Nanomicellar composition for high permeation and extended-release drug delivery system

Abstract

The present disclosure relates to a micellar composition, an active / passenger molecule / plant, animal or marine extract loaded micellar composition, process for the preparation of micellar composition and active / passenger molecule / plant, animal or marine extract loaded micellar composition. Remarkably, the process is simple, optionally employing any organic solvent. The micellar composition is invariably transparent and shows high permeation and an extended-release drug delivery system.

Description

[0001] NANOMICELLAR COMPOSITION FOR HIGH PERMEATION AND EXTENDED- RELEASE DRUG DELIVERY SYSTEM

[0002] FIELD OF THE INVENTION

[0003] The present disclosure relates to a micellar composition, an active / passenger molecule / plant, animal or marine extract loaded micellar composition, the process for the preparation of micellar composition and active / passenger molecule / plant, animal or marine extract loaded micellar composition.

[0004] BACKGROUND OF THE INVENTION

[0005] Polymeric micelles are nanosized structures formed by the self-association of amphiphilic block copolymers. Latter can be directly dissolved in water to form micelles or dissolved in an organic solvent (or non-solvent) and then added to an aqueous solvent to form micelles. Polymeric micelles are used in drug delivery because of their engaging characteristics, like high permeability and encapsulation efficiency, biocompatibility, low toxicity, core-shell arrangement, morphology, nano size, and relatively high stability Hemant K.S Yadav et. al, Nanocarriers for Drug Delivery, 2019).

[0006] The pharmaceutical industry continuously requires straightforward and scalable methods for manufacturing and preparation.

[0007] WO2023021492A1 discloses a stable nano micellar ophthalmic formulation consisting of cyclosporine, hydrogenated 40 polyoxyl castor oil (HCO RH 40), octoxynol-40, and an aqueous vehicle. In this document, the drug concentration is very low (0.09%). Manufacturing micelles of cyclosporine requires modification based on the form of cyclosporine used. The amorphous form and the form with characteristic XRD peaks at specific angles require wetting followed by complete dissolution at temperatures up to 70°C. However, less soluble forms need higher temperatures, up to 130°C. During the manufacturing steps, the solution must be closely controlled regarding API specification, process temperature, and time to prevent interconversion of forms, as this can lead to the formation of seeds / nucleus within the composition. These seeds may crystallise from the drug product during storage at higher temperatures, making the product unusable. The soft mesophasic or liquid crystalline form of cyclosporine as an intermediate in the non-aqueous phase could be responsible for the observed instability.

[0008] W02022264006A1 discloses the administration of cyclosporine formulation for patients undergoing cataract surgery. RU2765946C1 discloses an Oil-free oral supersaturated self-nano emulsifiable drug delivery system (SNEDDS) with micelle particles (<50 nm) containing PEG-40 hydrogenated castor oil, PEG-400, antioxidant ascorbic acid, and hydrophobic plant extracts.

[0009] WO2022112513A2 discloses iron oxide nanoparticles (IONS) in a cross-linked polymeric micelle (CCPM) for immunotherapy, cancer treatment, or anemia.

[0010] US20230078391A1 discloses pharmaceutical composition using a mixed polymeric micelle with an amphiphilic block copolymer, a lipopolymer (e.g., PEG-DSPE), and a drug (e.g., cabazitaxel) enclosed in the micelle.

[0011] W02001087227A2 discloses increased potency of therapeutic agents based on pH-sensitive polymeric micelles.

[0012] However, in the prior art, the described systems, their composition and processes involve complex preparation methods with multiple steps, high temperatures and limited capacity to carry active(s).

[0013] Therefore, there remains a need to provide highly permeable, controlled release formulations, with a high loading of active / passenger molecule / plant, animal or marine extract and preparation process employing a simple process step, involving processing at room temperature, for heat sensitive actives or hydrophilic actives such as proteins, peptides, gene delivery and / or avoiding use of organic solvents for products such as ocular or parenteral.

[0014] OBJECTIVES OF THE INVENTION

[0015] An objective of the present disclosure is to provide a micellar composition, and an active / passenger molecule / plant, animal or marine extract loaded micellar composition.

[0016] Another objective of the present disclosure is to provide a simple, scalable, and industry-viable process of preparing stable polymeric micellar composition and active / passenger molecule / plant, animal or marine extract loaded micellar composition.

[0017] Yet another objective of the present disclosure is to demonstrate the potential of the micellar composition to significantly enhance the penetration and permeation of encapsulated active / passenger molecule / plant, animal or marine extract across different biological barriers.

[0018] Yet another objective of the present disclosure is to ensure a sustained release of active / passenger molecule / plant, animal or marine extract at the target site.

[0019] Yet another objective of the present disclosure is to utilise the primary polymeric component, i.e. stearoyl polyoxyl-32 glycerides, lauroyl polyoxyl-32 glycerides / polyoxylglycerides in polymeric compositions.

[0020] Yet another objective of the present disclosure is to provide transparent polymeric micellar compositions for ocular and cosmetic applications, including face serums with suitable active(s) incorporation. Yet another objective is to formulate polymeric micelles devoid of organic solvents (water- soluble actives).

[0021] Yet another objective of the present disclosure is to describe a fast / less time-consuming process employing minimal equipment readily available in the industry and at room temperature.

[0022] Yet another objective of the present disclosure is to provide a process designed to be easily implementable in pharmaceutical manufacturing units, ensuring its practicality and feasibility.

[0023] SUMMARY OF THE INVENTION

[0024] In an aspect, the present disclosure provides a micellar composition comprising: a. a polymer matrix comprising i. 0.01% to 5% w / v of PEG 40 hydrogenated castor oil (HCO RH 40); and ii. 0.01% to 5% w / v of a polyoxyl glyceride; and b. 90% to 99.98% w / v of a solvent, wherein the ratio of amount of said PEG 40 hydrogenated castor oil to said polyoxylglyceride is in the range of 1 :5 to 5: 1 ; wherein said polyoxylglyceride is selected from the group consisting of lauroyl polyoxyl- 32 glycerides (Gelucire 44 / 14), stearoyl polyoxyl-32 glycerides (Gelucire 50 / 13) or combinations thereof; wherein the weight of polymer PEG 40 hydrogenated castor oil (HCO RH 40) or polyoxylglyceride is with respect to the volume of the micellar composition; and wherein, said polymer matrix is in the form of plurality of micelles characterised by an average particle size in the range of 5 nm to 50 nm as determined by particle size analyser (Delsa nano C analyser) and Transmission Electron Microscopy (TEM) or scanning Electron Microscopy (SEM).

[0025] In another aspect, the present disclosure provides a loaded micellar composition comprising: a) a polymer matrix comprising i. 0.01% to 5% w / v of PEG 40 hydrogenated castor oil (HCO RH 40); and ii. 0.01% to 5% w / v of a polyoxylglyceride; b) 60% to 99.3% w / v of a solvent selected from the group consisting of water or organic solvent selected from ethanol, ethyl acetate, isopropanol, acetone, isopropyl acetate or mixtures thereof, and c) 0.05% w / v to 30% w / v of an active / passenger molecule / plant, animal or marine extract selected from the group consisting of cannabinoids and other phytochemicals, antifibrinolytic drugs, hematologic agents, antibacterial agents, antifungals, antivirals, HMG-CoA reductase inhibitors, anticancer agents, corticosteroids, analgesics, monoclonal antibodies and benzylisoquinoline alkaloids, plant extracts, nutraceuticals, inorganic molecules and actives, proteins and peptides, and opioid antagonist; wherein said polyoxylglyceride is selected from the group consisting of lauroyl polyoxyl-32 glycerides (Gelucire 44 / 14), stearoyl polyoxyl-32 glycerides (Gelucire 50 / 13) or combinations thereof; wherein the active / passenger molecule / plant, animal or marine extract is located within the polymer matrix in the form of a plurality of micelles; and wherein the weight of PEG 40 hydrogenated castor oil (HCO RH 40) or polyoxylglyceride or active / passenger molecule / plant, animal or marine extract is with respect to the volume of the loaded micellar composition.

[0026] In another aspect, the present disclosure provides a process for preparation of a micellar composition, said process comprising the following steps: a. dissolving 0.01% to 5% w / v of said PEG 40 hydrogenated castor oil and 0.01% to 5% w / v of said polyoxylglyceride in 90% to 99.8% w / v of a solvent selected from the group consisting of water, or organic solvent selected from ethanol, ethyl acetate, isopropanol or mixtures thereof under continuous stirring; and b. optionally, removing organic solvent from said mixture to form a micellar composition; c. optionally, filtering the micellar composition through bacteria proof filters (0.22 micron (pm)); wherein the micellar composition comprising: a. a polymer matrix comprising i. 0.01% to 5% w / v of PEG 40 hydrogenated castor oil (HCO RH 40); and ii. 0.01% to 5% w / v of a polyoxylglyceride; and b. 90% to 99.98% w / v of a solvent selected from the group consisting of water or organic solvent selected from ethanol, ethyl acetate, isopropanol or mixtures thereof; wherein the weight of polymer PEG 40 hydrogenated castor oil (HCO RH 40) or polyoxylglyceride is with respect to the volume of the micellar composition; and wherein said polyoxylglyceride is selected from the group consisting of lauroyl polyoxyl-32 glycerides (Gelucire 44 / 14), stearoyl polyoxyl-32 glycerides (Gelucire 50 / 13) or combinations thereof.

[0027] In yet another aspect, a process for preparation of a loaded micellar composition, said process comprising the following steps: a. providing 0.01% to 5% w / v of said PEG 40 hydrogenated castor oil; b. providing 0.01% to 5% w / v of said polyoxylglyceride; c. providing 60% to 99.3% w / v of said solvent selected from the group consisting of water or organic solvent selected from ethanol, ethyl acetate, isopropanol or mixtures thereof; d. providing 0.05% w / v to 30% w / v of an active / passenger molecule / plant, animal or marine extract; e. mixing components provided in steps (a) to (d) above in any sequence, under continuous stirring to obtain a loaded micellar composition; f. optionally, removing the organic solvent from said loaded micellar composition; and g. optionally, filtering the loaded micellar composition through bacteria proof filters; wherein the loaded micellar composition comprising: a) a polymer matrix comprising i. 0.01% to 5% w / v of PEG 40 hydrogenated castor oil (HCO RH 40); and ii. 0.01% to 5% w / v of a polyoxylglyceride; b) 60% to 99.3% w / v of a solvent selected from the group consisting of water or organic solvent selected from ethanol, ethyl acetate, isopropanol or mixtures thereof; and c) 0.05% w / v to 30% w / v of an active / passenger molecule / plant, animal or marine extract selected from the group consisting of cannabinoids and other phytochemicals, antifibrinolytic drugs, hematologic agents, antibacterial agents, antifungals, antivirals, HMG-CoA reductase inhibitors, anticancer agents, corticosteroids, analgesics, monoclonal antibodies and benzylisoquinoline alkaloids, plant extracts, nutraceuticals, inorganic molecules and actives, proteins and peptides, and opioid antagonist; wherein said polyoxylglyceride is selected from the group consisting of lauroyl polyoxyl- 32 glycerides (Gelucire 44 / 14), stearoyl polyoxyl-32 glycerides (Gelucire 50 / 13), or combinations thereof; wherein the weight of PEG 40 hydrogenated castor oil (HCO RH 40) or polyoxylglyceride or active / passenger molecule / plant, animal or marine extract is with respect to the volume of the loaded micellar composition; and wherein the active / passenger molecule / plant, animal or marine extract is located within the plurality of micelles of the micellar composition.

[0028] In yet another aspect, the present disclosure provides the use of a micellar composition for loading an active / a passenger molecule / a plant, animal or marine extract within the plurality of micelles.

[0029] In yet another aspect, the present disclosure provides the use of a loaded micellar composition, wherein an active / a passenger molecule / a plant, animal or marine extract is loaded by the method of the present disclosure for the manufacture of medicament.

[0030] In yet another aspect, the present disclosure provides the use of the loaded micellar composition, wherein the medicament is used as a method of reducing inflammation for the skin, promote skin health, reduce skin pigmentation and as an antioxidant for the skin.

[0031] In yet another aspect, the present disclosure provides the use of the loaded micellar composition, wherein the medicament is for the use in a method for reducing ocular inflammation.

[0032] In yet another aspect, the present disclosure provides the use of the loaded micellar composition, wherein the medicament is used in managing conditions or diseases / disorders of the humans or animals (veterinary use) and is administered as an oral, topical, rectal, vaginal, parenteral, nasal, or transdermal route.

[0033] These and other features, aspects, and advantages of the present subject matter will become better understood in the following description. This summary is provided to introduce a selection of concepts in a simplified form. This summary is not intended to identify key features or essential features of the subject matter, nor is it intended to be used to limit the scope of the subject matter.

[0034] BRIEF DESCRIPTION OF DRAWINGS

[0035] To further clarify the advantages and features of the present disclosure, a more particular description of the disclosure will be rendered by reference to specific embodiments thereof, which are illustrated in the appended drawings. It is appreciated that these drawings depict only typical embodiments of the disclosure and are, therefore, not to be considered, limiting its scope. The disclosure will be described and explained with additional specificity and detail with the accompanying drawings in which:

[0036] Fig. 1 (a) HRTEM image of tranexamic acid (TXA) loaded polymeric micelles (PMs) (magnification 10,000 X), (b) FESEM images of TXA loaded PM and (c) TXA loaded PMs in Hgel. Fig. 2 illustrates DSC thermograms of TXA, blank PMs Hgel, TXA-PMs Hgel, and different excipients.

[0037] Fig. 3 illustrates NMR spectra of (a) TXA, (b) TXA-PMs Hgel, and (c) Blank PMs Hgel.

[0038] Fig. 4 illustrates rheology graphs for 5% TXA PMs Hgel.

[0039] Fig. 5 illustrates cumulative percentage drug release versus time graph for TXA formulations along with kinetic model fitting data for release mechanism of TXA from PMs-Hgel. All groups are significantly different (p-value> 0.05) from each other; TXA PMs Hgel formulation showed slower release than free TXA Hgel and TXA-MKT gel.

[0040] Fig. 6 illustrates (a): Ex vivo drug permeation of formulation across mice skin following topical application (n=6). Value points for all the formulations are significantly different at each time point (p<0.05 to 0.001 ). (b) Amount of TXA retained in mice skin following TXA-PMs Hgel, TXA-MKT gel, and Free TXA gel. Data are expressed as mean ± SD. TXA PMs Hgel groups showed significantly higher retention than all other groups (p value >0.05).

[0041] Fig.s 7a - 7d illustrate histology of mice skin following treatment of a) Naive control, b) Group 1 -Blank PMs Hgel, c) Group 2 -TXA PMs Hgel, and d) Group 3 -5% TXA-MKT gel.

[0042] Fig. 8 illustrates fluorescent images of skin tissue following treatment with FS-PMs Hgel (A, B, C) and free FS Hgel (D, E, F) at (I) 0.5 h (II) 2 h (III) 12 h.

[0043] Fig. 9 illustrates (a) % cell viability in L929 cells at varying concentrations of free TXA Hgel, TXA PMs Hgel, and blank PMs Hgel, (b) % cell viability in B16F10 melanoma cells at varying concentrations of free TXA Hgel, TXA PMs Hgel, blank Hgel, blank PMs and TXA-PMs. Data are expressed as mean ± SD. All values are similar when considered at the same concentration (p <0.001 ) and also at increasing concentrations of TXA (p <0.01 ).

[0044] Fig. 10 illustrates the Effects of TXA-PM and TXA-PM Hgel on melanin content in Bl 6F 10 melanoma cells. Data are expressed as mean + SD.#TXA-PMs and TXA-PMs Hgel treated groups showed significant inhibition in melanin content. The values obtained for untreated cells were considered 100% melanin content.

[0045] Fig. 11 illustrates particle size distribution of 5% Tranexamic acid loaded polymeric micelles.

[0046] Fig. 12 illustrates particle size distribution of 5% Tranexamic acid loaded polymeric micelles hydrogel.

[0047] Fig. 13 illustrates zeta potential of 5% (A) and 10% (B) Tranexamic acid loaded polymeric micelles.

[0048] Fig. 14, Fig. 14a illustrates differential scanning calorimetry (DSC) of cannabidiol loaded polymeric micelles, Fig. 14b illustrates FT-IR spectra of cannabidiol loaded polymeric micelles, Fig. 14c illustrates H’-NMR spectra of cannabidiol loaded polymeric micelles.

[0049] Fig. 15a to 15c illustrates NMR spectra of FS, blank PM and the FS loaded PM formulation. Fig. 16 illustrates 16a) the impact of formulation components on the particle size (PS) of PMs, 16b) the significance of A-HCO RH 40 and Gelucire 44 / 14 in optimising nanoparticle formulations for desired PDI, 16c) the significance of A-HCO RH 40 and Gelucire 44 / 14 in enhancing encapsulation efficiency.

[0050] Fig. 17 illustrates an overlay of the optimised design for the selected formulation with respect to PS (35.23 nm), PDI (0.244), and EE (81.547%) at specific concentrations of these excipients.

[0051] Fig. 18 illustrates the zeta potential of PMs ranging from -0.73 mV to -3.68 mV with an average of -1.97 mV, demonstrating the polymers used in the formulations are non-ionic.

[0052] Fig. 19 illustrates a dilution study of the optimised formulation at 5°C.

[0053] Fig. 20 shows a dilution study of the optimised formulation at 25 °C.

[0054] Fig. 21 illustrates a dilution study of the optimised formulation at 40°C.

[0055] Fig. 22 illustrates CBD-PMs' stability in simulated tear fluid (STF).

[0056] Fig. 23 illustrates the rheological analysis of CBD-PMs.

[0057] Fig. 24 illustrates the In Vitro release study of CBD-PMs and CBD-SUS.

[0058] Fig. 25 illustrates In Vivo drug permeation study of fluorescein isothiocyanate FITC-loaded PMs (FITC-PMs).

[0059] Fig. 26 illustrates 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay for cytotoxicity and cell viability studies of CBD-SUS, CBD-PMs, and CBD B (blank) on the SIRC (Statens Seruminstitut Rabbit Cornea) cell line.

[0060] Fig. 27 illustrates impact of different formulations on R28 retinal precursor cells across varying doses (0, 0.5, 1, 1.5, and 2 mg / mL).

[0061] Fig. 28 illustrates cellular uptake of fluorescein isothiocyanate FITC-loaded PMs (FITC-PMs) in corneal cell lines.

[0062] Fig. 29 illustrates evaluation of CBD-PMs on IL-6 levels in an inflammatory model of SIRC cells.

[0063] Fig. 30 illustrates evaluation of CBD-PMs on TNF-a levels in an inflammatory model of SIRC cells.

[0064] Fig. 31 illustrates FTIR findings by showcasing the stability of the molecular structure CBD.

[0065] Fig. 32 illustrates ATR-FTIR findings by showcasing the stability of the molecular structure CBD.

[0066] Fig. 33 illustrates the thermal stability of the CBD-PMs.

[0067] Fig. 34 illustrates histology of corneal tissue at different times following acute inflammation (Triton X treatment). Fig. 35 illustrates pharmacodynamic study of CBD-PMs on acute corneal inflammation.

[0068] Fig. 36 illustrates effect of CBD-PMs on IL-6 levels.

[0069] Fig. 37 illustrates effect of CBD-PMs on TNF-a levels.

[0070] Fig. 38 (a) and (b) illustrate FTIR of blank formulation compared to natural extracts-based- PMs formulation.

[0071] Fig. 39 illustrates particle size analysis of liquorice extract loaded PMs

[0072] Fig. 40 illustrates particle size analysis of PMs incorporated in secondary formulation.

[0073] Fig. 41 (a) and (b) illustrate zeta potential analysis of liquorice extract loaded PMs compared to PMs incorporated in secondary formulation.

[0074] Fig. 42 illustrates High-Resolution Transmission Electron Microscopy (HRTEM) of liquorice extract loaded PMs.

[0075] Fig. 43 illustrates rheological study of PMs incorporated secondary formulation.

[0076] Fig. 44 illustrates pharmacodynamics studies for atopic dermatitis using natural extracts- based-PMs formulation containing liquorice as an active.

[0077] DETAILED DESCRIPTION OF THE INVENTION

[0078] The following description with reference to the accompanying drawings is provided to assist in a comprehensive understanding of exemplary embodiments of the invention. It includes various specific details to assist in that understanding but these are to be regarded as merely exemplary.

[0079] Accordingly, those of ordinary skill in the art will recognize that various changes and modifications of the embodiments described herein can be made without departing from the scope of the invention. In addition, descriptions of well-known functions and constructions are omitted for clarity and conciseness.

[0080] The terms and words used in the following description and claims are not limited to the bibliographical meanings, but, are merely used by the inventor to enable a clear and consistent understanding of the invention. Accordingly, it should be apparent to those skilled in the art that the following description of exemplary embodiments of the present invention are provided for illustration purpose only and not for the purpose of limiting the scope of the invention as defined by the appended claims and their equivalents.

[0081] Reference in this specification to “one embodiment” or “an embodiment” means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the present disclosure. The appearance of the phrase “in an embodiment” in various places in the specification are not necessarily all referring to the same embodiment, nor are separate or alternative embodiments mutually exclusive of other embodiments. Moreover, various features are described which may be exhibited by some embodiments and not by others. Similarly, various requirements are described which may be requirements for some embodiments but not for other embodiments.

[0082] Moreover, although the following description contains many specifics for the purposes of illustration, anyone skilled in the art will appreciate that many variations and / or alterations to said details are within the scope of the present disclosure. Similarly, although many of the features of the present disclosure are described in terms of each other, or in conjunction with each other, one skilled in the art will appreciate that many of these features can be provided independently of other features. Accordingly, this description of the present disclosure is set forth without any loss of generality to, and without imposing limitations upon, the present disclosure.

[0083] The terms “comprises”, “comprising”, or any other variations thereof, are intended to cover a non-exclusive inclusion, such that a process or method that comprises a list of steps does not include only those steps but may include other steps not expressly listed or inherent to such process or method. Similarly, one or more devices or sub-systems or elements or structures proceeded by “comprises... a” does not, without more constraints, preclude the existence of other devices or other sub-systems or other elements or other structures or additional devices or additional sub-systems or additional elements or additional structures.

[0084] It is to be understood that the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise.

[0085] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. The apparatus, system, and examples provided herein are illustrative only and not intended to be limiting.

[0086] The systems disclosed in the prior art fail to provide a simple method of preparation that is possible to be performed at room temperature without the application of heating and without employing an organic solvent and that achieves high loading of actives and results in sustained release and delivery of actives in an efficient manner.

[0087] Therefore, there remains a need to provide a highly permeable, controlled release formulations, with a high loading of active / passenger molecule / plant, animal or marine extract. Further, there remains a need to provide controlled release formulations, which are mainly prepared by a simple preparation method.

[0088] In an aspect, the present disclosure provides a micellar composition comprising: a. a polymer matrix comprising i. 0.01% to 5% w / v of PEG 40 hydrogenated castor oil (HCO RH 40); and ii. 0.01% to 5% w / v of a polyoxylglyceride; and b. 90% to 99.98% w / v of a solvent, wherein the weight of polymer PEG 40 hydrogenated castor oil (HCO RH 40) or polyoxylglyceride is with respect to the volume of the micellar composition; wherein the ratio of the amount of said PEG 40 hydrogenated castor oil to said polyoxylglyceride is in the range of 1 :5 to 5: 1 ; wherein said polyoxylglyceride is selected from the group consisting of lauroyl polyoxyl- 32 glycerides (Gelucire 44 / 14), stearoyl polyoxyl-32 glycerides (Gelucire 50 / 13), or combinations thereof; and wherein said polymer matrix is in the form of a plurality of micelles characterised by having an average particle size in the range of 5 nm to 50 nm as determined by particle size analyser (Delsa nano C analyser) and Transmission Electron Microscopy (TEM) or scanning Electron Microscopy (SEM).

[0089] In an embodiment, the present disclosure provides a micellar composition comprising: a. a polymer matrix comprising i. 1% to 5% w / v of PEG 40 hydrogenated castor oil (HCO RH 40); and ii. 1% to 5% w / v of a polyoxylglyceride; and b. 90% to 98% w / v of a solvent, wherein the weight of polymer PEG 40 hydrogenated castor oil (HCO RH 40) or polyoxylglyceride is with respect to the volume of the micellar composition; wherein the ratio of amount of said PEG 40 hydrogenated castor oil (HCO RH 40) to said lauroyl polyoxyl-32 glycerides (Gelucire 44 / 14) is in the range of 1:5 to 5: 1; wherein said polyoxylglyceride is selected from the group consisting of lauroyl polyoxyl- 32 glycerides (Gelucire 44 / 14), stearoyl polyoxyl-32 glycerides (Gelucire 50 / 13), or combinations thereof; and wherein said polymer matrix is in the form of a plurality of micelles characterised by having an average particle size in the range of 5 nm to 50 nm as determined by particle size analyser (Delsa nano C analyser) and Transmission Electron Microscopy (TEM) or scanning Electron Microscopy (SEM).

[0090] In another embodiment, the present disclosure provides a micellar composition comprising: a. a polymer matrix comprising i. 3% to 5% w / v of PEG 40 hydrogenated castor oil (HCO RH 40); and ii. 3% to 5% w / v of a polyoxylglyceride; and b. 90% to 94% w / v of a solvent, wherein the weight of polymer PEG 40 hydrogenated castor oil (HCO RH 40) or polyoxylglyceride is with respect to the volume of the micellar composition; wherein the ratio of amount of said PEG 40 hydrogenated castor oil (HCO RH 40) to said lauroyl polyoxyl-32 glycerides (Gelucire 44 / 14) is in the range of 1:5 to 5: 1; wherein said polyoxylglyceride is selected from the group consisting of lauroyl polyoxyl- 32 glycerides (Gelucire 44 / 14), stearoyl polyoxyl-32 glycerides (Gelucire 50 / 13), or combinations thereof; and wherein said polymer matrix is in the form of a plurality of micelles characterised by having an average particle size in the range of 5 nm to 50 nm as determined by particle size analyser (Delsa nano C analyser) and Transmission Electron Microscopy (TEM) or scanning Electron Microscopy (SEM).

[0091] In a preferred embodiment, the present disclosure provides a micellar composition comprising: a. a polymer matrix comprising i. 5% w / v of PEG 40 hydrogenated castor oil (HCO RH 40); and ii. 5% w / v of a polyoxylglyceride; and b. 90% w / v of solvent, wherein the weight of polymer PEG 40 hydrogenated castor oil (HCO RH 40) or polyoxylglyceride is with respect to the volume of the micellar composition; wherein the ratio of amount of said PEG 40 hydrogenated castor oil (HCO RH 40) to said lauroyl polyoxyl-32 glycerides (Gelucire 44 / 14) is in the range of 1:1; wherein said polyoxylglyceride is lauroyl polyoxyl-32 glycerides (Gelucire 44 / 14); and wherein said polymer matrix is in the form of a plurality of micelles characterised by having an average particle size in the range of 47.0 ± 3.6 nm as determined by particle size analyser (Delsa nano C analyser) and Transmission Electron Microscopy (TEM) or Scanning Electron Microscopy (SEM).

[0092] In an embodiment, the polyoxylglyceride is selected from the group consisting of lauroyl polyoxyl-32 glycerides (Gelucire 44 / 14), stearoyl polyoxyl-32 glycerides (Gelucire 50 / 13), or combinations thereof.

[0093] In a preferred embodiment, the polyoxylglyceride is lauroyl polyoxyl-32 glycerides (Gelucire 44 / 14).

[0094] In another preferred embodiment, the polyoxylglyceride is stearoyl polyoxyl-32 glycerides (Gelucire 50 / 13).

[0095] In a most preferred embodiment, the polyoxylglyceride is lauroyl polyoxyl-32 glycerides (Gelucire 44 / 14). In an embodiment, the solvent in the micellar composition is selected from the group consisting of water or organic solvent selected from ethanol, ethyl acetate, isopropanol, acetone, isopropyl acetate, diethyl ether, dichloromethane or mixtures thereof.

[0096] In an embodiment, the solvent is water, suitable for the water-soluble active / passenger molecule / plant, animal or marine extract.

[0097] In an embodiment of the present disclosure, said organic solvent is selected from the ethanol, ethyl acetate, isopropanol, acetone, isopropyl acetate, diethyl ether, dichloromethane or mixtures thereof.

[0098] In another embodiment, the solvent is an organic solvent selected from ethanol, ethyl acetate, isopropanol or mixtures suitable for dissolving active / passenger molecules / plants. These animal or marine extracts are water-insoluble.

[0099] In an embodiment of the present disclosure, the loaded micellar composition of the present invention contains no organic solvent. The organic solvent forms a micellar composition and is later removed to produce a loaded micellar composition free of organic solvent.

[0100] In a preferred embodiment of the present disclosure, the solvent in the micellar composition is water.

[0101] In a preferred embodiment of the present disclosure, said organic solvent is selected from the group of ethanol, isopropanol, ethyl acetate or mixtures thereof, mainly when used for ocular products.

[0102] In a more preferred embodiment of the present disclosure, said organic solvent is ethanol.

[0103] In an embodiment of the present disclosure, preservatives, stabilisers, viscolysers, precipitation inhibitors, antioxidants, and pH modifying agents are added to the micellar composition of the present disclosure to result in a stable and safe product for long-term use and shelf-life.

[0104] In an embodiment of the present disclosure, the antioxidant is selected from the group consisting of butylated hydroxy anisole, butylated hydroxytoluene, sodium metabisulphite, sesamol, nor dihydroguaretic acid, curcumin, tetra hydro curcumin, EGCG and resveratrol.

[0105] In a preferred embodiment of the present disclosure, the antioxidant is sesamol and butylated hydroxyanisole.

[0106] In another aspect, the present disclosure provides a loaded micelles composition comprising: a) a polymer matrix comprising i. 0.01% to 5% w / v of PEG 40 hydrogenated castor oil (HCO RH 40); and ii. 0.01% to 5% w / v of a polyoxylglyceride; b) 60% to 99.3% w / v of a solvent selected from the group consisting of water or organic solvent selected from ethanol, ethyl acetate, isopropanol or mixtures thereof; and c) 0.05% w / v to 30% w / v of an active / passenger molecule / plant, animal or marine extract selected from the group consisting of cannabinoids and other phytochemicals, antifibrinolytic drugs, hematologic agents, antibacterial agents, antifungals, antivirals, HMG-CoA reductase inhibitors, anticancer agents, corticosteroids, analgesics, monoclonal antibodies and benzylisoquinoline alkaloids, plant extracts, nutraceuticals, inorganic molecules and actives, proteins and peptides, and opioid antagonist; wherein said polyoxylglyceride is selected from the group consisting of lauroyl polyoxyl-32 glycerides (Gelucire 44 / 14), stearoyl polyoxyl-32 glycerides (Gelucire 50 / 13), or combinations thereof; wherein the active / passenger molecule / plant, animal or marine extract is located within the polymer matrix in the form of a plurality of micelles; and wherein the weight of PEG 40 hydrogenated castor oil (HCO RH 40) or polyoxylglyceride or active / passenger molecule / plant, animal or marine extract is with respect to the volume of the loaded micellar composition.

[0107] In an embodiment of the present disclosure, said active / passenger molecule(s) / plant, animal or marine extract(s) is / are selected from the group consisting of Cannabidiol (CBD), Tranexamic acid (TXA), Desmopressin, Clopidogrel, Doxycycline, moxicycline, mofloxacin, Full Spectrum Cannabis (CBD) Extract, ciprofloxacin, Neosporin, betaxolol, Nitrofurantoin, Azithromycin, Oseltamivir, Famciclovir, Zanamivir, Berbermine hydrochloride, Hydroxyquinone, Paclitaxel, Docetaxel, Prednisone, Hydrocortisone, Mometasone, CBG (Cannabigerol), full-spectrum cannabis extract, Cyclosporine A, Acetylcysteine, Amphotericin B, Doxycycline, Fluconazole, Ketoconazole, Terbinafine, Kojic acid, Symradiance 399 (4- hexylresorcinol), a-arbutin, Clotrimazole, Buprenorphine, Naloxone, Ondansetron, Aripiprazole, Atorvastatin, Tadalafil, Melatonin, Vitamin B-12 , Boswellic acid and its derivatives, Green tea extract, Magnesium oxide, Zinc oxide, Vitamin C, human amniotic membrane (hAM) or its extract, benzoylated 2-(4-piperidinyl)-l,3-benzimidazole analogue, Prednisone, Triamcinolone, Budesonide, olopatadine, ketorolac, fluoromethalone, dexamethasone, bimatoprost, flurbiprofen, histatins, capsaicin, Biotin, Niacinamide, Turmeric, curcumin, , and extracts of Eiquorice, Centella, Blueberry, Mulberry, Ginseng, Witch Hazel, Amla, Neem, Coffee, Willow Bark, Hibiscus, Pomegranate, Tea Tree and Sea Weed or a combination thereof.

[0108] In another embodiment of the present disclosure, said active / passenger molecule / plant, animal or marine extract is selected from the group consisting of Cannabidiol (CBD), Tranexamic acid (TXA), Desmopressin, Clopidogrel, Doxycycline, Full Spectrum Cannabis (CBD) Extract, Nitrofurantoin, Azithromycin, Oseltamivir, Famciclovir, Zanamivir, Terbinafine, Clotrimazole, Buprenorphine, Naloxone, Ondansetron, Aripiprazole, Atorvastatin, Tadalafil, Melatonin, Vitamin B-12, Boswellic acid and its derivatives, Green tea extract, Magnesium oxide, Zinc oxide, Vitamin C, human amniotic membrane (hAM) or its extract, benzoylated 2- (4-piperidinyl)- 1 -benzimidazole analogue, kojic acid, symradiance 399 (4-hexylresorcinol), a- arbutin, Prednisone, Triamcinolone, Budesonide, olopatadine, histatins, capsaicin, Biotin, Niacinamide, Turmeric, and extracts of Centella, Liquorice, Blueberry, Mulberry, Ginseng, Witch Hazel, Amla, Neem, Coffee, Willow Bark, Hibiscus, Pomegranate, Tea Tree and Sea Weed or a combination thereof.

[0109] In another embodiment of the present disclosure, said active / passenger molecule / plant, animal or marine extract is selected from the group consisting of Cannabidiol (CBD), Tranexamic acid (TXA), Desmopressin, Clopidogrel, Doxycycline, Full Spectrum Cannabis (CBD) Extract, Nitrofurantoin, Azithromycin, Oseltamivir, Famciclovir, Zanamivir, Terbinafine, Clotrimazole, Buprenorphine, human amniotic membrane (hAM) or its extract, benzoylated 2- (4-piperidinyl)-l,3-benzimidazole analogue, kojic acid, symradiance 399 (4-hexylresorcinol), a-arbutin, Prednisone, Triamcinolone, Budesonide, olopatadine, histatins, capsaicin, Biotin, Niacinamide, Turmeric, extract of Liquorice, Centella, Blueberry, Mulberry, Ginseng, Witch Hazel, Amla, Neem, Coffee, Willow Bark, Hibiscus, Pomegranate, Tea Tree and Sea Weed or a combination thereof.

[0110] In another embodiment of the present disclosure, said active / passenger molecule / plant, animal or marine extract is selected from the group consisting of Cannabidiol (CBD), Tranexamic acid (TXA), Full Spectrum Cannabis (CBD) Extract, Desmopressin, Clopidogrel, Doxycycline, Nitrofurantoin, Prednisone, Triamcinolone, Budesonide, Olopatadine, Histatins, Capsaicin, Centella, Biotin, Niacinamide, Kojic acid, Symradiance 399 (4-hexylresorcinol), a-arbutin, Turmeric, extract of Liquorice, Blueberry, Mulberry, Ginseng, Witch Hazel, Amla, Neem, Coffee, Willow Bark, Hibiscus, Pomegranate, Tea Tree and Sea Weed or a combination thereof.

[0111] In a preferred embodiment of the present disclosure, said active / passenger molecule / plant, animal or marine extract is selected from Cannabidiol (CBD), Tranexamic acid (TXA), Niacinamide, Full Spectrum Cannabis (CBD) Extract, Biotin, Turmeric, Liquorice, Blueberry, Kojic acid, Symradiance 399 (4-hexylresorcinol), a-arbutin, extract of Centella, Mulberry, Ginseng, Witch Hazel, Amla, Neem, Coffee, Willow Bark, Hibiscus, Pomegranate, Tea Tree and Sea Weed or a combination thereof.

[0112] In a preferred embodiment of the present disclosure, said active / passenger molecule is selected from Tranexamic acid (TXA), Kojic acid, Symradiance 399 (4-hexylresorcinol), a-arbutin or a combination thereof.

[0113] In a preferred embodiment of the present disclosure, said active / passenger molecule is Tranexamic acid (TXA).

[0114] In another preferred embodiment of the present disclosure, said active / passenger plant extract is full-spectrum cannabis extract (FS).

[0115] In another preferred embodiment of the present disclosure, said active / passenger molecule is Niacinamide. In another preferred embodiment of the present disclosure, said active / passenger plant extract is Centella.

[0116] In another preferred embodiment of the present disclosure, said active / passenger molecule is Biotin.

[0117] In another preferred embodiment of the present disclosure, said active / passenger plant extract is Turmeric.

[0118] In another preferred embodiment of the present disclosure, said active / passenger plant extract is Liquorice.

[0119] In another preferred embodiment of the present disclosure, said active / passenger plant extract is Blueberry.

[0120] In another preferred embodiment of the present disclosure, said active / passenger plant extract is Mulberry.

[0121] In another preferred embodiment of the present disclosure, said active / passenger plant extract is Ginseng.

[0122] In another preferred embodiment of the present disclosure, said active / passenger plant extract is Witch Hazel.

[0123] In another preferred embodiment of the present disclosure, said active / passenger plant extract is Amla.

[0124] In another preferred embodiment of the present disclosure, said active / passenger plant extract is Neem.

[0125] In another preferred embodiment of the present disclosure, said active / passenger plant extract is Coffee.

[0126] In another preferred embodiment of the present disclosure, said active / passenger plant extract is Willow Bark.

[0127] In another preferred embodiment of the present disclosure, said active / passenger plant extract is Hibiscus.

[0128] In another preferred embodiment of the present disclosure, said active / passenger plant extract is Pomegranate.

[0129] In another preferred embodiment of the present disclosure, said active / passenger plant extract is Tea tree.

[0130] In another preferred embodiment of the present disclosure, said active / passenger plant extract is Sea Weed extract.

[0131] In another preferred embodiment of the present disclosure, said active / passenger molecule is Kojic acid. In another preferred embodiment of the present disclosure, said active / passenger molecule is Symradiance 399 (4-hexylresorcinol).

[0132] In another preferred embodiment of the present disclosure, said active / passenger molecule is a- arbutin.

[0133] In another preferred embodiment of the present disclosure, said active / passenger molecule is combination of cannabidiol and atorvastatin.

[0134] In an embodiment of the present disclosure, the loaded micellar composition further comprises a secondary polymer, hydrogel, precipitation inhibiting agents, in situ gelling composition, emulgel, cream, ointment base, or a combination thereof.

[0135] In an embodiment of the present disclosure, said secondary polymer is selected from the group consisting of Hydroxypropyl Methylcellulose (HPMC), Polyethylene Glycol (PEG), propylene glycol (PG), Polyvinyl Alcohol (PVA), Polycaprolactone, Polyvinyl Pyrrolidone (PVP), Polyvinyl Pyrrolidone (PVP) K30, Polyvinyl Pyrrolidone (PVP) K90, Crospovidone (PVPP), Sodium Alginate, Xanthan Gum, Guar Gum, Gellan gum, Pectin, HPMC Phthalate (HPMCP), Sodium Starch Glycolate (SSG), Poloxamer 188, Poloxamer 407, Carbopol 97 IP, Carbopol 934, Carbopol 940, Methacrylic Acid Copolymers, Gelatin, Carrageenan, Hydroxyethyl cellulose (HEC), Sodium Hyaluronate, Sodium Carboxymethylcellulose, silicone oils, Chitosan or a combination thereof.

[0136] In another embodiment of the present disclosure, said secondary polymer is selected from the group consisting of Hydroxypropyl Methylcellulose (HPMC), Polyethylene Glycol (PEG), propylene glycol (PG), Polyvinyl Alcohol (PVA), Polycaprolactone, Polyvinyl Pyrrolidone (PVP), HPMC Phthalate (HPMCP), Sodium Starch Glycolate (SSG), Poloxamer 188 and Poloxamer 407, Carbopol 97 IP, Carbopol 934, Carbopol 940, Methacrylic Acid Copolymers, Gelatin, Sodium Hyaluronate, Sodium Carboxymethylcellulose, silicone oils, Chitosan or a combination thereof.

[0137] In yet another embodiment of the present disclosure, said secondary polymer is selected from the group consisting of Hydroxypropyl Methylcellulose (HPMC), Polyethylene Glycol (PEG), Polyvinyl Alcohol (PVA), Polycaprolactone, Polyvinyl Pyrrolidone (PVP), HPMC Phthalate (HPMCP), Carbopol 971P, Carbopol 934, Carbopol 940, Methacrylic Acid Copolymers, Gelatin, Sodium Hyaluronate, Sodium Carboxymethylcellulose, Chitosan or a combination thereof.

[0138] In a preferred embodiment of the present disclosure, said secondary polymer is selected from the carpobol 934 and carbopol 980.

[0139] In an embodiment of the present disclosure, in situ gel-forming polymer is selected from the group consisting of; Hydroxypropyl Methylcellulose (HPMC), Sodium Carboxymethylcellulose (NaCMC), Gellan Gum, and Poloxamer 407, Sodium Alginate, Carbopol 97 IP, Carbopol 974P NF, Chitosan, Sodium Hyaluronate (Hyaluronic Acid), Xanthan Gum, Poly(lactic-co-glycolic acid) (PLGA), Polyvinyl Alcohol (PVA), Methylcellulose (MC), Polycarbophil, Alginic Acid, Polyethylene Glycol (PEG), Hydroxyethyl cellulose (HEC), Methacrylic Acid Copolymer, or combination thereof.

[0140] In another embodiment of the present disclosure, in situ gelling composition is selected from the group consisting of: Hydroxypropyl Methylcellulose (HPMC), Sodium Carboxymethylcellulose (NaCMC), Gellan Gum, Xanthan Gum, Poly(lactic-co-glycolic acid) (PLGA), Polyvinyl Alcohol (PVA), Methylcellulose (MC), Polycarbophil, Alginic Acid, Polyethylene Glycol (PEG), Hydroxyethyl cellulose (HEC), Methacrylic Acid Copolymer, or combination thereof.

[0141] In yet another embodiment of the present disclosure, in situ gel-forming polymer is selected from the group consisting of: Hydroxypropyl Methylcellulose (HPMC), Sodium Carboxymethylcellulose (NaCMC), Gellan Gum, Xanthan Gum, Poly(lactic-co-glycolic acid) (PLGA), Polyvinyl Alcohol (PVA), Alginic Acid, Methacrylic Acid Copolymer, or combination thereof.

[0142] In a preferred embodiment of the present disclosure, in situ gel-forming polymer is Sodium Hyaluronate (Hyaluronic Acid) or Polyethylene Glycol (PEG).

[0143] In an embodiment of the present disclosure, said hydrogel is selected from the group consisting of Polyacrylamide, Polyvinyl Alcohol (PVA), Sodium Polyacrylate, Hydroxyethyl Methacrylate (HEM A), Polyethylene Glycol (PEG), Polyvinyl Alcohol (PVA), Polycaprolactone, Polyvinyl Pyrrolidone (PVP), Polyvinyl Pyrrolidone K30, Polyvinyl Pyrrolidone K90, Crospovidone (PVPP), Carbopol 934, Carbopol 940, Chitosan, Alginate, Poly HEMA / Polyethylene Oxide (PEO), Gelatin, Hyaluronic Acid (HA), Silicone, Polyurethane, Poloxamer 188 and Poloxamer 407, Pectin, Polyvinylpyrrolidone (PVP), Collagen or combination thereof.

[0144] In another embodiment of the present disclosure, said hydrogel is selected from the group consisting of Polyacrylamide, Polyvinyl Alcohol (PVA), Sodium Polyacrylate, Hydroxyethyl Methacrylate (HEMA), Polyethylene Glycol (PEG), Polyvinyl Alcohol (PVA), Polycaprolactone, Polyvinyl Pyrrolidone (PVP), Polyvinyl Pyrrolidone K30, Crospovidone (PVPP), Chitosan, Alginate, Poly HEMA / Polyethylene Oxide (PEO), Poloxamer 188 and Poloxamer 407, Polyvinylpyrrolidone (PVP), Collagen or combination thereof.

[0145] In yet another embodiment of the present disclosure, said hydrogel is selected from the group consisting of Polyacrylamide, Polyvinyl Alcohol (PVA), Sodium Polyacrylate, Hydroxyethyl Methacrylate (HEMA), Polycaprolactone, Polyvinyl Pyrrolidone (PVP), Polyvinyl Pyrrolidone K30, Polyvinyl Pyrrolidone K90, Crospovidone (PVPP), Carbopol 940, Chitosan, Alginate, Polyurethane, Poloxamer 188 and Poloxamer 407, Polyvinylpyrrolidone (PVP), Collagen or combination thereof.

[0146] In a preferred embodiment of the present disclosure, said hydrogel is Carbopol 940, Polyethylene Glycol (PEG), and Carbopol 980. In an embodiment of the present disclosure, loaded micellar composition further comprising preservatives, stabilisers, viscolysers and / or precipitation inhibitors, antioxidants, sweeteners, flavour, perfume, color, cryoprotectant and pH modifying agents,

[0147] In an embodiment of the present disclosure, preservatives are selected from the group consisting of Oxychloro Complex, Phenoxyethanol, Benzalkonium Chloride (BAK), Sodium Benzoate, Potassium Sorbate, Methylparaben, Propylparaben, Chlorobutanol, Ethylene diamin tetra acetic acid (EDTA), Ascorbic acid, Tocopherols, Sodium metabisulfite, Sodium ascorbate, Benzyl alcohol, Boric acid, Citric acid, Benzoic acid, Polyquaternium- 1 , or combination thereof; and antioxidant is selected from the group consisting of Butylated hydroxyanisole (BHA), Butylated hydroxytoluene (BHT), Sodium metabisulphite, Sodium ascorbate, Sesamol, Nor dihydroguaretic acid, Curcumin, Tetra hydrocurcumin, EGCG, Resveratrol, or combination thereof.

[0148] In an embodiment of the present disclosure, viscolysers and / or precipitation inhibitors are selected from the group consisting of Hydroxypropyl methylcellulose, Pluronic L44, Polyvinylpyrrolidone K-90, Polyvinylpyrrolidone K-17, Eudragit, Poloxamer 407, or combination thereof.

[0149] In an embodiment of the present disclosure, stabilisers are selected from the group consisting of Ethylenediaminetetraacetic acid (EDTA), Butylated hydroxytoluene, Sodium gluconate, Tetrasodium glutamate diacetate, or combination thereof.

[0150] In an embodiment of the present disclosure, pH modifying agents are selected from the group consisting of Triethanolamine, Sodium hydroxide, Sodium chloride, Potassium hydroxide, Citric acid, Tartaric acid, Lactic acid, Potassium carbonate, di basic or monobasic salts of sodium or Potassium phosphate, Boric acid, Sodium borate, L-arginine, Potassium citrate, Phosphoric Acid, or combination thereof.

[0151] In an embodiment of the present disclosure, colorants are selected from the group consisting of Aluminium powder, Bismuth citrate, Bronze powder, Chromium oxide greens, D&C orange no. 10, D&C orange no. 4, D&C orange no. 11 and Dihydroxyacetone and cryoprotectant are selected from the group consisting of Glycerol and Dimethyl sulfoxide, or combination thereof and sweeteners are selected from the group consisting of Aspartame, Acesulfame potassium, Sucralose, Neotame, Advantame, Saccharin, Thaumatin and flavours are selected from the group of Anise, Cardamom, Essential oils, Spearmint, coolmint, or combination thereof.

[0152] In another aspect, the present disclosure provides a process for preparation of a micellar composition, said process comprising the following steps: a. dissolving 0.01% to 5% w / v of said PEG 40 hydrogenated castor oil and 0.01% to 5% w / v of said polyoxylglyceride in 90% to 99.8% w / v of a solvent selected from the group consisting of water, or organic solvent selected from ethanol, ethyl acetate, isopropanol or mixtures thereof under continuous stirring; b. optionally, removing organic solvent from said mixture to form a micellar composition; and c. optionally, filtering the formed micellar composition through bacteria proof filters of the size 0.22pm; wherein the micellar composition comprising: a. a polymer matrix comprising i. 0.01% to 5% w / v of PEG 40 hydrogenated castor oil (HCO RH 40); and ii. 0.01% to 5% w / v of a polyoxylglyceride; and b. 90% to 99.98% w / v of a solvent selected from the group consisting of water or organic solvent selected from ethanol, ethyl acetate, isopropanol or mixtures thereof; wherein the weight of polymer PEG 40 hydrogenated castor oil (HCO RH 40) or polyoxylglyceride is with respect to the volume of the micellar composition; and wherein said polyoxylglyceride is selected from the group consisting of lauroyl polyoxyl-32 glycerides (Gelucire 44 / 14), stearoyl polyoxyl-32 glycerides (Gelucire 50 / 13), or combinations thereof.

[0153] In an embodiment of the present disclosure, the ratio of amount of said PEG 40 hydrogenated castor oil to said polyoxyllglyceride is in the range of 1:5 to 5: 1.

[0154] In another embodiment of the present disclosure, the ratio of the amount of said PEG 40 hydrogenated castor oil to said polyoxylglyceride is in the range of 1:3 to 3:1.

[0155] In a preferred embodiment of the present disclosure, the ratio of the amount of said PEG 40 hydrogenated castor oil to said polyoxylglyceride is 1: 1.

[0156] In an embodiment, the polyoxylglyceride is selected from the group consisting of lauroyl polyoxyl-32 glycerides (Gelucire 44 / 14), stearoyl polyoxyl-32 glycerides (Gelucire 50 / 13), or combinations thereof.

[0157] In a preferred embodiment, the polyoxylglyceride is lauroyl polyoxyl-32 glycerides (Gelucire 44 / 14)

[0158] In another preferred embodiment, the polyoxylglyceride is stearoyl polyoxyl-32 glycerides (Gelucire 50 / 13).

[0159] In a most preferred embodiment, the polyoxylglyceride is lauroyl polyoxyl-32 glycerides (Gelucire 44 / 14).

[0160] These components are essential in ensuring skin, ocular and parenteral formulations' stability, safety, and efficacy. These components maintain the formulation's integrity and compatibility with sensitive skin and ocular tissues. In an embodiment of the present disclosure, the additives include Ascorbic acid, Glycerin, Sorbitol, Disodium EDTA, Citric acid, Tween 80, Span 20, Sodium alginate, Hydroxyethylcellulose, Sucralose, Peppermint oil, Mannitol, Stevia, Titanium dioxide, FD&C Blue No. 1, Lanolin, Cetyl alcohol, Dimethyl sulfoxide (DMSO), Propylene glycol, Parabens, Benzalkonium chloride, Lecithin, Glyceryl monostearate, Sodium lauryl sulfate, Sodium citrate, Sodium metabisulfite, Citric acid monohydrate, allantoin, dimethicone, Beeswax, Cocoa butter, Cetearyl alcohol, Caprylic / Capric triglyceride, Triethanolamine, Phospholipon S- 100, Phospholipon S75, Phospholipon 90G, Phospholipon 90H, Oleic acid, and Sodium carboxymethylcellulose.

[0161] In an embodiment of the present disclosure, preservatives are selected from the group consisting of Oxychloro complex, Phenoxyethanol, Benzalkonium chloride (BAK), Sodium benzoate, Potassium sorbate, Methylparaben, Propylparaben, Chlorobutanol, Ethylene diamine tetra acetic acid (EDTA), Ascorbic acid, Tocopherols, Sodium metabisulfite, Sodium ascorbate, Benzyl alcohol, Boric acid, Citric acid, Benzoic acid, Polyquaternium- 1 , or combination thereof. Examples of pH modifying agents include Triethanolamine, Sodium hydroxide, Citric acid, and Phosphoric acid.

[0162] In yet another aspect, the present disclosure provides a process for preparation of a loaded micellar composition, the process comprising steps of: a. providing 0.01% to 5% w / v of said PEG 40 hydrogenated castor oil; b. providing 0.01% to 5% w / v of said polyoxylglyceride; c. providing 60% to 99.3% w / v of said solvent selected from the group consisting of water or organic solvent selected from ethanol, ethyl acetate, isopropanol or mixtures thereof; d. providing 0.05% w / v to 30% w / v of an active / passenger molecule / plant, animal or marine extract; e. mixing components provided in steps (a) to (d) above in any sequence, under continuous stirring at a speed of 100 to 1000 rpm to obtain a loaded micellar composition; f. optionally, removing the organic solvent from said loaded micellar composition; and g. optionally, filtering the formed loaded micellar composition through bacteria proof filters; wherein the loaded micellar composition comprising: a) a polymer matrix comprising i. 0.01% to 5% w / v of PEG 40 hydrogenated castor oil (HCO RH 40); and ii. 0.01% to 5% w / v of a polyoxylglyceride; b) 60% to 99.3% w / v of a solvent selected from the group consisting of water or organic solvent selected from ethanol, ethyl acetate, isopropanol or mixtures thereof; and c) 0.05% w / v to 30% w / v of an active / passenger molecule / plant, animal or marine extract selected from the group consisting of cannabinoids and other phytochemicals, antifibrinolytic drugs, hematologic agents, antibacterial agents, antifungals, antivirals, HMG-CoA reductase inhibitors, anticancer agents, corticosteroids, analgesics, monoclonal antibodies and benzylisoquinoline alkaloids, plant extracts, nutraceuticals, inorganic molecules and actives, proteins and peptides, and opioid antagonist; wherein said polyox ylglyceride is selected from the group consisting of lauroyl polyoxyl- 32 glycerides (Gelucire 44 / 14), stearoyl polyoxyl-32 glycerides (Gelucire 50 / 13), or combinations thereof; and wherein the weight of PEG 40 hydrogenated castor oil (HCO RH 40) or polyoxylglyceride or active / passenger molecule / plant, animal or marine extract is with respect to the volume of the loaded micellar composition; wherein the active / passenger molecule / plant, animal or marine extract is located within the plurality of micelles of the micellar composition.

[0163] In an embodiment of the present disclosure, a process for preparation of a loaded micellar composition, the process comprising steps of: a. providing 2% to 5% w / v of said PEG 40 hydrogenated castor oil; b. providing 2% to 5% w / v of polyoxylglyceride; c. dissolving / sonicating / melting a. and b. polymers in the solvent; d. providing 70% to 99.3% w / v of a solvent selected from the group consisting of water or organic solvent selected from ethanol, ethyl acetate, isopropanol or mixtures thereof; e. providing 5% w / v to 30% w / v of an active / passenger molecule / plant, animal or marine extract; f. mixing components provided in steps (a) to (d) above in any sequence, under continuous stirring to obtain a loaded micellar composition; g. removing organic solvent, if used in step c., from said loaded micellar composition under continuous stirring at a temperature in the range from 35 to 55 °C; and h. optionally, filtering the formed loaded micellar composition through bacteria proof filters; wherein said polyoxylglyceride is selected from the group consisting of lauroyl polyoxyl- 32 glycerides (Gelucire 44 / 14), stearoyl polyoxyl-32 glycerides (Gelucire 50 / 13), or combinations thereof; and wherein the weight of PEG 40 hydrogenated castor oil (HCO RH 40) or polyoxylglyceride or active / passenger molecule / plant, animal or marine extract is with respect to the volume of the loaded micellar composition; wherein the active / passenger molecule / plant, animal or marine extract is located within the plurality of micelles of the micellar composition.

[0164] In an embodiment, the polyoxylglyceride is selected from the group consisting of lauroyl polyoxyl-32 glycerides (Gelucire 44 / 14), stearoyl polyoxyl-32 glycerides (Gelucire 50 / 13), or combinations thereof.

[0165] In a preferred embodiment, the polyoxylglyceride is lauroyl polyoxyl-32 glycerides (Gelucire 44 / 14)

[0166] In another preferred embodiment, the polyoxylglyceride is stearoyl polyoxyl-32 glycerides (Gelucire 50 / 13).

[0167] In a most preferred embodiment, the polyoxylglyceride is lauroyl polyoxyl-32 glycerides (Gelucire 44 / 14).

[0168] In an embodiment, the process involves further optional steps, such as adding a suitable secondary vehicle for improved administration.

[0169] In yet another aspect, the present disclosure provides the use of a micellar composition for loading an active / a passenger molecule / a plant, animal or marine extract within the plurality of micelles.

[0170] In yet another aspect, the present disclosure provides the use of a loaded micellar composition, wherein an active / a passenger molecule / a plant, animal or marine extract is loaded by the method of the present disclosure for the manufacture of medicament.

[0171] In yet another aspect, the present disclosure provides the use of the loaded micellar composition, wherein the medicament is used as a method of reducing inflammation for the skin, maintain skin barrier and health, skin rejuvenation and as an antioxidant for the skin.

[0172] In yet another aspect, the present disclosure provides the use of the loaded micellar composition, wherein the medicament is for the use in a method for reducing ocular inflammation.

[0173] In an embodiment, the medicament is for use in a method for managing conditions or diseases / disorders of the eye including inflammation, infection, dry eye disease, glaucoma, uveitis, and diabetic retinopathy, and modulating various receptors (like CB1, CB2, TRP channels (TRPV1-TRPM8), GPR55, GPR18, 5-HT1A, and A2A) located in ocular tissues, reducing intraocular pressure, inflammation, and nociceptive pain while providing neuroprotection.

[0174] In yet another aspect, the present disclosure provides the use of the loaded micellar composition, wherein the medicament is used in managing conditions or diseases / disorders of the humans or animals (veterinary use) and is administered as an oral, topical, rectal, vaginal, parenteral, nasal, or transdermal route.

[0175] The present disclosure provides a sustained release drug delivery system comprising the micelles forming composition in an embodiment. The drug delivery system is adapted to release the active / passenger molecule / plant, animal or marine extract at therapeutically effective levels each day over 48 hours or more days.

[0176] The present disclosure provides a high permeation, controlled release, and transparent formulation for topical or application by other routes, including ocular, vaginal, parenteral and oral routes, to mention a few. Depending upon the nature, the active / passenger molecule / plant, animal or marine extract is encapsulated in the core (hydrophobic) or shell (hydrophilic) to result in the improved stability, solubility, and permeability of the encapsulated actives / passenger molecule / plant, animal or marine extract. It may also reduce the toxicity of the actives / passenger molecule / plant, animal or marine extract due to its encapsulation and slow controlled release.

[0177] The micellar composition of the present disclosure is equally suitable for hydrophilic and lipophilic active / passenger molecule / plant, animal or marine extract. Large active / passenger molecule / plant, animal, or marine extract loading up to 500 % or more with respect to the polymer matrix was currently achievable.

[0178] The micellar composition of the present disclosure is a stable formulation in a temperature range of 4°C-40°C.

[0179] The polymeric micelles display an impressive ability to withstand dilution up to 150 to 500- folds, with the count rate of these micelles remaining consistent even when introduced into simulated tear fluid for up to two hours, exhibiting minimal variation.

[0180] Characteristics including viscosity and spreadability of the aqueous polymeric micelles (PMs) dispersion could be modified by directly incorporating secondary components, viz. polymers, hydrogels, and hydrocolloids, into the dispersion.

[0181] Various active / passenger molecules / plant, animal or marine extracts such as active pharmaceutical ingredients (cannabinoids, antifibrinolytic drugs, hematologic agents, cyclosporine, amphotericin B, doxycycline, taxanes, and benzylisoquinoline alkaloids) were loaded into the polymeric micelles of the current disclosure successfully.

[0182] Polymeric micelles are formulated for various routes of administration in the field of drug delivery selected from Oral, Topical, Ophthalmic, Intravenous (IV), Intramuscular (IM), Subcutaneous (SC or Sub-Q), Intradermal (ID), Intraperitoneal (IP), Intranasal, Intravaginal, Rectal, Inhalation, and Intrathecal.

[0183] Various active / passenger molecules / plant, animal or marine extracts are loaded into polymeric micelles for targeted and controlled delivery. These include anti-inflammatory drugs, antibiotics, anti-cancer drugs, anti-viral drugs, anti-fungal drugs, anti-psychotic drugs, pain relievers, anti-epileptic, anti-Parkinson, Corticosteroids, hormones and peptides, vitamins and nutrients, immunosuppressants, and cardiovascular medications.

[0184] Polymeric micelles offer benefits such as improved active / passenger molecule / plant, animal or marine extract solubility, enhanced stability, and the ability to deliver the active / passenger molecule / plant, animal, or marine extract directly to the desired site, making them versatile tools in pharmaceutical research and drug development. The choice of active / passenger molecule / plant, animal or marine extract and delivery system depends on the treatment's specific therapeutic goals and requirements.

[0185] Further, since these micelles are also prepared without the application of any heat or use of organic solvents, hence it is suitable to incorporate even heat-sensitive and / or hydrophilic (water-soluble) actives, including proteins, peptides, enzymes, monoclonal antibodies, and for gene delivery.

[0186] Natural extracts loaded PMs avoid issues encountered with the continuous use of corticosteroids, including immunosuppressant effects and a proneness to secondary infections.

[0187] Natural extracts / plant, animal or marine extract loaded PMs ensure skin hydration in addition to being antioxidant and anti-inflammatory to manage dry, irritated skin, which is a hallmark of most allergic and inflammatory conditions

[0188] EXAMPLES

[0189] The following examples are given by way of illustration of the present invention and should not be construed to limit the scope of the present disclosure. It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are intended to provide further explanation of the subject matter.

[0190] Materials:

[0191] Cannabidiol (CBD) was purchased from Yunnan Hemp Space Biotechnology Co. Ltd., China. Gelucire 44 / 14 was a kind gift sample by Gattefosse, France. Hydrogenated castor oil RH 40 (HCO RH 40) was purchased from Sigma- Aldrich Chemicals Pvt Ltd. Tranexamic Acid (TXA) and Liquorice extract was a kind gift sample by M / s Curetech Skincare Ltd.

[0192] Example 1: Pre-screening and characterisation of polymer blends

[0193] The analysis of various polymeric micelle formulations underscores the significant impact of polymer combinations, solvent choices, and concentrations on the micelles' stability, turbidity, and particle size, which are critical for effective skin drug delivery systems. Stability, indicated by sedimentation behaviour, was a key factor, with formulations such as HCO RH 40 and Gelucire 44 / 14 in ethanol showing no sedimentation within 24 hours, demonstrating superior stability and homogeneity. This is essential for ensuring consistent dosing and preventing phase separation. In contrast, formulations containing Octoxynol 40 (OC40), Gelucire 48 / 16, and Vit E TPGS demonstrated sedimentation within 24 hours, suggesting potential instability that could compromise therapeutic efficacy. Turbidity, which signals micellar instability, was noted in formulations with OC40, Vit E TPGS, and PF127, indicating large size and / or potential micelle aggregation. Aggregation can reduce bioavailability, limiting the effectiveness of the drug delivery system. In contrast, the HCO RH 40 and Gelucire 44 / 14 combination exhibited no turbidity in water or ethanol, suggesting a stable formulation with better drug encapsulation and delivery prospects. Smaller particles facilitate better permeability, and particle size is crucial for enhancing drug absorption through the skin. Formulations comprising HCO RH 40 and Gelucire 44 / 14 produced small particle sizes (44 nm and 29 nm; Table 1), making them ideal candidates for skin drug delivery due to their enhanced permeability. Conversely, formulations comprising OC40 and Gelucire 48 / 16 resulted in larger particle sizes (up to 490 nm), which may hinder skin absorption and reduce therapeutic potential. The choice of solvent was also significant, with ethanol-based formulations showing better stability and smaller particle sizes compared to methanol-based ones. Ethanol is the more suitable solvent for maintaining polymeric micelles' structural integrity and effectiveness in skin drug delivery systems.

[0194] This analysis provides a solid foundation for selecting optimal polymer and solvent combinations in future research to develop stable and effective drug delivery systems for the skin.

[0195] Table 1: Polymer combinations, concentrations, solvents, and their effects on sedimentation, turbidity, and particle size in polymeric micelle formulations.

[0196] Example 2: Preparation of PMs

[0197] Six polymers polyoxyl-32 stearate / polyoxylethylene stearates, lauroyl polyoxyl-32 glycerides / polyoxylglycerides, polyoxyethylene-polyoxypropylene, PEG 40 hydrogenated castor oil, D-a-tocopheryl polyethylene glycol succinate and ethoxylated alkyl phenol were selected for the formulation of the PMs. The concentration for all the chosen polymers was above the critical micellar concentration. Different responses, such as sedimentation, turbidity, and particle size, were considered to select the best formulation for further studies.

[0198] Optimised formulation of PMs was loaded with various drug molecules such as Tranexamic acid (TXA) (5-10%).

[0199] Example 3: Preparation of Tranexamic Acid (TXA) Loaded Polymeric Micelles (PMs) and TXA-PMs Hydrogel (Hgel)

[0200] 5% TXA was incorporated in proposed PMs. Ethanol, with its optimal boiling point and little or no toxicity potential, was chosen as the organic phase in the formulation. It allows for controlled evaporation and does not adversely affect most drugs (ICH and Q3C (R5), 2011). The combination of Gelucire 44 / 14 and Cremophor RH-40, with their complementary characteristics and amphiphilic structures, demonstrates favourable outcomes for the development of PMs loaded with TXA with improved permeation and encapsulation efficiency. After evaluating various concentrations of Carbopol 934P, it was determined that a concentration of 0.5 %w / v was optimal for its use as a secondary vehicle in the formulation of TXA-PMs Hgel preparation intended for skin delivery.

[0201] Example 4: Characterization of TXA-PMs and TXA-PMs Hgel Particle size, PDI, and zeta potential

[0202] The observations indicate a small size (47 nm) and a near neutral surface charge for the TXA- PMs. PMs have an outer hydrophilic shell and a hydrophobic core. TXA, being water soluble, will thus be accommodated in the shell, and as a result, the particle size of active loaded PMs was more than blank PMs (30 nm; data not shown). The particle size of the TXA-PM Hgel was found to vary between 400-500 nm (Fig.s 11-12). Lower PDI values predicted colloidal carriers' stability during storage and suggested their homogeneity. The size was determined to be optimal for efficient dermal administration, and stable colloidal carriers were suggested. The zeta potential of 5% Tranexamic acid-loaded polymeric micelles was -0.04± 0.06 (shown in Fig. 13).

[0203] Table 2: Characterization studies of the developed formulations (n=6).

[0204] Drug assay

[0205] As observed in Table 2 above, the developed PMs and Hgel revealed the drug assay of 93.21% and 88.34%, respectively. The decrease in drug content observed in TXA-PMs Hgel may be attributed to the loss during the incorporation of TXA-PMs nanodispersion in the gel base.

[0206] % EE and %DL

[0207] The %EE of the PMs and Hgel was significantly high, with 81.48% entrapment for TXA- PMs and 81.21% for TXA-PMs Hgel. The %DL was 176.4% and 232.5% with respect to the polymeric matrix for 5% TXA-PMs Hgel and 5% TXA-PMs, respectively. The carrier has demonstrated high carrying capacity, particularly for a highly hydrophilic molecule such as TXA.

[0208] Example 5: Surface Morphology of TXA-PMs

[0209] Field Emission Scanning Electron Microscopy (FE-SEM) and high-resolution transmission electron microscopy (HR-TEM) are used to evaluate the morphology of nanosystems as size and shape of the particles are critical aspects for the in vivo performance. The images obtained from FE-SEM and HR-TEM are represented in Fig. 1.

[0210] HR-TEM image (Fig. la; 10,000X) illustrates well-defined and uniform spherical structures with a consistent size distribution. Acquiring a perfectly spherical shape and the absence of any aggregates is attributed to selecting the right polymeric surfactant(s) and employing their optimal concentrations to ensure proper coverage of the micelles while stirring both phases to form PMs.

[0211] The FE-SEM images also confirmed PMs showing smooth and spherical particles with a regular shape (Fig. lb). The images revealed a homogeneous distribution of single PMs with no aggregation, indicating their stability and uniformity. These small-sized TXA-loaded PMs are considered suitable for efficient dermal delivery of TXA to the skin. FE-SEM image of TXA-PMs incorporated into the Hgel indicates a bee -hive gel structure with enmeshed PMs (Fig. 1c). The PMs maintained their shape and integrity in the Hgel.

[0212] Determination of pH The final formulation's pH was 5.7 ± 0.07 for TXA-PMs Hgel, indicating them suitable for dermal delivery. The pH of the formulation is evaluated to analyse the risk of irritation upon topical application and to confirm the skin-friendly nature of the topical formulation.

[0213] Example 6: Spectrum analysis DSC, FTIR,1H-NMR

[0214] DSC analysis

[0215] The thermogram of pure TXA (Fig. 2) showed an endothermic peak at 279.96° C (566.1J / g), which corresponds with its melting point of >260°C. Fig. 2 also includes the thermograms of Gelucire 44 / 14 and Cremophor RH-40. It is, however, evident that the original peaks of TXA and polymers disappear from the thermogram of the final formulation, which shows a broad peak at 120.45°C. Absence of distinct peaks of the excipients and TXA confirms the encapsulation of TXA inside the PMs system. The presence of an endothermic peak in the thermogram of formulation at a lower temperature implies the transformation of TXA into a nanoparticulate form.

[0216] Fourier transform infrared spectroscopy (FT-IR) analysis

[0217] The characteristic peaks observed in the FTIR spectrum of TXA confirmed the presence of all of its functional groups, viz. 3280-3500 cm'1corresponding to O-H stretching vibration of the carboxylic acid group (COOH), 1710-1720 cm1, corresponding to carbonyl group (C=O) of the carboxylic acid; 1630-1650 cm'1correspond to the amide group (C=O) stretching vibration; 1440- 1470 cm'1to amide group (N-H) bending vibration; C-N stretching at 1220- 1260 cm'1and in the FTIR spectrum of Carbopol 934P, band at 1700-1800 cm1, corresponding to carbonyl (C=O) group in the carboxylic acid and 3200-3600 cm1, indicating the stretching vibrations of the hydroxyl groups. Absence of characteristic TXA in the final formulation indicates encapsulation of TXA in PMs system.

[0218] 1H-NMR spectroscopy

[0219] The1H-NM R (Proton Nuclear Magnetic Resonance) spectrum of TXA was obtained to define information about the chemical environment and connectivity of hydrogen atoms within the molecule. TXA is composed of a cyclic structure with a carboxylic acid group and an amino acid side chain, and its NMR spectrum showed peaks in the region of 1-4 ppm corresponding to the protons attached to the methylene groups.

[0220] TXA PMs Hgel also showed the similar number of protons as for TXA Fig. 3 (a) which may be because of the signals by unentrapped TXA (18.79%) in the formulation. However, the increase in the number of protons observed in region of 4-5 ppm is attributable to the interaction between the protons of Cremophor RH-40 and proton of methylene group present in TXA.

[0221] In Fig. 3 (c), the peaks around 0.8- 1.2 ppm are attributed to the methyl (-CH3) protons in the hydrocarbon chains of Gelucire 44 / 14. The 1.2-2.0 ppm peaks correspond to the methylene (-CH2-) protons in the hydrocarbon chains in Gelucire 44 / 14. The peak at around 3.5 ppm is associated with the protons of Cremophor RH-40. Example 7: Rheological and Syringeability Studies

[0222] Syringeability study

[0223] The TXA-PMs Hgel demonstrated good syringeability, allowing for easy and smooth dispensing through a syringe without significant resistance or clogging. Suitable viscosity and shear-thinning behaviour contributed to its ability to be readily injected, making it ideal for biomedical and pharmaceutical applications with packaging and dispensing ease.

[0224] Rheological behaviour

[0225] The viscometric analysis was used to study micro-mechanical characteristics of Hgel. The study revealed shear-thinning and pseudoplastic behavior of TXA-PM Hgel. As shear stress increases from 1,280 Pa (247 Pa-s viscosity) to 2,030 Pa (29.6 Pa-s viscosity), the substantial decrease in viscosity shows that the Hgel becomes less viscous under mechanical stress, as shown in Fig. 4. This property is deemed suitable for topical applications, as it allows for a more straightforward application and spreads the formulation on the skin. Thus facilitating better penetration and distribution of TXA.

[0226] The analysis further demonstrated a positive correlation between shear stress and shear rate as given in Fig. 4. As shear stress increases, the shear rate progresses from 5.19 1 / s to 68.4 1 / s, indicating that the formulation transitions from a more viscous state at low shear rates to a less viscous, more flowable state at higher shear rates. This transition is vital for the performance of TXA-PMs Hgel during application as it will help maintain effective flow properties. This characteristic ensures that the TXA-PMs Hgel can adapt to the stresses encountered during application, promoting uniform coverage and effective delivery. As shear rate increases, the viscosity decreases (Fig. 4), reinforcing the shear-thinning characteristics of Hgel, facilitating ease of use while ensuring that the TXA is delivered effectively to the target area for melasma treatment. The lower viscosity at higher shear rates is particularly beneficial in enhancing skin penetration and improving the therapeutic efficacy of the drug, as it allows quicker absorption into the skin layers.

[0227] The pseudoplasticity of the TXA-PMs Hgel may be credited to the microstructure gelling with reverse micellar nature and ability to swell on hydration, resulting in a three-dimensional network that forms Hgel.

[0228] Example 8: In vitro Drug Release and Mechanism

[0229] In vitro release behavior and mechanism

[0230] In vitro release of prepared formulation was studied across dialysis membrane using phosphate buffered saline (pH 7.4) as the receptor medium. TXA-PMs Hgel released >97% TXA within 48 h. The release of free TXA from the Hgel matrix was significantly faster (>94% within 8 h) than the corresponding TXA-PMs Hgel. TXA-MKT gel also showed significantly faster release, which matched the free TXA Hgel (Fig. 5). The release data was fitted into different kinetic models. The regression coefficients were compared to identify the best fit model indicated by the highest r2values.

[0231] As expected, free TXA Hgel and the TXA-MKT gel showed first-order release kinetics while the TXA-PMs Hgel followed Higuchi release kinetics (r2=0.9845 and r2=0.9772 respectively). The Higuchi model is based on Fick's second law of diffusion and indicates that the release of TXA from PMs Hgel follows a square root of time. It suggests that the drug release is driven by the diffusion of TXA molecules through the polymeric matrix of PMs. The sustained release profile of TXA indicates this formulation's suitability for treating skin disorders, such as melasma, where long-term treatment is desired.

[0232] Example 9: Acute Dermal Irritation and Biocompatibility

[0233] Acute dermal irritation / toxicity study

[0234] Animals from all five groups were observed after applying their respective formulations. The application site was observed for the presence or absence of erythema and / or edema using a scoring method from 0 to 4 (absent to severe) at regular intervals post application upto 72 h. Based on the observations (zero scores), it is concluded that all treatments are safe, and there are no signs of any irritation / toxicity at the tested doses of TXA in Hgel either in the free or upon incorporation in the PMs.

[0235] Biocompatibility evaluation of TXA formulations through skin histology

[0236] After the dermal toxicity studies concluded, the animals were sacrificed, and the treated skin samples were observed for any changes on the cellular level through histological examination. No difference of serious concern in skin samples following various treatments was observed compared to the naive control group as revealed in table 3.

[0237] Table 3: Biocompatibility evaluation of TXA formulations - histology of mice skin following different treatments

[0238] Fig. 7a to Fig. 7d illustrates Histology of mice skin following treatment of a) Naive control, b) Group 1 -Blank PMs Hgel, c) Group 2 -TXA PMs Hgel, and d) Group 3 -5% TXA-MKT gel.

[0239] Ex-vivo permeation study

[0240] It is shown that PMs have permeated to the dermis layer of skin, as revealed by in vivo permeation studies, and release drugs for extended periods, as indicated by the in vitro / ex vivo studies. PMs improve skin delivery as their small size allows for a larger contact area with the skin and, consequently, the formation of a depot / reservoir in the skin. Micelles are reported to induce alterations in stratum corneum, which also enhances skin permeation. Hence, the current study was planned to monitor the flux across the skin, the extent of absorption, and the amount of TXA present (retained) in the skin 48 h post application (Fig. 6a). The permeation rate of TXA was higher in the initial h, indicating a rapid release of the drug from the PMs following the concentration gradient. Subsequently, the permeation rate decreased, suggesting a controlled and sustained release of TXA from the PMs. Flux and amount permeated of free TXA Hgel and TXA-MKT gel are significantly less (p-value> 0.05) than the TXA-PMs Hgel (5 %), establishing the higher permeability of TXA achieved by its incorporation into PMs (table 4).

[0241] Table 4

[0242] Comparison of various formulations of TXA in terms of total amount permeated, percentage permeation, flux, and permeability coefficient obtained during ex vivo permeation studies using mice skin (n=6).

[0243] NOTE- *5% TXA gel, 5% TXA PMs Hgel, and 5% TXA-MKT gel -amount of TXA applied per skin sample was 5000 pg / lOOmg dose. lOOmg formulations were loaded in each case.

[0244] The study concludes that the currently developed PMs are effective in considerably improving the skin permeation of TXA.

[0245] As previously discussed, topically, drugs must permeate and remain in deeper layers of skin in the required concentration for efficient management of hyperpigmentation conditions like melasma. The drug retention from TXA-PMs Hgel was 30.55 ± 6.36 pg / cm2,which was 150% higher than TXA-MKT gel (Fig. 6b).

[0246] Example 10: In vivo skin permeation in mice

[0247] In vivo skin permeation in mice using Confocal laser scanning microscopy (CLSM)

[0248] To support the ex vivo permeation and drug deposition findings, this study was carried out to visualise the path of Fluorescein (Fl) probe labelled PMs incorporated in the hydrogel (Fl-PMs Hgel) when applied to mice skin for 0.5, 2, and 12 h, using CLSM. Free Fl Hgel served as control and was applied similarly. The results are displayed in Fig. 8 for different time points. Fluorescence was detected at all time points in Fl-PMs Hgel-treated skin, but the signal for free Fl Hgel was either absent or faint compared to the Fl-PMs Hgel group. After 12 h of treatment, Fl-PMs Hgel showed appreciable fluorescence in the epidermis and dermis. This confirmed superior permeation and retention to deeper skin layers by the developed PMs as a carrier. Permeation to deeper layers where melanocytes are produced will be of interest for molecules like TXA, which are proposed for melasma treatment.

[0249] It may be noted that TXA is a BCS class III drug with very high hydrophilicity (logP as -1.6). Permeation by such molecules through the skin itself without any carrier may not be otherwise possible. In future studies, TEM micrographs can establish if the PMs travel intact upto these lower layers or are disrupted during transport. Several studies have suggested the transappedengeal route as the mechanism of skin absorption for PMs. These studies have reported the existence of PMs in hair follicles upon topical skin treatment. However, the current findings support our previous observations regarding the enhanced permeation and drug deposition capabilities of PMs Hgel.

[0250] Example 11: Cytotoxicity and Melanin Content Studies

[0251] Cytotoxicity study

[0252] Fig. 9 depicted the % viability of the L929 and Bl 6F 10 melanoma cells after exposure to various treatments when several control group cells were taken as 100% viable. Tested samples are considered safe, provided they exhibit % cell viability of more than 80%. All treatments at varying TXA concentrations were thus found safe.

[0253] Melanin content quantification

[0254] We then sought to confirm whether TXA-PMs and TXA-PMs Hgel resulted in decreased pigmentation as determined in terms of melanin estimation. Toward this, B16F10 cells were treated with blank PMs, free drug Hgel, TXA PMs, and TXA Hgel before measuring cellular melanin content (Fig. 10) As expected, TXA-PMs and TXA-PMs Hgel had significantly diminished concentration of melanin than the control group, free drug, and free drug Hgel. Compared with the reported works, TXA PMs Hgel exhibited substantially better performance in reducing melanin content.

[0255] Example 12: Stability Studies

[0256] Stability Studies

[0257] Accelerated Stability Studies

[0258] 5% TXA-PMs formulations stored at 25±2°C / 60±5% RH and 40±2°C / 75±5% RH exhibit minor changes in particle size, PDI, zeta potential, drug assay, and entrapment efficiency over three months. The formulations remain relatively stable, but higher temperatures cause slight decreases in these parameters. Overall, the data suggest good stability under both conditions, with only minor effects observed due to elevated storage conditions. The observed physical parameters at different time intervals (at 40±2°C / 75±5% RH and 25±2°C / 60±5% RH) are presented in table 5. The results show that the formulations in 1 and 3 months had no visible change and were observed to be stable. Table 5

[0259] Physical examination of formulations after regular intervals of time.

[0260] Example 13: Characterization of Full-Spectrum (FS) cannabis extract-loaded Polymeric Micelles (FS-PMs)

[0261] Characteristics peaks in FTIR spectra

[0262] The FTIR (Fourier Transform Infrared) spectroscopy provides valuable information about a compound's chemical composition and functional groups.

[0263] Table 6: Characteristics absorption peaks in IR of various components and the developed nanoformulations

[0264] The FTIR spectrum of the 1 % FS PMs also exhibits key functional groups from both the FS and the micelle-forming agents (hydrogenated castor oil RH 40 and gelucire 44 / 14). Shifts in the O-H, C=O, and C-O-C stretching vibrations compared to the spectra of the individual components suggest interactions between the FS and the micelle matrix, possibly through hydrogen bonding. All characteristic peaks in the final formulation confirm CBD's successful incorporation and encapsulation in the micelle system.

[0265] Nuclear magnetic resonance (spectroscopy)

[0266] The NMR spectra of FS, blank PMs, and FS PMs formulations demonstrate distinct and overlapping peaks corresponding to their respective molecular structures (Fig. 15). The FS spectrum displays characteristic aromatic protons in the 7-6 ppm region, olefinic and electronegative atom-adjacent protons in the 5-4 ppm region, and aliphatic protons in the 3.5-1 ppm region. The 1 % FS PMs formulation exhibits peaks from both FS and the blank polymeric micelles, with aromatic and olefinic protons indicating the successful incorporation of FS. The consistent presence of polymer backbone peaks confirms the structural integrity of the micelles.

[0267] DSC (Differential scanning colorimetry)

[0268] The thermal analysis of the components and formulations provides critical insights into their behaviour and suitability for micelles drug delivery systems. The pure FS exhibited two distinct endothermic peaks at 103.34°C and 122.81°C, with enthalpy changes of 17.07 J / g and 7184 J / g, respectively. Polymer 1 demonstrates a significant endothermic transition at 49.45°C with an enthalpy change of 124.9 J / g, indicative of a flexible and adaptable material suitable for low- temperature processing. Polymer 2, on the other hand, displays multiple thermal events, including a minor transition at 109.93°C (AH = 2.117 J / g) and a prominent endothermic peak at 128.25°C (AH = 7.859 J / g), followed by an exothermic degradation peak at higher temperatures, suggesting thermal stability up to a defined limit.

[0269] The blank polymeric micelles (PMs) exhibit a major endothermic transition at 122.80°C with a substantial enthalpy change of 13603 J / g, indicating a significant phase transition that reflects their thermal stability and structural integrity. The 1% FS -loaded polymeric micelles (FS PMs) display an endothermic peak at 118.76°C with a high enthalpy value of 6976 J / g, demonstrating strong interactions between FS and the micellar matrix, which enhances the encapsulation and stabilisation of the active ingredient. These findings emphasise the ability of the polymeric micelle system to protect FS from thermal degradation and provide controlled-release properties. Overall, the thermal data underline the materials' compatibility, stability, and processability under defined conditions. The distinct thermal transitions of FS, polymers, and micelles validate their selection for micellar formulations, ensuring enhanced stability and functionality. This detailed characterisation further supports the scalability of the formulations for manufacturing, making them ideal for controlled-release drug delivery applications.

[0270] Table 7: Thermal analysis of the components and formulations of FS-PMs

[0271] Particle Size and Zeta Potential:

[0272] The FS-PMs exhibited an average particle size of 198.5 ± 31.94 nm, ensuring optimal skin penetration, with a PDI of 0.324 ± 0.01, indicating a uniform size distribution. The zeta potential was measured at -2.09 ± 1.30 mV, confirming stable colloidal systems suitable for topical application. pH Studies:

[0273] The pH of FS-PMs was determined to be 7.2 ± 0.34, which is compatible with skin formulations, ensuring minimal irritation and preserving skin barrier function, particularly for sensitive or atopic skin conditions.

[0274] Drug Assay and Entrapment Efficiency:

[0275] FS-PMs achieved a high total drug content (TDC) of 95.40 ± 2.45%, with an entrapment efficiency (%EE) of 91.06 ± 4.28%, significantly outperforming traditional solid lipid nanoparticles (SLNs). Example 14: Morphology and Stability

[0276] Surface Morphology (FE-SEM and HR-TEM): Microscopic analysis revealed that FS-PMs were spherical, with a core-shell structure, exhibiting no aggregation, further confirming the stability and homogeneity of the micellar formulation.

[0277] In Vitro Drug Release:

[0278] FS-PMs demonstrated a 90.61% release of the active compound over 72 hours, following a Higuchi release model (r2= 0.953), indicative of sustained and controlled diffusion-driven drug release.

[0279] Example 15: Skin Permeation and Anti-inflammatory Efficacy

[0280] Ex Vivo Skin Permeation:

[0281] FS-PMs enhanced skin retention by 227% compared to free FS, retaining 76.59% of the applied dose over 72 hours, significantly improving active compound absorption into the skin.

[0282] Anti-inflammatory Performance (In Vivo and In Vitro):

[0283] In both the DNCB-induced in vivo atopic dermatitis model and LPS-induced in vitro fibroblast cell inflammation model, FS-PMs reduced TNF-a levels by 43.05%. FS-PMs also significantly reduced IL-6 levels in skin tissues, affirming their anti-inflammatory potential.

[0284] Example 16: Toxicity and Safety Studies

[0285] Cytotoxicity Study:

[0286] FS-PMs exhibited 85-88% cell viability in dermal fibroblast cell lines (L929), confirming their safety for skin application.

[0287] Acute Dermal Irritation / Toxicity Study:

[0288] In acute dermal irritation studies on Wistar female rats, FS-PMs scored zero for erythema and edema at all observed time points, demonstrating excellent skin compatibility with no irritation or adverse effects.

[0289] Example 17: Pharmacodynamic Studies in Rat Model of Atopic Dermatitis

[0290] Visual and Clinical Evaluation:

[0291] In the DNCB-induced in vivo atopic dermatitis rat model, FS-PMs showed significant improvement in skin condition, including reduced erythema and edema, by the 15th day of treatment. FS-PMs outperformed free FS and were comparable to the corticosteroid Topinate®.

[0292] Histological Analysis:

[0293] Histological analysis showed almost complete healing in FS-PM-treated rats, with minimal inflammation, erythema, or dryness, promoting faster wound healing and reducing inflammatory cell infiltration.

[0294] Biomarker Analysis: FS-PMs treatment significantly reduced pro-inflammatory cytokines TNF-a and IL-6 levels in rat skin, achieving more significant reductions than free FS or blank PMs, highlighting the potent anti-inflammatory effects of FS-PMs.

[0295] Example 18: Table 8: Face serum formulation with different active ingredients

[0296] Table 8 represents face serum formulations for different active ingredients. Although the subject matter has been described in considerable detail regarding certain preferred embodiments, other embodiments are possible. As such, the spirit and scope of the subject matter should not be limited to the description of the preferred embodiment contained therein. Example 19:

[0297] Table 9: Ocular formulation with different active ingredients Example 20:

[0298] Polymeric Micelles (PMs) co -encapsulating Tranexamic Acid (TXA) with other antipigmentation, hydrating and radiance-providing actives and further incorporation of formed PMs into a secondary vehicle

[0299] 5% TXA was combined with varying concentrations of one or more other components, i.e. kojic acid, hydroquinone, hyaluronic acid, a-arbutin, and symradiance 399 (4-hexylresorcinol). The combination of Gelucire 44 / 14 and Cremophor RH-40, with their complementary characteristics and amphiphilic structures, demonstrates favourable outcomes for developing PMs with improved permeation and encapsulation efficiency. Suitable antioxidants, like butylated hydroxyanisole, butylated hydroxytoluene, sodium metabisulphite, sesamol, nor dihydroguaretic acid, curcumin, tetra hydro curcumin, EGCG, resveratrol were added in PMs to prevent the oxidation of actives. After evaluating various concentrations of Carbopol 980, it was determined that a concentration of 0.3% w / v was optimal for its use as a secondary vehicle in the formulation intended for skin delivery.

[0300] Example 21:

[0301] Preparation of polymeric micelles combining cannabidiol (CBD) and atorvastatin (ATO) demonstrated promising potential for treating ocular inflammation

[0302] The development of polymeric micelles (PMs) combining cannabidiol (CBD) and atorvastatin (ATO) demonstrated promising potential for treating ocular inflammation. The micelles had a particle size of 25.60 ± 0.94 nm, a polydispersity index (PDI) of 0.33 ± 0.08, and a zeta potential of -1.3 ± 0.02 mV, indicating stability and uniformity. Entrapment efficiencies were 82.61% for ATO and 85.41% for CBD, with a neutral pH of 7.0 ± 0.34 and osmolarity of 280 ± 0.11 mOsm / L, suitable for ocular application. Drug release followed the Higuchi model, with ATO and CBD release reaching 21.39% and 29.69%, respectively, after 8 hours. In vivo studies showed prolonged retention in ocular tissues for up to 240 minutes, with drug permeation reaching the retina within 0.5 hours. Safety assessments revealed over 70% cell viability in SIRC cells, non-irritating effects in ocular and dermal tests, and efficient cellular uptake.

[0303] Efficacy studies demonstrated significant reductions in redness and inflammation, with TNF-a and IL-6 levels reduced by 65% and 60.36%, respectively, surpassing the marketed ketorolac formulation (46.6% and 38.48% inhibition). Histological analysis confirmed the preservation of the corneal structure with no signs of inflammation. In LPS -induced inflammation models using THP-1 cells, TNF-a levels dropped from 73.3 to 20.45 pg / mL, and IL-6 levels from 53.15 to 19.67 pg / mL, outperforming ketorolac. Overall, the combination of PMs demonstrated superior anti-inflammatory effects, safety, and stability, making them a promising alternative for managing ocular inflammation. Example 22: Preparation of Cannabidiol (CBD) Loaded Polymeric Micelles (PMs), (CBD- PMs)

[0304] Initially, the required amounts of HCO RH 40 and gelucire 44 / 14 polymers were accurately weighed. These polymers were then dissolved in an appropriate organic solvent, such as ethanol. If necessary, gentle heating and / or placing in an ultrasonic bath was done to ensure complete dissolution of the polymers. Next, CBD was dissolved in a small volume of the same organic solvent and mixed together. This polymeric-CBD solution was gradually added to hot distilled water with continuous stirring with a magnetic stirrer. This stirring was maintained until the organic solvent evaporated utterly, and the volume of the mixture was reduced to that of the aqueous phase, resulting in a homogeneous mixture. Thorough mixing was carried out to achieve uniform distribution of CBD throughout the PMs. The resulting micelle solution was filtered through a 0.22 pm filter to remove particulate matter or contaminants. A sterile filtration apparatus was utilised to get a sterile solution, which was then collected in a clean, sterile container suitable for storage. Finally, micelles were stored under appropriate conditions to ensure their stability, preparing a formulation conducive to sustained drug release in ocular applications.

[0305] Analysis of drug content in PMs

[0306] Following the established assay procedure, the CBD assay was found to be 98.80%±2.1, indicating that the optimisation strategies successfully achieved a near-complete CBD loading into the PMs.

[0307] Analysis of entrapment efficiency of CBD-PMs

[0308] The % EE of CBD in the optimised PMs (Fig. 16-17) indicates a significant ability of the formulation to retain CBD within micelles, was determined to be 81.45%±0.87, suggests that the formulation is capable of maintaining a substantial amount of CBD within its matrix. This high EE is crucial for ensuring sustained drug release, minimising the risk of rapid drug elimination, and enhancing the therapeutic efficacy of the formulation in ocular delivery. The experimental replication (n=6) further strengthens the reliability of the optimised process of the formulation and its results, thereby validating the EE's consistency and showcasing the polymeric system's effectiveness.

[0309] Particle Size (PS), Zeta potential and mobility in polymeric micelles

[0310] CBD-PMs showed uniformly small particle size of 30 nm, indicating their suitability for ocular application, as smaller particles are known to enhance drug permeation through the corneal barriers and improve retention within ocular tissues.

[0311] Low Zeta potential, ranging from -0.73 mV to -3.68 mV with an average of -1.97 mV, was observed, especially considering that the polymers used in the formulation are non-ionic. Despite the low negative ZP, the PMs remain stable in solution due to steric stabilisation, ensuring that the micelles do not aggregate. The non-ionic polymers typically stabilise micelles through steric hindrance, relying on the bulky polymer chains to prevent aggregation, rather than depending on strong electrostatic repulsion. Thus allowing the formulation to maintain homogeneity and consistency and ensuring proper drug distribution upon application. This stabilisation mechanism is particularly beneficial in ocular applications, where high charge densities lead to irritation of sensitive eye tissues.

[0312] Fig. 18 illustrates mobility values ranging from -5.695e-006 cm2 / Vs to -2.869e-005 cm2 / Vs, indicating that the micelles exhibit limited movement under an electric field, a reflection of their weak surface charge. However, this low mobility is consistent with the non-ionic nature of the polymers, which do not carry significant charge. Given the constant electric field of - 16.32 V / cm applied across all measurements, the data suggests that the formulation is stable and reproducible. The non-ionic nature of the polymers is a positive feature for ocular use, as it reduces the likelihood of irritation or toxicity resulting from charged particles interacting with the delicate eye tissues.

[0313] Dilution factor measurement

[0314] At various dilutions, the CBD-PMs (Fig.s 19 to 21) demonstrate stable PSs ranging from 31 nm to 42 nm while maintaining a low PDI between 0.12 and 0.254 at a temperature in the range of 5 °C to 25 °C, ensuring better penetration into tissues / biological membranes. The system's stability at ambient temperature suggests that it can be used without cold storage, adding practical value to the formulation.

[0315] At 40°C, there is a slight increase in PS to 64 nm, but there is no loss of structural integrity, and the size is still small enough. This resilience at elevated temperatures highlights the formulation's robustness, ensuring its efficacy in various storage and application environments.

[0316] Short term stability analysis of CBD-PMs in simulated tear fluid (STF)

[0317] The stability of CBD-PMs in simulated tear fluid (STF) evaluated through count rate measurements over 2 hours, as shown in Fig. 22, demonstrated a favourable stability profile, with only a gradual decline in count rate, indicating limited degradation of the micelles over time. This steady count rate behaviour reflects the ability of the formulation to maintain a consistent concentration of CBD-PMs within STF, which is crucial for sustained therapeutic delivery in ocular applications.

[0318] The count rate, measured in kilocounts per second (kcps), is directly proportional to the concentration of dispersed nanoparticles, providing a reliable indicator of micelle stability in suspension. At the initial measurement (0.5 hours), the CBD-PMs displayed a count rate of 5252.86 ± 114.23 kcps, indicating a high concentration of intact nanoparticles in the fluid. By 1 hour, the count rate remained similar, slightly decreasing to 4891.86 ± 144.31 kcps. This minimal reduction in count rate suggests that the micelles effectively resist aggregation or degradation in STF, highlighting the robustness of the formulation (p > 0.05). After 1.5 and 2 hours, the count rate showed a slight, gradual decrease, reaching 4841.71 ± 187.31 kcps and 4767.57 ± 147.36 kcps, respectively. This minor decline over the entire duration of the study further supports the micelles' stability, as most particles remained suspended without significant loss or breakdown (p>0.05 for all time points compared to 0.5 hours). The use of excipients, particularly hydrogenated castor oil RH 40, was instrumental in achieving this stability. As a non-ionic surfactant with an appropriate HLB, RH 40 reduced surface tension, promoting stable micelle formation and preventing particle aggregation in the tear fluid environment.

[0319] These findings suggest that the formulation's design, including the careful selection of excipients, successfully addresses the challenges of stability and solubility in a tear-like fluid, providing a promising platform for CBD delivery in ocular therapies.

[0320] Optical microscopy of polymeric micelles

[0321] The CBD-PMs were analysed under 40x magnification, which revealed small, round morphology and the absence of aggregation or structural irregularities.

[0322] Field emission scanning electron microscopy (FE-SEM)

[0323] The CBD-PMs of the present disclosure were analysed using a field emission scanning electron microscopy (FE-SEM) at an accelerating voltage of 15 kV, with a working distance of 8.0 mm and a magnification of 150,000x. The results demonstrated that the PMs exhibit a uniform and well-defined spherical shape, indicating a highly organised structure. Notably, the nanoparticles were found to maintain their integrity throughout the drying process, ensuring an accurate representation of their morphology. These findings suggest that the micelles are structurally stable, essential for their functionality in delivery systems. The observed small, spherical morphology is consistent with the characteristics expected for effective delivery vehicles, capable of encapsulating and releasing CBD in a controlled manner.

[0324] In conjunction with the FE-SEM results, analysis of dynamic light scattering (DLS) studies confirmed PS of approximately 30 nm, which is mainly known to be advantageous for ocular drug delivery, as it has been known to enhance the solubility of the drug and improve its bioavailability by facilitating better permeation through the corneal barriers. The combination of the spherical morphology, small PS, and structural stability suggests that the CBD-PMs are well-suited for encapsulating CBD and ensuring its efficient delivery, potentially improving the therapeutic efficacy of CBD in ocular applications.

[0325] On analysing the roughness of the obtained FESEM images of CBD-PMs, using Gwyddion software, the Ra was found to be 12.0731 nm, indicating moderate surface irregularities, which could be beneficial for enhancing interactions between the micelles and ocular tissues. The Rq value of 15.2815 nm, higher than Ra, indicates a significant presence of peaks and valleys on the surface, contributing to an increased surface area for drug release and interaction with biological tissues. The Rp of 57.9842 nm and Rv of 52.5164 nm reflect the extremes of surface roughness, suggesting the presence of pronounced features that may enhance bioadhesion. The positive skewness value (0.0236737) indicates that the surface has a near-symmetrical distribution of peaks and valleys, which can be advantageous for consistent adhesion to the ocular surface, crucial for increasing the residence time of the micelles in the treatment of uveitis. The kurtosis value (3.36373) suggests a surface with moderate peak sharpness, which may facilitate optimal retention without irritating the delicate ocular tissues, thus improving delivery efficiency. Moderate roughness can increase the effective surface area, promoting dissolution and enhancing drug release. For CBD-PMs, these roughness characteristics can be advantageous for achieving sustained release, which is essential for managing chronic ocular inflammation like uveitis. At the same time, surface roughness can impact the stability of the micelles by influencing their aggregation tendencies because the particles with higher roughness have more contact points, which may increase the likelihood of aggregation. Thus, understanding these characteristics helps design stable formulations without compromising therapeutic efficacy.

[0326] High-resolution transmission electron microscopy (HRTEM)

[0327] The CBD-PMs stained with phosphotungstic acid (PTA) were analysed using High-resolution transmission electron microscopy (HRTEM) at a scale of 500 nm for their structural properties, demonstrating that the nanoparticles appeared well-dispersed, with minimal aggregation, a crucial aspect for formulations intended for the sensitive ocular environment. When zoomed in to 100 nm, the spherical morphology of the PMs became more prominent, which is essential for ensuring smooth interaction with ocular tissues and minimising irritation upon application. The magnifications used in the analysis, ranging from 150,000x to 300,000x, enabled precise observations of the nanoparticle surfaces and their structural integrity. The micelles showed a consistent spherical shape, with an average PS of 30 nm. This small size is mainly advantageous for ocular drug delivery as it facilitates better permeation through the corneal layers and improves retention in the ocular tissues, which is critical for sustained therapeutic effects.

[0328] The PTA staining, performed in a phosphate buffer at pH 6.8, effectively increased the electron density around the micelles, enhancing contrast and enabling precise identification of individual particles. pH analysis of CBD-PMs

[0329] The CBD-PMs pH was approximately 6.03 ± 0.7, which aligns well with the physiological pH of tears (around 7.4). This is crucial for ocular delivery, as formulations with pH values close to that of natural tears are less likely to cause discomfort or irritation when applied to the eye.

[0330] Osmolarity measurement analysis of CBD-PMs

[0331] The osmolarity of the CBD-PMs formulation of the present disclosure, measured using the freezing point depression method in a calibrated osmometer, was found to be 224 mOsm / L, which is close to the physiological osmolarity of the eye, -300 mOsm / L, thereby rendering it suitable for ocular treatment. This proximity to isotonicity is crucial for ocular applications, as it ensures that the formulation will not cause significant osmotic stress when applied to the eye's delicate tissues. The osmometer was calibrated using standard solutions with known osmolarity values. Solutions that are either too hypertonic (high osmolarity) or hypotonic (low osmolarity) can lead to irritation, discomfort, or even damage to the ocular surface, causing symptoms like stinging, redness, or tearing. However, the osmolarity of 224 mOsm / L of the CBD-PMs formulation of the present disclosure is sufficiently balanced, suggesting that the formulation will maintain the eye's natural osmotic balance, minimising the risk of irritation and enhancing patient comfort.

[0332] The PMs of the present disclosure offer multiple advantages for ocular drug delivery, such as their amphiphilic nature enhances the solubility and stability of hydrophobic compounds like CBD, their small PS ensures efficient drug penetration across the corneal barriers, and PMs further promote sustained drug release, potentially improving therapeutic outcomes by extending the retention time of CBD in the ocular environment. Moreover, the near-neutral pH and physiological osmolarity of the CBD-PMs aids in maintaining the structural integrity of the ocular tissues, minimising the risk of inflammation or adverse reactions, which is often a concern with topical ophthalmic formulations.

[0333] Differential scanning calorimetry (DSC) analysis

[0334] Analysis of the differential scanning calorimetry (DSC) data of the CBD-PMs of the present disclosure revealed critical thermal properties of both the individual components of the PMs and the encapsulated system (shown in Fig. 14a). Pure CBD showed a melting endothermic peak at 68.33°C, with an enthalpy of 18.27 J / g, indicating its highly crystalline nature. HCO RH 40, a surfactant used in the PMs formulation, exhibited peak at 357.02°C with an enthalpy of 50.20 J / g.

[0335] Gelucire 44 / 14, a lipid excipient used in the formulation, showed multiple transitions with peaks at 44.88°C and 203.64°C, with an enthalpy of 41.9 J / g. These peaks corresponding to the melting points of various lipid components, indicated by the complex structure of gelucire that includes glycerides and esters.

[0336] The blank PMs peaked at 125.9°C, with a significantly higher enthalpy of 1527 J / g, suggesting the melting and thermal transition of the polymeric material used to form the micelles. The CBD-PMs DSC curve peaked at 103.40°C, with a very high enthalpy of 2276 J / g. The shift in the melting point and the increase in enthalpy of the CBD-PMs compared to the blank PMs indicated successful encapsulation of CBD within PMs. The slight temperature increase suggested that CBD's crystalline structure is altered within micelles, likely due to its interaction with the polymer matrix. The higher enthalpy of the CBD-PMs further indicates that CBD is well-dispersed and stabilised in the polymeric system, enhancing its thermal stability.

[0337] Fourier transform infrared (FTIR) analysis

[0338] FTIR spectra of CBD alone (Fig.14b) showed distinct peaks at 3413, 3520, 2923, 2856, 1442.24, 1241, 1582, and 1627 cm The firm peaks around 3413 and 3520 cm1correspond to O-H stretching vibrations, indicating the presence of hydroxyl groups in CBD, while the peaks at 2923 and 2856 cm1are attributed to C-H stretching in alkanes. The peaks at 1442.24 and 1241 cm1suggest the presence of C-C and C-0 stretching vibrations, and the peaks at 1582 and 1627 cm1are likely due to C=C stretching in the aromatic ring of CBD.

[0339] FTIR spectra of HCO RH 40, a common surfactant used in the formulation, showed peaks at 3443.37, 2920.51, 1732, 1353, and 1461 cm with the broad peak at 3443.37 cm1attributed to O-H stretching and the peak at 1732 cm1corresponding to the ester carbonyl group (C=O), which is crucial for surfactant stability.

[0340] Similarly, FTIR spectra of Gelucire 44 / 14 alone exhibited peaks at 3436, 2920, 1732, 1462, and 1106 cm The overlapping peak at 1732 cm1with HCO RH 40 indicates the presence of ester bonds, while the peak at 1106 cm1corresponds to C-0 stretching, which supports its role as a lipid-based excipient.

[0341] The FTIR spectra of blank PMs showed characteristic peaks at 3448.67, 1640.67, and 692.25 cm reflecting the polymeric matrix. The broad peak at 3448.67 cm1corresponds to O-H stretching, while the peak at 1640.67 cm1indicated the presence of C=O stretching, which may be due to the polymer backbone.

[0342] The FTIR spectra of CBD-loaded PMs, on the other hand, showed peaks at 3433.52, 1636.64, and 698.71 cm ', with a slight shift in the O-H and C=O stretching peaks compared to the blank PMs, indicating the successful incorporation of CBD into micelles matrix. The subtle change in peaks, especially in the 1636.64 cm1region, suggested interactions between CBD and the PMs, likely due to hydrogen bonding or hydrophobic interactions. The overall transmittance (T%) increase in the CBD-PMs, observed at 62%, compared to the blank PMs at 56%, further confirms the efficient encapsulation of CBD within the micelles system.

[0343] Analysis of 'II NMR for CBD-PMs

[0344] ’ H NMR spectra of pure CBD (Fig. 14 c) showed characteristic peaks at 0.8, 1.6, and 1.8 ppm, corresponding to the protons in the alkyl chains and methyl groups. These peaks reflect the hydrophobic nature of CBD, with signals attributed to the protons of the methylene (-CH2-) and methyl (-CH3) groups in its structure.

[0345] 1H NMR spectra of HCO RH 40, a surfactant, and gelucire 44 / 14, a lipid-based excipient, exhibited broad peaks between 3.6 and 3.8 ppm and an additional peak at 4.8 ppm. The broad peak at 3.6-3.8 ppm is likely due to the protons of ethylene oxide units in the polymer chains of the surfactant and excipient. In comparison, the peak at 4.8 ppm corresponds to the protons attached to oxygen in the ester or hydroxyl groups. These signals indicated the amphiphilic nature of the surfactants used in the formulation, which play a key role in stabilising the polymeric micelle's structure.

[0346] ’ H NMR spectra of blank PMs displayed a broad peak at 4.7-4.9 ppm, indicating the presence of hydrogen-bonded protons in the polymer matrix. This broad signal is likely due to the interactions between the hydrophilic segments of the polymer and water molecules, suggesting that the PMs are in a hydrated state.

[0347] 1H NMR spectra of CBD-PMs (Fig. 14c) showed a broad peak between 4.7 and 4.9 ppm and a sharp peak at 3.4 ppm. The broad peak at 4.7-4.9 ppm corresponds to the hydrogen -bonded protons in the polymer matrix, as observed in the blank PMs. However, the sharp peak at 3.4 ppm indicated a distinct interaction between CBD and the polymer matrix. This peak likely arises from the protons in the CBD molecule interacting with the hydrophilic regions of the micelles, signifying that CBD is well encapsulated within the PMs. The absence of the alkyl chain signals (0.8, 1.6, 1.8 ppm) in the CBD-PMs suggests that the CBD is encapsulated within the hydrophobic core of the micelles, further stabilising the system. These findings demonstrate that incorporating CBD into the polymeric micelles alters its chemical environment, confirming successful encapsulation and improved solubility within the PMs system.

[0348] Rheological analysis of CBD-PMs

[0349] The rheological properties of CBD-PMs were evaluated to determine their suitability for ocular delivery applications. The results are depicted in Fig. 23, providing insight into the behaviour of the formulation under various stress and shear conditions. Fig. 23 illustrates the viscosity profile of the formulation over time, from a low value of 0.000261 Pa- s at 6 seconds and peaking to 93.2 Pa-s at 12 seconds, indicating a significant increase in resistance to flow as the system began to establish its microstructure. The subsequent decrease in viscosity over time suggested a shear-thinning behaviour, essential for facilitating easy application while ensuring sufficient retention on the ocular surface.

[0350] At a shear stress of 490 Pa, the viscosity was 93.2 Pa-s, but it dropped to 23.3 Pa-s when the shear stress was reduced to 245 Pa. This behaviour demonstrates CBD-PMs' advantages for ocular applications, as it allows for lower viscosity during the application, facilitating smoother flow and distribution across the ocular surface.

[0351] Fig. 23, with viscosity plotted against shear rate, illustrates a pronounced decrease in viscosity from 93.2 Pa- s at a shear rate of 5.26 1 / s to 2.48 Pa- s at a shear rate of 100 1 / s. This significant reduction in viscosity under increased shear conditions indicates disruption of the polymeric network, flowability enhancement upon administration of the CDB-PMs formulation, and properties critical for ensuring patient comfort and maximising the therapeutic potential of the CBD formulation.

[0352] In Vitro release study of CBD-PMs and CBD-SUS

[0353] CBD-PMs exhibited a sustained release pattern, reaching 82.52% at 24 hours (Fig. 24). At the 12-hour mark, 65.48% of the CBD had been released, indicating a gradual and controlled diffusion mechanism. Conversely, CBD-SUS showed a rapid release profile, reaching 99.21% release within the first 12 hours. Most of the drug was released early, driven by the more significant PS and faster dissolution of CBD in the suspension.

[0354] The data were fitted to multiple kinetic models to understand the release mechanisms better.

[0355] The korsmeyer-peppas model strongly correlated with CBD-PMs (r2= 0.9634), indicating a predominantly diffusion-controlled release mechanism. This is typical for PMs, where the drug is released slowly from the hydrophobic core through a controlled diffusion process. For CBD- SUS, the correlation was lower (r2= 0.9117), indicating that while diffusion played a role, other mechanisms, such as particle dissolution and surface erosion, also contributed to the overall release behaviour.

[0356] On the other hand, the zero-order model showed an excellent fit for CBD-SUS (r2= 0.9721), indicating that after the initial fast release, the release rate became constant over time, characteristic of systems where drug release is independent of concentration. However, CBD- PMs did not fit the Zero-order model (r2= 0.7785), supporting the hypothesis that the release is diffusion-controlled rather than constant.

[0357] In Vivo Drug Permeation Study

[0358] In vivo, permeation, distribution, and retention of PMs were investigated using fluorescence microscopy by comparing FITC-loaded PMs (FITC-PMs) to a free FITC solution within rat ocular tissues over time intervals of 0.5, 1, and 2 hours (as shown in Fig. 25). The green fluorescence indicated FITC localisation within the ocular tissues, and the fluorescence intensity provided insights into each formulation's permeation efficiency and retention capabilities.

[0359] At the 0.5-hour time, the fluorescent images revealed that the green fluorescence representing FITC-PMs was primarily concentrated at the outer epithelial layer of the cornea, suggesting that the nanoparticles were beginning to permeate the ocular surface. Free FITC solution also showed a similar intensity distribution.

[0360] By the 1-hour time, a noticeable increase in the depth and distribution of the green fluorescence was observed for FITC-PMs. The fluorescence spread deeper into the corneal tissue, suggesting that the PMs had permeated beyond the epithelial surface, likely reaching more profound layers of the cornea, such as the substantia propria. The more extensive distribution indicated that the FITC-PMs were actively diffusing through the corneal layers, enhancing their potential to reach targeted ocular structures. The free FITC showed some penetration level but lacked the significant spread and intensity observed in the micellar formulation, implying quicker clearance from the ocular surface.

[0361] At 2 hours, the fluorescence of FITC-PMs was widely distributed throughout the corneal tissue and potentially reaching the anterior chamber. This extended distribution suggested that FITC- PMs had successfully navigated through ocular barriers, exerting their therapeutic effects in deeper ocular tissues. In contrast, the intensity of the free FITC solution diminished, indicating its clearance and limited capacity to penetrate deeply into ocular structures.

[0362] In the cornea, at 0.5 hours, the mean intensity for free FITC was 10.111, whereas, for FITC- PMs, it was 8.784. However, by 1 hour, FITC-PMs showed a significant increase in intensity to 28.988, while for free FITC, it was 12.659, indicating better retention and sustained release with micelles. At 2 hours, FITC-PMs demonstrated a further increase in intensity to 35.991, while the intensity of free FITC decreased to 7.944.

[0363] For the retina, which presents significant physiological barriers, the initial mean intensity for free FITC at 0.5 hours was 0.995, whereas FITC-PMs had a mean intensity of 0.715. FITC- PMs showed an enhanced mean intensity of 11.52 at 2 hours, while the free FITC formulation remained at a low intensity of 1.427. These results indicate that FITC-PMs have an advantage of even penetrating upto the posterior ocular tissues, despite the challenges posed by physiological barriers of the eye

[0364] In the vitreous humour, at 0.5 hours, the free FITC exhibited a higher initial mean intensity of 26.246 compared to FITC-PMs (9.142). However, FITC-PMs displayed a marked increase in intensity at 1 hour (13.304) and sustained a high mean intensity of 35.595 at 2 hours, whereas the free FITC intensity decreased to 7.944. This finding suggests that FITC-PMs provide more sustained release and retention in the vitreous humour, unlike the burst release and rapid clearance seen with the free FITC solution.

[0365] Following ANOVA, the F-value of 6.4719 and a p-value of 0.0257 indicates that the difference in mean intensities between FITC-PMs and free FITC was statistically significant (p<0.05). Additionally, the tissue type effect on fluorescence intensity was substantial, with an F-value of 8.6093 and a p-value of 0.0048 (p<0.05). These results confirm that permeation intensity varies significantly between different ocular tissues and the two formulations, highlighting the superior performance of FITC-PMs in enhancing drug penetration and retention.

[0366] Cytotoxicity studies

[0367] The result of study of three different formulations: CBD-SUS, CBD-PMs, and CBD B (blank) on the SIRC (Statens Seruminstitut Rabbit Cornea) cell line, in MTT (3 -(4, 5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide) assay provides a detailed insight into the cytotoxicity and cell viability of these formulations in ocular drug delivery, where minimising toxicity while ensuring therapeutic efficacy is crucial (Fig. 26).

[0368] The CBD-SUS formulation shows a low average cell viability of 68.24 ± 5.13%, indicating cytotoxicity.

[0369] The CBD-PMs formulation, comprising polymeric micelles made from Gelucire 44 / 14 and HCO RH 40, exhibits good cell viability at an average of 84.43 ± 3.98% (p<0.05 compared to CBD-SUS). This suggests that encapsulating CBD in micelles provides a protective effect, reducing direct exposure of the free drug to corneal cells and thereby enhancing cell viability. The higher compatibility of this formulation indicates that it could potentially reduce irritation or adverse reactions on the ocular surface compared to the suspension formulation, making it a more suitable candidate for sustained ocular delivery.

[0370] Interpretation of metabolic cell activity / viability data

[0371] The metabolic cell activity and viability data, as measured by relative fluorescence units (RFU), provide insight into the impact of different formulations on R28 retinal precursor cells across varying doses (0, 0.5, 1, 1.5, and 2 mg / mL) (Fig. 27).

[0372] For cells treated with CBD-PMs, the RFU values remained comparable to those of the control group across all tested doses. This result suggests that CBD-PMs are highly biocompatible and do not adversely affect the metabolic activity or viability of R28 cells. The data indicate that the polymeric micelle formulation of CBD is a safe delivery system, as it maintains cell viability even at the highest dose of 2 mg / mL.

[0373] The CBD-SUS group showed RFU values lower than the control and CBD-PMs groups at all doses. This marginal reduction in cell viability suggests that the suspension formulation might significantly impact cellular metabolism, potentially due to differences in the solubility or release profile of CBD or the presence of excipients in the suspension. Nevertheless, the viability levels observed with CBD-SUS remain within an acceptable range, indicating that CBD is not overtly cytotoxic to R28 cells. Across all formulations, there was no significant dose-dependent reduction in RFU values, even as the concentration increased from 0.5 to 2 mg / mL. This lack of a negative dose-response trend further highlights the safety and tolerability of the tested formulations on R28 cells. Notably, the CBD-PMs formulation demonstrated the most consistent and favourable viability profile, comparable to the untreated control group, reinforcing its potential as a safe and effective drug delivery system for ocular applications.

[0374] Cellular uptake in corneal cell lines

[0375] In Fig. 28, the left column represents Free FITC, and the right column represents FITC labelled PMs, and the differences in cellular uptake and distribution between the two are observed. In the case of Free FITC, the fluorescence intensity is relatively faint and uneven, indicating that the free FITC does not efficiently enter the cells. The fluorescence appears diffuse and scattered, suggesting that whatever amount of free FITC enters the cytoplasm is not retained.

[0376] In contrast, the FITC-PMs show significantly brighter and more intense green fluorescence, indicative of enhanced cellular uptake. The encapsulation of FITC within the micelles facilitates uptake and controlled release, resulting in a sustained and concentrated intracellular fluorescence signal. The fluorescence in these images appears more localised and intense within specific regions of the cells, suggesting that PMs promote uptake and are also retained within the cells. This underscores the superior performance of CBD-PMs as a delivery system, with enhanced cellular uptake, better retention, and more vigorous fluorescence intensity compared to free FITC.

[0377] Evaluation of CBD-PMs on IL-6 and TNF-a Levels in an Inflammatory Model of SIRC Cells

[0378] This study investigates the effects of CBD-PMs on interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-a) levels in SIRC (Statens Seruminstitut Rabbit Cornea) cells under inflammation-induced conditions (Table 10). The inflammatory response was induced using lipopolysaccharides (LPS), and the cells were treated with various formulations over 24 hours (Fig. 29-30).

[0379] Table 10: Average IL-6 and TNF-a Levels in SIRC Cells Treated with CBD-PMs

[0380] *Significant difference compared to LPS Control (p < 0.05)

[0381] The Control group exhibited low IL-6 levels (15.49 ± 1.23), while the LPS Control (positive) group showed a significant increase in IL-6 (53.16 ± 4.11), confirming that inflammation was effectively induced. The Free CBD Suspension demonstrated a moderate anti-inflammatory effect (IL-6 levels 49.11 ± 3.85). In contrast, CBD-PMs significantly reduced IL-6 levels to 30.20 ± 2.67 (p < 0.05), suggesting that this formulation effectively mitigates inflammation. The Marketed Formulation (Ketorolac eye drops; ACULAR LS™) produced a comparable average IL-6 level of 31.60 ± 2.75 (p < 0.05), indicating that CBD-PMs may perform similarly to established treatments in reducing pro-inflammatory cytokines.

[0382] Similarly, TNF-a levels showed a significant increase in the LPS Control group (73.33 ± 5.08) compared to the Control group (15.64 ± 1.35), confirming successful induction of inflammation. The Free CBD Suspension resulted in TNF-a levels of 68.07 ± 4.76, indicating a limited reduction in inflammation. However, the CBD-PMs group substantially reduced TNF- a levels (32.74 ± 3.02, p < 0.05), demonstrating a significant anti-inflammatory effect. The Marketed Formulation produced a similar effect, with TNF-a levels of 32.88 ± 2.89 (p < 0.05), highlighting the comparable efficacy of CBD-PMs to an established anti-inflammatory treatment.

[0383] In-vivo safety study The in vivo safety study of CBD-PMs was conducted on rabbits to assess potential dermal and ocular irritation. Both acute and chronic tests were performed, following Schedule Y guidelines, which typically require testing on rats and rabbits to ensure comprehensive safety data.

[0384] Acute Dermal Irritation / Corrosion Study

[0385] In the acute dermal irritation study, three rabbits and rats were observed at various time intervals (Oh, one h, 24h, 48h, and 72h) to assess skin reactions, particularly erythema (redness) and edema (swelling) following application and scored from 0-4 with no to severe reactions. The results showed a zero score, indicating no visible signs of irritation or damage were observed throughout the study. This suggests that the topical application of CBD-PMs is well-tolerated and does not cause skin irritation in rabbits / rats.

[0386] Similar safe results (zero score) were obtained following a Single Instillation Acute Eye Irritation / Corrosion Study (0-72h), Repeat Instillation Acute Eye Irritation / Corrosion Study (0- 72h), and Chronic Repeat Instillation Eye Irritation / Corrosion Study (0-7 day)

[0387] These studies collectively demonstrate that CBD-PMs exhibit excellent safety profiles for both dermal and ocular applications. CBD-PMs can be considered safe for use in topical and ocular formulations with no evidence of irritation or corrosion observed in acute, repeat, or chronic exposure scenarios.

[0388] Ocular tolerance evaluation

[0389] The evaluation of ocular tolerance for CBD-PMs was conducted with a focus on varying exposure times to assess their impact on corneal tissue. The study employed histopathological examination to observe inflammatory or pathological changes after applying different formulations.

[0390] In the case of CBD-PMs, tissues were treated for durations of 0.5, 1, and 2 hours. At the 0.5- hour mark, the corneal tissue was observed to be lined by intact epithelium, with underlying structures, including the substantia propria and limiting membrane, showing no signs of inflammation or pathology. In subsequent 1-hour and 2-hour also, the corneal tissue did not demonstrate any adverse effects.

[0391] Photostability Study of CBD-PMs and Blank-PMs

[0392] The photostability analysis of CBD-PMs conducted over a 10-day exposure period revealed significant differences in stability based on whether clear or amber glass containers were used for storage. The non-exposed control exhibited excellent stability, with an assay of 98.8±2.1%, EE of 81.45±0.87%, and a PS of 33±1.6 nm with a low PDI of 0.239±0.09, indicating a well- dispersed formulation. Similarly, when stored in amber glass, which offers protection from light exposure, samples maintained a drug assay of 96.21±1.87% and EE of 78.1±1.21 %. Similarly, there was no significant change in PS (36±1.84 nm) and PDI to 0.247±1.2 (Fig. 31).

[0393] On the other hand, the formulations stored in transparent glass showed marked deterioration due to light exposure, with CBD assay dropping to 62±2.42% and EE falling to 54.2±2.61%. The PS increased significantly to 67±2.14 nm, with a higher PDI of 0.31±2.13, indicating considerable aggregation and instability. These results underscore the critical role of storage conditions in maintaining CBD-PMs' stability, with amber glass providing a protective environment that preserves both drug content and formulation characteristics. In contrast, transparent glass leads to significant degradation under photo stress conditions.

[0394] Table 11: Photostability Study of CBD-PMs and Blank-PMs

[0395] The FTIR analysis revealed significant differences in the spectral characteristics of the samples. The clear bottle sample (Bl) exhibited a notable reduction in peak intensity, particularly within the fingerprint region (1000-1500 cm '). This reduction in peak intensity indicates potential chemical degradation due to light exposure, likely resulting in structural changes to the CBD molecules or the micelle matrix. In contrast, the amber bottle sample (BIA) retained the peak intensities, mirroring the non-exposed control (BIN). This suggests that the amber packaging effectively mitigates photodegradation, preserving the chemical integrity of the CBD-PMs formulation.

[0396] The ATR-FTIR analysis corroborated the FTIR findings by showcasing the stability of the molecular structure in the BIA sample.

[0397] The amber bottle sample (BIA) exhibited a DSC thermal profile similar to the non-exposed control (BIN), indicating that it effectively protected the formulation from thermal degradation and maintained its stability under heat.

[0398] The combined findings from FTIR, ATR-FTIR, and DSC analyses (Fig. 31-33) highlight the critical role of proper packaging in maintaining the stability and efficacy of CBD-PMs during storage and transport, ensuring that environmental factors do not compromise the therapeutic potential of the formulation. Stability Studies

[0399] At 25±2°C / 60±5% RH, the formulations demonstrated excellent stability over six months. The pH remained relatively stable (slightly changed from 6.03 to 5.82). The PS increased marginally from 33 nm to 38 nm, with a low PDI ranging from 0.239 to 0.182, suggesting a consistent size distribution favourable for drug delivery.

[0400] Although slightly decreasing from -1.97 mV to -1.86 mV, the zeta potential values remained within a range that supports good stability by minimising micelle aggregation. Notably, the drug assay was almost similar (98.8% at 0 time to 95.2% at 6 months), while the EE remained high, ranging from 81.45% to 77.1%. In contrast, at 40±2°C / 75±5% RH, the PS increased from 33 nm to 58 nm, indicating potential aggregation. The zeta potential values also changed from

[0401] -1.97 mV to -1.72 mV. The drug assay results at this higher temperature showed a significant reduction, from 98.8% to 69%, indicating a loss of CBD retention within the formulation. Similarly, the encapsulation efficiency dropped from 81.45% to 57.1%, suggesting a decline in the ability of the micelles to encapsulate CBD under these conditions effectively. Overall, these findings emphasise that while the 25 °C storage condition supports the stability and efficacy of the CBD-PMs, the 40°C environment poses significant challenges, leading to decreased stability and potential loss of therapeutic effectiveness.

[0402] Table 12: Physical examination of formulations after regular intervals of time (N=6)

[0403] Pharmacodynamic study of acute corneal inflammation evaluation

[0404] In this study, Fig. 34 depicts the effects of various treatments on ocular inflammation in rats, which was induced using triton X-100, a surfactant known to cause acute corneal inflammation. Inflammation was induced by exposing the eyes to a triton X-100 solution prepared by diluting triton X-100 with water in a 1:9 ratio. The treatments being compared include CBD-PMs, CBD- SUS, and a marketed formulation of Ketorolac (ACULAR LS™), a commonly used antiinflammatory medication. The effectiveness of these treatments was assessed through visual inspection, histopathological analysis, and measurement of inflammatory biomarkers IL-6 and TNF-a (Fig. 35).

[0405] The control groups provide a clear baseline for comparison. The positive control (C+VE), representing the untreated, inflamed state, shows significant redness and swelling, while the negative control (C-VE) means a healthy, uninflamed eye with no inflammation or redness. The progression from the pre-treatment state to the first and second-time points in the CBD-PMs treated group illustrates an apparent inflammation reduction. The CBD-SUS group, which represents free CBD in a suspension, shows a less pronounced decrease in redness than the CBD-PMs group. This suggests that free CBD is somewhat effective but does not provide the same rapid or sustained anti-inflammatory effect as when encapsulated in micelles. The Ketorolac (ACULAR LS™) group demonstrates an anti-inflammatory effect similar to CBD- PMs. Evaluation of CBD-PMs on IL-6 and TNF-a Levels in an Inflammatory Model of Dynamic Study with Eye Tissue Induced by LPS

[0406] This study investigates CBD-PMs' effects on interleukin-6 (IL-6) and tumour necrosis factoralpha (TNF-a) levels in rat eyes following acute corneal inflammation. Following the induction of inflammation, the rat eyes were treated with various formulations: blank PMs, CBD-PMs, and a marketed formulation (ACULAR LS™, by Allergan Pvt. Ltd.). The effects of these formulations on IL-6 and TNF-a levels were evaluated after 24 hours of treatment following the induction of inflammation (Table 13).

[0407] Table 13: Average IL-6 and TNF-a Levels in eyes following various treatments The evaluation of CBD-PMs reveals their significant potential as a therapeutic strategy for reducing IL-6 and TNF-a levels in an acute inflammatory model induced by LPS comparable to the marketed formulation (Fig. 36-37).

[0408] Example 23: Natural extract loaded PMs formulation

[0409] FTIR of liquorice extract loaded PMs formulation The FTIR comparison (Fig. 38a, 38b) shows significant differences between the blank and active-loaded formulations. The O-H stretching peak shifted from 3448.21 cm1in the blank to 3436.20 cm1in the final formulation, indicating hydrogen bonding or interactions. The C-H stretching region shows the loss of the 2960.20 cm ' peak in the final formulation. The C=O stretching peak shifted from 1731.72 cm1to 1737.77 cm suggesting interactions with new components. In the amide / double bond region, a new peak at 1666.49 cm1appears in the final formulation. Minor shifts were observed in the fingerprint region, with peaks like 1160.47 cm1and 2084.14 cm1disappearing. These changes confirm the successful incorporation of active ingredients or additional components in the final formulation.

[0410] Particle size analysis for liquorice extract loaded PMs:

[0411] The micellar system showed an average diameter of 20.5 nm, which is optimal for efficient skin permeation while minimising the risk of irritation (Fig. 39). This precision is further underscored by the standard deviation of 0.84 nm, highlighting the high uniformity in particle size distribution and the reproducibility of the production process.

[0412] Particle size analysis for PMs incorporated into a secondary formulation:

[0413] Topical formulations, such as those used for anti-inflammatory or cosmetic purposes, are designed to stay localised within the epidermis or upper dermis. This helps minimise systemic absorption and reduce the risk of side effects. PMs are this and free flowing dispersion that may not be convenient to apply except as a spray or concentrate. In other cases, it may be convenient to change the PM dispersion to a gel / cream / or other semi solid product achieved by using various excipients as described above. Larger particles (800 nm and above) thus obtained tend to remain on the skin's surface or are limited to the outer skin layers, allowing for a controlled, sustained release of active ingredients without entering systemic circulation. Released PM will permeate into the skin. This characteristic makes larger particles suitable for applications like atopic dermatitis and anti-eczema treatments, where maintaining a localised effect is crucial (Fig. 40).

[0414] Zeta potential analysis for liquorice extract loaded PMs

[0415] The zeta potential values of the micellar system ranged between -0.23 mV and 0.66 mV, with an average zeta potential of 0.21 mV (Fig. 41a). A near-neutral zeta value indicates stable formulations.

[0416] Zeta potential analysis for liquorice extract loaded PMs formulation

[0417] The PMs incorporated secondary formulation demonstrated good stability under normal storage conditions, ensuring long-term efficacy and reliability. The zeta potential values for these samples range from -16.99 mV to -24.42 mV, with an average of -20.59 mV (Fig. 41b).

[0418] High-Resolution Transmission Electron Microscopy (HRTEM) of liquorice extract loaded PMs

[0419] The liquorice extract loaded PMs appear to be well-defined and relatively uniform in size, which is essential for their functionality. Their spherical morphology suggests that the amphiphilic polymers in the formulation are effectively self-assembling (Fig. 42). Rheological study of natural extract loaded PMs formulation

[0420] The formulation exhibits shear-thinning behaviour, where viscosity decreases with increasing shear rate. It is ideal for topical drug delivery as it spreads quickly under application while maintaining stability at rest (Fig. 43). The potential presence of yield stress ensures the formulation remains intact during storage but flows readily upon application. These rheological properties enhance its usability, ensuring even application, good skin adherence, and optimal drug release at the target site.

[0421] Drug assay for natural extract loaded PMs formulation

[0422] The drug assay ranged between 90-95%, indicating an efficient manufacturing process.

[0423] Pharmacodynamics studies for atopic dermatitis using natural extract loaded PMs formulation containing liquorice as an active ingredient.

[0424] The pharmacodynamic study in a rat model of atopic dermatitis demonstrates the efficacy of the formulation (Fig. 44) compared to a marketed formulation (Lobate® Gn Cream containing Clobetasol and Neomycin). The naive group maintained healthy skin throughout the study, while the positive group, left untreated, showed progressive worsening of symptoms, including redness, thickening, and lesions. The final formulation significantly reduced inflammation, redness, and scaling, with notable healing observed by Day 17, comparable to the marketed formulation. Though both currently developed formulations and marketed steroid creams effectively improve skin conditions, the potential of the current formulation is evident as an alternative therapeutic option for managing atopic dermatitis, offering comparable or superior benefits but no steroid-related side effects.

Claims

We Claim:

1. A micellar composition, comprising: a. a polymer matrix comprising i. 0.01% to 5% w / v of PEG 40 hydrogenated castor oil (HCO RH 40); and ii. 0.01% to 5% w / v of a polyoxylglyceride; and b. 90% to 99.98% w / v of a solvent, wherein the ratio of the amount of said PEG 40 hydrogenated castor oil (HCO RH 40) to said polyoxylglyceride is in the range of 1 :5 to 5: 1 ; wherein said polyoxylglyceride is selected from the group consisting of lauroyl polyoxyl- 32 glycerides, stearoyl polyoxyl-32 glycerides or combinations thereof; wherein the weight of polymer PEG 40 hydrogenated castor oil (HCO RH 40) or polyoxylglyceride is with respect to the volume of the micellar composition; and wherein said polymer matrix is in the form of a plurality of micelles characterised by an average particle size in the range of 5 nm to 50 nm as determined by particle size analyser (Delsa nano C analyser) and Transmission Electron Microscopy (TEM) or Scanning Electron Microscopy (SEM).

2. The micellar composition as claimed in claim 1 , wherein said solvent is selected from the group consisting of water, ethanol, ethyl acetate, acetone, isopropyl acetate, isopropanol, or mixtures thereof.

3. A loaded micellar composition comprising: a) a polymer matrix comprising i. 0.01% to 5% w / v of PEG 40 hydrogenated castor oil (HCO RH 40); and ii. 0.01% to 5% w / v of a polyoxylglyceride; b) 60% to 99.3% w / v of a solvent selected from the group consisting of water or organic solvent selected from ethanol, ethyl acetate, acetone, isopropyl acetate, isopropanol or mixtures thereof; and c) 0.05% w / v to 30% w / v of an active / passenger molecule / plant, animal or marine extract selected from the group consisting of cannabinoids and other phytochemicals, antifibrinolytic drugs, hematologic agents, antibacterial agents, antifungals, antivirals, HMG-CoA reductase inhibitors, anticancer agents, corticosteroids, analgesics, monoclonal antibodies and benzylisoquinoline alkaloids, plant extracts, nutraceuticals, inorganic molecules and actives, proteins and peptides, and opioid antagonist;wherein said polyoxylglyceride is selected from the group consisting of lauroyl polyoxyl-32 glycerides, stearoyl polyoxyl-32 glycerides or combinations thereof; wherein the active / passenger molecule / plant, animal or marine extract is located within the polymer matrix in the form of a plurality of micelles; and wherein the weight of polymer PEG 40 hydrogenated castor oil (HCO RH 40) or polyoxylglyceride or active / passenger molecule / plant, animal or marine extract is with respect to the volume of the loaded micellar composition.

4. The loaded micellar composition as claimed in claim 3, wherein said active / passenger molecule / plant, animal or marine extract is selected from the group consisting of Cannabidiol (CBD), Tranexamic acid (TXA), Desmopressin, Clopidogrel, Doxycycline, Nitrofurantoin, Azithromycin, Oseltamivir, Famciclovir, Zanamivir, Berbermine hydrochloride, Hydroxyquinone, Paclitaxel, Docetaxel, Prednisone, Hydrocortisone, Mometasone, CBG (Cannabigerol), full-spectrum cannabidiol extract, Cyclosporine A, Acetylcysteine, Amphotericin B, Doxycycline, amoxicillin, dexamethasone, Fluoromethalone, Fluconazole, Ketoconazole, Ketorolac, Terbinafine, Kojic acid, Clotrimazole, Buprenorphine, Naloxone, Ondansetron, Aripiprazole, Atorvastatin, Tadalafil, Melatonin, Vitamin B-12 , Boswellic acid and its derivatives, Green tea extract, Magnesium oxide, Zinc oxide, Vitamin C, human amniotic membrane (hAM) or its extract, Kojic acid, Benzoylated 2-(4-piperidinyl)-l,3-benzimidazole analogue, Prednisone, Triamcinolone, Budesonide, olopatadine, histatins, capsaicin, Biotin, Niacinamide, and extracts of Centella, Turmeric, Eiquorice, Blueberry, Mulberry, Ginseng, Witch Hazel, Amla, Neem, Coffee, Willow Bark, Hibiscus, Pomegranate, Tea Tree and Sea Weed, or combination thereof.

5. The loaded micellar composition as claimed in claim 3, further comprising secondary polymer, hydrogel, in situ gelling composition, emulgel, cream, ointment base, lipidic particles, or a combination thereof, wherein said secondary polymer is selected from the group consisting of Hydroxypropyl Methylcellulose (HPMC), Polyethylene Glycol (PEG), Polyvinyl Alcohol (PVA), Polycaprolactone, Polyvinyl Pyrrolidone (PVP), Polyvinyl Pyrrolidone (PVP) K30, Polyvinyl Pyrrolidone (PVP) K90, Crospovidone (PVPP), Sodium Alginate, Xanthan Gum, Guar Gum, Pectin, HPMC Phthalate (HPMCP), Sodium Starch Glycolate (SSG), Poloxamer 188 and Poloxamer 407, Carbopol 97 IP, Carbopol 934, Carbopol 940, Methacrylic Acid Copolymers, Gelatin, Carrageenan, Hydroxyethyl cellulose (HEC), Sodium Hyaluronate, (Sodium Carboxymethylcellulose), Chitosan or a combination thereof, wherein said in situ gelling composition is selected from the group consisting of: Hydroxypropyl Methylcellulose (HPMC), Sodium Carboxymethylcellulose (NaCMC), Gellan Gum, and Poloxamer 407, Sodium Alginate, Carbopol 97 IP, Carbopol 974P NF, Chitosan, Sodium Hyaluronate (Hyaluronic Acid), Xanthan Gum, Poly(lactic-co-glycolicacid) (PLGA), Polyvinyl Alcohol (PVA), Methylcellulose (MC), Polycarbophil, Alginic Acid, Polyethylene Glycol (PEG), Hydroxyethyl cellulose (HEC), Methacrylic Acid Copolymer, or combination thereof, wherein said hydrogel is selected from the group consisting of Polyacrylamide, Polyvinyl Alcohol (PVA), Sodium Polyacrylate, Hydroxyethyl Methacrylate (HEMA), Polyethylene Glycol (PEG), Polyvinyl Alcohol (PVA), Polycaprolactone, Polyvinyl Pyrrolidone (PVP), Polyvinyl Pyrrolidone K30, Polyvinyl Pyrrolidone K90, Crospovidone (PVPP), Carbopol 934, Carbopol 940, Chitosan, Alginate, Poly HEMA / Polyethylene Oxide (PEO), Gelatin, Hyaluronic Acid (HA), Silicone, Polyurethane, Poloxamer 188 and Poloxamer 407, Pectin, Polyvinylpyrrolidone (PVP), Collagen or combination thereof.

6. The loaded micellar composition as claimed in claim 3, further comprising preservatives, stabilisers, viscolysers and / or precipitation inhibitors, antioxidants, sweeteners, flavour, perfume, color, cryoprotectant and pH modifying agents, wherein preservatives are selected from the group consisting of Oxychloro Complex, Phenoxyethanol, Benzalkonium Chloride (BAK), Sodium Benzoate, Potassium Sorbate, Methylparaben, Propylparaben, Chlorobutanol, Ascorbic acid, Tocopherols, Sodium metabisulfite, Sodium ascorbate, Benzyl alcohol, Boric acid, Citric acid, Benzoic acid, Ethylene diamin tetra acetic acid (EDTA), Polyquaternium- 1 or combination thereof; and antioxidant is selected from the group consisting of Butylated hydroxy anisole, Butylated hydroxytoluene, Sodium metabisulphite, Sesamol, Nor dihydroguaretic acid, Curcumin, Tetra hydrocurcumin, EGCG, Resveratrol, or combination thereof. wherein stabilisers are selected from the group consisting of ethylenediaminetetraacetic acid, butylated hydroxy toluene, sodium gluconate, tetrasodium glutamate diacetate, or combination thereof and viscolysers and / or precipitation inhibitors are selected from the group consisting of Hydroxypropyl methylcellulose, Pluronic L44, Polyvinylpyrrolidone K- 90, Polyvinylpyrrolidone K-17, Eudragit, Poloxamer 407, or combination thereof. wherein pH modifying agents are selected from the group consisting of Triethanolamine, Sodium Hydroxide, Sodium chloride, Potassium hydroxide, Citric acid, Tartaric acid, Lactic acid, Potassium carbonate, di basic or monobasic salts of sodium or potassium phosphate, Boric acid, Sodium borate, L-arginine, Potassium citrate, and Phosphoric acid, or combination thereof. wherein colorants are selected from the group consisting of Aluminium powder, Bismuth citrate, Bronze powder, Chromium oxide greens, D&C orange no. 10, D&C orange no. 4, D&C orange no. 11 and Dihydroxyacetone and cryoprotectant are selected from the Glycerol and Dimethyl sulfoxide group, or combination thereof. wherein sweeteners are selected from the group consisting of Aspartame, Acesulfame potassium, Sucralose, Neotame, Advantame, Saccharin, and Thaumatin and flavours areselected from the group of Anise, Cardamom, Essential oils, Spearmint, Coolmint, or combination thereof.

7. A process for preparation of a micellar composition, said process comprising the following steps: a. dissolving 0.01% to 5% w / v of said PEG 40 hydrogenated castor oil and 0.01% to 5% w / v of said polyoxylglyceride in 90% to 99.8% w / v of a solvent selected from the group consisting of water, or organic solvent selected from ethanol, ethyl acetate, acetone, isopropyl acetate, isopropanol or mixtures thereof under continuous stirring; b. optionally, removing organic solvent from said mixture to form a micellar composition; and c. optionally, filtering the formed micellar composition through bacteria proof filters; wherein the micellar composition comprises: a. a polymer matrix comprising i. 0.01% to 5% w / v of PEG 40 hydrogenated castor oil (HCO RH 40); and ii. 0.01% to 5% w / v of a polyoxylglyceride; and b. 90% to 99.98% w / v of a solvent selected from the group consisting of water or organic solvent selected from ethanol, ethyl acetate, acetone, isopropyl acetate, isopropanol or mixtures thereof; wherein the weight of polymer PEG 40 hydrogenated castor oil (HCO RH 40) or polyoxylglyceride is with respect to the volume of the micellar composition; and wherein said polyoxylglyceride is selected from the group consisting of lauroyl polyoxyl- 32 glycerides, stearoyl polyoxyl-32 glycerides or combinations thereof.

8. The process as claimed in claim 7, wherein the ratio of amount of said PEG 40 hydrogenated castor oil to said lauroyl polyoxyl-32 glycerides is in the range of 1:5 to 5:1.

9. A process for preparation of a loaded micellar composition, said process comprising the following steps: a. providing 0.01% to 5% w / v of said PEG 40 hydrogenated castor oil; b. providing 0.01% to 5% w / v of said polyoxylglyceride; c. providing 60% to 99.3% w / v of a solvent selected from the group consisting of water or organic solvent selected from ethanol, ethyl acetate, acetone, isopropyl acetate, isopropanol or mixtures thereof; d. providing 0.05% w / v to 30% w / v of an active / passenger molecule / plant, animal or marine extract;e. mixing components provided in steps (a) to (d) above in any sequence, under continuous stirring, to obtain a loaded micellar composition; f. optionally, removing the organic solvent from said loaded micellar composition; and g. optionally, filtering the loaded micellar composition through bacteria proof filters; wherein the loaded micellar composition comprises: a) a polymer matrix comprising i. 0.01% to 5% w / v of PEG 40 hydrogenated castor oil (HCO RH 40); and ii. 0.01% to 5% w / v of a polyoxylglyceride; b) 60% to 99.3% w / v of a solvent selected from the group consisting of water or organic solvent selected from ethanol, ethyl acetate, acetone, isopropyl acetate, isopropanol or mixtures thereof; and c) 0.05% w / v to 30% w / v of an active / passenger molecule / plant, animal or marine extract selected from the group consisting of cannabinoids and other phytochemicals, antifibrinolytic drugs, hematologic agents, antibacterial agents, antifungals, antivirals, HMG-CoA reductase inhibitors, anticancer agents, corticosteroids, analgesics, monoclonal antibodies and benzylisoquinoline alkaloids, plant extracts, nutraceuticals, inorganic molecules and actives, proteins and peptides, and opioid antagonist; wherein said polyoxylglyceride is selected from the group consisting of lauroyl polyoxyl- 32 glycerides, stearoyl polyoxyl-32 glycerides or combinations thereof; wherein the weight of PEG 40 hydrogenated castor oil (HCO RH 40) or polyoxylglyceride or active / passenger molecule / plant, animal or marine extract is with respect to the volume of the loaded micellar composition; and wherein the active / passenger molecule / plant, animal or marine extract is located within the plurality of micelles of the micellar composition.

10. The process as claimed in claim 9, wherein said active / passenger molecule / plant, animal or marine extract is selected from the group consisting of Cannabidiol (CBD), Tranexamic acid (TXA), Desmopressin, Clopidogrel, Doxycycline, Nitrofurantoin, Azithromycin, Oseltamivir, Famciclovir, Zanamivir, Berbermine hydrochloride, Hydroxyquinone, Paclitaxel, Docetaxel, Prednisone, Hydrocortisone, Mometasone, CBG (Cannabigerol), fullspectrum cannabidiol extract, Cyclosporine A, Acetylcysteine, Amphotericin B, Fluconazole, Ketoconazole, Terbinafine, Clotrimazole, Buprenorphine, Naloxone, Ondansetron, Aripiprazole, Atorvastatin, Tadalafil, Melatonin, Vitamin B-12 , Boswellic acid and its derivatives, Green tea extract, Magnesium oxide, Zinc oxide, Vitamin C, human amniotic membrane (hAM) or its extract, benzoylated 2-(4-piperidinyl)-l,3-benzimidazole analogue, Triamcinolone, Budesonide, olopatadine, histatins, capsaicin, Biotin,Niacinamide, and extracts of Centella, Turmeric, Liquorice, Blueberry, Mulberry, Ginseng, Witch Hazel, Amla, Neem, Coffee, Willow Bark, Hibiscus, Pomegranate, Tea Tree, Sea Weed or combinations thereof.

11. The process as claimed in claim 9, wherein said active / passenger molecule is Tranexamic acid (TXA).

12. The process as claimed in claim 9, further secondary polymer, hydrogel, in situ gelling composition, emulgel, cream, ointment base, lipidic particles or a combination thereof; wherein said secondary polymer is selected from the group consisting of Hydroxypropyl Methylcellulose (HPMC), Polyethylene Glycol (PEG), Polyvinyl Alcohol (PVA), Polycaprolactone, Polyvinyl Pyrrolidone (PVP), Polyvinyl Pyrrolidone (PVP) K30, Polyvinyl Pyrrolidone (PVP) K90, Crospovidone (PVPP), Sodium Alginate, Xanthan Gum, Guar Gum, Pectin, HPMC Phthalate (HPMCP), Sodium Starch Glycolate (SSG), Poloxamer 188 and Poloxamer 407, Carbopol 971P, Carbopol 934, Carbopol 940, Methacrylic Acid Copolymers, Gelatin, Carrageenan, Hydroxyethyl cellulose (HEC), Sodium Hyaluronate, (Sodium Carboxymethylcellulose), Chitosan or a combination thereof; wherein said in situ gel-forming polymer is selected from the group consisting of: Hydroxypropyl Methylcellulose (HPMC), Sodium Carboxymethylcellulose (NaCMC), Gellan Gum, and Poloxamer 407, including Sodium Alginate, Carbopol 971P, Carbopol 974P NF, Chitosan, Sodium Hyaluronate (Hyaluronic Acid), Xanthan Gum, Poly(lactic-co- glycolic acid) (PLGA), Polyvinyl Alcohol (PVA), Methylcellulose (MC), Polycarbophil, Alginic Acid, Polyethylene Glycol (PEG), Hydroxyethyl cellulose (HEC), Methacrylic Acid Copolymer, or a combination thereof. wherein said hydrogel is selected from the group consisting of Polyacrylamide, Polyvinyl Alcohol (PVA), Sodium Polyacrylate, Hydroxyethyl Methacrylate (HEMA), Polyethylene Glycol (PEG), Polyvinyl Alcohol (PVA), Polycaprolactone, Polyvinyl Pyrrolidone (PVP), Polyvinyl Pyrrolidone K30, Polyvinyl Pyrrolidone K90, Crospovidone (PVPP), Carbopol 934, Carbopol 940, Chitosan, Alginate, Poly HEMA / Polyethylene Oxide (PEO), Gelatin, Hyaluronic Acid (HA), Silicone, Polyurethane, Poloxamer 188 and Poloxamer 407, Pectin, Polyvinylpyrrolidone (PVP), Collagen or combination thereof.

13. The process as claimed in claim 11, wherein said active / passenger molecule is 5% to 10% Tranexamic acid (TXA), and further comprises 0.5 %w / v Carbopol 934P as a secondary polymer to provide a hydrogel composition.

14. The process as claimed in claim 9, wherein said active / passenger molecule / plant, animal or marine extract is full-spectrum (FS) cannabis extract or cannabidiol (CBD).

15. The process as claimed in claim 14, further comprising step of addingpreservatives, stabilisers, viscolysers, precipitation inhibitors, antioxidants, and pH modifying agents to the mixture obtained in steps (c, d or e), wherein the preservatives are selected from the groupconsisting of Oxychloro Complex, Phenoxyethanol, Benzalkonium Chloride (BAK), Sodium Benzoate, Potassium Sorbate, Methylparaben, Propylparaben, Chlorobutanol, Ethylene diamin tetra acetic acid (and EDTA), Ascorbic acid, Tocopherols, Sodium metabisulfite, Sodium ascorbate, Benzyl alcohol, Boric acid, Citric acid, Benzoic acid, Polyquaternium- 1 , or a combination thereof, and the pH modifying agents are selected from the group consisting of Triethanolamine, Sodium Hydroxide, Sodium chloride, Potassium hydroxide, Citric acid, Tartaric acid, Lactic acid, Potassium carbonate, di basic or monobasic salts of sodium or potassium phosphate, boric acid, sodium borate, L-arginine, Potassium citrate, Phosphoric acid or a combination thereof. .

16. The process as claimed in claim 9, wherein said active / passenger molecule / plant, animal or marine extract is liquorice extract.

17. Use of a micellar composition as claimed in claim 1, for loading an active / a passenger molecule / a plant, animal or marine extract within the plurality of micelles.

18. Use of a loaded micellar composition, wherein an active / a passenger molecule / a plant, animal or marine extract is loaded by the method as claimed in claim 9 for the manufacture of medicament.

19. Use of the loaded micellar composition, as claimed in claim 18, wherein the medicament is for use in a method for managing conditions or diseases / disorders of the skin, including reduction of inflammation, oxidative stress, irritation, itchiness, redness, pigmentation, melasma, wrinkles, ageing, photo-ageing, and improving skin health, skin barrier, appearance and brilliance of skin and skin rejuvenation.

20. Use of the loaded micellar composition, as claimed in claim 18, wherein the medicament is for use in a method for managing conditions or diseases / disorders of the eye including inflammation, infection, dry eye disease, glaucoma, uveitis, and diabetic retinopathy, and modulating various receptors (like CB1, CB2, TRP channels (TRPV1-TRPM8), GPR55, GPR18, 5-HT1A, and A2A) located in ocular tissues, reducing intraocular pressure, inflammation, and nociceptive pain while providing neuroprotection.

21. Use of the loaded micellar composition, as claimed in claim 18, wherein the medicament is used in managing conditions or diseases / disorders of the humans or animals (veterinary use) and is administered as an oral, topical, rectal, vaginal, parenteral, nasal, or transdermal route.

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