Pharmaceutical Compositions for Stable Amorphous API Solubility
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Solution Overview
Problem
Many active pharmaceutical ingredients (APIs) in today's drug pipeline have low to no aqueous solubility, complicating their delivery and leading to poor bioavailability, and current methods like amorphous solid dispersions (ASDs) face challenges in selecting the right polymer matrix, which can cause thermal degradation and recrystallization issues.
Innovation Solution
Novel pharmaceutical compositions combining APIs with polymers and optionally surfactants in varying ratios, formulated into spray dried dispersions (SDD) and extrudates, enhancing solubility and bioavailability, particularly for cannabinoid-based medications, using pharmaceutically acceptable carriers and excipients.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If amorphous solid dispersions (ASDs) are used to improve solubility and bioavailability, then the dissolution rate and solubility increase, but thermal degradation and recrystallization issues occur during processing and storage
Solution Approach 1:
The patent applies parameter changes by modifying the physical state of the API from crystalline to amorphous form, and by adjusting processing parameters such as temperature, humidity, and processing time to prevent thermal degradation and recrystallization while maintaining improved solubility and bioavailability
Solution Approach 2:
The patent uses composite materials by combining the amorphous API with polymers and other excipients to create a stable matrix that prevents recrystallization and thermal degradation, thereby maintaining reliability during processing and storage while preserving the solubility benefits
2Reliability
If processing temperatures are reduced to prevent thermal degradation, then API stability improves, but the dissolution and mixing efficiency decrease
Solution Approach 1:
The patent applies parameter changes by optimizing the balance between temperature and processing time, using lower temperatures combined with extended processing durations to maintain API stability while achieving adequate dissolution and mixing efficiency through controlled parameter adjustment
3Stability of the object's composition
If residence time is reduced to prevent recrystallization, then physical stability improves, but mixing and dissolution completeness decrease
Solution Approach 1:
The patent applies parameter changes by adjusting multiple process parameters simultaneously, including reducing residence time to prevent recrystallization while compensating for mixing completeness through optimized shear rates, temperature profiles, and polymer selection to achieve both physical stability and manufacturing precision
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 compositions improve the solubility and bioavailability of APIs, ensuring stable shelf-life and therapeutic effectiveness, addressing issues early in the development process to save time and costs, and are effective in treating fibrotic and inflammatory conditions of the lung, liver, kidney, and prostate.
Implementation Method 1
SDD has been commonly used to produce amorphous solid dosage forms for improving the bioavailability of poorly soluble crystalline API. The primary purpose of spray drying poorly soluble crystalline APIs is to achieve an amorphous molecularly dispersed state of the API in the matrix of choice.
Implementation Method 2
HME has been established as an efficient technology for the enhancement of solubility and bioavailability of poorly soluble drugs. During the melt extrusion process, the dissolution of APIs into the polymer matrix is accelerated under the influence of shear and heat.
Implementation Method 3
The polymers also prevent the recrystallization of the drug, maintain drug supersaturation and provide improved physical stability of API in accelerated temperature and humidity conditions which increases the overall shelf-life of the drug product. The amorphous solid dispersions produced via HME are expected to possess lower molecular mobilities and API molecules 'freeze' inside a matrix of choice to inhibit the nucleation and crystallization processes.
Data Source
AI summary
The invention relates to pharmaceutical compositions or formulations and comprises (I) a compound of Formula (I) or Formula (II); (ii) one or more pharmaceutically acceptable polymers; and (iii) optionally one or more pharmaceutically acceptable surfactants and/or one or more pharmaceutically acceptable surfactant-like materials; and (iv) optionally one or more pharmaceutically acceptable carriers and/or one or more pharmaceutically acceptable excipients; and (v) optionally one or more solvents, in varying ratios. The invention also discloses their preparation and methods of use thereof wherein the pharmaceutical compositions or formulations are administered in therapeutically effective amounts to provide a physiological effect in an individual or animal.