Enterically-Coated Lyospheres for Targeted GI Delivery
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Solution Overview
Problem
Existing methods for preparing enterically-coated dosage forms for biological macromolecular therapeutic agents face challenges such as poor powder flow, chemical instability, and inadequate capsule integrity, leading to inconsistent drug delivery and stability issues.
Innovation Solution
The process involves preparing enterically-coated lyospheres by mixing the therapeutic agent with a sugar and a binding-gel forming agent in an aqueous medium, freezing the mixture, and then separating water to form robust lyospheres that can withstand coating steps and release the therapeutic agent effectively in targeted regions of the gastrointestinal tract.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If conventional lyophilized bulk powder is used and blended with excipients to improve powder flow, then powder flow is improved, but chemical instability and degradation of macromolecules occur due to physical stress and chemical interactions
Solution Approach 1:
The invention segments the macromolecule into individual microcapsules containing the therapeutic agent, rather than using bulk powder. Each microcapsule is independently coated with enteric polymer, isolating the macromolecule from excipients and physical stress during processing while maintaining flow properties through the microcapsule format
Solution Approach 2:
The invention introduces enteric polymer coating as an intermediary layer between the macromolecule and the gastrointestinal environment. This coating protects the macromolecule from chemical degradation and physical stress during handling, while the coating itself is designed to be stable and non-interfering with the therapeutic agent
2Adaptability or versatility
If enteric coating is applied to improve targeted delivery, then delivery specificity is improved, but capsule integrity and coating adhesion deteriorate due to softening and peeling
Solution Approach 1:
The invention changes the physical state and composition parameters of the enteric coating formulation. The coating is applied as a spray or dip coating using optimized polymer concentrations and molecular weights that provide adequate adhesion while maintaining capsule integrity. The coating formulation parameters are adjusted to prevent softening and peeling during storage and handling
Solution Approach 2:
The invention uses composite enteric coating materials that combine multiple polymers or polymer components with specific properties. The coating composition is designed to provide both targeted delivery functionality and mechanical strength, using composite polymer systems that resist softening and peeling while maintaining colonic specificity
3Device complexity
If bulk powder formulation is used to simplify processing, then manufacturing complexity is reduced, but dose uniformity and manufacturing precision deteriorate due to poor flow and inconsistent loading
Solution Approach 1:
The invention segments the dosage form into individual microcapsules that can be uniformly distributed and counted. Each microcapsule contains a defined dose of the therapeutic agent, and the microcapsules can be filled into capsules or tablets with precise control, achieving dose uniformity while maintaining processing simplicity through the standardized microcapsule format
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
This approach results in dosage forms with improved flow properties, reduced chemical instability, and enhanced capsule integrity, allowing for targeted and effective delivery of therapeutic agents to specific regions of the gastrointestinal tract, such as the ileum, ileo-caecal junction, and colon.
Implementation Method 1
mixing the therapeutic agent, a sugar, and a binding-gel forming agent in an aqueous medium to form an aqueous medium mixture
Implementation Method 2
freezing said unitary volumes to form unitary forms
Implementation Method 3
separating water from said unitary forms to yield the lyospheres
Data Source
Figure 1A~1B
Figure 2
Figure 3A~3B
AI summary
The present invention provides a process for preparing enterically-coated lyospheres comprising a therapeutic agent comprising: a.) providing lyospheres comprising the therapeutic agent; b.) coating said lyospheres with an enteric polymer coating composition; and c.) isolating said enterically-coated lyospheres. In other embodiments, the invention provides dosage forms comprising a lyosphere comprising an effective amount of a therapeutic agent and an enteric polymer coating. In some embodiments, the therapeutic agent in the process or dosage form is a polypeptide, a protein, a peptide, a lipopeptide, a glycoprotein, a fusion protein, a protein conjugate, a cytokine, an enzyme, an antibody, an oligonucleotide, a vaccine vector, small molecule, a live virus, an inactivated virus, a virus-like particle, a viral protein subunit, an adjuvant, microbiome, a prebiotic, a probiotic, or an ectobiotic. In some embodiments of the present invention, after oral administration the dosage forms containing the enterically-coated lyospheres provide a method of delivering a therapeutic agent to the ileum, ileo-caecal junction, colon or a combination thereof in a subject.