DRUG ABSORPTION AND DISSOLUTION TEST APPARATUS

Abstract

A drug absorption and dissolution testing apparatus (101) resembles different parts of gastrointestinal tract through multi-chamber system (102). The apparatus has precise control systems over temperature and pH (103), along with the peristaltic pumping mechanism (104) to regulate media flow. The apparatus has a real-time sensor (105) monitoring critical parameters, advanced microprocessor control system (106) accounts for the operations and also processes data. Apparatus include a biomimetic membrane (107) that emulates an intestinal wall for enhancing fluid recovery, the flow-through cell design (108), independent testing stations (108) allows formulation testing in parallel and simultaneously, and a friendly interface (111) to enable effective control and analysis of data. The apparatus made from advanced materials (110) to make it durable and easy to clean. Further, offers functionalities for simulating biorelevant media, introducing an enzyme, and microbiome simulation, which further adds value in predicting in-vivo drug behaviour and optimization of pharmaceutical formulations.

Specification

Description:The following is a step-by-step description of the invention, detailing the components, and their functionalities mentioned below:

The novel drug absorption and dissolution test apparatus (101) features a multi-chamber system (102) designed to replicate different segments of the gastrointestinal tract, consisting of three primary chambers. The Gastric Chamber (201) simulates the stomach environment with a 250 mL capacity, constructed from borosilicate glass for chemical resistance and equipped with a jacket for precise temperature control. The Duodenal Chamber (202), representing the duodenum, has a capacity of 100 mL and shares the same glass construction and temperature control features. The largest, the Intestinal Chamber (203), simulates the small intestine with a 500 mL capacity and similar design. Each chamber includes ports for adding media, sampling, and sensor insertion, and they are interconnected with biocompatible tubing to facilitate media flow between them.

Temperature and pH Control System (103), each compartment of the device has its independent control system for temperature and pH. Circulating water jackets of around each compartment connected to a circulating water bath make Temperature Control System work. Platinum resistance thermometers, (Pt100) deliver temperature feedback to the microprocessor, and temperatures remain within ±0.1°C of set point, which is usually 37°C-the closest approximation to biological temperature in the human body. The pH Control system consists of a pH probe attached with every chamber and is connected to the microprocessor. Hence, pH is regulated in an automated mode with the aid of pre-prepared acidic or basic solution for adding the same through peristaltic pumps. Thus, pH gradients could be created that replicate the changeover from stomach with pH 1-3 to intestine with pH 6-7.4.

Peristaltic Pumping Mechanism (104), features a sophisticated multi-channel peristaltic pump system designed to manage media flow between chambers and replicate the mechanical stresses of the gastrointestinal tract. The Inter-Chamber Flow mechanism utilizes peristaltic pumps to facilitate the movement of media from the gastric chamber to the duodenal chamber and then to the intestinal chamber, accurately simulating the passage of a drug through the GI tract. Each chamber is equipped with its own Circulation Pump to ensure homogeneous mixing of the media while applying mechanical stress to the drug formulation. Additionally, dedicated Sampling Pumps enable automated sampling from each chamber. All pumps are controlled by a microprocessor, allowing for programmable flow rates and patterns to effectively simulate various physiological conditions.

The Integrated Sensor System (105) is a generic network of sensors installed to monitor, in real time, a set of key parameters around the apparatus. These are high-precision pH sensors, that measures the pH in each chamber, temperature sensors, that are based on Pt100 probes for precise temperature, and UV-Vis spectrophotometers, with fiber-optic probes which can measure concentrations in real-time drug concentrations. Additionally, conductivity sensors monitor the ion concentration and media composition, while pressure sensors, distributed along the flow path, measure system pressure and detect blockages.

The Microprocessor Control System (106), managing all aspects, from data acquisition, which permanently samples sensor data at 1 Hz, to process control, which controls adjustable pump speeds, temperature, and pH levels to keep conditions at an optimum level, as well as the control for the user interface that allows the live stream of information to the user and input from the user. The system supports data processing and storage, processing raw data and computing parameters such as dissolution rates for later analysis. The microprocessor performs diagnostics about the system as a whole, detecting faults and offering networking capabilities so that access is possible remotely. These functions are operated on custom software that minimizes the time the user spends performing the operations and makes the data easier to analyse.

Biomimetic Membrane System (107), which functioned as an imitation of the intestinal wall. The membrane composition comprising a lipid bilayer supported by a porous polymer substrate, very similar to the intestinal epithelium, has been used. This membrane is installed in a special holder, which divides the intestinal chamber into two compartments: the lumen side and the receiver side. System The system offers permeability customization. Drug absorption studied at various conditions, such as under physiological or pathological conditions, by simulating variable intestinal permeability by using various membrane compositions. In addition, integrated electrodes 704 measure TEER as an assessment tool for the membrane integrity.

The Flow-Through Cell Design (108) is important as it would allow for continuous sampling and analysis. Cell constructions, fabricated from inert materials, like PEEK or PTFE, are compatible with the flow path in each chamber. A sampling mechanism comprises a semi-permeable membrane, through which only dissolved drug molecules can pass by, hence keeping out undissolved particles. These cells are related to online analysis systems, that include UV-Vis spectrophotometers, by which the drug concentrations are continuously monitored in real time. The system also supports the possibility of automated sampling; samples are collected at preprogrammed intervals for offline analysis if necessary.

The Multiple Test Stations feature enhances the apparatus by enabling higher throughput and comparative studies. The station configuration includes four independent test stations, each equipped with its own chambers, pumps, and sensors. These stations are managed through central control, with a single microprocessor synchronizing operation and data collection. Despite this central control, independent parameter control allows each station to be programmed with unique test conditions, enabling the simultaneous evaluation of various formulations. The user interface supports comparative analysis, providing an easy way to compare data from different stations for efficient formulation optimization.

The Advanced Materials (110) used in the apparatus are selected to ensure durability, chemical resistance, and minimal interference with test samples. The chamber materials consist of borosilicate glass, chosen for its chemical resistance and transparency, while flow path materials, such as PTFE or PEEK, are used for tubing and fittings to prevent interaction with test samples. Sensor housing materials are made from chemically resistant polymers, ensuring long-term accuracy and stability. Additionally, the structural materials, including corrosion-resistant stainless steel or anodized aluminum, provide durability and ease of cleaning for the non-wetted parts of the apparatus.

The User-Friendly Interface (111) enhances the apparatus by providing an intuitive, easy-to-use platform for operation and data analysis. A large touchscreen display serves as the primary control point, offering high-resolution access to system functions. The intuitive software features a graphical user interface for setting up tests, monitoring experiments, and analysing results. Users benefit from real-time data visualization, with graphical representations of key parameters like drug concentration, pH, and temperature across all chambers. The system also offers data export capabilities, allowing raw and processed data to be exported in formats such as CSV or Excel. A method library provides pre-programmed test protocols that users can customize, while user access control ensures secure access and data integrity through authentication features.

Method of performing an Invention:

The typical operational workflow of the apparatus follows a structured sequence to ensure precise and efficient testing. It begins with method setup, where the user selects or creates a test method, defining key parameters like media composition, pH profiles, flow rates, and sampling intervals for each chamber. In the system preparation step, the apparatus assists the user in preparing the system by loading media, installing the biomimetic membrane, and conducting system checks. Next, the sample loading phase involves loading the drug formulation into the gastric chamber, either manually or through automated dispensing. During test execution, the microprocessor controls the test's progression, maintaining the specified conditions while collecting data. Real-time monitoring allows the user to observe drug dissolution and absorption through the interface. Upon completion, data analysis tools are provided to calculate dissolution profiles, absorption rates, and other pharmacokinetic data. Finally, the cleaning and preparation step guides the user through system cleaning to prepare for the next test.

The apparatus offers several advanced features and capabilities that enhance its ability to simulate real-life physiological conditions. It supports biorelevant media simulation, allowing users to mimic fasted or fed states in different parts of the GI tract. Enzyme integration enables the addition of enzymes such as pepsin or pancreatin to simulate digestive processes in the appropriate chambers. Through hydrodynamic control, the apparatus can recreate various flow conditions, from turbulent stomach mixing to laminar intestinal flow. The system also supports formulation behaviour imaging, with optional imaging systems to visually monitor dosage form disintegration or swelling during tests.

Furthermore, absorption modeling software tools allow the extrapolation of in vivo absorption profiles from in vitro data, aiding in bioavailability and pharmacokinetics predictions. The apparatus can simulate the effects of food on drug dissolution and absorption, and through variable volume simulation, it adjusts chamber volumes over time to mimic changes in GI fluid volumes. Finally, it includes microbiome simulation, incorporating models to simulate the influence of the gut microbiome on drug metabolism and absorption.

The Validation and Calibration features of the apparatus ensure accurate and reliable performance. It includes calibration protocols with automated routines for calibrating all sensors and pumps, maintaining precision. A set of standard reference materials is provided for system validation and for conducting inter-laboratory comparisons. The system also supports performance qualification, with built-in protocols for installation qualification (IQ), operational qualification (OQ), and performance qualification (PQ) to comply with regulatory standards. Additionally, an audit trail (1404) securely logs all operations, including test runs, calibrations, and system modifications, in a tamper-evident format, ensuring data integrity.

The Data Management and Connectivity features of the apparatus ensure secure, efficient handling of data and integration with external systems. Secure data storage ensures that all test data is safely stored on the system, with options for automatic backup to network storage. Connectivity allows the system to integrate seamlessly with laboratory information management systems (LIMS) for efficient data transfer. Remote monitoring provides secure off-site access, enabling authorized users to monitor tests and retrieve data remotely. Additionally, the system supports software updates, allowing for secure internet-based updates and feature enhancements.

The Safety Features of the apparatus are designed to ensure user safety and protect the system during operation. Overpressure protection is achieved through pressure relief valves and software-controlled pump shutoffs, which prevent dangerous pressure buildup. Leak detection systems are integrated to quickly identify and alert users to any fluid leaks, ensuring prompt action can be taken. An emergency stop button is prominently positioned to allow immediate halting of all system operations in case of an emergency. Additionally, the system can be connected to an uninterruptible power supply (UPS), safeguarding against data loss or potential system damage caused by power fluctuations.

This novel drug absorption and dissolution test apparatus marks a significant advancement in pharmaceutical testing technology. By integrating multiple physiologically relevant features and enabling real-time monitoring, it provides a flexible and user-friendly platform that empowers researchers to predict in vivo drug behaviour with greater accuracy. The apparatus's capabilities to reduce the reliance on animal testing and expedite the development of more effective pharmaceutical formulations enhance its value as a vital asset in drug development and formulation optimization. Its innovative design not only supports more efficient research but also contributes to more ethical practices within the pharmaceutical industry.
, Claims:1. An apparatus for drug absorption and dissolution test, the apparatus (101) comprising:
a) a multi-chamber system (102) simulating different segments of the gastrointestinal tract;
b) a temperature and pH control system (103) for each chamber;
c) a peristaltic pumping mechanism (104) for controlling media flow between chambers;
d) an integrated sensor system (105) for real-time monitoring of test parameters;
e) a microprocessor control system (106) for managing apparatus operations and data processing;
f) a biomimetic membrane system (107) simulating the intestinal wall;
g) a flow-through cell design (108) for continuous sampling and analysis;
h) multiple test stations (109) for simultaneous testing of various formulations;
i) advanced materials (110) for apparatus construction; and
j) a user-friendly interface (111) for apparatus control and data analysis.

2. The apparatus for drug absorption and dissolution test as claimed in claim 1, wherein the multi-chamber system (102) comprises:
a) a gastric chamber (201);
b) a duodenal chamber (202); and
c) an intestinal chamber (203).

3. The apparatus for drug absorption and dissolution test as claimed in claim 1, wherein the temperature and pH control system comprises:
a) water jackets surrounding each chamber connected to a circulating water bath; and
b) pH probes and automatic pH adjustment mechanisms in each chamber.

4. The apparatus for drug absorption and dissolution test as claimed in claim 1, wherein the peristaltic pumping mechanism comprises:
a) inter-chamber flow pumps;
b) circulation pumps for each chamber; and
c) sampling pumps.

5. The apparatus for drug absorption and dissolution test as claimed in claim 1, wherein the integrated sensor system comprises:
a) pH sensors;
b) temperature sensors;
c) UV-Vis spectrophotometers;
d) conductivity sensors; and
e) pressure sensors.

6. The apparatus for drug absorption and dissolution test as claimed in claim 1, wherein the microprocessor control system is configured to perform:
a) data acquisition;
b) process control;
c) user interface control;
d) data processing and storage;
e) system diagnostics; and
f) networking capabilities.

7. The apparatus for drug absorption and dissolution test as claimed in claim 1, wherein the biomimetic membrane system comprises:
a) a lipid bilayer supported on a porous polymer substrate;
b) a membrane holder separating the intestinal chamber into lumen and receiver sides;
c) customizable membrane compositions for simulating various intestinal permeabilities; and
d) integrated electrodes for measuring transepithelial electrical resistance.

8. The apparatus for drug absorption and dissolution test as claimed in claim 1, wherein the flow-through cell design (108) comprises:
a) cells constructed of inert materials;
b) semi-permeable membranes for selective sampling;
c) direct connection to UV-Vis spectrophotometers for online analysis; and
d) an automated sampling system.

9. The apparatus for drug absorption and dissolution test as claimed in claim 1, wherein the multiple test stations (109) comprise:
a) four independent test stations;
b) central control via a single microprocessor;
c) independent parameter control for each station; and
d) comparative analysis capabilities.

10. The apparatus for drug absorption and dissolution test as claimed in claim 1, further comprising:
a) biorelevant media simulation capabilities;
b) enzyme integration for simulating digestive processes;
c) hydrodynamic control for simulating different GI tract conditions;
d) formulation behavior imaging systems;
e) absorption modeling software;
f) simulated food effect capabilities;
g) variable volume simulation; and
h) microbiome simulation capabilities.

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