DISSOLUTION TEST APPARATUS FOR EVALUATING SUSTAINED AND CONTROLLED DRUG DELIVERY

Abstract

The dissolution test apparatus (100) is designed to evaluate sustained and controlled drug delivery systems by simulating various gastrointestinal conditions. It features a multi-compartment design (101) with chambers representing the stomach, duodenum, jejunum, ileum, and colon. An advanced pH control system (102) dynamically adjusts pH, while the enzymatic delivery system (103) introduces enzymes. Mechanical stress simulation (104) mimics physiological forces, and the continuous flow system (105) maintains sink conditions with absorption simulation. Integrated sensors and real-time monitoring (106) ensure precise measurements, managed by a computer-controlled automation system (107). The modular design (108) allows for flexibility across different tests, and a simulated meal delivery system (109) evaluates food effects on drug release. This apparatus provides comprehensive, physiologically relevant conditions for testing drug dissolution and absorption.

Specification

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

The novel dissolution test apparatus for sustained and controlled drug delivery systems comprises several interconnected modules, each designed to simulate specific aspects of the gastrointestinal environment. The following detailed description outlines the structure and function of each component, as well as their integration into a comprehensive testing system.

The multi-compartment design (101) of the apparatus features a series of interconnected chambers, each specifically tailored to simulate different regions of the gastrointestinal (GI) tract for drug testing and dissolution studies. The Gastric Chamber, with a 250 mL capacity, mimics the stomach environment and can be adjusted to replicate both fasted and fed states. The Duodenal Chamber, representing the small intestine's first section, holds 50 mL, while the Jejunal Chamber and Ileal Chamber, which simulate the middle and terminal parts of the small intestine, hold 200 mL each. The Colonic Chamber, designed to replicate the large intestine, has a capacity of 300 mL. All chambers are constructed from inert, transparent materials like borosilicate glass, allowing for clear visual observation during testing. The chambers are also jacketed for precise temperature control, ensuring conditions are consistent with physiological body temperatures. Additionally, they are equipped with stirring mechanisms to simulate intestinal motility, sampling ports for easy access to test samples, and media inlet/outlet ports to facilitate fluid exchange, simulating the passage of substances through the GI tract. This design enables comprehensive and accurate analysis of drug dissolution and absorption across different regions of the GI system.

The Advanced pH Control System (102) is designed to dynamically manage and adjust pH levels across the different chambers of the multi-compartment apparatus, mimicking the changing pH conditions along the gastrointestinal (GI) tract. The system features high-precision pH sensors in each chamber, which continuously monitor the pH levels in real-time. These sensors are connected to an Automated Titration System that uses peristaltic pumps to deliver precise amounts of acid (0.1 N HCl) or base (0.1 N NaOH) solutions from connected reservoirs. To enable rapid pH adjustments, the system also includes Buffer Reservoirs with pre-calibrated solutions. A Microprocessor Control Unit manages the entire process, automatically adjusting pH levels based on real-time sensor data or pre-programmed pH profiles. This setup allows the apparatus to replicate the dynamic pH transitions seen in the GI tract, such as the acidic environment of the stomach (pH 1-3) transitioning to the neutral to slightly alkaline conditions of the intestines (pH 6-7.4). This precise control is crucial for accurate drug dissolution and absorption studies that require pH-sensitive conditions.

The Enzymatic Delivery System (103) is designed to replicate the enzymatic environment of the gastrointestinal (GI) tract, ensuring accurate simulation of digestion and drug breakdown processes during testing. The system features Enzyme Reservoirs, which are temperature-controlled to store solutions of key digestive enzymes such as pepsin, pancreatin, and lipase. These enzymes are delivered with precision using Precision Pumps, which accurately dispense the enzyme solutions into specific chambers of the apparatus. Enzyme Activity Sensors continuously monitor the enzymatic activity in real-time, ensuring that the desired enzymatic environment is maintained. The process is controlled by a Microprocessor Control Unit, which coordinates the timing of enzyme delivery with pH changes and GI transit times. This allows the system to adjust enzyme addition based on pre-programmed schedules or in response to dynamic changes in the test environment, ensuring that physiologically relevant enzymatic conditions are maintained throughout the test.

The Mechanical Stress Simulation Module (104) is designed to replicate the physical forces exerted on substances as they move through the gastrointestinal (GI) tract, enhancing the accuracy of drug dissolution and absorption studies. This module includes Peristaltic Simulation Units, which are flexible, inflatable membranes that rhythmically contract around each chamber, mimicking the peristaltic movements that propel food and drugs through the GI system. The Pressure Control System regulates the intensity and frequency of these contractions, ensuring they align with the natural motility patterns of specific GI regions. Additionally, Agitation Mechanisms provide programmable stirring rates and patterns within each chamber, simulating the mixing and churning of contents. All these mechanical processes are coordinated by a Microprocessor Control Unit, which adjusts the timing and strength of the mechanical stresses based on programmed profiles, simulating the unique motility characteristics of different GI regions like the stomach, small intestine, and colon. This allows for a more realistic simulation of drug release and transit through the GI tract.

The Continuous Flow System (105) is designed to simulate the dynamic flow of fluids and drug absorption in the gastrointestinal (GI) tract during drug testing. It utilizes Peristaltic Pumps to control the flow of dissolution media between interconnected chambers, replicating the natural movement of fluids between different GI regions. The Absorption Simulation Chamber, a dialysis-based system, actively removes dissolved drugs to simulate drug absorption and maintain sink conditions, preventing saturation of the dissolution media. Fresh Media Reservoirs continuously replenish the media, ensuring that the chemical environment remains consistent throughout the testing process. Finally, the Waste Collection System gathers the removed media and absorbed drug, mimicking the elimination processes of the body. The flow rates are precisely controlled to replicate physiological transit times and maintain realistic volumes within each chamber, enhancing the simulation's accuracy.

The Integrated Sensors and Real-time Monitoring (106) system provides continuous and precise measurements during drug testing, enhancing the accuracy of results. It features a UV-Vis Spectrophotometer, which continuously monitors drug concentration by measuring light absorbance. Fiber Optic Probes are strategically placed in each chamber to allow real-time, in-situ measurements of drug concentrations without disturbing the test environment. Temperature Sensors in each chamber ensure that the dissolution media remains at the precise temperature required for accurate simulation. All data from these sensors is collected and processed by a Data Acquisition System, enabling comprehensive real-time monitoring and control of the experimental conditions. This system ensures precise, dynamic feedback on drug release, dissolution, and environmental conditions throughout the testing process.

he Computer-controlled Automation System (107) is a comprehensive, fully integrated system that oversees every aspect of the dissolution test process. At its core is a Central Processing Unit that manages and coordinates the entire system, ensuring precision and consistency throughout the test. A User Interface, typically a touchscreen display, allows users to easily configure and monitor the test parameters. The Data Storage and Analysis Module handles the management of all collected data, offering in-depth analysis and generating detailed reports. Furthermore, Network Connectivity enables remote monitoring and control, providing flexibility and ensuring real-time supervision, even from off-site locations. This automation minimizes human intervention, reducing errors and enhancing the reliability of the results.

The Modular Design (108) of the apparatus enhances its versatility and adaptability for various testing needs. It incorporates Interchangeable Chamber Modules, which facilitate quick reconfiguration to accommodate different test protocols, allowing researchers to customize their experimental setup easily. The use of Universal Connectors ensures seamless compatibility between different modules, promoting flexibility in the assembly and integration of components. Additionally, Calibration Ports are included for straightforward maintenance and calibration of sensors, enabling precise measurements and reliable data collection over time. This modular approach not only streamlines the testing process but also enhances the overall efficiency and functionality of the apparatus.

The Simulated Meal Delivery System (109) is designed to accurately replicate the physiological effects of food on drug release and absorption during testing. It comprises Meal Simulant Reservoirs that store standardized food components, ensuring consistency in experimental conditions. Precision Pumps are employed for the accurate delivery of these meal simulants into the system, allowing researchers to mimic realistic dietary scenarios. The Mixing Chambers facilitate the thorough combination of meal components with the dissolution media, ensuring uniform distribution throughout the test environment. Additionally, a Microprocessor Control Unit governs the timing and composition of the meal delivery, allowing for precise control over the experimental variables. This comprehensive system enables the evaluation of how food intake influences drug behaviour, providing valuable insights for optimizing therapeutic strategies.

Method of Performing the Invention:

The optimal method for utilizing this novel dissolution test apparatus involves a carefully planned workflow that maximizes the apparatus's capabilities while ensuring reproducibility and reliability of results. The following steps outline the best practice for performing dissolution tests on sustained and controlled drug delivery systems:

1. Apparatus Preparation:
a) Verify that all modules are properly connected and functioning.

b) Calibrate all sensors (pH, temperature, UV-Vis spectrophotometer) according to standard protocols.
c) Prepare and load all required media, buffer solutions, and enzyme solutions into their respective reservoirs.

2. Test Protocol Setup:
a) Input the specific test parameters into the user interface, including:
- pH profile for each chamber
- Enzyme addition schedule
- Mechanical stress patterns
- Flow rates and transit times between chambers
- Sampling times and frequencies
b) If simulating fed conditions, program the meal delivery schedule and composition.

3. Sample Preparation:
a) Prepare the dosage form according to the product specifications.
b) If required, attach any necessary sinkers or holders to the dosage form.

4. Test Initiation:
a) Verify that all chambers are at the correct starting conditions (temperature, pH, media composition).
b) Introduce the prepared dosage form into the gastric chamber.
c) Initiate the test sequence through the user interface.

5. Test Monitoring:
a) Monitor the real-time data display for any anomalies or deviations from the expected profile.
b) If necessary, collect manual samples at predetermined time points for offline analysis.

6. Data Analysis:
a) Upon test completion, review the collected data using the data analysis module.
b) Generate dissolution profiles and calculate relevant parameters (e.g., f2 similarity factor, dissolution efficiency)
c) Compare results with predetermined acceptance criteria.

7. Apparatus Cleaning and Maintenance:
a) Run the automated cleaning cycle to flush all chambers and tubing.
b) Inspect all components for any signs of wear or damage.
c) Replace any disposable components (e.g., filters, tubing) as necessary.

8. Documentation:
a) Compile a comprehensive test report including all relevant data, observations, and calculated parameters.
b) Archive raw data and processed results according to established data management protocols.

Operation and Workflow:

1. Test Setup:
- The operator inputs the test parameters via the user interface.
- The automation system prepares the chambers with appropriate media and conditions.

2. Dosage Form Introduction:
- The test sample is introduced into the gastric chamber.

3. Test Execution:
- The system automatically adjusts pH, enzyme levels, mechanical stresses, and flow rates according to the programmed physiological profile.
- Real-time monitoring provides continuous data on drug release and test conditions.

4. Data Collection and Analysis:
- The data acquisition system collects all sensor data.
- The data storage and analysis module processes the data and generates reports.

5. Test Completion:
- Upon completion, the system automatically cleans and prepares for the next test.

This novel dissolution test apparatus provides a comprehensive simulation of the gastrointestinal environment, enabling more accurate and predictive testing of sustained and controlled drug delivery systems. Its modular design and advanced automation features make it a versatile and efficient tool for pharmaceutical research, development, and quality control.
, Claims:1. A dissolution test apparatus (100) for evaluating sustained and controlled drug delivery systems, comprising:
a) a multi-compartment design (101) with interconnected chambers simulating different regions of the gastrointestinal tract;
b) an advanced pH control system (102) capable of dynamically adjusting pH in each chamber;
c) an enzymatic delivery system (103) for introducing gastrointestinal enzymes;
d) a mechanical stress simulation module (104) for applying controlled forces to the dosage form;
e) a continuous flow system (105) with an absorption simulation chamber;
f) integrated sensors and real-time monitoring capabilities (106);
g) a computer-controlled automation system (107) for managing all aspects of the dissolution test;
h) a modular design (108) allowing adaptation to different dosage forms; and
i) a simulated meal delivery system (109) for evaluating food effects on drug release.

2. The dissolution test apparatus as claimed in claim 1, wherein the multi-compartment design (101) comprises:
a) a gastric chamber simulating the stomach environment (110);
b) a duodenal chamber representing the duodenum (111);
c) a jejunal chamber simulating the jejunum (113);
d) an ileal chamber representing the ileum (114); and
e) a colonic chamber simulating the colon (115).

3. The dissolution test apparatus as claimed in claim 1, wherein the advanced pH control system (102) comprises:
a) pH sensors in each chamber;
b) an automated titration system;
c) buffer reservoirs; and
d) a microprocessor control unit for managing pH adjustments.

4. The dissolution test apparatus as claimed in claim 1, wherein the enzymatic delivery system (103) comprises:
a) enzyme reservoirs;
b) precision pumps for enzyme delivery;
c) enzyme activity sensors; and
d) a microprocessor control unit for managing enzyme delivery.

5. The dissolution test apparatus as claimed in claim 1, wherein the mechanical stress simulation module (104) comprises:
a) peristaltic simulation units;
b) a pressure control system;
c) agitation mechanisms;
d) a microprocessor control unit for coordinating mechanical stress simulations; and

6. The dissolution test apparatus as claimed in claim 1, wherein continuous flow system (105) comprises:
a) peristaltic pumps for controlled media flow;
b) an absorption simulation chamber;
c) fresh media reservoirs; and
d) a waste collection system.

7. The dissolution test apparatus as claimed in claim 1, wherein the integrated sensors and real-time monitoring (106) capabilities comprise:
a) a UV-Vis spectrophotometer;
b) fiber optic probes for in-situ drug concentration measurements;
c) temperature sensors in each chamber; and
d) a data acquisition system.

8. The dissolution test apparatus as claimed in claim 1, wherein the computer-controlled automation system (107) comprises:
a) a central processing unit;
b) a user interface;
c) a data storage and analysis module; and
d) network connectivity for remote monitoring and control.

9. The dissolution test apparatus as claimed in claim 1, wherein the modular design (108) comprises:
a) interchangeable chamber modules;
b) universal connectors; and
c) calibration ports.

10. The dissolution test apparatus as claimed in claim 1, wherein the simulated meal delivery system (109) comprises:
a) meal simulant reservoirs;
b) precision pumps for meal simulant delivery;
c) mixing chambers; and
d) a microprocessor control unit for managing meal delivery.

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