Spray Drying Active Domains in Matrix for Bioavailability
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Solution Overview
Problem
Formulating low-solubility active agents into small, stable amorphous or crystalline domains for improved bioavailability and delivery is challenging due to their tendency to agglomerate and crystallize, leading to poor bioavailability and irregular absorption.
Innovation Solution
A spray drying process forming a composition of active agents and matrix materials, where a suspension is heated to create a spray solution, atomized into droplets, and solvent evaporation results in active-rich and active-poor domains, with the matrix material aiding in maintaining domain size and stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If low-solubility active agents are formulated into small domains, then bioavailability is improved, but the active agents tend to agglomerate and crystallize
Solution Approach 1:
A matrix material acts as an intermediary between the active agent domains and the external environment. The matrix prevents direct contact between active agent domains, thereby preventing agglomeration and crystallization while maintaining small domain sizes. The matrix material stabilizes the amorphous state of the active agent by providing a protective environment that inhibits molecular reorganization into crystalline structures.
Solution Approach 2:
The patent utilizes changes in physical parameters during spray drying, including temperature gradients, solvent evaporation rates, and supersaturation levels. By controlling these parameters, the active agent is rapidly deposited into small domains while the matrix material simultaneously forms a protective barrier. The rapid parameter changes prevent the active agent from having sufficient time to agglomerate or crystallize.
2Reliability
If the active agent is kept in amorphous state, then solubility and bioavailability are enhanced, but the active agent tends to crystallize
Solution Approach 1:
The matrix material is pre-positioned around the active agent domains during the spray drying process, creating a protective shell before the active agent has a chance to crystallize. This preliminary action of matrix deposition stabilizes the amorphous state by physically constraining the active agent molecules and preventing them from reorganizing into crystalline structures during storage.
Solution Approach 2:
The patent exploits the phase transition from liquid to solid during spray drying. The rapid solvent evaporation causes the active agent to freeze into an amorphous state within the matrix material. This controlled phase transition locks the active agent in its amorphous configuration, preventing subsequent crystallization while maintaining enhanced solubility.
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 process produces stable, small active-rich domains dispersed in a matrix, enhancing bioavailability by controlling particle size and preventing agglomeration, leading to improved absorption and prolonged active agent concentration.
Implementation Method 1
The spray solution is atomized to form droplets
Implementation Method 2
At least a portion of the first solvent and the second solvent is removed to form solid particles
Implementation Method 3
said active precipitates during the drying of said droplet
Data Source
AI summary
Disclosed are processes for forming compositions comprising small domains of an active agent and a matrix material, and methods of using them. A suspension of an active agent, a matrix material, a first solvent, and a second solvent is formed at a temperature T1, heated to a temperature T2 and spray dried.