, then manufacturing process is simple, but content uniformity deteriorates
Solution Approach 1:
The patent applies preliminary action by pre-dissolving the low-dose API in a solvent before mixing with the high-dose API. This preliminary dissolution step ensures uniform distribution of the low-dose API at the molecular level before the mixing process, thereby achieving content uniformity without compromising manufacturing simplicity.
Solution Approach 2:
The patent changes the physical state parameter of the low-dose API from solid to dissolved state in a solvent. This parameter change enables uniform mixing at the molecular level, significantly improving content uniformity while maintaining ease of manufacture through the subsequent evaporation step.
2Quantity of substance
If low concentration formulation is used, then dosage target is achieved, but content uniformity deteriorates
Solution Approach 1:
The patent changes the concentration parameter by using a relatively high concentration formulation (e.g., 5% or higher) instead of low concentration. This high concentration approach ensures that even small volumes contain sufficient API while the pre-dissolution step maintains uniform distribution, thereby achieving both dosage accuracy and content uniformity.
3Volume of moving object
If small volume suspension is prepared, then dosage target is achieved, but content uniformity deteriorates
Solution Approach 1:
The patent applies preliminary action by pre-dissolving the low-dose API in a solvent before preparing the small volume suspension. This ensures uniform distribution of the API at the molecular level before the final suspension is formulated, enabling accurate dosage delivery in small volumes with maintained content uniformity.
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
This method achieves stable and uniform delivery of APIs and excipients, maintaining at least 60% of their original concentration for up to 12 months at elevated temperatures, significantly improving content uniformity and stability compared to aqueous-based formulations.
Implementation Method 1
co-dissolving API-1 and API-2 in a common solvent
Implementation Method 2
removing the solvent and recovering a mixture of API-1 and API-2
Data Source
AI summary
Methods for preparing suspensions of active pharmaceutical ingredients for ensuing drug delivery. The suspension may include a mixture of a relatively low dosage API and a relatively high dosage API or a mixture of an API with a suitable excipient.