Layered Tablet for Extended Release of Active Substances
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Solution Overview
Problem
Formulating dosage forms that achieve prolonged release of active ingredients poorly soluble at high pH values, particularly in the intestinal environment, while also managing the release of a second active ingredient with better solubility at high pH values, is challenging due to differences in solubility and absorption sites within the gastrointestinal tract.
Innovation Solution
A layered tablet dosage form with compartments containing the first active ingredient and an emulsifier, along with optional surfactants and retardants, designed to maintain a long residence time in the stomach, allowing gradual release and absorption in the small intestine, while the second compartment with a retardant ensures delayed release of the second active ingredient.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If a coating or matrix is used to achieve prolonged release of a basic active ingredient, then the release duration is extended, but the active ingredient dissolves poorly in the alkaline environment of the intestine causing ineffective release
Solution Approach 1:
The dosage form is divided into multiple compartments (first compartment with poorly soluble basic active ingredient, second compartment with more soluble active ingredient, third compartment with acid-labile coating). Each compartment is designed to release its contents at different locations in the gastrointestinal tract, ensuring that the basic active ingredient is released in the acidic stomach environment where it dissolves effectively, while other compartments provide complementary release patterns.
Solution Approach 2:
Different compartments are assigned different release properties and chemical compositions tailored to their specific functions. The first compartment contains the basic active ingredient with acidic properties for stomach release, the second compartment contains more soluble ingredients for intestinal release, and the third compartment has acid-labile coating for protected delivery. This local differentiation ensures each active ingredient is released in the optimal pH environment.
2Adaptability or versatility
If a dosage form is designed to release two active ingredients with different dissolution behavior, then both ingredients can be delivered, but the more soluble active ingredient can only be released with a delay
Solution Approach 1:
The dosage form is segmented into distinct compartments: the first compartment releases the basic active ingredient in the stomach, the second compartment (with acid-labile coating) releases the more soluble active ingredient in the intestine, and the third compartment provides additional controlled release. This segmentation allows each ingredient to be released at the optimal time and location without unnecessary delays.
Solution Approach 2:
The acid-labile coating on the second compartment is pre-designed to dissolve at the specific pH conditions of the intestine. This preliminary preparation ensures that when the dosage form reaches the intestine, the coating rapidly dissolves and releases the more soluble active ingredient without unnecessary delay, while the first compartment has already released its contents in the stomach.
3Reliability
If the stomach pH is neutral after eating, then the basic active ingredient dissolves better, but the prolonged release effect is reduced
Solution Approach 1:
The dosage form utilizes the dynamic pH changes in the gastrointestinal tract to its advantage. The first compartment is designed to release the basic active ingredient in the acidic stomach environment, taking advantage of the naturally occurring acid periods. The system adapts to the physiological rhythm of stomach emptying and pH variation, ensuring release occurs during acidic phases while maintaining prolonged overall release through the multi-compartment design.
Solution Approach 2:
The invention exploits the periodic acidification of the stomach that occurs naturally during digestion cycles. By timing the release of the basic active ingredient to coincide with these periodic acidic phases, the dosage form achieves both effective dissolution and prolonged release duration throughout the day, as multiple release cycles can occur with each dosage form administration.
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 dosage form enables prolonged and linear release of both active ingredients, optimizing bioavailability by ensuring the first active ingredient dissolves in the stomach and the second active ingredient is released appropriately in the intestine, addressing the solubility and absorption challenges.
Implementation Method 1
The emulsifier according to the invention is capable of increasing the solubility of a first active ingredient at high pH values
Implementation Method 2
at least one surfactant, in particular an anionic surfactant, more preferably a metal soap
Implementation Method 3
the second compartment (b) contains the second active ingredient and at least one retardant
Data Source
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AI summary
A pharmaceutical form is described, which makes it possible to uniformly release an active substance over an extended period of time. The pharmaceutical form comprises an emulsifier with a polyalkylene oxide structural motif. The pharmaceutical form is suitable for releasing a second active substance alongside the first active substance. A uniform release is achieved even if the two active substances have completely different properties in terms of solubility. A production method for the pharmaceutical form and the use thereof are also described.