Amorphous Solid Dispersions for Poorly Soluble API Absorption
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Solution Overview
Problem
Many active pharmaceutical ingredients (APIs) exhibit poor aqueous solubility and low oral bioavailability, leading to absorption variations due to food intake and inter-subject variability.
Innovation Solution
Development of amorphous solid dispersions (ASDs) comprising APIs like cabozantinib, venetoclax, abiraterone, alectinib, pazopanib, lurasidone, and vilazodone, combined with surfactants, hydrophilic polymers, and optionally acids and adsorbents, to enhance solubility and bioavailability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If APIs are administered in conventional crystalline form, then manufacturing is simple, but aqueous solubility and oral bioavailability are poor
Solution Approach 1:
The patent transforms the API from crystalline state to amorphous state, fundamentally changing the physical state parameter. This phase transition from ordered crystalline structure to disordered amorphous structure dramatically increases aqueous solubility while maintaining pharmaceutical stability through careful selection of amorphous-forming excipients
Solution Approach 2:
The patent creates composite amorphous solid dispersion systems by combining the amorphous API with specific excipients including hydrophilic polymers (HPMC, PEG, PVP), surfactants (TPGS, polysorbate), and co-solvents. This composite approach enhances solubility through multiple mechanisms: polymer-API interactions, surfactant micelle formation, and co-solvent effects
2Reliability
If conventional formulations are used, then formulation is simple, but oral bioavailability is low
Solution Approach 1:
The patent employs parameter changes by transitioning the API to amorphous state and optimizing excipient ratios (e.g., HPMC:API ratio, PEG molecular weight selection). These parameter modifications enhance dissolution rate and bioavailability while maintaining manufacturability through established granulation and compression processes
Solution Approach 2:
The patent introduces hydrophilic polymers and surfactants as intermediary substances that facilitate API dissolution and absorption. These intermediaries form complexes with the hydrophobic API, improving its wettability and solubility without requiring complex delivery systems
3Reliability
If standard dosing is used, then administration is straightforward, but absorption varies with food intake
Solution Approach 1:
The patent modifies the physical-chemical parameters of the API through amorphization and excipient combination, creating a formulation with improved dissolution characteristics that is less sensitive to gastric pH changes and food effects. The amorphous form maintains higher solubility across different gastrointestinal conditions compared to crystalline forms
Solution Approach 2:
The patent ensures continuous drug availability by enhancing dissolution rate and maintaining supersaturation in the gastrointestinal tract. The amorphous solid dispersion system provides sustained drug release and absorption regardless of food intake, eliminating the need for strict fasting requirements
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 ASDs improve oral bioavailability and reduce food-effect variability, allowing for lower doses and more consistent drug absorption.
Implementation Method 1
a surfactant in an amount of about 5% to about 60% by weight of the ASD, wherein the surfactant comprises phospholipids or their derivatives such as lecithin, polyethylene glycol (PEG), a block copolymer of polyethylene glycol and polypropylene glycol, sodium lauryl sulfate (SLS), TPGS
Implementation Method 2
a hydrophilic polymer in an amount of about 1% to about 80% by weight of the ASD
Implementation Method 3
an amorphous solid dispersion (ASD) that comprises: a) an active pharmaceutical ingredient (API)
Data Source
AI summary
Provided are pharmaceutical compositions which include an amorphous solid dispersion comprising i) a lipophilic active pharmaceutical ingredient such as abiraterone, alectinib, pazopanib, cabozantinib, venetoclax, lurasidone, or vilazodone or a salt thereof, ii) a hydrophilic polymer, iii) optionally a surfactant, iv) optionally an adsorbent, and v) optionally an acid. Also described are methods for preparing such pharmaceutical compositions and treating a subject in need thereof. In one aspect, disclosed herein is an amorphous solid dispersion comprising an active pharmaceutical ingredient.