Double-Layer Hard Capsules Using Aqueous Dip Molding for Delayed Release
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing technologies face challenges in achieving both rapid gastric resistance and controlled intestinal release of pharmaceuticals in capsules, while maintaining mechanical stability and avoiding the use of solvent-based melts that pose safety and handling issues.
Innovation Solution
A double dipping process is used to create a two-layered hard capsule shell, with an inner layer of water-soluble HPMC and an outer layer of HPMCAS, both formed from aqueous melts, ensuring complete coverage and uniform film formation without solvent-based issues.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a one-piece soft capsule with two layers is used, then the capsule can provide delayed-release functionality, but the encapsulation process cannot be used for production of two-piece hard capsules and the mechanical properties are insufficient
Solution Approach 1:
The capsule shell is divided into two separate hard pieces (cap and body) that can be manufactured independently using dip molding, then assembled together. This segmentation allows each piece to be optimized for mechanical strength while maintaining the delayed-release functionality through the enteric coating on the inner layer.
Solution Approach 2:
The capsule employs a composite structure with an inner layer of gelatin providing mechanical flexibility and an outer layer of HPMCAS providing enteric resistance. This composite material approach combines the advantages of both materials to achieve both mechanical properties and delayed-release functionality.
2Reliability
If the capsule is designed to pass through the stomach into the intestine before dissolving, then the pharmaceutical release is controlled, but too much pharmaceutical may be released in the first step under pH 1.2 conditions or too little in the second step under pH 6.8 conditions
Solution Approach 1:
The capsule shell has different properties at different locations: the inner layer is made of gelatin that is soluble in both gastric and intestinal fluids, while the outer layer is made of HPMCAS that is specifically resistant to gastric acid but soluble in intestinal fluids. This local differentiation of material properties enables precise control over dissolution timing.
Solution Approach 2:
The dissolution behavior is controlled by changing the pH parameter of the environment. The HPMCAS outer layer remains intact at pH 1.2 (stomach) but dissolves at pH 6.8 (intestine), while the gelatin inner layer dissolves in both. This parameter-driven dissolution control ensures the pharmaceutical is released only in the intestine.
3Ease of manufacture
If solvent-based melts are used in the dip molding process, then the capsule shell can be formed, but safety and handling issues arise
Solution Approach 1:
The harmful solvent component is completely removed from the melt composition. Instead of using traditional solvent-based melts, the invention employs water-based or solvent-free alternative melts that can still effectively deposit the polymer coating, thereby eliminating safety and handling issues while maintaining manufacturability.
4Stability of the object's composition
If the capsule wall is made sufficiently stable for storage under different relative humidity conditions, then mechanical properties are maintained, but the capsule may not dissolve rapidly enough in the stomach
Solution Approach 1:
The capsule wall is segmented into two functional layers: the inner gelatin layer that provides rapid dissolution in the stomach and the outer HPMCAS layer that provides stability during storage. This segmentation allows each layer to optimize its specific function without compromising the other.
Solution Approach 2:
Different regions of the capsule wall have different material properties optimized for their specific functions. The inner layer uses gelatin for rapid dissolution, while the outer layer uses HPMCAS for stability and enteric resistance. This local quality differentiation resolves the contradiction between stability and dissolution rate.
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 achieves targeted drug release profiles and mechanical stability, reducing variability and safety risks, while adhering to USP dissolution requirements and ensuring enteric characteristics.
Implementation Method 1
double dipping process, that is by two consecutive dip molding steps on the same mold pin
Implementation Method 2
each dip molding step is done with a different polymer melt
Data Source
Figure 1
Figure 2
Figure 3
AI summary
The invention discloses double layered delayed-release hard capsules made by double dipping, that is by two consecutive dip molding steps on the same mold pin without removing the film, provided by the first dip molding step, from the mold pin between the two dip molding steps, but dipping the mold pin with this first film in the second dip molding step, each dip molding step is done with a different polymer melt, providing a double layered delayed-release capsule.