DISINTEGRATION APPARATUS FOR RAPID DISSOLUTION

Abstract

A modular hydrodynamic disintegration apparatus for rapid tablet dissolution is disclosed. The apparatus features a temperature-controlled chamber housing multiple dissolution vessels, each equipped with hydrodynamic agitation systems using interchangeable paddle assemblies and programmable rotation patterns. Real-time monitoring sensors, including turbidity and pH probes, track disintegration within the vessels. A microprocessor control system manages operational parameters and adapts conditions based on real-time data. The modular design allows customization, and an automated sampling system facilitates aliquot extraction triggered by sensor inputs. An integrated analysis module provides real-time quantification of drug release. The system supports adaptive testing protocols, optimizing hydrodynamic conditions for fast-release formulations. Additionally, it enables simultaneous comparative testing of multiple oral dosage forms under identical or varying conditions, offering insights into disintegration profiles and drug release kinetics.

Specification

Description:The hydrodynamic disintegration apparatus 100 is designed for accelerating and optimizing fast-release tablet dissolution in a monitored and analysable process. Vessel (each one managed by the hydrodynamic agitation system 103, which includes interchangeable paddle assemblies 105 to allow for versatility and easily different testing protocols) within a temperature-controlled chamber 101. The system provides programmable rotation patterns (106) to simulate multiple hydrodynamic conditions, such as constant speed, stepwise changes, sinusoidal variation, and reverse rotation.

The monitoring sensors (107) in each dissolution vessel perform in situ monitoring of disintegration, such as turbidity sensors, conductivity probes, dynamic light scattering sensors, and pH probes. The-clock feedback is during the dissolution process. A microprocessor control system (108) controls its operation, thus allowing for accurate control over parameters and adaptive mechanisms automatically altering hydrodynamic conditions based on sensor measurements in real-time.

The equipment is designed with modular design (109) so as to adapt changes with selected parts, according to the applied requirements of research or the industries. To enhance sampling efficiency, there is an automated sampling system (110) provided extract aliquots from the vessels according to some of the appropriate triggers detected by the sensors; it processes the extracted data and feeds it into an integrated analysis module (111), which offers real-time quantification of drug release and detailed reports.

Interchangeable paddle assemblies (105) are supporting USP Type 2 paddles, crescent shaped paddles, mesh paddles, and multi-blade paddles. This allows the user to use the apparatus to most any drug formulation. Programmable rotation patterns (106) ensure that the hydrodynamic conditions are close approximations of physiological and experimental needs.

The system is sample and test adaptively-it is able to modify the speed of rotation and the flow of the media based upon sensor feedback. Thus, key phases, including the initial first burst release, is viewed at a more advanced sampling rate to capture rapid changes that otherwise be missed. There is a module for comparative analysis, meaning that several formulations are tested simultaneously and the profiles of disintegration of various tablets are compared.

In operation, it initiates by conditioning the apparatus according to a predefined protocol and adding tablets into the dissolution vessels containing appropriate media. The data monitored in real-time monitoring and adaptive control. The aliquots thus extracted by the automated sampling and analysis, and detailed data and generating comprehensive reports.

Temperature-Controlled Chamber (101)
The Temperature-Controlled Chamber (101) is composed of a main outer housing and is constructed from high-grade stainless steel, with provisions for double-walled construction together with a circulating water jacket to create a uniform temperature. The testing environment is stabilized, and the temperature range is easily controlled within an operating range of 25°C to 40°C (+/-0.1°C) to simulate various physiological conditions.
A transparent observation window is installed in the door of the chamber, allowing viewing of the test process without disturbing the controlled environment. Internal LED lighting of the chamber provides further clarity for visualization.

Dissolution Vessels (102)
The dissolution apparatus are accommodating hundreds of dissolution vessels (102) that are running from 6 to 12 apparatus. This accommodates running several formulations and replicates simultaneously. Each vessel is made of borosilicate glass and has a capacity of 1000 mL with clear graduations for measuring the volume exactly. The vessels have a hemispherical bottom to minimize dead zones and ensure that the hydrodynamics are uniform. Removal for cleaning is very easy, and interchangeable versions are produced to accommodate different testing protocols and vessel geometries (such as a "peak" vessel for small volume disintegration testing).

Hydrodynamic Agitation System (103)
The hydrodynamic agitation system 103 provides an accurately controlled fluid dynamics to each dissolution vessel. The system includes:
a) A high-precision stepper motor that operates at speeds between 25 and 250 rpm ±1 rpm.
b) An inert materials drive shaft, such as PTFE-coated stainless steel, to prevent chemical reactions.
c) A designed coupling mechanism that facilitates paddle assemblies easy mounting and de-mounting.
The microprocessor control system (108) drives the motor to achieve rotation patterns and instantaneous control of speed. Such control allows simulation of various gastrointestinal motility states that range from minimal stomach mixing to more vigorous agitation of types encountered in the small intestine.
Interchangeable Paddle Assemblies (105)
The equipment includes a interchangeable paddle assemblies (105) that are changed for offering diverse hydrodynamics conditions. The interchangeable paddle assemblies (105) include the following:
a) USP Type 2 paddle is used for standard testing protocols.
b) Crescent-shaped paddle is utilized to have increased mixing in the lower part of the vessel.
c) Mesh paddle assembly with softer agitation of friable tablets.
d) Multi-blade paddle with created complex fluid dynamics.
For each paddle assembly is developed from inert materials, and tool-free locking allows for rapid exchange. The modular approach permits the researcher to hydrodynamic conditions to specific formulations and study influence of different fluid dynamics on disintegration behaviour.

Programmable Rotation Patterns (106)
The microprocessor control system (108) enables implementing programmable rotation patterns (106) for each dissolution vessel. Such patterns include:
a) Continuous rotation at a constant speed.
b) Step-like variation in speed to mimic the different phases of gastrointestinal transit.
c) Sinusoidal variations in speed to mimic peristaltic contractions.
d) Brief cycles of retroperistalsis to facilitate mixing and avoid coning.
users design, store, and recall their own rotation profiles from the user interface, so testing with standardized protocols or novel hydrodynamic conditions can be carried out.

Real-Time Disintegration Monitoring Sensors (107)
An array of real-time Disintegration Monitoring Sensors (107) is mounted on each dissolution vessel to monitor the break-up process on-line. These are:
a) Fiber-optic turbidity sensors measuring scattered light to track break-up of tablet particles.
b) Conductivity probes which can detect changes in ionic concentration as the tablet breaks up.
c) Dynamic light scattering sensors for real-time measurement of particle size.
d) pH probes monitoring any local pH changes during the break-up process.
Spatial measurements of the break-up process are taken by placing sensors at several locations in the vessel. Sensor data is constantly transmitted back to the microprocessor control system (108) for immediate processing and presentation.

Microprocessor Control System (108)
The whole equipment is controlled by a highly advanced microprocessor control system (108). This includes:
a) Controlling and coordinating all operational parameters such as temperature, agitation speed, sampling times.
b) Data extracted and processed from various sensors
c) Insertion of the user-testing protocols
d) Friendly interface in running and displaying results
e) Storage and retrieval of test data and test protocols
f) Separation of device external to the laboratory and Laboratory Information Management Systems.
The microprocessor employs a specially developed algorithm that incorporates adaptive control mechanisms. For example, the agitation speed is controlled in real-time against disintegration data to provide hydrodynamic conditions constantly consistent within the test.

Modular Design (109)
The modular design allows easy modifications, servicing and upgrading of the apparatus, in the long run. Some of the main modular components include:
a) Exchangeable dissolution vessels of different sizes and designs
b) Exchangeable paddle assemblies and sensor modules.
c) Removable temperature control units for easy servicing.
d) Plug-and-play modules of sampling and analysis.
This modular design is not only beneficial in making the equipment more versatile but also less tedious to maintain with minimal time lost. It immediately absorbs new technologies and test methods when it is available.

Automated Sampling System (110)
The automated sampling system (110) comprises
a) A multi-channel peristaltic pump that supports precision sampling over low volume.
b) Sample transfer through PTFE tubing resists a broad range of solvents. Therefore, this tubing resists a broad range of solvents and allows safe transfer of samples.
c) Rotating carousel for holding vials containing the samples in them and connects directly to the analysis module
d) Automated cleaning and purging system prevents cross-contamination among samples.
The automated sampling system (110) is programmed to collect samples at predetermined time points and as a consequence of an event sensed by the real-time disintegration monitoring sensors (107). This capability is particularly helpful in capturing fast disintegration profiles of the fast-release formulations.

Integrated Analysis Module (111)
This integrated analysis module 111 enables in situ, real-time quantification of drug release along with the disintegration metrics. It comprises:
a) a dual-beam UV-Vis spectrophotometer for relatively rapid, non-destructive analysis of the most commonly encountered drug compounds.
b) An optional HPLC module for more complex formulations and multi-component analysis.
c) A flow-through cuvette system providing continuous monitoring without sample waste.
d) Automated data processing algorithms for real-time calculation of dissolution profiles.
The analysis module is directly interfaced to the microprocessor control system (108), which provides smooth data integration and real-time changes in the testing protocol according to the analytical results.

User Interface and Data Management
The user interface is a large, high-resolution touchscreen display. Supported by the interface are:
a) Real-time visualization of disintegration profiles and sensor data.
b) Intuitive controls for setting up and modification of test protocols.
c) Visible alerts in case of any deviation and anomalies during testing
d) Extensive tools for data analysis like statistical functions and graphing capabilities.
The system also includes safe data storage and transfer-out and hence ensures data integrity standards. It produces rich reports in any format and easily connects to LIMS for effortless transfer of data.

Safety Features
The equipment has several safety features that guarantee safety to the operator as well as the integrity of tests:
a) Automatic shut-off in case of temperature or motor failure.
b) Vessel misalignment and improper paddle attachment-detecting sensors
c) Splash guards and containment systems for spill prevention
d) User authentication and access control to guard against unauthorized use, modification of protocol
These safety features ensure reliable operation and maintain validity of test results.

Method of Performing the Invention
The method of performing the hydrodynamic disintegration apparatus is by adopting a step-wise method that makes full use of each component.

1. System Preparation
a) Turn on the equipment and equilibrate the temperature-controlled chamber (101) to a testing temperature set between 37 °C ± 0.5°C simulating body conditions.
b) Install the correct interchangeable paddle assemblies (105) depending on the type of tablet formulation to be evaluated.
c) Condition the real-time disintegration monitoring sensors (107) with standard solutions provided with the equipment.

2. Test Protocol Setup
a) Touchscreen input and uploading a preformatted test protocol, at least containing the following:
- Test duration
- Rotation speed and pattern of paddle
- Sampling
- Frequency of sensor data acquisition
- Analysis parameters
b) For fast-release tablets, the normal testing protocol may be
- Test duration, 30 min.
- Initial paddle speed of 50 rpm, increasing to 100 rpm after 5 minutes
- Sample every 30 seconds for the first 5 minutes and then every minute after this
- Sensor data are collected continuously at 1 Hz rate

3. Preparation of the Culture Broth and Charging of Vessels:
a) Prepare the dissolution media according to pharmacopeial standards and bio relevant formulations.
b) Accurately measure and transfer 900 mL of the prepared media into each of multiple dissolution vessels.
c) Equilibrate the media to the test temperature.

4. Tablet Introduction and Test Initiation:
a) Insert the tablets into the tablet holders positioned specifically to hold them in a rigid position within the hydrodynamic flow.
b) Simultaneously lower all tablet holders into their respective vessels with automation.
c) The test protocol initiates immediately from the user interface which activates the hydrodynamic agitation system (103) and sets data logging into motion.

5. Real-Time Monitoring and Adaptive Control:
a) On the screen, monitor real-time disintegration profiles composed of data from turbidity, conductivity, and particle size probes and sensors.
b) During the disintegration phase a microprocessor control system 108 receives pre-programmed points, and adjustment of paddle rotation speed automatically takes place if points occur sooner and later than forecast; this provides similar hydrodynamic conditions among formulations.
6. Automated sampling and analysis:
a) The automated sampling system (110) collects samples at preset time intervals and according to disintegration time real-time data.
b) Samples are transferred immediately to the integrated analysis module (111) for spectrophotometric and chromatographic analysis.
c) The drug release profiles are computed in real-time and correlated with disintegration data.

7. Data Processing and Reporting:
a) At the end of the test, the automated sampling system 110 compile with all the sensor data, analytical results, and also the test parameters.
b) The system provides a general report of:
- Disintegration profiles time vs. particle size distribution.
- Drug release kinetics.
- Statistical analysis of replicates.
- Any deviation from the protocol that has been programmed.
c) Automated backup and the data can be exported in format(s) of choice for example CSV, PDF, and transferred directly to a LIMS.

8. System Cleaning and Preparation for Next Test:
a) The automatic cleaning system cleans the sampling lines and flow cells of the analytical wetted components with suitable solvents.
b) Vessels and paddle assemblies are removed and cleaned, and all work carried out according to standard procedures.
c) The system performs a self-diagnostic check to ensure that all units are functioning correctly for the next test.
, Claims:1. A modular hydrodynamic disintegration apparatus 100 for rapid tablet dissolution, comprising:
a) a temperature-controlled chamber (101);
b) multiple dissolution vessels (102) housed within said temperature-controlled chamber (101);
c) a hydrodynamic agitation system (103) for each dissolution vessel (104), comprising interchangeable paddle assemblies (105) and means for implementing programmable rotation patterns (106);
d) real-time disintegration monitoring sensors (107) positioned within each dissolution vessel (104);
e) a microprocessor control system (108) for managing operational parameters and data acquisition;
f) a modular design (109) allowing for customization of components;
g) an automated sampling system (110) for extracting aliquots from the dissolution vessels; and
h) an integrated analysis module 111 for real-time quantification of drug release.

2. The apparatus as claimed in claim 1, wherein the real-time disintegration monitoring sensors (107) comprise at least one of: turbidity sensors, conductivity probes, dynamic light scattering sensors, and pH probes.

3. The apparatus as claimed in claim 1, wherein the interchangeable paddle assemblies (105) include one of: a standard USP Type 2 paddle, a crescent-shaped paddle, a mesh paddle, and a multi-blade paddle.

4. The apparatus as claimed in claim 1, wherein the programmable rotation patterns (106) include at one of: constant rotation at a fixed speed, stepwise changes in rotation speed, sinusoidal variations in speed, and brief periods of reverse rotation.

5. The apparatus as claimed in claim 1, wherein the microprocessor control system (108) is used to implement adaptive control mechanisms that adjust operational parameters based on real-time disintegration data.

6. The apparatus as claimed in claim 1, wherein the automated sampling system (110) is capable of being triggered by specific events detected by the real-time monitoring sensors (107).

7. A method for evaluating the disintegration of fast-release tablet formulations using the apparatus as claimed in claim 1, comprising the steps of:
a) preparing the apparatus according to a predefined protocol;
b) introducing tablets into the dissolution vessels containing appropriate media;
c) initiating the disintegration test with real-time monitoring and adaptive control;
d) performing automated sampling and analysis; and
e) processing data and generating comprehensive reports.

8. The method as claimed in claim 8, further comprising the step of automatically adjusting hydrodynamic conditions based on real-time disintegration data.

9. The method as claimed in claim 8, wherein the predefined protocol includes specific parameters for fast-release formulations, including increased sampling frequency during the initial disintegration phase.

10. A system for comparative analysis of multiple fast-release oral dosage forms, comprising the apparatus as claimed in claim 1 used to simultaneously test different formulations under identical and varying hydrodynamic conditions, enabling direct comparison of disintegration profiles and drug release kinetics.

Documents