Veterinary Tablet Granule Coating for Bitter Taste Masking
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Solution Overview
Problem
Developing a pharmaceutical formulation for veterinary medicine that combines pimobendan and an ACE inhibitor, such as benazepril, is challenging due to stability issues and bitter taste, which affects bioavailability and acceptance by animals.
Innovation Solution
A pharmaceutical tablet formulation with granules coated in multiple layers, using polymethacrylate polymers to mask the bitter taste and enhance stability, where benazepril is embedded in a carrier core coated with polymers that prevent immediate release and protect against moisture, ensuring bioequivalence and improved stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional pharmaceutical forms are used for oral administration, then the active substance can be administered, but the resorption shows considerable inter- and intra-individual fluctuations and the bitter taste reduces acceptance by animals
Solution Approach 1:
The tablet is segmented into multiple granules with different functions: enteric-coated granules containing the ACE inhibitor (to protect from stomach acid and control release), uncoated granules containing pimobendan (for immediate release), and excipient granules. This segmentation allows each component to be optimized independently for stability, release control, and palatability.
Solution Approach 2:
An enteric coating layer acts as an intermediary between the ACE inhibitor and the stomach environment. This coating protects the bitter-tasting ACE inhibitor from direct contact with saliva and stomach acid, masking the unpleasant taste while ensuring controlled release in the intestine, thereby improving animal acceptance and resorption consistency.
2Stability of the object's composition
If the ACE inhibitor is exposed to moisture, then it undergoes hydrolysis and degradation, but protection requires complex formulation strategies
Solution Approach 1:
An enteric coating film is applied to the granules containing the ACE inhibitor. This thin film barrier protects the moisture-sensitive ACE inhibitor from hydrolysis and degradation by preventing direct contact with moisture in the stomach and environment, while allowing controlled release in the intestine. This approach provides effective protection with relatively simple implementation.
3Reliability
If the ACE inhibitor is released immediately upon contact with saliva, then bioavailability is achieved, but the bitter taste is detected and animal acceptance is reduced
Solution Approach 1:
The enteric coating serves as an intermediary barrier that prevents the ACE inhibitor from contacting saliva and being detected by the animal's taste receptors. The coating is designed to remain intact through the mouth and stomach, only dissolving in the alkaline environment of the intestine, thus masking the bitter taste while ensuring eventual bioavailability.
Solution Approach 2:
The enteric coating is designed to respond to pH changes as it transitions from the acidic stomach environment to the alkaline intestinal environment. This parameter change (pH-dependent dissolution) triggers the release of the ACE inhibitor at the appropriate location, ensuring both palatability during administration and bioavailability upon release.
4Reliability
If a combination of pimobendan and ACE inhibitor is formulated, then synergistic therapeutic effect is achieved, but stability issues and taste masking become more complex
Solution Approach 1:
The combination formulation is segmented into functionally distinct granule populations: enteric-coated granules for the ACE inhibitor (protecting stability and masking taste), uncoated granules for pimobendan (allowing immediate release), and excipient granules. This segmentation enables each active ingredient to be optimized for its specific requirements while maintaining a relatively simple overall tablet structure.
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 provides a synergistic combination that exceeds the activity of single active substances, ensuring stable and effective delivery of both pimobendan and benazepril, improving compliance and acceptance by masking the bitter taste and maintaining stability.
Implementation Method 1
using polymethacrylate polymers to mask the bitter taste
Implementation Method 2
ACE inhibitors are generally very difficult to formulate into dosage forms, as most ACE inhibitors on contact with some of the commonly used pharmaceutical ingredients undergo degradation at accelerated rates due to cyclization via internal nucleophilic attack to form substituted diketopiperazines or hydrolysis of the side chain ester group
Implementation Method 3
where benazepril is embedded in a carrier core coated with polymers that prevent immediate release and protect against moisture, ensuring bioequivalence and improved stability
Data Source
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AI summary
The invention is directed to a pharmaceutical tablet formulation for the veterinary medical sector containing an instable ACE inhibitor or a pharmaceutically acceptable salt thereof as a first pharmaceutically active substance, and pimobendan or a pharmaceutically acceptable salt thereof as a second pharmaceutically active substance, comprising granules which contain carrier core particles coated with at least one layer wherein the first pharmaceutically active substance is present, the granules being embedded in a tablet matrix wherein the second pharmaceutically active substance is present. It is provided a "fixed-dose-combination" which allows to ease the treatment and administration of the medication, improves the medication compliance by reducing the pill burden to the animal holder and enables the better observation of and adherence to the therapy by decreasing the number of tablets to be administered. The lower number of tablets leads to a lower treatment failure rate, minimizes dosage mistakes and avoids confusions by false dose intake and slower development of resistance.