SYSTEM FOR DRUG RELEASE AND MONITORING

Abstract

A transdermal patch system (100) enables real-time drug release monitoring through integrated microfluidics, sensors, and wireless communication. The system comprises a drug reservoir (101) with an active pharmaceutical ingredient, a rate-controlling membrane (102), and a collection chamber (103) with micro-channels (104) for fluid transport. Miniaturized sensors (105) detect drug concentrations, while a microprocessor (106) controls sampling, data analysis, and pharmacokinetic calculations. The patch features an auto-sampler mechanism (107) with a micro-needle array (108) for minimally invasive sampling and a microfluidic system (109) for precise fluid management. Wireless communication modules (110) transmit data to external devices using Bluetooth Low Energy (BLE) or LPWAN protocols. The system includes energy harvesting for power efficiency and interfaces with a smartphone application for real-time monitoring, parameter adjustments, alerts, and data export. This system supports personalized medicine, ensuring accurate drug delivery and advanced pharmacokinetic studies.

Specification

Description:The transdermal patch system 100 for real-time drug release studies based has advanced, on-line monitoring of drug release by combining microfluidics and sensors with wireless communication module 110. This is achieved through a drug reservoir 101 containing the active pharmaceutical ingredient, which goes through a rate-controlling membrane (102) to provide a steady release of the drug. The collected drug is then received in a collection chamber (103) with an array of micro-channels (104) for easy fluid flow.

The system includes miniaturized sensors (105) that detect the concentration of drugs in the extracted fluid. Such sensors are electrochemical, optical, and impedance-based so as to guarantee accurate results on drug level determination. A microprocessor (106) regulates the time for sampling, calculates data by the sensors, and computes pharmacokinetic parameters. The system contains an internal calibration unit along with a known concentration of a drug, which is periodically checked to provide a guarantee of the accuracy of the sensor.

The patch contains an auto-sampler mechanism (107) in the form of a micro-needles array (108) to sample the interstitial fluid almost painlessly. Each hollow micro-needle is 150-500 micrometers long and the inner diameter is 25-50 micrometers. Based on the control exerted by the microprocessor 106, the microfluidic system (109), including micro-channels and micropump, ensures the management of collected fluid with precision and transports it towards the sensor.

The wireless communication module (110) transmits processed data in real-time for use by other devices. The module employs Bluetooth Low Energy or LPWAN protocols which utilize an efficient, low power approach to communication. It includes as a power supply 111 to energize the electronic components; Furthermore, the system provides an energy harvesting mechanism that harnesses ambient energy to extend the lifetime of a battery.

Transdermal patch system 100 designed for real-time drug release wherein each part has a following function: -

Transdermal patch System (100) The whole device is considered as a wearable patch. Various layers have been constructed, along with other internal components, to administer drugs through the skin.

Drug Reservoir (101): This drug reservoir 101 is for holding the pharmaceutical substance to be delivered over time through the skin. It is normally used to deliver the drug in a controlled release.

• Rate-Controlling Membrane (102): It is located below the drug reservoir 101 with this thin membrane acts to regulate the amount of drug being eluted from the reservoir into the collection chamber. Hence, it controls both dosage and the timing of delivery.

Collection Chamber (103): It is positioned at the adjacent bottom of the rate-limiting membrane, it is the chamber where the drug accumulates first before being released into the skin.

Micro-Channels (104): The small circles located on patch are referred to as micro-channels through which the drug flow uniformly to enable controlled delivery.

Miniaturized Sensors (105): These are implantable sensors with small circles, which measure the flow of the drug as well as concentration and other live parameters.

Microprocessor (106): That tiny box on the side is a microprocessor that manages the entire system. Here, it analyzes the data seen by sensors (105) and controls the scheduling, dose, etc.

Auto-Sampler Mechanism (107): Essentially, this is part of the patch itself. It is mainly composed of two parts:
Micro-Needle Array (108): As depicted by small pins below the patch, essentially for minimally invasive sampling. This offers a chance to take tiny samples of fluid in skin from the patch.

Microfluidic System (109): This system allows samples to flow through small channels toward sensors and storage spaces in the patch.

Wireless Communication Module (110): The module is depicted as a small circle with signal lines. This module allows data to be transmitted from the patch to a secondary device such as a smartphone or computer.

Power Supply (111): It is in the form of a rectangular shape near the microprocessor, providing power to the entire electronics that runs for the electronics within the patch, such as sensors, microprocessor, and wireless module.

The transdermal patch system 100 communicates to the smartphone application, which allows the users to access the important functionalities: any real-time drug release profiles, adjustable sampling intervals, and the possibility of setting alerts for specific thresholds of drug concentration. Data also exported for additional analysis, so this system is able to find more value in clinical studies and personalized medicine.

Transdermal Patch Integrated with the Auto-Sampler:
The new transdermal patch consists of several layers which serve a particular purpose in the drug delivery and sampling process.
-The outermost layer forms a protective backing layer, usually consisting of a flexible, water-resistant material such as polyethylene or polyester. This layer prevents drug loss and protects the patch from environmental factors.
-Below the support layer is the collection chamber (103) that contains the active pharmaceutical ingredient in a suitable vehicle. The reservoir is a matrix system or a membrane-controlled system according to the release kinetics desired.
-A rate-controlling membrane 102 is positioned below the drug reservoir 101. This usually uses copolymers of ethylene-vinyl acetate and silicone, and it determines the diffusion of drugs from the reservoir to the collection chamber.
-This design primarily features the collection chamber 103. It forms a thin planar compartment positioned between the rate-controlling membrane 102 and the skin-contacting adhesive layer, designed to collect samples of drug that diffuse through the rate-controlling membrane 102.

Miniaturized sensors (105) are provided inside the collection chamber. These electrochemical sensors, optical sensors, and any other type that is detect and measure the concentration of the drug in real-time.

A skin-adhering adhesive layer comprises the patch bottom, the skin to which the patch is applied adhering excellently and creating a sealed environment through which drug delivery and sampling are take place.

Auto-Sampler Mechanism
The auto-sampler mechanism 107 of the system contributes importantly for it allows minimal-invasive continuous drug sampling by way of diffusion through the patch.
-A micro-needle array (108) is embedded in the patch structure and arranged such that it penetrates the stratum corneum until reaching the upper layers of the epidermis. The micro-needles are usually 150-500 micrometers in length and made from biocompatible materials, such as silicon, metal, or biodegradable polymers.
All the micro-needles in the array are tubular, with an inner diameter of 25-50 micrometers and draw out small volumes of interstitial fluid.
The micro-needles are attached to a microfluidic system (109) consisting of micro-channels and micro-pumps. This system ensures the transport of the samples collected from the micro-needles into the collection chamber 103 for analysis.
A micro-pump is powered by the microprocessor 106, controls the rate and volume of the sampling. The latter is piezoelectrically, electroosmotically, or mechanically actuated pump.

Sensor Array and Data Acquisition
The sensor array is placed in the collection chamber 103 is required for the real-time determination of concentrations of drugs.
Based on the physico-chemical properties of the drug under study, various types of sensors are employed. It includes electrochemical sensors for those drugs, which are subject to redox reactions, or optical sensors utilizing principles of fluorescence or absorbance for suitable molecules of drugs.
Impedance sensors for monitoring changes in electrical properties related to drug concentration.
The sensors are fabricated by micro fabrication so that it is miniaturized and incorporated into the structure of the patch.
The sensor is connected to a circuit, signal conditioning circuit that amplifies as well as filters the signal from the sensor.
An analog-to-digital converter (ADC) converts the conditioned sensor signals to digital information for processing within the microprocessor 106.
A microprocessor (106) provides a brain of the system that controls functions and processes collected data.
The microprocessor 106, such as the low-power ARM Cortex-M series, is a form of programming that dictates sampling intervals, sensor measurement, and information processing.
It performs algorithms, with particular focus given to signal processing algorithms, which include noise reduction and calibration of sensor outputs.
The microprocessor 106 also controls the micropump in the auto-sampler, regulating the sampling process either according to some predefined protocols or according to measured drug concentrations.
Real-time data analysis is carried out: calculation of drug release rates, cumulative release, and so on.

Power Supply 111 and Energy Management
A thin, flexible battery is built into the patch structure to power electronic components.
Advanced power management circuits have to be used in order to minimize energy usage, enabling extended operation of the patch.
Energy harvesting technologies, including thermoelectric generators based on the temperature gradient between the skin and environment, complement the power received from the battery.

Wireless Communication Module 110
A wireless communication module (110) allows for data transmissibility and remote control of the patch.
A low-power Bluetooth or Bluetooth Low Energy module is available for near field communication with smartphones or dedicated receivers.
Alternatively, if the communication distance needs to be longer, a low-power wide-area network module, such as LoRa or NB-IoT, included.
The wireless communication module (110) allows for real-time data transfer, remote adjustment of sampling settings, and also possible telemedicine integration.

Software and User Interface
A dedicated smartphone application is developed to communicate with the patch, which is used by researchers or health care professionals to:
a. Display real-time drug release profiles.
b. Modify sampling parameters.
c. Generate alerts at predefined thresholds of drug concentrations.
d. Transfer the data for further analysis.
The data obtained is uploaded and stored in the cloud securely, hence facilitating remote pharmacokinetic modeling.

Wireless communication module (110)
Internal calibration system with a small reservoir of known drug concentration, periodically sampled to check for accuracy of sensor response.
Machine learning algorithms deployed within the microprocessor 106 to detect anomalous readings in sensor signals and detect counter drift over time.
Self-diagnostic system is to continuously check the functionality of all the components within. In case of malfunction or replacement needs, it senses and alerts the user.

Method for performing the invention
The method of the drug release using this system of transdermal patch with an integrated auto-sampler is in the following steps:
1. Patch Preparation and Application:
An appropriate formulation technique is utilized to load the drug of interest into the reservoir of the patch.
- The patch is placed directly onto a hygienic, dry skin surface, most often the upper arm or chest.
- The contact of the adhesive layer between the micro-needle array 108 and skin is ensured due to the adhesive.

2. Initialization and Calibration:
- When it is placed, the microprocessor 106 executes an initial self-diagnostic test to confirm proper functionality of all parts.
- It uses the internal calibration system to calibrate the sensor array
Determination of any baseline value to neutralize background signals

3. Sampling and Measurement Protocol
The microprocessor 106 activates the auto-sampler mechanism that pokes the microneedles on to stratum corneum.
Initial sampling was performed at regular short intervals (e.g., every 5 min) to actually capture the early phase of drug delivery.
Sampling interval had to be increased as soon as the release profile is stabilized; for example, to a period of every 15-30 min in order to preserve power and minimize irritation of the skin. - The volume of interstitial fluid is transferred by a micropump from each sampling location; typically 1-5 µL.

4. Real-time Data Analysis:
- The microprocessor 106 continually analyzes the data from the sensors and computes release rates and drug concentrations.
- It makes real-time computations on the pharmacokinetic parameters that involve lag time, steady-state flux, and cumulative release.
- The data are wirelessly transmitted to a paired smartphone or dedicated receiver

5. Adaptive Sampling:
- The microprocessor 106 actually controls the sampling protocol depending on the monitored release profile.
- For instance, if a burst release is monitored, the sampling rate is stepped up in order to capture this phase.

6. Data Visualization and Interpretation:
- Real time drug release profile is captured by the researchers through making use of the smartphone application.
- It provides a warning about any notable deviation in the release pattern.
- Data is exported for further analysis using dedicated pharmacokinetic modeling software.

7. Long-term Follow-up:
- The patch continues monitoring the drug release for the time intended during the study; this takes up to 24 hours or even several days according to the drug, and the design of the patch.
- The power management system minimizes energy usage on the battery, which is supplemented by energy harvesting.

8. Patch Removal and Recovery of Data:
At the end of the study period, the patch is carefully removed from the skin surface.
The remaining data are recovered from the patch's memory.
-The patch is disposed of appropriately according to the local medical waste management procedure specified in regulations.

9. Post-Study Analysis:
- The data that has been collected is analyzed in thorough detail for comparisons with the profiles of drugs released in vivo with the predictions from in vitro.
- It is possible to model drug absorption and distribution kinetics in detail using time course data at high resolution.
, Claims:1. A patch system 100 for real-time drug release, comprising:
a drug reservoir (101) containing an active pharmaceutical ingredient;
a rate-controlling membrane (102) adjacent to said drug reservoir 101;
a collection chamber (103) situated between said rate-controlling membrane and a skin-contacting adhesive layer;
an array of micro-channels (104) within said collection chamber;
a plurality of miniaturized sensors (105) embedded in said collection chamber;
a microprocessor (106) for controlling sampling and data analysis;
an auto-sampler mechanism (107) integrated into the patch, comprising:
i) a micro-needle array (108) for minimally invasive sampling, and
ii) a microfluidic system (109) for sample collection and transport;
a wireless communication module (110) for data transmission; and
a power supply (111) for energizing electronic components of the system.

2. A method for real-time monitoring of drug release from a transdermal patch of the system as claimed in claim 1, comprising the steps of:
a) applying a transdermal patch to a subject's skin;
b) activating the auto-sampler mechanism 107 to collect interstitial fluid samples at predetermined intervals;
c) analyzing said samples using the miniaturized sensors 105 to determine drug concentration;
d) processing the miniaturized sensor 105 data using the microprocessor 106 to calculate drug release kinetics; and
e) transmitting the processed data wirelessly to an external device for real-time monitoring and analysis.

3. The system as claimed in claim 1, wherein the miniaturized sensors 105 are selected from group consisting of electrochemical sensors, optical sensors, and impedance-based sensors.

4. The system as claimed in claim 1, wherein the micro-needle array 108 comprises hollow micro-needles with a length of 150-500 micrometers and an internal diameter of 25-50 micrometers.

5. The system as claimed in claim 1, wherein the microfluidic system 109 comprises micro-channels 104 and a micropump controlled by the microprocessor 106 for regulating sampling rate and volume.

6. The system as claimed in claim 1, further comprising an internal calibration unit featuring a reservoir of known drug concentration for periodic sampling to ensure sensor accuracy.

7. The system as claimed in claim 1, wherein the microprocessor 106 is programmed to execute algorithms for signal processing, noise reduction, and calculation of pharmacokinetic parameters.

8. The system as claimed in claim 1, wherein the wireless communication module 110 utilizes Bluetooth Low Energy (BLE) or a low-power wide-area network (LPWAN) protocol for data transmission.

9. The system as claimed in claim 1, further comprising an energy harvesting mechanism to supplement the power supply 111.

10. A smartphone application for interfacing with the transdermal patch system as claimed in claim 1, comprising modules for:
a) visualizing real-time drug release profiles;
b) adjusting sampling parameters;
c) setting alerts for specific drug concentration thresholds; and
d) exporting collected data for further analysis.

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