MULTI-COMPARTMENT CAPSULES FOR COMPLEX DRUG REGIMENS

Abstract

A multi-compartment capsule (100) for delivering complex drug regimens is made up of a variety of separate compartments (101, 102, 103, 104, 105). In one version, each of these different compartments has the release of distinct drugs or formulations. The smart compartments (106, 107, 108, 109, 110) have an individual release mechanism, such as time-dependent, pH-responsive, enzymatic, temperature-sensitive, and osmotic. A smart sensor system (112) monitors physiological parameters, adjusting drug release with an identification system 111 for tracking properly. This product makes use of 3D printing (113) and accurate filling (114) to manufacture the capsule. It simplifies complicated medication regimens, fosters compliance, and allows for the provision of personalized medicine through controlled drug delivery customized to the patient's needs.

Specification

Description:Basic Multi-Compartment Structure (101) This invention is based on a capsule shell made of different distinct inner compartments 101, 102, 103, 104, 105. The shell is made from a biocompatible, digestible, hydroxypropyl methylcellulose, or gelatin material. The construction would dissolve instantly in the stomach, and then the contents would begin leaking out of the inner compartments.

Each compartment is a separate, usually spherical or cylindrical unit, 1-5 mm in diameter. The compartments are placed in the capsule shell in such a way that maximises inner space without damaging any of the units.
Each unit wall is made of polymeric materials selected for their release properties. An example would be:
- Compartment 101: Use a pH-sensitive polymer such as Eudragit L100-55 that dissolves at pH > 5.5, designed to target release in the duodenum.
- Compartment 102: Use a time-controlled release polymer, such as hydroxypropyl cellulose (HPC), which is designed to degrade at a programmed rate after 4 hours following ingestion.
- Compartment 103: Use an enzymatic trigger via a peptide bond that is cleaved by pancreatic enzymes to release within the small intestine.
- Compartment 104: It uses a temperature sensitive polymer like poly(N-isopropylacrylamide), (PNIPAM), that changes the conformation at body temperature to release the drug.
Compartment 105: This works based on an osmotic mechanism which incorporates a semipermeable membrane with an osmotic agent to initiate the drug release over an extended period.

Integrated smart sensor: Miniature sensors are integrated in some selected compartments with the ability to detect specific physiological parameters or biomarkers. This could again be electrochemical or optical in nature and integrated in the compartment wall.

For instance, such a glucose-responsive sensor in one chamber can monitor blood glucose concentrations and cause the release of insulin from another chamber. A smart delivery system that could adapt in real-time to the drug's pharmacokinetics relative to the patient's current physiological state is realized.

These are powered by a small biocompatible battery or by energy harvesting from the gastrointestinal environment. The data of the sensor can be communicated remotely through low-power radiofrequency communication to an external device, thus enabling monitoring and analysis of the patient's response to a medicinal treatment.

Advanced Manufacturing Process (113, 114): The multi-compartment capsules were fabricated using a two-step process:
1. 3D Printing (113): The structural framework of the chambers is created using a high-resolution 3D printer. The chambers are printed out so that their size and shape can be controlled down to a few micrometers, and also in their spatial arrangements. The walls of the compartment are produced through biocompatible resins or polymers by layering the liquid materials that cure by light exposure.

2. Precise Filling System (114): The printed compartment structures are filled with the appropriate drug formulation by a high-precision automated filling system. Precise filling systems may also dispense liquid, powder, or gel formulations in very small volumes into each compartment.

Filled compartments are then assembled and encapsulated in the outer capsule shell. The whole process is carried under sterile conditions to ensure integrity and safety of the final product.

Customizable Release Profiles (106, 107, 108, 109, 110): Individual compartments can be designed with unique release profiles tailored to the specific drug contained within that compartment and to the desired therapeutic effect. This is achieved through a combination of :
- Polymer choice: Using various types and molecular weight of polymers to modulate release or degradation rates.
- Coating thickness: Variation of the coating film or compartment wall thickness for modulation of release onset.
- Excipient addition: Pore-forming agents, plasticizers, etc., will be added to further fine-tune the release kinetics.

An example of a capsule targeting hypertension and diabetes would comprise
- Compartment 106: A class of antihypertensive drug with immediate release, based on polymer that dissolves quickly.
- Compartment 107: pH-sensitive compartment that on reaching the stomach releases a proton pump inhibitor
- Compartment 108: Enzymatically triggered release in the small intestine of an incretin mimetic
- Compartment 109: Temperature-sensitive release of metformin timed to coincide with meals
- Compartment 110: An osmotic system for controlled, sustained delivery of a long-acting analogue of insulin.

Identification and Tracking System (111): To ensure proper identification and to maximize patient compliance, every capsule comes with an identification system. This identification system may comprise:
Color coding: Each chamber of the patients' compartment is assigned a specific color that should be visible through the transparent portion of the outer shell of the capsule so that the patient will easily identify what he's taking through it.
- The outer capsule shell shall have a unique code or pattern that can be easily read and recorded using embossing.
- RFID tagging: Incorporate a small, ingestible RFID tag in one of the compartments so that electronic tracking and verification of medication can take place.

This identification system not only helps in the proper administration but also allows the provider to follow the compliance of the patient accurately. This brings in very valuable information on medication adherence and effectiveness when accessed in conjunction with a smartphone app or electronic health record system.

Method of Performing the Invention
The best usage of this multi-compartment capsule system will be the combination of all of these five described embodiments. The fundamental framework, as used in Embodiment 1, is the base; the smart sensor integration, as outlined in Embodiment 2, makes this more adaptive to drug release; and advanced manufacturing, as highlighted in Embodiment 3, ensures that the assembling of these capsules will always be precise and consistent.

The Embodiment 4 customizable release profiles offer tailored therapeutic regimens. Through the identification and tracking system in Embodiment 5, this enhances further the safety and monitoring of compliance. Together, these elements create a truly holistic and highly effective drug delivery system.

Capsules are oral products and are typically taken once a day. Once consumed, the outer shell of the capsule gets wet and dissolves in the stomach, releasing the individual compartments. Then, these separate compartments follow their predetermined release profile to provide its drug payload at an appropriate time and location within the gastrointestinal tract.

Such a multi-compartment capsule would streamline the medication regimen for patients with complex medical conditions and multiple medications. Physiological parameters relevant to treatment are continuously monitored by the smart sensor system; drug release is activated and maintained at optimal therapeutic levels.

The data that the identification and tracking system provides will allow healthcare providers to monitor compliance by the patient and to make appropriate adjustments in treatment plans. This is a closed-loop system of drug delivery, monitoring, and adjustment, which definitely represents the future of personalized medicine.
, Claims:1. A multi-compartment capsule for administering a complex drug regimen, comprising:
a) an outer capsule shell (100) designed to disintegrate upon ingestion;
b) multiple distinct compartments (101, 102, 103, 104, 105) contained within said outer capsule shell, each compartment capable of containing a different drug or formulation;
c) wherein each compartment is engineered with unique properties controlling the release of its contents, selected from the group consisting of:
i) time-dependent release mechanisms (106);
ii) pH-responsive materials (107);
iii) enzymatic triggers (108);
iv) temperature-sensitive polymers (109); and
v) osmotic systems (110);
d) a smart sensor system (112) integrated into at least one compartment, capable of monitoring physiological parameters or detecting specific biomarkers;
e) an identification system (111) for proper identification and tracking of the capsule; and
f) wherein the capsule is manufactured using a combination of 3D printing techniques (113) and precision filling systems (114).

2. A method of manufacturing a multi-compartment capsule for administering a complex drug regimen, comprising the steps of:
a) 3D printing (113) multiple distinct compartments (101, 102, 103, 104, 105) using biocompatible polymers;
b) filling said compartments with different drugs or formulations using a precision filling system (114);
c) integrating a smart sensor system (112) into at least one compartment;
d) assembling the filled compartments and encasing them within an outer capsule shell (100); and
e) applying an identification system (111) to the assembled capsule.

3. The multi-compartment capsule of claim 1, wherein the smart sensor system (112) is capable of triggering drug release based on detected physiological parameters or biomarkers.

4. The multi-compartment capsule of claim 1, wherein the 4. The multi-compartment capsule of claim 1, wherein the identification system (111) comprises at least one of color coding, embossing, or RFID tagging.

5. The multi-compartment capsule of claim 1, wherein the number, size, and release properties of the compartments are customizable based on specific therapeutic needs.

6. A method of treating a patient with multiple medical conditions using the multi-compartment capsule of claim 1, comprising:
a) selecting appropriate drugs for each of the patient's conditions;
b) assigning each drug to a specific compartment (101, 102, 103, 104, 105) based on desired release profiles;
c) manufacturing the multi-compartment capsule using 3D printing (113) and precision filling (114) techniques;
d) administering the capsule to the patient; and
e) monitoring the patient's response and compliance using data from the smart sensor system (112) and identification system (111).

7. The multi-compartment capsule of claim 1, wherein at least one compartment utilizes a pH-responsive polymer (107) for targeted release in a specific region of the gastrointestinal tract.

8. The multi-compartment capsule of claim 1, wherein at least one compartment incorporates a temperature-sensitive polymer (109) that changes conformation at body temperature to release its drug contents.

9. The method of claim 2, further comprising the step of programming the smart sensor system (112) to detect specific physiological parameters or biomarkers relevant to the patient's conditions.

10. The multi-compartment capsule of claim 1, wherein the outer capsule shell (100) is composed of a material selected from the group consisting of hydroxypropyl methylcellulose (HPMC) and gelatin.

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