Nanocrystalline Solid Dispersion Compositions for Dissolution
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for preparing pharmaceutical compositions face challenges such as unpredictable physical stability, atypical dissolution behavior, and chemical instability of amorphous solid dispersions, particularly with hydrophobic drugs, which affect the solubility and bioavailability of active ingredients.
Innovation Solution
A novel one-step process involving the use of a crystallization inducer and a pharmaceutical active, where a solution of both is spray dried to produce discrete particles with the active ingredient in a nanocrystalline form dispersed within a matrix of the crystallization inducer, enhancing the dissolution rate and stability of the active ingredient.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If amorphous solid dispersions are used to improve dissolution rate, then dissolution rate is enhanced, but physical stability becomes unpredictable and chemical instability increases
Solution Approach 1:
The invention utilizes phase transition from amorphous to crystalline state by controlling the drying process. The amorphous solid dispersion is converted to a crystalline solid dispersion through controlled crystallization during spray drying, which provides both enhanced dissolution rate and improved physical stability. The crystalline structure prevents unpredictable physical changes while maintaining high dissolution performance.
Solution Approach 2:
The invention changes the physical state parameter from amorphous to crystalline by adjusting drying conditions and temperature parameters. This parameter change transforms the unstable amorphous phase into a stable crystalline phase, resolving the contradiction between dissolution rate enhancement and physical stability.
2Speed
If nanoparticle size is reduced to enhance dissolution, then dissolution rate improves, but dispersion stability deteriorates due to agglomeration
Solution Approach 1:
The invention creates a composite material system where nanocrystals are embedded in a matrix material. This composite structure prevents agglomeration of nanoparticles while maintaining their high surface area, thus preserving dissolution rate enhancement without sacrificing dispersion stability. The matrix provides steric stabilization to the nanocrystals.
Solution Approach 2:
The matrix material acts as an intermediary between the nanocrystals and the dissolution medium. It prevents direct interaction between nanocrystals that would lead to agglomeration, while still allowing efficient drug release. The matrix mediates the balance between maintaining nanoparticle dispersion and enabling rapid dissolution.
3Quantity of substance
If amorphous form is used to improve solubility, then apparent solubility increases, but recrystallization occurs during shelf-life and dissolution
Solution Approach 1:
The invention employs controlled phase transition during manufacturing to achieve a stable crystalline form that maintains high solubility. By controlling the crystallization process during spray drying, the drug is transformed from an unstable amorphous phase to a stable crystalline phase that does not undergo unwanted recrystallization during storage, thus maintaining both solubility and shelf-life stability.
4Speed
If polymeric matrices are used to create solid dispersions, then dissolution rate is enhanced, but hygroscopic nature causes phase separation and physical instability
Solution Approach 1:
The invention extracts or removes the problematic polymeric matrix component that causes hygroscopicity and phase separation. By eliminating the polymer and using a non-hygroscopic alternative matrix, the invention maintains dissolution rate enhancement while removing the source of physical instability and phase separation during storage.
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 results in a composition with improved solubility, stability, and bioavailability, as the nanocrystalline form of the active ingredient is maintained, ensuring enhanced dissolution kinetics and physical stability, thereby overcoming the limitations of traditional methods.
Implementation Method 1
A solution of crystallization inducer-pharmaceutical active is spray dried to form discrete particles
Implementation Method 2
use of a crystallization inducer and pharmaceutical active, where a solution of both is spray dried to produce discrete particles with the active ingredient in a nanocrystalline form
Data Source
Figure 1
Figure 2
Figure 3
AI summary
The present invention relates to nanocrystalline solid dispersion compositions having discrete particles, wherein each discrete particle comprises crystals of at least one pharmaceutical active; veterinary active; nutraceutical active dispersed in the matrix of at least one crystallization inducer and/or coexisting with crystals of crystallization inducer, optionally along with pharmaceutically acceptable excipients. The present invention also encompasses a novel one-step process for generation of nanocrystalline solid dispersions. The present invention is particularly of use for improving the dissolution of pharmaceutical actives, veterinary actives; nutraceutical actives exhibiting dissolution-limited bioavailability. Dissolution enhancement is because of the decreased crystallite size of the pharmaceutical active.