FORMULATION AND DEVELOPMENT OF NEPAFENAC OCULAR PATCHES FORSUSTAINED RELEASE WITHIN THE EYE

Abstract

The present invention relates to a formulation and development of nepafenac ocular patches for sustained release within the eye. The ocular patch comprises a biodegradable polymeric matrix that encapsulates nepafenac, a bioadhesive layer that ensures secure adherence to the eye, and an optional rate-controlling membrane to modulate drug release rates. By leveraging biocompatible materials such as chitosan or hyaluronic acid, the patch offers a controlled, sustained release of nepafenac, enhancing drug bioavailability and therapeutic efficacy while minimizing systemic exposure and side effects. The patch is particularly beneficial for treating postoperative inflammation and pain in various ocular conditions, significantly improving patient compliance by reducing the frequency of dosing compared to traditional eye drop formulations.

Specification

Description:FIELD OF INVENTION
The present invention relates to a field of ophthalmic drug delivery systems and particularly to a formulation and development of nepafenac ocular patches for sustained release within the eye.
BACKGROUND OF THE INVENTION
Ocular inflammation is a common postoperative complication and can occur in various ocular diseases, often leading to patient discomfort and, if untreated, potential complications that could affect visual acuity. Anti-inflammatory therapies, particularly those involving non-steroidal anti-inflammatory drugs (NSAIDs) such as nepafenac, are essential in managing inflammation and associated pain. However, conventional nepafenac formulations, typically in eye drop form, present limitations that impact their therapeutic effectiveness.
The primary challenge with traditional eye drop formulations is the rapid clearance of the drug from the ocular surface due to natural tear turnover, blinking, and drainage through the nasolacrimal duct. This rapid clearance necessitates frequent administration, leading to fluctuations in drug concentration at the target site, which can result in suboptimal therapeutic effects. Additionally, patient compliance with frequent dosing schedules can be poor, especially among elderly individuals or those with dexterity issues, further compromising treatment efficacy.
Ocular drug delivery presents unique challenges compared to other drug delivery routes due to the eye's natural protective barriers, including the corneal epithelium and the blood-aqueous and blood-retinal barriers. These barriers limit drug penetration and absorption, requiring higher or more frequent dosing to achieve therapeutic levels, which increases the risk of systemic side effects and reduces patient comfort.
In response to these challenges, sustained drug delivery systems for the eye have been explored to prolong drug residence time, minimize dosing frequency, and maintain consistent therapeutic levels. However, few effective, patient-friendly options currently exist for sustained ocular drug delivery, especially for delivering NSAIDs like nepafenac. Current sustained-release approaches, such as eye gels or implants, can be invasive, uncomfortable, or limited in their ability to adhere to the ocular surface while providing controlled, sustained drug release.
Therefore, there exists a need for an innovative ocular drug delivery system that can provide a sustained release of nepafenac directly at the site of action, allowing consistent therapeutic effects over an extended period.
OBJECTS OF THE INVENTION
Some of the objects of the present disclosure, which at least one embodiment herein satisfies, are as follows.
It is an object of the present disclosure to ameliorate one or more problems of the prior art or to at least provide a useful alternative
An object of the present disclosure is to provide a formulation and development of nepafenac ocular patches for sustained release within the eye that is designed to overcome the limitations of traditional eye drop formulations.
An object of the present disclosure is to provide a formulation and development of nepafenac ocular patches for sustained release within the eye that enable a controlled and prolonged release of nepafenac, maintaining therapeutic drug levels on the ocular surface over an extended period, thereby reducing the frequency of administration.
Another object of the present disclosure is to provide formulation and development of nepafenac ocular patches for sustained release within the eye that offer a non-invasive, comfortable alternative to frequent eye drop administration, making it easier for patients to adhere to prescribed treatment regimens, particularly beneficial for those who face challenges with regular dosing.
Still another object of the present disclosure is to provide a formulation and development of nepafenac ocular patches for sustained release within the eye that improve drug residence time on the ocular surface by incorporating bioadhesive materials, ensuring nepafenac remains at the target site for enhanced absorption and efficacy.
Still another object of the present disclosure is to provide a formulation and development of nepafenac ocular patches for sustained release within the eye that localize drug delivery to the ocular tissues, thus reducing the likelihood of systemic absorption and associated side effects, while achieving therapeutic concentrations at the site of inflammation.
Yet another object of the present disclosure is to provide a formulation and development of nepafenac ocular patches for sustained release within the eye that allow for customization of drug release rates by modifying the matrix composition, thickness, or by adding a rate-controlling membrane, making it suitable for different clinical needs and patient-specific treatment plans
Yet another object of the present disclosure is to provide a formulation and development of nepafenac ocular patches for sustained release within the eye that facilitate nepafenac permeation through the eye's protective barriers by including optional permeation enhancers, overcoming typical challenges related to ocular drug delivery.
Other objects and advantages of the present disclosure will be more apparent from the following description, which is not intended to limit the scope of the present disclosure.
SUMMARY OF THE INVENTION
The following presents a simplified summary of the invention in order to provide a basic understanding of some aspects of the invention. This summary is not an extensive overview of the present invention. It is not intended to identify the key/critical elements of the invention or to delineate the scope of the invention. Its sole purpose is to present some concept of the invention in a simplified form as a prelude to a more detailed description of the invention presented later.
The present invention provides an ocular patch system designed for the sustained release of nepafenac, a non-steroidal anti-inflammatory drug (NSAID), directly onto the ocular surface. This patch aims to maintain therapeutic drug levels in the eye over an extended period, reducing the need for frequent administration and improving patient compliance. The patch contains a biodegradable polymeric matrix, such as chitosan or hyaluronic acid, which encases nepafenac in a controlled-release form. This matrix is paired with a bioadhesive layer that ensures the patch remains in place on the ocular surface, allowing nepafenac to be continuously released directly at the target site. For further control over the release rate, an optional semi-permeable membrane can be included, which modulates drug diffusion to suit specific therapeutic needs.
The ocular patch offers a customizable release profile that can be tailored by adjusting the matrix composition, thickness, and rate-controlling membrane. This flexibility allows for variable release durations (e.g., 12 to 48 hours) to meet clinical requirements. Additionally, permeation enhancers may be incorporated to optimize drug absorption across ocular barriers, further enhancing bioavailability. Non-invasive and comfortable, the patch represents a significant advancement over conventional eye drops, providing continuous, targeted drug delivery with fewer applications. This invention thus addresses the limitations of traditional eye drops, offering a more effective and patient-friendly approach for managing ocular inflammation and related conditions.
BRIEF DESCRIPTION OF THE DRAWINGS
So that the manner in which the above recited features of the present invention can be understood in detail, a more particular description of the invention, briefly summarized above, may have been referred to by embodiments, some of which are illustrated in the appended drawings. It is to be noted, however, that the appended drawings illustrate only typical embodiments of this invention and are therefore not to be considered limiting of its scope, for the invention may admit to other equally effective embodiments.
These and other features, benefits, and advantages of the present invention will become apparent by reference to the following text figure, with like reference.
DETAILED DESCRIPTION OF THE INVENTION
The following description is of exemplary embodiments only and is not intended to limit the scope, applicability or configuration of the invention in any way. Rather, the following description provides a convenient illustration for implementing exemplary embodiments of the invention. Various changes to the described embodiments may be made in the function and arrangement of the elements described without departing from the scope of the invention. The invention relates to a novel ocular patch designed for the sustained release of nepafenac, a non-steroidal anti-inflammatory drug (NSAID), to treat ocular inflammation and pain. The ocular patch is a biocompatible, biodegradable system that adheres to the ocular surface, allowing for prolonged drug delivery and improved therapeutic outcomes.
1. Composition of the Ocular Patch:
A. Drug Component: Nepafenac is the active pharmaceutical ingredient (API) incorporated into the ocular patch. The amount of nepafenac can vary depending on the desired therapeutic effect, typically ranging from 0.1% to 5% w/w of the total patch formulation. The formulation may include different salt forms of nepafenac to enhance solubility and bioavailability.
B. Matrix Polymer: The matrix of the ocular patch comprises biodegradable polymers that serve as the primary matrix for drug encapsulation and sustained release. Suitable polymers include:
• Chitosan: A natural polysaccharide known for its biocompatibility and biodegradability, which can enhance drug permeation through ocular tissues.
• Hyaluronic Acid: A hydrophilic polymer that retains moisture and provides a favorable environment for drug release and absorption.
• Polyvinyl Alcohol (PVA): A synthetic polymer that offers excellent film-forming properties and mechanical strength.
The choice of polymer will influence the release kinetics of nepafenac, and the matrix can be modified by altering the polymer concentration and blending different polymers to achieve desired characteristics.
C. Bioadhesive Layer: To ensure the ocular patch adheres securely to the eye, a bioadhesive layer is included. This layer may be composed of polymers such as polyacrylic acid or carbomer. The bioadhesive properties enhance the patch's residence time on the ocular surface, promoting localized drug delivery.
D. Rate-Controlling Membrane: An optional semi-permeable membrane may be integrated into the patch to regulate the release of nepafenac further. This membrane can be made from materials such as ethylene-vinyl acetate (EVA) or polyvinyl acetate (PVA). By adjusting the thickness and permeability of the membrane, the release rate of the drug can be precisely controlled to match specific therapeutic needs.
E. Permeation Enhancers (Optional): To improve the bioavailability of nepafenac, permeation enhancers such as dimethyl sulfoxide (DMSO), cyclodextrins, or surfactants may be added to the formulation. These agents can facilitate drug absorption through the corneal epithelium, enhancing therapeutic efficacy.
2. Preparation Method:
The ocular patch is prepared using the following general steps:
A. Drug and Polymer Mixture: Nepafenac is dissolved or dispersed in a suitable solvent, which may include water or organic solvents. The selected biodegradable polymer is then added to this solution, followed by mixing to ensure a homogenous distribution of the drug within the matrix.
B. Casting the Patch: The resulting mixture is cast onto a flat surface or a substrate. The thickness of the cast film can be adjusted based on the desired final thickness of the ocular patch. The solvent is allowed to evaporate under controlled conditions to form a solid matrix containing nepafenac.
C. Application of the Bioadhesive Layer: Once the matrix is dried, a bioadhesive polymer layer is applied to one side of the matrix film. This can be done using a similar casting technique or by applying a pre-prepared bioadhesive solution.
D. Optional Rate-Controlling Membrane: If a rate-controlling membrane is used, it is laminated onto the bioadhesive layer, forming a multi-layered structure that encapsulates the nepafenac within the patch.
E. Cutting and Packaging: The patch is cut into appropriate sizes for ocular application and packaged in a moisture-proof environment to maintain stability and prevent contamination.
3. Mechanism of Drug Release:
Upon application to the ocular surface, the patch adheres to the eye due to the bioadhesive layer. Nepafenac is gradually released through the matrix by diffusion and, if applicable, through the rate-controlling membrane. The release kinetics can be controlled by the composition and design of the matrix and membrane, allowing for sustained therapeutic concentrations over an extended period (e.g., 12 to 48 hours).
4. Applications and Advantages:
The ocular patch is designed for treating various conditions, including:
• Postoperative inflammation following cataract surgery or refractive surgery.
• Chronic ocular inflammatory conditions such as uveitis.
• Pain management following ocular surgeries or trauma.
The key advantages of this ocular patch include:
• Sustained Release: Prolonged therapeutic action with reduced dosing frequency.
• Enhanced Patient Compliance: Non-invasive and comfortable compared to traditional eye drops, leading to improved adherence to treatment regimens.
• Reduced Systemic Exposure: Localized delivery minimizes systemic side effects associated with oral or systemic NSAID administration.
• Customizable Formulation: The ability to tailor the release profile according to clinical needs enhances treatment effectiveness.
Overall, the novel ocular patch represents a significant advancement in the field of ophthalmic drug delivery, offering a safe, effective, and patient-friendly solution for managing ocular inflammation and pain.
While considerable emphasis has been placed herein on the specific features of the preferred embodiment, it will be appreciated that many additional features can be added and that many changes can be made in the preferred embodiment without departing from the principles of the disclosure. These and other changes in the preferred embodiment of the disclosure will be apparent to those skilled in the art from the disclosure herein, whereby it is to be distinctly understood that the foregoing descriptive matter is to be interpreted merely as illustrative of the disclosure and not as a limitation.

, Claims:We Claim,
1. A formulation and development of nepafenac ocular patches for sustained release within the eye, comprising:
a biodegradable polymeric matrix containing nepafenac;
a bioadhesive layer to ensure adherence to the ocular surface;
a rate-controlling membrane to modulate the release rate of nepafenac.
2. The ocular patch according to claim 1, wherein the biodegradable polymeric matrix is selected from the group consisting of chitosan, hyaluronic acid, polyvinyl alcohol, or a combination thereof.
3. The ocular patch according to claim 1, wherein the bioadhesive layer comprises a polymer selected from polyacrylic acid, carbomer, or a combination thereof.
4. The ocular patch according to claim 1, wherein the rate-controlling membrane is made from a material selected from ethylene-vinyl acetate, polyvinyl acetate, or a combination thereof.
5. The ocular patch according to claim 1, further comprising one or more permeation enhancers selected from dimethyl sulfoxide (DMSO), cyclodextrins, or surfactants to facilitate drug absorption.
6. The ocular patch according to claim 1, wherein the nepafenac is present in a concentration ranging from 0.1% to 5% w/w of the total patch formulation.
7. The ocular patch according to claim 1, wherein the patch provides sustained release of nepafenac over a duration of 12 to 48 hours.
8. The ocular patch according to claim 1, wherein the patch is configured to treat postoperative inflammation or pain associated with ocular surgery.

Dated this: 30-10-2024

Dr. Amrish Chandra
IN/PA 2959

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