Tacrolimus Solid Dispersion Bioequivalence
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current solid dispersion formulations of macrolide compounds, such as tacrolimus, lack bioequivalence to FDA-approved formulations, necessitating the development of alternative formulations that maintain immunosuppressive activity while ensuring bioavailability.
Innovation Solution
A pharmaceutical formulation comprising a combination of a solid dispersion and a non-dispersed form of a macrolide compound, where 50% to 85% of the macrolide is in solid dispersion form, processed with carriers like HPMC, fillers, disintegrants, and lubricants, to create an oral dosage form that is bioequivalent to FDA-approved products.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a solid dispersion formulation of macrolide is used, then the immunosuppressive activity is maintained, but the bioequivalence to FDA-approved formulations is not achieved
Solution Approach 1:
The macrolide compound is divided into two distinct forms: a solid dispersion portion (50-85% of total macrolide) and a non-dispersed portion (15-50% of total macrolide). This segmentation allows each form to contribute differently to the overall performance, with the solid dispersion providing controlled release and the non-dispersed form ensuring rapid onset, thereby achieving bioequivalence while maintaining immunosuppressive activity.
Solution Approach 2:
The formulation creates a composite structure by combining two different physical forms of the same macrolide compound. The solid dispersion (macrolide + carrier material) is mixed with non-dispersed macrolide particles, creating a composite formulation that leverages the advantages of both forms to achieve the desired bioequivalence profile.
2Productivity
If the entire macrolide is formulated as solid dispersion, then processing complexity increases, but the bioavailability is improved
Solution Approach 1:
Instead of converting 100% of the macrolide to solid dispersion form, the invention applies partial action by converting only 50-85% to solid dispersion while leaving 15-50% in non-dispersed form. This partial conversion achieves the necessary bioavailability enhancement without the full processing complexity that would result from complete solid dispersion formulation.
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 formulation achieves bioequivalence with FDA-approved products, demonstrated by similar absorption rates and extent, reducing processing complexity and eliminating undesirable solvents, thereby making the product more economical and effective.
Implementation Method 1
a solid dispersion of the macrolide along with a non-dispersed form of the macrolide
Implementation Method 2
demonstrated by similar absorption rates and extent
Data Source
AI summary
The present invention relates to a pharmaceutical formulation and process for preparing the same comprising an oral dosage formulation, such as a capsule formulation, of a macrolide compound, such as tacrolimus, wherein the capsule formulation contains both a solid dispersion of the macrolide along with a non-dispersed form of the macrolide. The pharmaceutical formulation according to the invention is bioequivalent to the FDA approved product according to a bioavailability study conducted in humans.