Topical NANO-dispersion compositions and their preparation thereof

Abstract

The present invention relates to a topical nano-dispersion composition comprising one or more non-steroidal anti-inflammatory drugs (NSAIDs), muscle relaxants, local anesthetics, analgesics, gabapentinoids, alone or combinations thereof. The composition includes a dispersed phase containing drug(s), lipids, surfactants, amphiphilic penetration enhancers, and solvents, along with an aqueous phase. The nano-dispersion has particle sizes below 300 nm with unimodal particle size distribution, offering enhanced skin permeability and controlled drug release for up to 24 hours. The composition can be formulated into gels, creams, patches, lotions, liquid, or sprays, providing improved patient compliance through non-greasy, fast-absorbing formulations with extended shelf life.

Description

[0001] TOPICAL NANO-DISPERSION COMPOSITIONS AND THEIR PREPARATION THEREOF FIELD OF INVENTION The present invention relates to the field of pharmaceutical compositions, particularly to topical aqueous nano-dispersion formulations for the transdermal delivery of drugs such as NSAIDs, muscle relaxants, local anesthetics, analgesics, gabapentinoids, alone or combinations thereof. These compositions offer enhanced skin penetration, controlled release, and improved stability, intended for treating pain, inflammation, and other drug related indications and conditions. BACKGROUND OF THE INVENTION Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to alleviate pain, reduce inflammation, and lower fever, addressing conditions such as headaches, arthritis, sprains, and other forms of long-term pain. The marketed products include a variety of NSAIDs, such as ibuprofen, diclofenac, and naproxen, in multiple dosage forms: oral, topical, and intravenous. Despite their effectiveness, NSAIDs are associated with adverse effects, including gastrointestinal issues, skin irritation, and systemic toxicity, particularly when used over prolonged periods. To mitigate these risks, topical formulations have emerged as a favored route of administration due to their ability to deliver therapeutic benefits directly to the affected site with reduced systemic side effects. One of the challenges in topical NSAID formulations, especially with drugs like diclofenac, lies in its stability. Many of these formulations are prone to physical stability issues such as emulsion breakdown, phase separation, and are chemically unstable (drug degradation over time), also have poor skin penetration. Furthermore, the high concentrations of organic solvents (e.g., ethanol, acetone, DMSO) used in many existing products often cause skin irritation and other adverse reactions over time. Several prior art references address formulations related to topical dispersions and emulsions, highlighting various strategies to enhance drug solubility and stability. For instance: - **US20210137829A1** discloses a substantially water-free, oil-based structured lipid / surfactant system. This formulation stabilizes active agents and is dilutable at will to form a final composition, with oily domains sized between 5 and 150 nm. - **US8158687B2** reveals "ISAMULSION" droplets, which consist of nano- sized oil droplets with self-assembled hydrophilic domains, improving solubility and dispersion of active agents. - **WO2014208901A1** describes a stable "pre-emulsion" composed of poorly soluble drugs, surfactants, and mixed solvents. This pre-emulsion can be later diluted in water to form an oil-in-water emulsion, suitable for storage and distribution. - **WO2008058366** discloses a method of creating an oil-in-water emulsion by emulsifying a triglyceride oil with macrogol 15 hydroxystearate, resulting in sub-200 nm droplets in the final emulsion. - Shishu Goindi et al. (AAPS PharmSciTech, 2016) demonstrate the critical role of adding water dropwise to a surfactant-oil mixture to spontaneously form a microemulsion, ensuring stability and consistency in the formulation. Although these prior arts provide insights into nano-sized emulsion and dispersion systems, there remains a need for a shelf-stable, aqueous-based nano-dispersion that ensures high skin permeability and fast onset of action for NSAIDs and other drugs like muscle relaxants, analgesics, local anesthetics, and gabapentinoids, alone or in combination. Furthermore, the reduction or elimination of skin-irritating organic solvents, and simplification of the manufacturing process, are essential goals not fully addressed in existing technologies. The present invention addresses these gaps by developing a shelf-stable, nano-dispersion composition in aqueous or gel form, that enhances skin absorption of poorly soluble drugs, reduces the need for harmful solvents, and provides a commercially viable, cost-effective manufacturing method. The process emphasizes the preparation of a primary dispersion, which plays a critical role in achieving the desired particle size and ensuring shelf stability for 18 months or more, in accordance with International Council for Harmonisation (ICH) guidelines for accelerated and long-term stability testing. OBJECTS AND SUMMARY OF THE INVENTION The invention provides a topical aqueous or gel form of nano-dispersion composition designed to enhance the delivery and efficacy of drugs such as NSAIDs, muscle relaxants, local anesthetics, analgesics, and gabapentinoids alone and their combinations through the skin. The composition consists of a dispersed phase containing the active drug(s) entrapped in a lipidic or polymeric carrier, surfactants with a specific hydrophilic-lipophilic balance (HLB), amphiphilic penetration enhancers, and solvents with defined dielectric constants. The aqueous phase comprises water and may also contain chelating agents, stabilizers, buffering agents or gelling agents. The formulation exhibits nanoparticle sizes below 300 nm with a polydispersity index (PDI) of less than 0.5, ensuring uniform monomodal particle size distribution. The nano-dispersion improves skin permeability by at least two- fold compared to conventional formulations, offers a controlled release profile over 6 to 24 hours, and remains physically and chemically stable under accelerated and long-term ICH storage conditions. It is an object of the present invention to formulate topical pharmaceutical compositions preferably comprising NSAIDs, muscle relaxants / anti- spasmodic, local anesthetics, Analgesics or Gabapentin and other GABA derivatives (Gabapentinoids) or their pharmaceutically acceptable salts / derivatives alone and combinations thereof, which exhibit a fast onset of action, improved skin absorption due to enhanced skin permeability. It is an object of the present invention to develop an aqueous based topical nano-dispersion composition having fast onset of action and improved skin permeability, using specific excipients like one or more amphiphilic penetration enhancers and a simple, cost-effective manufacturing process. It is an object of the present invention to develop a gel-based topical nano- dispersion composition having fast onset of action and improved skin permeability, using specific excipients like one or more amphiphilic penetration enhancers and a simple, cost-effective manufacturing process. Another object of the present invention is to develop a topical nano-dispersion composition comprising an effective amount of NSAIDs or their pharmaceutically acceptable salt(s) / derivatives and a pharmaceutically acceptable carrier, wherein the composition is in the form of nano-dispersion, gel, emulgel, lotion, cream, ointment, spray, liquid, etc. Another object of the present invention is to develop a topical nano-dispersion composition comprising an effective amount of one or more muscle relaxant / anti-spasmodic alone or in combination with NSAID or local anesthetics or Gabapentin or Analgesics and other GABA derivatives (Gabapentinoids) and a pharmaceutically acceptable carrier, wherein the composition is in the form of nano-dispersion, gel, emulgel, lotion, cream, ointment, spray, liquid, etc. Another object of the present invention is to develop a topical nano-dispersion composition comprising an effective amount of one or more local anesthetic alone or in combination with NSAID or muscle relaxant / anti-spasmodic or analgesic and a pharmaceutically acceptable carrier, wherein the composition is in the form of nano-dispersion, gel, emulgel, lotion, cream, ointment, spray, liquid, etc. Another object of the invention is to develop topical pharmaceutical compositions of NSAIDs or their pharmaceutically acceptable salts / derivatives, using a simple and cost-effective process. Another object of the present invention is to develop a topical nano-dispersion composition comprising an effective amount of Diclofenac or its pharmaceutically acceptable salt(s) / derivatives alone or in combination with NSAID or local anesthetic or analgesic or muscle relaxant / anti-spasmodic and a pharmaceutically acceptable carrier, wherein the composition is in the form of nano-dispersion, gel, emulgel, lotion, cream, ointment, spray, liquid, etc. Yet another object of the invention is to develop topical pharmaceutical compositions comprising Diclofenac or its pharmaceutically acceptable salts / derivatives alone or in combination with NSAID or local anesthetic or analgesic or muscle relaxant / anti-spasmodic thereof, which exhibit a fast onset of action, improved skin absorption, due to better skin permeability. Another object of the invention is to develop topical pharmaceutical compositions of NSAIDs, preferably Diclofenac or its pharmaceutically acceptable salts / derivatives, alone or in combination with NSAID or local anesthetic or analgesic or muscle relaxant / anti-spasmodic, using a simple and cost-effective process. Another object of the present invention is to develop a topical nano-dispersion composition comprising an effective amount of Thiocolchicoside or its pharmaceutically acceptable salt(s) and a pharmaceutically acceptable carrier, wherein the composition is in the form of nano-dispersion, gel, emulgel, lotion, cream, ointment, spray, liquid, etc. Yet another object of the invention is to develop topical pharmaceutical compositions comprising Thiocolchicoside or its pharmaceutically acceptable salts thereof, which exhibit a fast onset of action, improved skin absorption, due to better skin permeability. Another object of the invention is to develop topical pharmaceutical compositions of muscle relaxants / anti-spasmodic, preferably Thiocolchicoside or its pharmaceutically acceptable salts, using a simple and cost-effective process. Another object of the present invention is to develop a topical nano-dispersion composition comprising an effective amount of lidocaine or its pharmaceutically acceptable salt, alone or in combination with a NSAID or analgesic or muscle relaxant / anti-spasmodic and a pharmaceutically acceptable carrier, wherein the composition is in the form of nano-dispersion, gel, emulgel, lotion, cream, ointment, spray, liquid, etc. Yet another object of the invention is to develop topical pharmaceutical compositions comprising lidocaine or its pharmaceutically acceptable salts thereof, alone or in combination with a NSAID or analgesic or muscle relaxant / anti-spasmodic which exhibit a fast onset of action, improved skin absorption, due to better skin permeability. Another object of the invention is to develop topical pharmaceutical compositions of local anesthetic, preferably Lidocaine or its pharmaceutically acceptable salts, using a simple and cost-effective process. Yet another object of the present invention is to develop a topical aqueous nano-dispersion composition based on a platform technology “EANC TECHNOLOGY” by which the drug(s) / active(s) are encapsulated in nano- sized dispersed phase carrier droplets of nano-dispersion for effective delivery of drugs or actives through skin or mucosa or biological membrane. The following embodiments further describe the objects of the present invention in accordance with the best mode of practice. However, the disclosed invention is not restricted to the embodiments hereinafter described. BRIEF DESCRIPTION OF ACCOMPANYING DRAWINGS The following drawings form a part of the present specification and are included to further illustrate aspects of the present disclosure. The disclosure may be better understood by reference to the drawings in combination with the detailed description of the specific embodiments presented herein. Figure 1 depicts the Transmission Electron Microscopy (TEM) image of Diclofenac Diethylamine, Methyl salicylate and Menthol Nano-dispersion formulation of Example 34, which shows well defined spherical nanoparticles with particle size below 300nm. Electron Microscope (FEI, Netherlands) at 120 kV with a 4K Eagle bottom-mount CCD camera was used to capture the image, in accordance with an embodiment of the present disclosure. Figure 2 depicts a magnified version of the image in Figure 1, in accordance with an embodiment of the present disclosure. DETAILED DESCRIPTION OF THE INVENTION Those skilled in the art will be aware that the present disclosure is subject to variations and modifications other than those specifically described. It is to be understood that the present disclosure includes all such variations and modifications. The disclosure also includes all such steps, features, compositions, and compounds referred to or indicated in this specification, individually or collectively, and any and all combinations of any or more of such steps or features. Definitions For convenience, before further description of the present disclosure, certain terms employed in the specification, and examples are delineated here. These definitions should be read in the light of the remainder of the disclosure and understood as by a person of skill in the art. The terms used herein have the meanings recognized and known to those of skill in the art, however, for convenience and completeness, particular terms and their meanings are set forth below. The present invention can be more readily understood by reading the following detailed description of the invention and studying the included examples. The terms “topical aqueous nano-dispersion composition” and “topical nano- dispersion composition” are used interchangeably. The terms “entrapped” and “encapsulated” are used interchangeably. The terms “composition” and “formulation” have been used interchangeably. The terms “gel component”, “gel phase”, “gel agent dispersion” and “gelling agent dispersion” have been used interchangeably. The term “primary dispersion” refers to a dispersion obtained by adding some water to the dispersed phase components, wherein the weight ratio of surfactant to water ranges from 1:0.1 to 1:1.5. When a critical amount (as defined by surfactant to water ratio) of water is added to the dispersed phase components under controlled conditions of temperature and stirring, we obtain considerable particle size reduction. The terms “secondary dispersion” and “secondary nano-dispersion” are used interchangeably and refer to the nano-dispersion composition of the present disclosure obtained by adding a primary dispersion to rest of the aqueous phase / water. The dispersed phase may comprise one or more drug selected from non- steroidal anti-inflammatory drugs (NSAIDs) or salts thereof, muscle relaxants, local anaesthetics, analgesics, gabapentinoids, or combinations thereof, one or more lipid and / or polymer, one or more surfactant with a combined hydrophilic-lipophilic balance (HLB) ranging from 3 to 25, one or more amphiphilic penetration enhancer, and one or more solvent with a dielectric constant ranging from 2 to 38. The term "topical pharmaceutical composition" is used herein to include a pharmaceutical composition that can be applied to skin or mucosa. Topical pharmaceutical compositions may, for example, be used to confer therapeutic benefits to a patient or cosmetic benefits to a consumer. Topical pharmaceutical compositions can be used for both topical and transdermal administration of substances. "Pharmaceutical composition” and "composition" as used herein are equivalent terms referring to a composition of active ingredients or drugs for pharmaceutical use. The term "penetration enhancer" is used herein to include an agent that improves the transport of molecules such as an active agent or drugs into or through the skin. Various conditions may occur at different sites in the body, either in the skin or below the skin, creating a need for the target delivery of compounds. For example, in the treatment of osteoarthritis, the delivery of the active agent into deep underlying joint tissue may be necessary to achieve therapeutic benefit. Thus, a "penetration enhancer" may be used to assist in the delivery of an active agent directly to the skin or underlying tissue or indirectly to the site of the disease. A penetration enhancer may be a pure substance or may comprise a mixture of different chemical entities. The terms "permeation enhancer" and "penetration enhancer," as disclosed herein, are intended to be equivalent, both referring to an agent that aids in the absorption of a compound through the skin. “Surfactant” or “surface active agent” are amphiphilic molecules and are thus absorbed in the interface. At the interface, they align themselves such that they reduce the surface or interfacial tension. Surfactants have covalently bonded oxygen-containing hydrophilic groups, which are bonded to hydrophobic parent molecules / structures. Surfactants can be ionic or non-ionic. The non-ionic surfactants are not ionized in water and contain both hydrophilic groups (e.g., oxyethylene-CH2CH2O-, ether groups, hydroxyl groups-OH or-CONH2 amide groups, etc.) and lipophilic groups (e.g., hydrocarbons which can be natural fatty alcohols or synthetic alcohols, acids, or glyceryl esters / oils). Non-ionic surfactants can be selected from fatty alcohol ethoxylate, fatty acid or glycerol or sugar or polyoxyethylene or propylene glycol esters, alkyl phenol ethoxylate, and fatty acid alkoxylate. "Solvent" means a solvent or solvent system or combination of solvents wherein a substantial portion of a topically active drug may be solubilized therein. “Chelating agent” means chemical compounds that react with metal ions to form a stable, water-soluble complex, such as EDTA and ethylene glycol tetra- acetic acid (EGTA). “Gelling agents” are the gel-forming agents when dissolved in a liquid phase forms a weakly cohesive internal structure. They are organic hydrocolloids, natural polymers / gums, carbopols, or hydrophilic inorganic substances. As used herein in the specifications, the term ‘nano-dispersion’ refers to solid lipid nano-dispersion, lipid nano-dispersion, nano-emulsion, polymeric nanoparticulate dispersion, lipid-polymer hybrid nano-dispersion, aqueous dispersions of lipids or polymers or combination, and spontaneous nano systems. "Thickening agent" means any agent useful as an aid to thicken or add structure to a topical pharmaceutical composition. These agents impart physical stability and increase viscosity. Nonlimiting examples of thickening agents are gums (natural and synthetic) and natural polysaccharides, mineral thickeners, oils, waxes, and synthetic polymeric thickeners. Additionally, a thickening agent refers to one or more agents that, in combination, result in a viscosity suitable for dermatologic applications. “Drug(s)” referred to herein without limitation may include one or more actives / APIs, NSAIDs, analgesic, muscle relaxant / antispasmodic, local anesthetics and gabapentinoids alone or in combination. The non-steroidal anti-inflammatory drugs (NSAID) referred to herein include, without limitation, Diclofenac, flurbiprofen, ibuprofen, naproxen, fenoprofen, pirprofen, carprofen, oxaprozin, tiaprofenic acid, acetylsalicylic acid, diflunisal, etodolac, etofenamate, ketoprofen flufenamic acid, indomethacin, ketorolac, meclofenamate, mefenamic acid, nabumetone, oxyphenbutazone, phenylbutazone, piroxicam, meloxicam, salsalate, sodium salicylate, sulindac, tenoxicam, tolmetin, and celecoxib, methyl salicylate, aceclofenac, bromfenac, loxoprofen, acemetacin, nimesulide, etoricoxib, O-ethoxy benzamide, choline salicylate, Benorylate, benzydamine, Nefopam, Dexketoprofen, Nepafenac, Gatifloxacin, Dexibuprofen, Zaltoprofen, Parecoxib and their pharmaceutically acceptable salts or derivatives. The analgesic referred to herein without limitation may include Non-Narcotic Analgesics or Narcotic Analgesic. The non-narcotic analgesic is selected from Fenoverine or Tapentadol, and the narcotic analgesic is selected from Buprenorphine Hydrochloride, Butorphanol Tartrate, Remifentanil Hydrochloride, or Tramadol, and their pharmaceutically acceptable salts or derivatives. The muscle relaxant referred to herein without limitation may include other substances of natural or chemical origin like: Capsaicin, thiocolchicoside, metaxalone, tizanidine, methocarbamol, carisoprodol, orphenadrine, dantrolene, cyclobenzaprine, idrocilamide, tolperisone, eperisone, Piperidinoethoxy, Phenyramidol, Iso-dihydo-ethaverine chloride, Chlormezanone, Baclofen, Phenprobamate, Panchronium Bromide, Mebeverine, Flavoxate Hydrochloride, Atricurium Dibesylate, Vecuronium Bromide, Pipecuronium Bromide, Rocuronium Bromide and their pharmaceutically acceptable salts or derivatives. The anesthetic referred to herein without limitation may include other substances of natural or chemical origin like Lidocaine, Ropivacaine, Benzocaine, Tetracaine, Prilocaine, Pramoxine, Dibucaine, Oxybuprocaine, Proxymetacaine, ketamine, menthol etc. and their pharmaceutically acceptable salts or derivatives. The Gabapentinoids referred to herein without limitation may include Gabapentin, pregabalin, mirogabalin, baclofen, phenibut and other GABA derivatives and their pharmaceutically acceptable salts or derivatives. Diclofenac salts referred to herein without limitation include Diclofenac Sodium, Diclofenac Potassium, Diclofenac Diethylamine, Diclofenac Epolamine or any other salts and derivatives of Diclofenac or Combination thereof. As used herein, all numerical values relating to amounts, weights, and the like are defined as "about". Each value is plus or minus 10%. For example, the phrase "about 10% w / w" is to be understood as "9% to 11% w / w." Therefore, amounts within 10% of the claimed value are encompassed by the scope of the claims. As used herein, "% w / w" refers to the percent weight of the total composition. As used herein, the term "effective amount" refers to the amount necessary to treat or cure a patient in need thereof. The said invention shows various advantages over the conventional topical formulations like: a) The size reduction and the physical stability enhancement obtained by this method impart several desirable characteristics to the products such as longer-term physical stability to the product and chemical stability to the drug encapsulated in nano-sized dispersed phase carrier droplets of nano- dispersion. b) The simplicity and cost-effectiveness of the technology. c) Free from high amounts of harmful solvents (like ethanol, isopropyl alcohol, DMSO and acetone) that causes skin irritation, dryness of skin and develop various skin reactions on long term usage. d) Improved delivery of drugs via topical route for better therapeutic response, for drugs which have poor aqueous solubility, permeation ability, and thus low bioavailability. e) The invention results in a platform technology “EANC TECHNOLOGY” that can be applied to topical / transdermal delivery of a variety of drugs or actives / APIs into the deeper layers of skin for effective drug delivery. In another embodiment of the present invention, a topical nano-dispersion composition comprises: - a dispersed phase comprising one or more drug selected from non- steroidal anti-inflammatory drugs (NSAIDs) or salts thereof, muscle relaxants, local anaesthetics, analgesics, gabapentinoids, or combinations thereof, one or more lipids and / or polymers, one or more surfactants with a combined hydrophilic-lipophilic balance (HLB) ranging from 3 to 25, one or more amphiphilic penetration enhancer, one or more solvent with a dielectric constant ranging from 2 to 38; and - an aqueous phase comprising water, wherein the surfactant to water weight ratio in the nano-dispersion composition ranges from 1:6 to 1:36. In another embodiment of the present invention the topical aqueous nano- dispersion composition further comprises an aqueous phase comprising one or more chelating agents and one or more stabilizers or antioxidants. In another embodiment of the present invention, the topical nano-dispersion composition can also be prepared in the form of a gel by incorporating a gel component comprising a gelling agent, an alkali / buffering agent, and water. In another embodiment of the present invention the topical aqueous nano- dispersion composition further comprises a gel phase comprising one or more gelling agents or thickening agents dispersed in purified water and the dispersion neutralized using an alkali / buffering agent or its solution. In another embodiment of the present invention, a topical gel nano-dispersion composition, comprises: - a dispersed phase comprising one or more drug selected from non- steroidal anti-inflammatory drugs (NSAIDs) or salts thereof, muscle relaxants, local anaesthetics, analgesics, gabapentinoids, or combinations thereof, one or more lipids and / or polymers, one or more surfactants with a combined hydrophilic-lipophilic balance (HLB) ranging from 3 to 25, one or more amphiphilic penetration enhancer, one or more solvent with a dielectric constant ranging from 2 to 38; - an aqueous phase comprising water, a gelling agent, and an alkali / buffering agent, wherein the surfactant to water weight ratio in the nano-dispersion composition ranges from 1:6 to 1:36. In another embodiment of the present invention the topical aqueous nano- dispersion composition is prepared without use of a gelling agent or thickening agent. In another embodiment of the present invention, the dispersed phase further comprises water, and wherein the surfactant to water weight ratio in the dispersed phase ranges from 1:0.1 to 1:1.5 for considerable particle size reduction. In another embodiment of the present invention the topical gel nano- dispersion composition comprises: i) a primary dispersion, wherein drug(s) is in the dispersed phase, comprising one or more lipids and / or polymer, one or more non-ionic surfactant(s) with a combined HLB ranging from 3 to 25, one or more amphiphilic penetration enhancers, one or more solvents with a dielectric constant ranging from 2 to 38, and water, wherein the surfactant(s) to water weight ratio ranges from 1: 0.1 to 1: 1.5 for considerable nano size reduction or particle size (mean or average) below 300nm. ii) an aqueous phase comprising one or more chelating agents and one or more stabilizers or antioxidants. iii) a gel phase comprising one or more gelling agents or thickening agents dispersed in purified water and the dispersion neutralized using an alkali / buffering agents or its solution. In another embodiment of the present invention the topical nano-dispersion composition is prepared by the following steps: i) preparing a primary dispersion, wherein one or more drug is dissolved in one or more lipids and / or polymers, one or more surfactant with a combined HLB ranging from 3 to 25, one or more amphiphilic penetration enhancers, and one or more solvents with dielectric constant ranging from 2 to 38 to form an oily nano-dispersion concentrate, to which water is added under controlled conditions of temperature and stirring rate for considerable particle size reduction, wherein the weight ratio of surfactant to water ranges from 1:0.1 to 1:1.5, and ii) adding the primary dispersion into an aqueous phase under stirring, followed by homogenization to obtain the topical nano-dispersion composition. In another embodiment, the process of producing a gel nano-dispersion composition comprises the following steps: - i) preparing a primary dispersion, wherein one or more drug is dissolved in one or more lipids and / or polymers, one or more surfactant with a combined HLB ranging from 3 to 25, one or more amphiphilic penetration enhancers, and one or more solvents with dielectric constant ranging from 2 to 38 to form an oily nano-dispersion concentrate, to which water is added under controlled conditions of temperature and stirring rate for considerable particle size reduction, wherein the weight ratio of surfactant to water ranges from 1:0.1 to 1:1.5, - ii) adding the primary dispersion into an aqueous phase under stirring, followed by homogenization to obtain the topical nano-dispersion product, - iii) preparing a gel component, wherein a gelling agent is dispersed in purified water using a high-shear disperser and is neutralized using an alkali / buffering agent, - iv) adding the gel component slowly to the topical nano-dispersion product of step (ii) while stirring, followed by continuous homogenization to obtain a gel nano-dispersion composition. In another embodiment, there are two instances where water is added in the process. There is a first portion of water which is added during the preparation of the dispersed phase. Further, there is a second portion of water which is added to the dispersed phase as part of the aqueous phase. In yet another embodiment, a portion of water is added during the preparation of the dispersed phase for achieving particle size reduction. In another embodiment of the present invention, the process of preparing the nano-dispersion composition comprises the following features: (a) the aqueous phase further comprises one or more chelating agents, stabilizers or antioxidants, or alkali / buffering agents; and / or (b) the drug concentration is between about 1.0% to about 6.0% w / w of the total composition; and / or (c) the lipid concentration is between about 1% w / w and about 30% w / w of the total composition; and / or (d) the surfactant is present in an amount of more than about 1.0% w / w of the primary dispersion; and / or (e) the amphiphilic penetration enhancer concentration is between about 0.1% and about 20% w / w of the total composition; and / or (f) the solvent concentration is up to 12% w / w of the total composition. In another embodiment of the present invention, the process of preparing the nano-dispersion composition comprises the following features: (a) the chelating agent is selected from Ethylenediaminetetraacetic acid (EDTA), disodium EDTA, calcium disodium EDTA, or salts thereof; the stabilizer or antioxidant is selected from alpha-tocopherol, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), ascorbic acid, or sodium metabisulfite; alkali / buffering agent is selected from sodium hydroxide or triethanolamine solution; and / or (b) the drug is selected from Non-steroidal anti-inflammatory drugs (NSAIDs) or salts thereof, muscle relaxants, local anaesthetics, analgesics, gabapentinoids, or combinations thereof, wherein the NSAIDs and salts thereof is selected from Diclofenac, flurbiprofen, ibuprofen, naproxen, fenoprofen, pirprofen, carprofen, oxaprozin, tiaprofenic acid, acetylsalicylic acid, diflunisal, etodolac, etofenamate, ketoprofen, flufenamic acid, indomethacin, ketorolac, meclofenamate, mefenamic acid, nabumetone, oxyphenbutazone, phenylbutazone, piroxicam, meloxicam, salsalate, sodium salicylate, sulindac, tenoxicam, tolmetin, celecoxib, methyl salicylate, aceclofenac, bromfenac, loxoprofen, acemetacin, nimesulide, etoricoxib, O- ethoxy benzamide, choline salicylate, benorylate, benzydamine, nefopam, dexketoprofen, nepafenac, gatifloxacin, dexibuprofen, zaltoprofen, or parecoxib; the muscle relaxant is selected from capsaicin, thiocolchicoside, metaxalone, tizanidine, methocarbamol, carisoprodol, orphenadrine, dantrolene, cyclobenzaprine, idrocilamide, tolperisone, eperisone, piperidinoethoxy, phenyramidol, iso-dihydro-ethaverine chloride, chlormezanone, phenprobamate, pancuronium bromide, mebeverine, flavoxate hydrochloride, atracurium besylate, vecuronium bromide, pipecuronium bromide, or rocuronium bromide; the local anesthetic is selected from lidocaine, ropivacaine, benzocaine, tetracaine, prilocaine, pramoxine, dibucaine, oxybuprocaine, proxymetacaine, ketamine, or menthol; the analgesic is selected from non-narcotic and narcotic analgesics, wherein the non-narcotic analgesic is selected from fenoverine or tapentadol, and the narcotic analgesic is selected from buprenorphine hydrochloride, butorphanol tartrate, remifentanil hydrochloride, or tramadol; the gabapentinoid is selected from gabapentin, pregabalin, mirogabalin, baclofen, or phenibut; and / or (c) the lipid is selected from medium-chain and long-chain triglycerides (MCT / LCT), esters of fatty acids with C1-C36, alkanols such as isopropyl myristate, oleic acid decyl ester, ethyl oleate, C6-C12 alkanoic acid esters, C12-C18 saturated and unsaturated fatty alcohols, oils, phospholipids, phosphatidylcholines (PC) and its derivatives, or lecithins; and / or (d) the surfactant is selected from fatty esters of sorbitan (polyol esters / span series), polyoxyethylene esters / polysorbates, D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), sucrose esters, polyoxyl hydrogenated castor oil surfactants, fatty acid esters of glycerol, polyglycerol esters, propylene glycol fatty esters, sulfate surfactants, sulfonate surfactants, docusate sodium, cetyltrimethylammonium bromide (CTAB), sodium lauryl sulfate, and poloxamers or pluronic block copolymers; and / or (e) the amphiphilic penetration enhancer is selected from fatty acids such as caprylic acid, capric acid, lauric acid, myristic acid, palmitic acid, oleic acid, stearic acid, linolenic acid, arachidonic acid, cetylpyridinium chloride, sodium deoxycholate, sodium caprate, sodium hydroxy benzoyl amino caprylate, dodecyl dimethyl amino propionate, triacetin, glycerol esters, glyceryl oleate, glyceryl monostearate, cocoyl caprylocaprate, terpenes (limonene or others), or their mixtures; and / or (f) the solvent is selected from unsaturated and saturated fatty alcohols, dipolar aprotic solvents with a chain length of C5 to C20, such as pentanol, dodecanol, octadecanol (stearyl alcohol / oleyl alcohol), octyldodecanol, or methyl pyrrolidone (NMP). In another embodiment of the present invention the topical aqueous nano- dispersion composition is prepared without use of nanonization machine or equipment. In another embodiment of the present invention, wherein drug(s) or active(s) is entrapped in the lipidic / polymeric carrier. In an embodiment of the present invention, the topical nano-dispersion pharmaceutical composition comprises a nano-carrier system as the dispersed phase wherein one or more NSAIDs, analgesics, muscle relaxants / antispasmodics, local anesthetics, gabapentinoids, alone or their combination are entrapped (Drug entrapment) with at least 50% w / w of the total dose and wherein the particle size of the nano-dispersion is less than 950 nm, less than 900 nm, less than 800 nm, less than 700 nm, less than 600 nm, less than 500 nm, less than 400 nm or less than 300 nm. In an embodiment of the present invention, the particle size of the nano-carrier dispersion is preferably less than 200 nm, more preferably less than 150 nm. In an embodiment of the present invention, Drug Entrapment (Entrapped drug concentration) of nano dispersion composition / formulation is proportional to the total drug concentration (total drug loading in nano dispersion composition). If total drug concentration or drug dose in nano dispersion composition or formulation is 1%, 2%, 4% or 6%w / w then drug entrapment is at least 60%, 50%, 45% or 40%w / w respectively of total drug concentration or drug dose. In an embodiment of the present invention, the composition has polydispersity index less than 0.5 with unimodal particle size distribution. In another embodiment of the present invention the topical nano-dispersion composition is shelf-stable. In another embodiment of the present invention, a portion of drug(s) is released immediately and other portion as prolonged (depot). In another embodiment, the composition has a controlled release profile of entrapped drug over a period of 6 to 24 hours. In another embodiment of the present invention, the topical aqueous nano- dispersion composition is in the form of a gel, lotion, emulgel, cream, ointment, spray or liquid. In other embodiments, the composition is formulated into a dosage form selected from transdermal patches, impregnated dressings, or topical sprays. In one embodiment, one or more NSAIDs and their acceptable salts used in the topical aqueous nano-dispersion composition are chosen from the group consisting of Diclofenac, flurbiprofen, ibuprofen, naproxen, fenoprofen, pirprofen, carprofen, oxaprozin, tiaprofenic acid, acetylsalicylic acid, diflunisal, etodolac, etofenamate, ketoprofen, flufenamic acid, indomethacin, ketorolac, meclofenamate, mefenamic acid, nabumetone, oxyphenbutazone, phenylbutazone, piroxicam, meloxicam, salsalate, sodium salicylate, sulindac, tenoxicam, tolmetin, and celecoxib, methyl salicylate, aceclofenac, bromfenac, loxoprofen, acemetacin, nimesulide, etoricoxib, O-ethoxy benzamide, choline salicylate, Benorylate, benzydamine, Nefopam, Dexketoprofen, Nepafenac, Gatifloxacin, Dexibuprofen, Zaltoprofen, Parecoxib and combinations thereof. In another embodiment, the preferable NSAID for topical aqueous nano- dispersion composition is selected from diclofenac, diclofenac sodium, diclofenac diethylamine, diclofenac potassium, diclofenac epolamine, diclofenac ammonium, and mixtures thereof, or any other pharmaceutically acceptable salts or derivatives of diclofenac. In another embodiment of the present invention, one or more drugs other than NSAIDs like analgesic, muscle relaxants / anti-spasmodic, local anesthetics and gabapentinoids can be used in the topical aqueous nano-dispersion composition. In another embodiment of the present invention, one or more drugs other than NSAIDs can be used in the topical aqueous nano-dispersion composition. In another embodiment, the topical aqueous nano-dispersion composition may comprise analgesic as Non-Narcotic Analgesics or Narcotic Analgesic. In another embodiment, the topical aqueous nano-dispersion composition, the non-narcotic analgesic is selected from Fenoverine or Tapentadol, and the narcotic analgesic is selected from Buprenorphine Hydrochloride, Butorphanol Tartrate, Remifentanil Hydrochloride, or Tramadol and their pharmaceutically acceptable salts or derivatives etc. In another embodiment of the present invention, one or more local anesthetics (e.g., Lidocaine, Ropivacaine, Benzocaine, Tetracaine, Prilocaine, Pramoxine, Dibucaine, Oxybuprocaine, Proxymetacaine, Ketamine, Menthol and their salts or derivatives, etc.) can be used in the topical aqueous nano- dispersion composition. In yet another embodiment of the present invention, one or more muscle relaxant / antispasmodic used in the topical aqueous nano-dispersion composition are chosen from the group consisting of Capsaicin, thiocolchicoside, metaxalone, tizanidine, methocarbamol, carisoprodol, orphenadrine, dantrolene, cyclobenzaprine, idrocilamide, tolperisone, baclofen, eperisone, Piperidinoethoxy, Phenyramidol, Iso-dihydo-ethaverine chloride, Chlormezanone, Phenprobamate, Panchronium Bromide, Mebeverine, Flavoxate Hydrochloride, Atricurium Dibesylate, Vecuronium Bromide, Pipecuronium Bromide, Rocuronium Bromide, and their salts or derivatives, etc. In another embodiment of the present invention, one or more gabapentinoids (e.g.: Gabapentin, pregabalin, mirogabalin, baclofen, phenibut and their salts or derivatives, etc.) can be used in the topical aqueous nano-dispersion composition. In an embodiment of the present invention, one or more lipids used in the topical aqueous nano-dispersion composition are selected from medium- chain and long chain triglycerides (e.g., caproic acid, caprylic acid, capric acid, and lauric acid), Fatty alcohols, Oils, Esters of fatty acids with C1-C36, and with alkanols e.g., cetyl palmitate, lanolin, isopropyl myristate, isopropyl stearate, oleic acid decyl ester, ethyl oleate, or C6-C12-Alkanoic acid esters- especially caprylic / capric acid esters—with saturated fatty alcohols, especially C12-C18 saturated and unsaturated fatty alcohols, oils, phospholipids, phosphatidylcholines (PC), dipalmitoylphosphatidylcholine (DPPC), distearoyl phosphatidylcholine (DSPC), palmitoyl stearoyl phosphatidyl choline (DSPC), mono-phosphatidyl glycerols, bisphosphatidyl glycerols, and tris-phosphatidyl glycerols palmitoyl oleyl choline (PODC), soy lecithin, rapeseed lecithin, corn or sunflower lecithin, egg lecithin, Epicorn 200, Epicorn 100, phospholipon 90G, LIPOID R-100 (Rapeseed), LIPOID H- 100(Sunflower), LIPOID-S100 (Soybean), LIPOID-S75, Phosal 50PG, dioleyl phosphatidylcholine (DOPC), oleyl palmitoyl phosphatidylcholine (POPC), and their corresponding -serines, -ethanol amines, -glycerol derivatives and others. In another embodiment of the present invention, concentration of one or more lipid used in the topical aqueous nano-dispersion composition is between about 1%w / w and about 30% w / w of the total composition. In one embodiment of the present invention, one or more surfactant used in the topical aqueous nano-dispersion composition are chosen from the group consisting of Fatty acid esters of Sorbitan (Polyol esters / span series), Polyoxyethylene esters / polysorbates (polysorbate-20,-40, -60, -65, polysorbate 80, and polysorbate-85 etc.,), D-tocopheryl polyethylene glycol (1000) succinate (TPGS), Sucrose esters (Surfhope® sugar ester D-1216, sucrose laurate), polyoxyl hydrogenated castor oil surfactants [Cremophor / Kolliphor EL (Cr EL), Cremophor / Kolliphor RH 40 (Cr RH 40) or others], fatty acid esters of glycerol (GMS, GML, GMO etc.,), polyglycerol esters, propylene glycol fatty esters, labrasol, sulfate surfactants, sulfonate surfactants, Docusate sodium (Dioctyl sodium sulfosuccinate), CTAB, Sodium Lauryl sulphate and poloxamers (pluronic block copolymers) etc. In another embodiment of the present invention the surfactant is more than about 1.0% w / w of the dispersed phase. In another embodiment of the present invention, optionally a polymer could also be added, which acts as a carrier. The said polymer referred to herein include, without limitation, polyvinylpyrrolidones (PVPs), polyethylene glycols (PEGs), polyvinyl alcohol (PVAs), polylysine, polyglycine, cellulose & its derivatives, hyaluronate derivatives, and natural polymers etc. In another embodiment of the present invention wherein primary dispersion additionally comprises a polymer selected from polyvinylpyrrolidones (PVPs), polyethylene glycols (PEGs), polyvinyl alcohol (PVAs), polylysine, polyglycine, cellulose & its derivatives, hyaluronate derivatives, and natural polymers etc. In yet another embodiment of the present invention, one or more amphiphilic penetration enhancers used in the topical aqueous nano-dispersion composition are selected from glyceryl oleate, fatty acids such as caprylic acid, capric acid, undecylenic acid, lauric acid, myristic acid, palmitic acid, oleic acid, stearic acid, linolenic acid, arachidonic acid, cetylpyridinium chloride, edetate disodium dihydrate, sodium deoxycholate, sodium deoxy- glycolate, sodium glycocholate, sodium caprate, sodium taurocholate, sodium hydroxy benzoyl amino caprylate, dodecyl dimethyl amino propionate, Triacetin, glycerol esters, glyceryl oleate, glyceryl monostearate, N-Methyl- pyrrolidone, Cocoyl caprylocaprate, Dimethylacetamide, Limonene, other terpenes and their mixtures thereof. In preferred embodiments, the amount of amphiphilic permeation enhancer is from about 0.001% to about 20.0% w / w. In a more preferred embodiment, the compositions contain about 0.01% to about 12.0% w / w permeation enhancer. In a preferred embodiment, the compositions contain about 0.02% to about 10.0% w / w permeation enhancer. In another embodiment, the amphiphilic penetration enhancer is present in a concentration between about 0.1% and about 20%w / w of the total composition. In another embodiment of the present invention, the amphiphilic penetration enhancer is used in combination with a hydrophilic penetration enhancer selected from propylene glycol, polyethylene glycol, or N-methyl pyrrolidone. In another embodiment of the present invention, the surface orientation and loading of the amphiphilic penetration enhancer are monitored by measuring the surface charge or zeta potential using Malvern Zetasizer or Electrophoretic light scattering (ELS) and Electroacoustic methods. In another embodiment of the present invention, the solvent used in the topical aqueous nano-dispersion composition is selected from the group of unsaturated and saturated fatty alcohols with a chain length of C5 to C20 and dipolar aprotic solvent. For example, pentanol, octanol, decanol, dodecanol, tetradecanol, hexadecanol, octadecanol (stearyl alcohol / oleyl alcohol), NMP, and Octyldodecanol etc., In yet another embodiment of the present invention, the amount of solvent used in the topical aqueous nano-dispersion composition is up to about 12% of the total composition. In another embodiment of the present invention the solvent is an amphipathic solvent with dielectric constant ranging from 2 to 38. In the preferred embodiment solvent is oleyl alcohol in a range of 0.5-10.0%, preferably 5.0%. According to one of the embodiments, the additional solvent may be selected from propanol, butanol, butylene glycol, propylene glycol, glycerol, Benzyl alcohol / α-Cresol, triethyl citrate, diethylene glycol monoethyl ether and polyethylene glycols like PEG 200, PEG 400, and others etc. According to one of the embodiments, the composition is free of ethanol. In an embodiment of the present invention, the nano-carrier system of the topical aqueous nano-dispersion composition comprises one or more NSAIDs, muscle relaxants / antispasmodics, local anesthetic, analgesics, gabapentinoids alone or combination thereof, one or more lipids, one or more surfactant(s) with an HLB of between 3 to 25, one or more amphiphilic penetration enhancers, solvent or combination of solvents or solvent system with a dielectric constant ranging between 2 to 38 and water, wherein the surfactant(s) to water weight ratio in primary nano dispersion ranges from 1 : 0.1 to 1 : 1.5 for considerable nano size reduction or particle size below 300nm. In an embodiment of the present invention, the topical aqueous nano- dispersion composition is prepared in four steps wherein the primary dispersion is prepared initially by mixing drug(s), one or more lipids, one or more surfactant(s) with a combined HLB ranging from 3 to 25, one or more amphiphilic penetration enhancers, one or more solvents with a small amount of water, and then the primary dispersion is dispersed into the aqueous phase under stirring to obtain the secondary nano-dispersion. The secondary nano- dispersion is added to the gelling agent dispersion while mixing or homogenization to obtain the gel nano-dispersion composition. In an embodiment of the present invention, the topical gel nano-dispersion composition is prepared using the following steps: a) Preparing a primary dispersion, in which one or more lipids, one or more surfactant(s) with an combined HLB ranging from 3 to 25, one or more amphiphilic penetration enhancers, an solvent with a dielectric constant ranging from 2 to 38 to dissolve the drug(s) selected from one or more NSAIDs, muscle relaxants, analgesics and local anesthetics, gabapentinoids alone or their combinations to form an oily nano-dispersion concentrate to which water is added under controlled conditions of temperature and stirring rate to obtain primary dispersion, b) Dispersing the primary dispersion into the aqueous phase under stirring, followed by homogenization to obtain a secondary nano-dispersion, wherein the aqueous phase contains a chelating agent and one or more stabilizers or antioxidants, c) Preparing a gel component, wherein the gelling agent is dispersed in purified water using a high shear disperser and the dispersion is neutralized using an alkali / buffering agent or its solution e.g., sodium hydroxide / triethanolamine solution, d) slowly adding the secondary nano-dispersion of step (b) to the gel component of step (c) under continuous stirring / homogenization to obtain the topical gel nano-dispersion formulation. In another embodiment, the aqueous phase comprises purified water or alkaline / buffer aqueous solution or surfactant solution or aqueous phase comprising of one or more chelating agents or stabilizers / antioxidants. In another embodiment of the present invention the surfactant(s) to water ratio in total nano-dispersion formulation ranges from 1:6 to 1:36. In an embodiment of the present invention, the topical aqueous nano- dispersion composition is prepared using a simple and cost-effective process. No high-cost nano-size reduction machines / equipments are used in the manufacturing. Also, the preparation of primary dispersion with water is critical to form a stable dosage form or product. If the oily components are directly added to the aqueous phase without initially forming a primary dispersion a coarse emulsion is obtained. In another embodiment of the present invention the water in primary dispersion contains alkali, buffering agents, surfactants, polyols, sugars, amino acids, hydrophilic solvents, water soluble excipients or their combinations. In another embodiment of the present invention the topical aqueous nano- dispersion composition is prepared without use of a gelling or thickening agent. Gelling agents used in the present invention are selected from Methyl Cellulose, Hydroxyethylcellulose, Hydroxypropylcellulose, Hydroxypropylmethylcellulose, Carboxy Methylcellulose, HPMC K4M, HPMC K15M, HPMC K100M and HPMC K100LV CR, Carbopol 974P, Carbopol®910, carbopol®934, Carbopol® 934P, Carbopol® 940, Carbopol® 941, Carbopol 980, Pectins (Low methoxy and High methoxy), , Gelatin, Starches, Alginates, Polyvinyalcohol, Povidones (All types), Hypromellose, modified starch, natural gums, xanthan, guar gum, locust bean gum, gum Arabic, acacia gum, gum karaya, Carrageenans (Kappa, Iota and lambda), Bentonite magma, Agar, Gellan Gum, Chitosan, Polyacrylamides, Polyethylene glycol based gelling agents, silica based gelling agents, Microcrystalline silica, Clays, HPMC-2910, HPMC, Carbomers, Carbopol® Aqua Polymers, Carbopol® Aqua SF-1 Polymer, Carbopol® Aqua SF-1 OS Polymer, Carbopol® Aqua SF-2 Polymer, Carbopol® Aqua CC Polymer, Carbopol® 934 Polymer, Carbopol® 940 Polymer, Carbopol® 941 Polymer, Carbopol® 980 Polymer, Carbopol® 981 Polymer, Carbopol® 1342 Polymer, Carbopol® 1382 Polymer, Carbopol® 2984 Polymer, Carbopol® 5984 Polymer, Carbopol® SC-200 Polymer, Carbopol® Silk 100 Polymer, Carbopol® Ultrez Polymers, Carbopol® Ultrez 10 Polymers, Carbopol® Ultrez 20 Polymers, Carbopol® Ultrez 21 Polymer, Carbopol® Ultrez 30 Polymer, Carbopol® ETD 2020 Polymer and Carbopol® ETD 2050 Polymer etc. Permeation enhancers, also referred to as penetration enhancers or accelerants or absorption promoters, facilitate drug absorption through the skin by a reversible decrease in barrier resistance. Enhancers can act on the stratum corneum's intracellular keratin, influence desmosomes, modify the intercellular lipid domains or alter the nature of the stratum corneum. In general, enhancers can be divided into two large groups: small polar solvents, e.g., ethanol, propylene glycol, dimethyl sulfoxide and amphiphilic compounds containing a polar head and a hydrophobic chain, e.g. fatty acids and fatty alcohols, 1-dodecylazepan-2-one (Azone), 2-nonyl-1,3-dioxolane (SEPA 009), dodecyl-2-dimethylaminopropanoate (DDAIP). According to another embodiment, one or more polymers may optionally be added as a carrier, and the polymer is selected from polyvinylpyrrolidone (PVPs), polyethylene glycols, poloxamers, polyvinyl alcohols, polylysine, polyglycine, cellulose & its derivatives, hyaluronate derivatives, and natural polymers etc. In another embodiment of the present invention the Gelling or thickening agents are neutralized with alkali / buffering agent or its solution as required. In another embodiment of the present invention a thickening agent may be added. Nonlimiting examples of thickening agents (natural and synthetic) are gums, natural polysaccharides, mineral thickeners, oils, waxes, and synthetic polymeric thickeners and others. Antioxidants may be required to prevent drug or final nano-dispersion formulation oxidation. Antioxidants that can be used in accordance with the current invention include but are not limited to sodium bisulfite, butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), sodium / potassium metabisulfite, tocopherols, uric acid, lipoic acid, tert-Butylhydroquinone (TBHQ), propyl gallate and ascorbic acid, its derivatives (like ascorbyl palmitate and others). Usually, antioxidants do not affect drug absorption or cause skin irritation. As per the preferred embodiment antioxidant is butylated hydroxytoluene in a range of 0.01-1.0%, preferably 0.5%. In another embodiment of the present invention the secondary nano dispersion comprises chelating agent as disodium EDTA, and antioxidants as sodium metabisulfite, wherein both are present in range of 0.01% - 0.5%. In another embodiment of the present invention the topical aqueous nano- dispersion composition has a pH range from about 4.0 to about 10.0. Compositions of the present invention may have a pH range from about 4.0 to about 10.0, preferably from about 6.0 to about 9.0, and more preferably from about 7.0 to about 8.6 pH, pH adjusters / buffering agents that can be used in accordance with the present invention include but are not limited to citric acid, sodium phosphate, sodium citrate, sodium / potassium hydroxide, Triethanolamine, diethanolamine, diethylamine, glycine and other pharmaceutically acceptable buffering system. Another embodiment of the present invention describes a topical nano- dispersion composition comprising: - i) From about 1% to about 6% by weight of Diclofenac or its salts or derivatives; - ii) From about 0.1% to about 15.0% by weight of methyl salicylate; - iii) From about 0.1% to about 10% by weight of menthol; - iv) Up to about 12% by weight of oleyl alcohol; - v) From about 1.0% to about 30% by weight of MCT oil; - vi) From about 0.1% to about 10% by weight of oleic acid or octyldodecanol; - vii) Up to about 2% by weight of carbomer, xanthan gum, or gelling agent; - viii) From about 1.0% to about 12% by weight of polyoxyl 40 hydrogenated castor oil or polysorbate 80; - ix) From about 0.01% to about 1.0% by weight of BHT or alpha- tocopherol; - wherein the formulation contains water q.s. to 100% of the total formulation. Another embodiment of the present invention describes a topical aqueous nano-dispersion composition comprising: - i) From about 1% to about 5% by weight of Diclofenac or its salts; - ii) Up to about 10% by weight of oleyl alcohol or N-methyl pyrrolidone (NMP); - iii) From about 1.0% to about 30% by weight of MCT oil or oleic acid; - iv) From about 0.1% to about 10% by weight of octyldodecanol or limonene; - v) Up to about 2% by weight of carbomer, xanthan gum, or gelling agent; - vi) From about 1.0% to about 12% by weight of polyoxyl 40 hydrogenated castor oil or polysorbate 80; - vii) From about 0.01% to about 1.0% by weight of BHT or alpha- tocopherol; - wherein the formulation contains water q.s. to 100% of the total formulation. Another embodiment of the present invention describes a topical aqueous nano-dispersion composition comprising: i) From about 1% to about 3% by weight of Diclofenac or its salts. ii) From about 0.1% to about 15.0% by weight of Methyl salicylate iii) From about 0.1% to about 5% by weight of Menthol iv) From about 1.0 % to about 12% of MCT Oil v) From about 0.1 % to about 6% of Oleic acid / Octyldodecanol vi) Up to about 2% of Carbomer vii) From about 1.0% to 12% of Polyoxyl 40 hydrogenated castor oil viii) Polyoxyl 40 hydrogenated castor oil to Primary dispersion water ratio from 1:0.1 to 1:1.5 ix) From about 0.01 to about 0.5% of BHT / Alpha tocopherol wherein the formulation contains water Qs. to 100%. Another embodiment of the present invention describes a topical aqueous nano-dispersion composition comprising: i) From about 1% to about 3% by weight of Diclofenac or its salts. ii) From about 0.01% to about 0.25% by weight of Capsaicin or Thiocolchicoside iii) From about 0.1% to about 10.0% by weight of Methyl salicylate iv) From about 0.1% to about 5% by weight of Menthol v) Up to about 3% by weight of Oleylalcohol vi) From about 1.0 % to about 6% of MCT Oil vii) From about 0.1 % to about 5% of Oleic acid / Octyldodecanol viii) Up to about 2% of Carbomer ix) From about 1.0% to 9% of Polyoxyl 40 hydrogenated castor oil x) Polyoxyl 40 hydrogenated castor oil to Primary dispersion water ratio from 1:0.1 to 1:1.5 xi) From about 0.01 to about 0.5% of BHT / Alpha tocopherol wherein the formulation contains water Qs. to 100% Another embodiment of the present invention describes a topical aqueous nano-dispersion composition comprising: i) From about 1% to about 3% by weight of Diclofenac or its salts. ii) From about 0.01% to about 2.0% by weight of Lidocaine or its salts iii) From about 0.1% to about 10.0% by weight of Methyl salicylate iv) From about 0.1% to about 5% by weight of Menthol v) Up to about 4% by weight of Oleylalcohol vi) From about 1.0 % to about 6% of MCT Oil vii) From about 0.1 % to about 5% of Oleic acid / Octyldodecanol viii)Up to about 2% of Carbomer ix) From about 1.0% to 8% of Polyoxyl 40 hydrogenated castor oil x) Polyoxyl 40 hydrogenated castor oil to Primary dispersion water ratio from 1:0.1 to 1:1.5 xi) From about 0.01 to about 1.0% of BHT / Alpha tocopherol wherein the formulation contains water Qs. to 100% Another embodiment of the present invention describes a topical aqueous nano-dispersion composition comprising: i) From about 1% to about 3% by weight of Diclofenac or its salts. ii) From about 0.01% to about 5.0% by weight of Gabapentin or its salts. iii) From about 0.1% to about 10.0% by weight of Methyl salicylate iv) Up to about 5% by weight of Oleylalcohol v) From about 1.0 % to about 8% of MCT Oil vi) Up to about 5% by weight of Sodium oleate vii) From about 0.1 % to about 5% of Oleic acid / Octyldodecanol viii)Up to about 2% of Carbomer / Xanthan gum ix) From about 1.0% to 8% of Polyoxyl 40 hydrogenated castor oil / Sodium oleate x) Polyoxyl 40 hydrogenated castor oil to Primary dispersion water ratio from 1:0.1 to 1:1.5 xi) From about 0.01 to about 1.0% of BHT / Alpha tocopherol wherein the formulation contains water Qs. to 100% Yet another embodiment of the present invention describes a topical nano- dispersion composition comprising: - One or more nonsteroidal anti-inflammatory drugs (NSAIDs), Local anaesthetics, Gabapentinoids, and / or muscle relaxants, selected from the group consisting of Ketoprofen, Ibuprofen, Capsaicin, Thiocolchicoside, Etofenamate, Lidocaine HCl, Gabapentin, and Methyl salicylate; - From about 0.1% to about 5% by weight of Menthol; - An antioxidant selected from the group consisting of BHT and Alpha- Tocopherol in a concentration from about 0.1% to about 0.7% by weight; - A penetration enhancer, lipid, solvent and a surfactant selected from the group consisting of Isopropyl myristate, MCT Oil, Oleic acid, Oleyl alcohol, Polyoxyl 40 hydrogenated castor oil, and Octyldodecanol in a concentration of 1-30%; - Up to 2% by weight Carbomer 980 or other gelling agent, - and Purified water q.s. Another embodiment of the present invention describes a topical nano- dispersion composition comprising one or more of 0.01% to 0.5% of disodium EDTA, sodium metabisulfite, alkali / buffering components. Another embodiment of present invention describes a topical aqueous nano- dispersion composition comprising: - A primary dispersion comprising: - One or more nonsteroidal anti-inflammatory drugs (NSAIDs) and / or muscle relaxants, selected from the group consisting of Ketoprofen, Ibuprofen, Capsaicin, Thiocolchicoside, Etofenamate, Lidocaine HCl, Gabapentin, and Methyl salicylate; - From about 0.1% to about 10% by weight of Menthol; - An antioxidant selected from the group consisting of BHT and Alpha- Tocopherol in a concentration from about 0.1% to about 0.3% by weight; - A penetration enhancer selected from the group consisting of Isopropyl myristate, MCT Oil, Oleic acid, Oleyl alcohol, Polyoxyl 40 hydrogenated castor oil, and Octyldodecanol in a concentration of 1-30%; - An aqueous phase comprising 0.01% to 0.5% by weight: - Disodium EDTA, - Sodium metabisulphite, - Purified water; and - A gelling agent component comprising: - Up to 2.0% by weight Carbomer or other gelling agent, - Sodium hydroxide / triethanolamine to neutralize, - Purified water. In another embodiment the NSAID is ketoprofen or ibuprofen amount ranges from 1.0% to 2.0% w / w. In another embodiment the muscle relaxant Thiocolchicoside is in an amount of 0.25% w / w. In another embodiment the Methyl salicylate is present in an amount ranging from 10% to 15% w / w. In another embodiment the Lidocaine HCl is present in an amount ranging from 1% to 2% w / w. In another embodiment of the present invention the topical nano-dispersion composition of Diclofenac or its pharmaceutically acceptable salts / derivatives or combinations thereof comprises: i. a primary dispersion, in which BHT, Alpha Tocopherol, Diclofenac sodium, Triethyl citrate, Butylene glycol, Docusate Sodium, Sorbitan monooleate, medium-chain triglycerides (MCT) Oil, Octyldodecanol, Oleyl Alcohol, are mixed using a high-shear mixer to obtain a homogeneous mixture. Finally, Polyoxyl 40 hydrogenated castor oil and purified water is added slowly with high shear mixing to obtain primary dispersion. ii. an aqueous phase comprising Polyoxyl 40 hydrogenated castor oil, EDTA and sodium metabisulfite, wherein primary dispersion is dispersed under stirring followed by homogenization to obtain secondary nano- dispersion. iii. a gel phase comprising aqueous carbomer dispersion is neutralized using an alkali / buffering solution. Secondary nano dispersion is slowly added to the gel phase (gelling agent dispersion) while high shear mixing and followed by homogenization process to obtain the uniform gel nano-dispersion formulation. In another embodiment of the present invention a topical nano-dispersion composition of Diclofenac or its pharmaceutically acceptable salts, methyl salicylate and menthol comprise: i. a primary dispersion, in which BHT, Alpha Tocopherol, Diclofenac Diethylamine, Menthol, Methyl Salicylate, MCT Oil, Octyldodecanol, Oleyl Alcohol, Polyoxyl 40 hydrogenated castor oil, Oleic acid, and with or without polymers are mixed using a high-shear mixer to obtain a homogeneous mixture. Finally, Polyoxyl 40 hydrogenated castor oil and purified water is added slowly with high shear mixing to obtain primary dispersion. ii. an aqueous phase comprising EDTA and sodium metabisulfite, wherein primary dispersion is dispersed under stirring followed by homogenization to obtain secondary nano-dispersion. iii. a gel phase comprising aqueous carbomer dispersion is neutralized using an alkali / buffering solution. Secondary nano dispersion is slowly added to the gel phase (gelling agent dispersion) while high shear mixing, followed by homogenization to obtain the gel nano-dispersion formulation. After complete addition of secondary nano dispersion, the contents were mixed until the homogeneous formulation (Final Product) is obtained. According to other embodiments, nano-dispersions are evaluated via Microscopy technique using Electron Microscope (TEM); pH measured using pH meter; Viscosity is measured using Viscometer, Droplet / particle size was evaluated using Zeta-sizer or nano-sizer of MALVERN instruments, UK. Having described the invention with reference to certain preferred embodiments, other embodiments will become apparent to one skilled in the art from consideration of the specification. Further the pharmaceutical composition of the present invention can be used for relief of pain and inflammation associated with musculoskeletal, joint, and soft tissue disorders and management of neuropathic pain. It can also be used for the acute treatment of migraine attacks, for treatment of primary dysmenorrhea, for neuropathic pain associated with post-herpetic neuralgia and other pain and inflammation related disorders. Further the pharmaceutical composition of the present invention can be used for the treatment and management of acute and chronic pain associated with inflammatory conditions, especially those involving the musculoskeletal system. These include osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis. It can also be used for acute pain due to minor strains, sprains, and contusions. Further the pharmaceutical composition of the present invention can be used in the required dose or as prescribed by the physician depending on the condition it is being used for. Further the pharmaceutical composition of the present invention can be applied to an affected area of the skin of the patient. Further the pharmaceutical composition of the present invention can be used once or twice a day or as prescribed by the physician. In an embodiment, a method of treating inflammation, pain, or muscle spasms comprises administering a therapeutically effective amount of the composition to a patient in need thereof is disclosed. In an embodiment, the composition is used for the treatment and management of pain and inflammation associated with musculoskeletal, joint, and soft tissue disorders, and management of neuropathic pain. In an embodiment, a method, wherein the composition is used for the treatment and management of acute and chronic pain associated with inflammatory conditions, especially those involving the musculoskeletal system, including osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis is disclosed. In an embodiment, a method, wherein the composition is used for the acute treatment of migraine attacks and primary dysmenorrhea is disclosed. In an embodiment, a method, wherein the composition is used for the treatment and management of acute pain due to minor strains, sprains, and contusions is disclosed. In an embodiment, a method of applying the topical aqueous nano-dispersion composition, comprising applying the composition to an affected area of the skin of a patient in need of treatment for pain, inflammation, or muscle spasms is disclosed. In an embodiment, a method of applying the topical aqueous nano-dispersion composition, comprising applying the composition to an affected area of the skin of a patient in need of treatment for pain, inflammation is disclosed. Further the pharmaceutical composition of the present invention contains all skin friendly topically acceptable pharmaceutical ingredients and are devoid of any harmful solvents, which cause skin toxicity & related issues on long- term use. The pharmaceutical composition of the present invention is non-sticky, non- greasy, non-staining and does not cause dryness of skin, a common side effect of formation containing higher amounts of solvents. The pharmaceutical composition of the present invention is shelf-stable, that is physical, chemical and nano characteristics remain within specified limits even at accelerated conditions of 40°C & 75% RH for at least 6 months and at long-term conditions of 25°C & 60% RH for minimum of 18 months or more. In an embodiment, the composition has a shelf life of at least 2 years under recommended ICH storage conditions. In the pharmaceutical composition of the present invention the Major Portion of drug(s) is entrapped in a well-designed nanoparticulate structure. In another embodiment, the nano-dispersion enhances the skin permeability of the drug by at least 2-fold compared to conventional topical formulations. In different embodiments, the drug(s) or its salt is encapsulated within a lipidic nanocarrier selected from nanoemulsions, nanodispersions, solid lipid nanoparticles, nanostructured lipid carriers, polymeric nanoparticles, or lipidic- polymeric nanoparticles. In different embodiments, the combination of Diclofenac with another NSAID, muscle relaxant, local anesthetic, analgesic, or gabapentinoid exhibits a synergistic effect in treating pain and inflammation. In another embodiment, the composition is used in combination with oral or systemic administration of NSAIDs, analgesics, local anesthetics, muscle relaxants or gabapentanoids for enhanced therapeutic efficacy. Further the pharmaceutical composition of the present invention has specifically positioned potent skin penetration enhancers on the surface of nanoparticles which ensures rapid and deeper penetration into skin layers, further these biodegradable nanoparticles encapsulating diclofenac / drug release the drug continuously in the skin layers to give prolonged effect. The pharmaceutical composition of the present invention not only ensures immediate release of drug from nanoparticles and from its matrix on application to skin but also enables depot (prolonged / controlled) release to target areas of skin for effective treatment. The present invention is further defined by reference to the following examples, describing in detail methods for the preparation and testing of the said pharmaceutical composition. It will be apparent to those skilled in the art that modifications, both to materials and methods, may be made without departing from the scope of the invention. The following examples are set out to illustrate the invention and do not limit the scope of the present invention. Example 1: Component% w / wPercent Range (% w / w) t Purified water (in SND) 35.3 QS. Primary dispersion (PD): BHT, alpha-tocopherol, Diclofenac sodium, Triethyl citrate, Butylene glycol, Docusate sodium, Sorbitan monooleate, Octyldodecanol, MCT, Oleyl alcohol and purified water were mixed using high shear mixer until homogeneous mixture is obtained. Finally, Polyoxyl 40 hydrogenated castor oil is added slowly to the above mixture to obtain Primary dispersion. Polyoxyl 40 hydrogenated castor oil is also added in Secondary Nano dispersion. Secondary Nano Dispersion (SND) Primary dispersion was slowly added to the aqueous solution of EDTA, Polyoxyl 40 hydrogenated castor oil and sodium metabisulphite / Propyl gallate, while processing with high shear mixer. After complete addition of Primary Dispersion, the mixture was further homogenized / high pressure homogenization (optimized parameters) to obtain uniform Secondary Nano Dispersion. Carbopol 980 (carbomer) was dispersed in purified water using a high shear disperser. It was mixed until lumps free dispersion appeared. Finally, dispersion was neutralized using sodium hydroxide solution / Triethanolamine solution. After optimal neutralization, contents were mixed for 60 minutes to obtain Gelling Agent Dispersion. Gelling Agent Dispersion was taken in a mixing vessel, Secondary Nano Dispersion was slowly added to the gelling agent dispersion while mixing. After complete addition of secondary nano dispersion, the contents were mixed and followed by homogenization until the homogeneous formulation (Final Product) is obtained.

[0002] 5 EXAMPLES 2-4: Component Example 2 Example 3 Example 4 Polyoxyl 40 hydrogenated 1.6 4.5 - castor oil (in PD) t

[0003] Procedure: Primary dispersion (PD): tocopherol, Diclofenac sodium, Triethyl citrate, Butylene glycol, Triacetin, Lecithin, Isopropyl myristate and Oleyl alcohol were mixed using high shear mixer until homogeneous mixture is obtained. Finally, Polyoxyl 40 hydrogenated castor oil and Purified water is added slowly to the above mixture to obtain Primary dispersion. Example 3: BHT, alpha-tocopherol, Diclofenac sodium, Benzyl alcohol, Oleic acid, Oleyl alcohol, MCT, Propyl gallate and Polyoxyl 40 hydrogenated castor oil were mixed using high shear mixer until homogeneous mixture is obtained. Finally purified water is added slowly to the above mixture to obtain Primary dispersion. Example 4: BHT, alpha-tocopherol, Diclofenac Potassium, Benzyl alcohol, Docusate sodium, Sorbitan monooleate, Triacetin, Lecithin, Octyl- dodecanol and Isopropyl myristate were mixed using high shear mixer until homogeneous mixture is obtained. Finally, Polysorbate 80 and Purified water is added slowly to the above mixture to obtain Primary dispersion. Secondary Nano Dispersion (SND): Common steps for 2-4 Examples Primary dispersion was slowly added to the aqueous solution of EDTA and sodium metabisulphite, Polyoxyl 40 hydrogenated castor oil (Example 2) while processing with high shear mixer. After complete addition of Primary Dispersion, the mixture was further processed for 30 minutes to obtain Secondary Nano Dispersion. Carbopol 980 (carbomer) was dispersed in purified water using a high shear disperser. It was mixed until lumps free dispersion appeared. Finally, dispersion was neutralized using sodium hydroxide solution / Triethanolamine solution. After optimal neutralization, contents were mixed for 60 minutes to obtain Gelling Agent Dispersion. Gelling Agent Dispersion was taken in a mixing vessel, Secondary Nano Dispersion was slowly added to the gelling agent dispersion while mixing. After complete addition of secondary nano dispersion, the contents were mixed and followed by homogenization until the homogeneous formulation (Final Product) is obtained.

[0004] 5 EXAMPLES: 5-10 Example Example Example Example Example Example Component 5 6 7 8 9 10 Sorbitan 0.5 - - 0.6 0.75 1.0 stearate Sodium Qs. to Qs. to - Qs. to Qs. to Qs. to hydroxide neutralize neutralize neutralize neutralize neutralize to Procedure: Primary dispersion (PD): Example 5: BHA, alpha-tocopherol, Diclofenac diethylamine, N-methyl 0 pyrrolidone, Butylene glycol, Docusate sodium, sorbitan stearate, Octyl- dodecanol, MCT and Oleyl alcohol were mixed using high shear mixer until homogeneous mixture is obtained. Finally, Polyoxyl 35 castor oil and purified water are added slowly to the above mixture to obtain Primary dispersion. Example 6: BHA, alpha-tocopherol, Diclofenac sodium, Butylene glycol, N- 5 Methyl pyrrolidone, Poloxamer 407, Triacetin, phospholipid / Lecithin, Isopropyl myristate and oleyl alcohol were mixed using high shear mixer until homogeneous mixture is obtained. Finally, Polyoxyl 35 castor oil and Purified water is added slowly to the above mixture to obtain Primary dispersion. Example 7: BHA, alpha-tocopherol, Dimethylacetamide, Oleic acid, Diclofenac 0 sodium, Oleyl alcohol, MCT, Propyl gallate and Polyoxyl 35 castor oil were mixed using high shear mixer until homogeneous mixture is obtained. Finally, purified water is added slowly to the above mixture to obtain Primary dispersion. Example 8: BHT, Alpha-tocopherol, Diclofenac sodium, Butylene glycol, N- Methyl pyrrolidone, sorbitan stearate, phospholipid / Lecithin, Octyl-dodecanol, Oleyl alcohol and MCT were mixed using high shear mixer until homogeneous mixture is obtained. Finally, Polysorbate 80 and purified water is added slowly to the above mixture to obtain Primary dispersion. Example 9: Alpha-tocopherol, Diclofenac sodium, Polyvinylpyrrolidone, Dimethylacetamide, Butylene glycol, sorbitan stearate, MCT, Octyldodecanol and Oleyl alcohol were mixed using high shear mixer until homogeneous mixture is obtained. Finally, Polyoxyl 35 castor oil and purified water are added slowly to the above mixture to obtain Primary dispersion. Example 10: Alpha-tocopherol, Diclofenac sodium, Butylene glycol, Dimethylacetamide, Poloxamer 407, Docusate sodium, sorbitan stearate, Triacetin, Lecithin, Octyldodecanol, isopropyl myristate were together mixed using high shear mixer until homogeneous mixture is obtained. Finally, Polysorbate 80 and purified water is added slowly to the above mixture to obtain Primary dispersion. Secondary Nano Dispersion (SND): Common steps for 5-10 Examples Primary dispersion was slowly added to the aqueous solution of EDTA and sodium metabisulphite, and Polyoxyl 40 hydrogenated castor oil (Example 8) while mixing with high shear mixer. After complete addition of Primary Dispersion, the mixture was further processed for 30 minutes to obtain Secondary Nano Dispersion. Carbopol 980 (carbomer) was dispersed in purified water using a high shear disperser. It was mixed until lumps free dispersion appeared. Finally, dispersion was neutralized using sodium hydroxide solution / Triethanolamine solution. After optimal neutralization, contents were mixed for 60 minutes to obtain Gelling Agent Dispersion. Gelling Agent Dispersion was taken in a mixing vessel, Secondary Nano Dispersion was slowly added to the gelling agent dispersion while mixing. After complete addition of secondary nano dispersion, the contents were mixed and followed by homogenization until the homogeneous formulation (Final Product) is obtained.

[0005] EXAMPLES: 11-16 Exampl Exampl Exampl Exampl Exampl Exampl Component e 11 e 12 e 13 e 14 e 15 e 16 t Disodium 0.01 0.05 0.05 0.05 0.05 0.5 EDTA li Primary dispersion (PD) / Drug phase: Example 11: BHT, Diclofenac sodium, N-methyl pyrrolidone, Poloxamer 407, Lecithin / Phospholipid, Limonene, Oleyl alcohol, Octyl dodecanol and MCT were mixed using high shear mixer until homogeneous mixture is formed to obtain Drug phase. Example 12: BHT, Diclofenac sodium, N-methyl pyrrolidone, Lecithin / Phospholipid, Poloxamer 407, Oleyl alcohol, Octyl dodecanol, Limonene and MCT were mixed using high shear mixer until homogeneous mixture is formed to obtain drug phase. Example 13: BHT, Diclofenac sodium, N-methyl pyrrolidone,Poloxamer 407, Lecithin / Phospholipid, Oleyl alcohol, MCT, Octyl dodecanol and Limonene were mixed using high shear mixer until homogeneous mixture is obtained. Finally, purified water was added slowly to the above mixture to obtain Primary dispersion. Example 14: BHT, Diclofenac sodium, N-methyl pyrrolidone, Lecithin / Phospholipid, MCT, Octyl dodecanol and Limonene were mixed using high shear mixer until homogeneous mixture is formed to obtain Drug phase. Example 15: BHA, BHT, Diclofenac sodium, N-methyl pyrrolidone, Lecithin / Phospholipid, Poloxamer 407, MCT, Octyl dodecanol, Limonene and Poloxamer 407 were mixed using high shear mixer until homogeneous mixture is obtained. Finally, purified water was added slowly to the above mixture to obtain Primary dispersion. Example 16: BHT, Diclofenac sodium, N-methyl pyrrolidone, Lecithin / Phospholipid, MCT, Octyl dodecanol and Limonene were mixed using high shear mixer until homogeneous mixture is formed to obtain Drug phase. Secondary Nano Dispersion (SND): Common steps for 11-16 Examples Primary dispersion / Drug phase was slowly added to the aqueous solution of EDTA and sodium metabisulphite, Polyoxyl hydrogenated castor oil (Example 11,12,13,14 and 16) and Poloxamer 407 (Example 11, 14 and 15) while mixing with high shear mixer. After complete addition of Primary Dispersion, the mixture was further processed for 30 minutes to obtain Secondary Nano Dispersion. Carbopol 980 (carbomer) was dispersed in purified water using a high shear disperser. It was mixed until lumps free dispersion appeared. Finally, dispersion was neutralized using sodium hydroxide solution / Triethanolamine solution. After optimal neutralization, contents were mixed for 60 minutes to obtain Gelling Agent Dispersion. Gelling Agent Dispersion was taken in a mixing vessel, Secondary Nano Dispersion was slowly added to the gelling agent dispersion while mixing. After complete addition of secondary nano dispersion, the contents were mixed and followed by homogenization until the homogeneous formulation (Final Product) is obtained.

[0006] EXAMPLES: 17-20 Example 17 Example Example 19 Example 20 Component 18 Potassium sorbate 0.1 - - 0.1 Procedure: Primary dispersion (PD) / Drug phase: Example 17: BHA, Diclofenac sodium, Alpha tocopherol, N-methyl pyrrolidone, Lecithin / Phospholipid, Limonene, Octyl dodecanol and MCT, Polyoxyl 40 hydrogenated castor oil were mixed using high shear mixer until homogeneous mixture is obtained. Finally, purified water was added slowly to the above mixture to obtain Primary dispersion. Example 18: BHT, Diclofenac sodium, N-methyl pyrrolidone, Alpha- tocopherol, Lecithin / Phospholipid, Oleyl alcohol and MCT were mixed using high shear mixer until homogeneous mixture is obtained. Finally, purified water was added slowly to the above mixture to obtain Primary dispersion. Example 19: BHT, Diclofenac sodium, N-methyl pyrrolidone, Lecithin / Phospholipid, Limonene and MCT were mixed using high shear mixer until homogeneous mixture is formed to obtain Drug phase. Example 20: BHT, Alpha Tocopherol, Diclofenac sodium, N-methyl pyrrolidone, Lecithin / Phospholipid, Limonene and MCT were mixed using high shear mixer until homogeneous mixture is obtained. Finally, purified water was added slowly to the above mixture to obtain Primary dispersion. Secondary Nano Dispersion (SND): Common steps for 17-20 Examples Primary dispersion / Drug phase was slowly added to the aqueous solution of Disodium EDTA, Sodium metabisulphite, Poly oxyl 40 hydrogenated castor oil and Potassium sorbate (Example 17 & 20) while mixing with high shear mixer. After complete addition of Primary Dispersion, the mixture was further processed for 30 minutes to obtain Secondary Nano Dispersion. Carbopol 980 (carbomer) was dispersed in purified water using a high shear disperser. It was mixed until lumps free dispersion appeared. Finally, dispersion was neutralized using sodium hydroxide solution / Triethanolamine solution. After optimal neutralization, contents were mixed for 60 minutes to obtain Gelling Agent Dispersion. Gelling Agent Dispersion was taken in a mixing vessel, Secondary Nano Dispersion was slowly added to the gelling agent dispersion while mixing. After complete addition of secondary nano dispersion, the contents were mixed and followed by homogenization until the homogeneous formulation (Final Product) is obtained. EXAMPLES: 21-24 Example Example 22 Example 23 Example 24 Component 21 Sodium Metabisulphite 0.09 0.05 0.25 0.05 Procedure: Primary dispersion (PD) / Drug phase: Example 21: BHT, Diclofenac sodium, N-methyl pyrrolidone, Sorbitan stearate, Lecithin / Phospholipid, Limonene, Octyl dodecanol and MCT were mixed using high shear mixer until homogeneous mixture is obtained. Finally, purified water was added slowly to the above mixture to obtain Primary dispersion. Example 22: BHT, Diclofenac sodium, N-methyl pyrrolidone, Sorbitan oleate, Lecithin / Phospholipid, Oleyl alcohol and MCT were mixed using high shear mixer until homogeneous mixture is obtained. Finally, purified water was added slowly to the above mixture to obtain Primary dispersion. Example 23: BHT, Diclofenac sodium, N-methyl pyrrolidone, Sorbitan oleate, Lecithin / Phospholipid, Oleic acid, Limonene, Octyl dodecanol and MCT were mixed using high shear mixer until homogeneous mixture is formed to obtain Drug phase. Example 24: BHT, Diclofenac sodium, N-methyl pyrrolidone, Alpha Tocopherol, Sorbitan stearate, Sorbitan oleate, Lecithin / Phospholipid, Limonene, Oleyl alcohol and MCT were mixed using high shear mixer until homogeneous mixture is obtained. Finally, purified water was added slowly to the above mixture to obtain Primary dispersion. Secondary Nano Dispersion (SND): Common steps for 21-24 Examples Primary dispersion / Drug phase was slowly added to the aqueous solution of Disodium EDTA, Sodium metabisulphite, Poly oxyl 40 hydrogenated castor oil, Poloxamer 407 (Example 21) and Potassium sorbate (Example 24) while mixing with high shear mixer. After complete addition of Primary Dispersion, the mixture was further processed for 30 minutes to obtain Secondary Nano Dispersion. Carbopol 980 (carbomer) was dispersed in purified water using a high shear disperser. It was mixed until lumps free dispersion appeared. Finally, dispersion was neutralized using sodium hydroxide solution / Triethanolamine solution. After optimal neutralization, contents were mixed for 60 minutes to obtain Gelling Agent Dispersion. Gelling Agent Dispersion was taken in a mixing vessel, Secondary Nano Dispersion was slowly added to the gelling agent dispersion while mixing. After complete addition of secondary nano dispersion, the contents were mixed and followed by homogenization until the homogeneous formulation (Final Product) is obtained. EXAMPLES: 25-28 Example Example 26 Example 27 Example 28 Component 25 Sodium Metabisulphite 0.09 0.05 0.05 0.05 Procedure: Primary dispersion (PD) / Drug phase: Example 25: BHT, Diclofenac sodium, N-methyl pyrrolidone, Lecithin / Phospholipid, Limonene, Octyl dodecanol and MCT were mixed using high shear mixer until homogeneous mixture is obtained. Finally, purified water was added slowly to the above mixture to obtain Primary dispersion. Example 26: BHT, Diclofenac diethylamine, Benzyl alcohol, N-methyl pyrrolidone, Oleic acid, Lecithin / Phospholipid, Oleyl alcohol and MCT were mixed using high shear mixer until homogeneous mixture is formed to obtain Drug phase. Example 27: BHT, Diclofenac sodium, N-methyl pyrrolidone, Oleic acid, Lecithin / Phospholipid, Limonene, Octyl dodecanol and MCT were mixed using high shear mixer until homogeneous mixture is formed to obtain Drug phase. Example 28: BHT, Diclofenac sodium, N-methyl pyrrolidone, Alpha Tocopherol, Lecithin / Phospholipid, Limonene and MCT were mixed using high shear mixer until homogeneous mixture is obtained. Finally, purified water was added slowly to the above mixture to obtain Primary dispersion. Secondary Nano Dispersion (SND): Common steps for 25-28 Examples Primary dispersion / Drug phase was slowly added to the aqueous solution of Disodium EDTA, Sodium metabisulphite, Poly oxyl 40 hydrogenated castor oil, Poloxamer 407 (Example 25) and Potassium sorbate (Example 28) while mixing with high shear mixer. After complete addition of Primary Dispersion, the mixture was further processed for 30 minutes to obtain Secondary Nano Dispersion. Carbopol 980 (carbomer) was dispersed in purified water using a high shear disperser. It was mixed until lumps free dispersion appeared. Finally, dispersion was neutralized using sodium hydroxide solution / Triethanolamine solution. After optimal neutralization, contents were mixed for 60 minutes to obtain Gelling Agent Dispersion. Gelling Agent Dispersion was taken in a mixing vessel, Secondary Nano Dispersion was slowly added to the gelling agent dispersion while mixing. After complete addition of secondary nano dispersion, the contents were mixed and followed by homogenization until the homogeneous formulation (Final Product) is obtained. EXAMPLES: 29-32 Example Example Example 31 Example 32 Component 29 30 Disodium EDTA 0.05 0.05 0.05 0.05 oce ue Primary dispersion (PD) / Drug phase: Example 29: BHT, Diclofenac sodium, N-methyl pyrrolidone, Oleic acid, Sorbitan oleate, Lecithin / Phospholipid, Limonene, Octyl dodecanol and MCT were mixed using high shear mixer until homogeneous mixture is obtained. Finally, purified water was added slowly to the above mixture to obtain Primary dispersion. Example 30: BHT, Diclofenac epolamine, N-methyl pyrrolidone, Benzyl alcohol, Oleic acid, Lecithin / Phospholipid, Oleyl alcohol and Soybean oil were mixed using high shear mixer until homogeneous mixture is formed to obtain drug phase. Example 31: BHT, Diclofenac sodium, N-methyl pyrrolidone, Lecithin / Phospholipid, Limonene, Poloxamer 407, Octyl dodecanol, and MCT were mixed using high shear mixer until homogeneous mixture is formed to obtain drug phase. Example 32: BHT, Diclofenac sodium, N-methyl pyrrolidone, Sorbitan oleate, Lecithin / Phospholipid, Limonene, Poloxamer 407, Octyl dodecanol and MCT were mixed using high shear mixer until homogeneous mixture is obtained. Finally, purified water was added slowly to the above mixture to obtain Primary dispersion. Secondary Nano Dispersion (SND): Common steps for Examples 29-32 Primary dispersion / Drug phase was slowly added to the aqueous solution of Disodium EDTA, Sodium metabisulphite, Polysorbate 80, Poloxamer 407 (Example 29) and Potassium sorbate (Example 32) while mixing with high shear mixer. After complete addition of Primary Dispersion, the mixture was further homogenized / high pressure homogenization (optimized parameters) to obtain uniform Secondary Nano Dispersion. Carbopol 980 (carbomer), xanthan gum (Example 31) was dispersed in purified water using a high shear disperser. It was mixed until lumps free dispersion appeared. Finally, dispersion was neutralized using sodium hydroxide solution / Triethanolamine solution (Example 29, 30 and 32). After optimal neutralization, contents were mixed for 60 minutes to obtain Gelling Agent Dispersion. Gelling Agent Dispersion was taken in a mixing vessel, Secondary Nano Dispersion was slowly added to the gelling agent dispersion while mixing. After complete addition of secondary nano dispersion, the contents were mixed and followed by homogenization until the homogeneous formulation (Final Product) is obtained.

[0007] EXAMPLES 33, 35 & 36: Topical compositions of NSAIDs with Methyl salicylate (with & without menthol and polymer) Component Example 33 Example 35 Example 36 / / / Octyldodecanol 2.0 - 2.6 Method of preparation: A primary dispersion, in which BHT, Alpha Tocopherol, Diclofenac Diethylamine, Menthol, Methyl Salicylate, MCT Oil, Octyldodecanol, Oleyl Alcohol, Polyoxyl 40 hydrogenated castor oil, and oleic acid, with or without polymers and propylene glycol are mixed using a high-shear mixer to obtain a homogeneous mixture. Finally, purified water is added slowly with high shear mixing to obtain primary dispersion, where the weight ratio of surfactant(s) to water ranges from 1: 0.1 to 1: 1.5. An aqueous phase comprising EDTA and sodium metabisulfite, wherein primary dispersion is dispersed under stirring or homogenization to obtain secondary nano-dispersion. A gel phase comprising aqueous carbomer dispersion is neutralized using an alkali / buffering solution. Secondary nano-dispersion is slowly added to the gel phase (gelling agent dispersion) while mixing or homogenizing to obtain the gel nano-dispersion formulation.

[0008] Example 34 & 37: Topical compositions of NSAIDs with menthol and methyl salicylate Component Example 34 Example 37 Percentage range (topical (topical gel (w / w) t Sodium metabisulphite 0.04 - 0.01% to 0.5% Method of preparation: BHT, Alpha Tocopherol, Diclofenac Diethylamine, Menthol, Methyl Salicylate, MCT Oil, Octyldodecanol, Oleyl Alcohol, Polyoxyl 40 hydrogenated castor oil and oleic acid are mixed using a high-shear mixer to obtain a homogeneous mixture. Finally, purified water is added slowly with high shear mixing to obtain a primary dispersion, wherein the weight ratio of surfactant(s) to water ranges from 1: 0.1 to 1: 1.5. In an aqueous phase comprising EDTA and sodium metabisulfite, the primary dispersion is added under stirring, followed by homogenization to obtain the nano-dispersion composition. 5 A gel phase comprising aqueous carbomer dispersion (Example 2) is neutralized using an alkali / buffering solution. The nano-dispersion composition is slowly added to the gel phase (gelling agent dispersion) while mixing, followed by homogenization to obtain the gel nano-dispersion 0 composition. EXAMPLES (38-42): Topical compositions with NSAIDs and / or muscle relaxants Component Example Example Example Example Example 42 Alpha – 0.3 0.3 0.25 0.2 0.1 Tocopherol to e Gel component 25 30 25 30 30 1. BHT, Alpha Tocopherol, NSAID or NSAID-Muscle relaxant combination(s), Menthol, Methyl salicylate, MCT Oil, IPM (Example 6), Octyldodecanol, Octanol (Example 9) Oleyl alcohol, Polyoxyl 40 hydrogenated castor oil, 0 Triethanolamine, and Oleic acid mixed using a high-speed mixer until a homogeneous mixture obtained. Finally, purified water is added in a stream to this mixture while mixing the contents with high-speed mixer to obtain primary dispersion. 2. Primary dispersion slowly added to the aqueous solution of EDTA and 5 sodium metabisulphite while mixing with high-speed mixer. After the complete addition of the nano-carrier system, it is mixed / processed for 30-45 minutes to obtain Secondary Nano Dispersion. 3. Carbomer 980 dispersed in purified water using a high shear disperser. mixed until lump-free dispersion is formed. Finally, dispersion neutralized 0 using sodium hydroxide / Triethanolamine solution. After optimal neutralization, contents mixed for 60-75 minutes to obtain uniform Gelling component. 4. The gelling component taken in a manufacturing vessel. Secondary Nano Dispersion slowly added to the gelling component whilst mixing. After the complete addition of secondary nano-dispersion, the contents are mixed until 5 the homogeneous / uniform product is obtained. Examples 43-46: Topical formulation of lidocaine & combination with NSAID and Gabapentin (derivatives) Component Example 43 Example 44 Example 45 Example 46 Oleyl Alcohol 2.5 3.2 2.0 0.75 ) e 00 t) Method of Preparation: 1. BHT, Alpha Tocopherol, Lidocaine HCl, Diclofenac diethylamine, Menthol, Methyl salicylate, Capsaicin, Gabapentin (3 gm in Primary dispersion and 2 gm in Secondary nano dispersion), MCT Oil, Sodium Oleate (example 13), Octyldodecanol, Oleyl alcohol, Polyoxyl 40 hydrogenated castor oil, Oleic acid and triethanolamine (example 11) mixed using high shear mixer until homogeneous mixture obtained. Finally purified water is added in a stream to this mixture while mixing the contents with high shear mixer to obtain Primary dispersion. 2. Primary dispersion slowly added to the aqueous solution of EDTA and sodium metabisulphite, while mixing with high shear mixer. After complete addition of primary dispersion, the mixture mixed / processed for 30 min to obtain Secondary Nano Dispersion. 3. Carbomer 980 was dispersed in purified water using a high shear disperser. It was mixed until lumps free dispersion appeared. Finally, dispersion was neutralized using sodium hydroxide solution. After optimal neutralization, contents mixed for 60 minutes to obtain Gelling Agent Dispersion. 4. Gelling Agent Dispersion taken in a mixing vessel. Secondary Nano Dispersion slowly added to the gelling agent dispersion while mixing. After complete addition of secondary nano dispersion, the contents mixed / processed until the homogeneous formulation (Final Product) obtained. Example 47 to 50: Topical compositions of NSAIDs with Methyl salicylate and Menthol. Component Example 47 Example 48 Example 49 Example 50 (% w / w) (% w / w) (% w / w) (% w / w) Purified water Qs to 100 Qs to 100 Qs to 100 Qs to 100 A primary dispersion, in which BHT, BHA, Diclofenac Diethylamine, Menthol, Methyl Salicylate, MCT Oil, Octyldodecanol, Benzyl alcohol (in example 18), Oleyl Alcohol, Polyoxyl 40 hydrogenated castor oil and oleic acid were mixed using a high-shear mixer to obtain a homogeneous mixture. Finally, purified water is added slowly with high shear mixing to obtain primary dispersion, where the weight ratio of surfactant(s) to water ranges from 1: 0.1 to 1: 1.5. An aqueous phase comprising EDTA and sodium metabisulfite, wherein primary dispersion is dispersed under stirring or homogenization to obtain secondary nano-dispersion. A gel phase comprising aqueous carbomer dispersion is neutralized using an alkali / buffering solution. Secondary nano-dispersion is slowly added to the gel phase (gelling agent dispersion) while mixing or homogenizing to obtain the gel nano-dispersion formulation.

[0009] Examples 51 to 53: Topical compositions of NSAIDs with Methyl salicylate and Menthol. Component Example 51 Example 52 Example 53 (% w / w) (% w / w) (% w / w) t e Secondary nano 70.0 70.0 65.0 dispersion General method of preparation: A primary dispersion, in which BHT, Alpha Tocopherol, Diclofenac Diethylamine, Menthol, Methyl Salicylate, MCT Oil, Octyldodecanol, Oleyl Alcohol, Polyoxyl 40 hydrogenated castor oil, and oleic acid were mixed using a high-shear mixer to obtain a homogeneous mixture. Finally, purified water is added slowly with high shear mixing to obtain primary dispersion, where the weight ratio of surfactant(s) to water ranges from 1: 0.1 to 1: 1.5. An aqueous phase comprising EDTA and sodium metabisulfite, wherein primary dispersion is dispersed under stirring or homogenization to obtain secondary nano-dispersion. A gel phase comprising aqueous carbomer dispersion is neutralized using an alkali / buffering solution. Secondary nano-dispersion is slowly added to the gel phase (gelling agent dispersion) while mixing or homogenizing to obtain the gel nano-dispersion formulation.

[0010] Example 54 to 57: Topical compositions of NSAIDs with Methyl salicylate and Menthol. Component Example 54 Example 55 Example 56 Example 57 (% w / w) (% w / w) (% w / w) (% w / w) Secondary nano dispersion 65.0 65.0 70.0 70.0 A primary dispersion, in which BHT, Alpha Tocopherol, Diclofenac Diethylamine, Menthol, Methyl Salicylate, MCT Oil, Octyldodecanol, Oleyl Alcohol, Poloxamer 407, Polyoxyl 40 hydrogenated castor oil, and oleic acid were mixed using a high-shear mixer to obtain a homogeneous mixture. Finally, purified water is added slowly with high shear mixing to obtain primary dispersion, where the weight ratio of surfactant(s) to water ranges from 1: 0.1 to 1: 1.5. An aqueous phase comprising EDTA and sodium metabisulfite, wherein primary dispersion is dispersed under stirring or homogenization to obtain secondary nano-dispersion. A gel phase comprising aqueous carbomer dispersion is neutralized using an alkali / buffering solution. Secondary nano-dispersion is slowly added to the gel phase (gelling agent dispersion) while mixing or homogenizing to obtain the gel nano-dispersion formulation.

[0011] Example 58 to 61: Topical compositions of NSAIDs with Methyl salicylate and Menthol. Component Example 58 Example 59 Example 60 Example 61 (% w / w) (% w / w) (% w / w) (% w / w) Disodium EDTA 0.05 0.05 0.05 0.05 A primary dispersion, in which BHT, BHA, Diclofenac Diethylamine, Menthol, Methyl Salicylate, MCT Oil, oleic acid, Linseed oil, Soy bean Oil, Octyldodecanol, Oleyl Alcohol, and Polyoxyl 40 hydrogenated castor oil were mixed using a high-shear mixer to obtain a homogeneous mixture. Finally, purified water is added slowly with high shear mixing to obtain primary dispersion, where the weight ratio of surfactant(s) to water ranges from 1: 0.1 to 1: 1.5. An aqueous phase comprising EDTA and sodium metabisulfite, wherein primary dispersion is dispersed under stirring or homogenization to obtain secondary nano-dispersion. A gel phase comprising aqueous carbomer dispersion is neutralized using an alkali / buffering solution. Secondary nano-dispersion is slowly added to the gel phase (gelling agent dispersion) while mixing or homogenizing to obtain the gel nano-dispersion formulation. Example 62 to 65: Topical compositions of NSAIDs with Methyl salicylate and Menthol. Component Example 62 Example 63 Example 64 Example 65 (% w / w) (% w / w) (% w / w) (% w / w) Polyoxyl 40 4.5 4.5 4.0 4.0 hydrogenated General method of preparation: A primary dispersion, in which BHT, Alpha Tocopherol, BHA, Diclofenac Diethylamine / Diclofenac epolamine, Menthol, Methyl Salicylate, MCT Oil, Octyldodecanol, Oleyl Alcohol, Polyoxyl 40 hydrogenated castor oil, and oleic acid were mixed using a high-shear mixer to obtain a homogeneous mixture. Finally, purified water is added slowly with high shear mixing to obtain primary dispersion, where the weight ratio of surfactant(s) to water ranges from 1: 0.1 to 1: 1.5. An aqueous phase comprising EDTA and sodium metabisulfite, wherein primary dispersion is dispersed under stirring or homogenization to obtain secondary nano-dispersion. A gel phase comprising aqueous carbomer dispersion is neutralized using an alkali / buffering solution. Secondary nano-dispersion is slowly added to the gel phase (gelling agent dispersion) while mixing or homogenizing to obtain the gel nano-dispersion formulation.

[0012] Example 66 to 69: Topical compositions of NSAIDs with Methyl salicylate and Menthol. Component Example 66 Example 67 Example 68 Example 69 (% w / w) (% w / w) (% w / w) (% w / w) Purified water 37.09 46.13 35.27 36.87 General method of preparation: A primary dispersion, in which BHT, Alpha Tocopherol, Diclofenac Diethylamine, Menthol, Methyl Salicylate, MCT Oil, Octyldodecanol, Oleyl Alcohol, Polysorbate 80, Polyoxyl 40 hydrogenated castor oil, and oleic acid were mixed using a high-shear mixer to obtain a homogeneous mixture. Finally, purified water is added slowly with high shear mixing to obtain primary dispersion, where the weight ratio of surfactant(s) to water ranges from 1: 0.1 to 1: 1.5. An aqueous phase comprising EDTA and sodium metabisulfite, wherein primary dispersion is dispersed under stirring or homogenization to obtain secondary nano-dispersion. A gel phase comprising aqueous carbomer dispersion is neutralized using an alkali / buffering solution. Secondary nano-dispersion is slowly added to the gel phase (gelling agent dispersion) while mixing or homogenizing to obtain the gel nano-dispersion formulation. Percent ranges of each component from example 1 to example 69. S. No. Components Range in % w / w 16Sodium metabisulphite0.01 to 0.5 In this invention, the details regarding the composition and processing of a variety of nano-dispersions with optimal particle size and improved stability are provided in various embodiments. All such nano-dispersion formulations were found to be shelf-stable.

[0013] Particle size distribution data (Zetasizer, Malvern UK) of Formulation Example 2 to 32 S. No. Example No. Particle size (nm) *PDI Example 21 184.8 0.200

[0014] Stability Data of Formulation Example 1 at Accelerated Conditions (40⁰C & 75%RH) for up to 3 months: Time Particle Size / Diclofenac pH Viscosity PDI* Assay Stability Data of Formulation Example 18 at Accelerated stability (40°C / 75% RH) condition for up to 6 months: Time Particle Diclofenac pH Viscosity Assa 0 Stability Data of Formulation Example 18 at Long term stability (25°C / 60% RH) condition for up to 20 months: Time Particle Diclofenac pH Viscosity Size / PDI* Assay

[0015] 5 Stability Data of Formulation Example 34 at Accelerated Conditions (40⁰C & 75%RH) for up to 6 months: Time Point Particle Diclofenac pH Viscosity Diclofenac Size Assa Entra ment mn 10 Stability Data of Formulation Example 34 at 30°C&75%RH and 25°C&60%RH for up to 12 months: Test 40°C&75%RH 30°C&75%RH 25°C&60%RH I ii l M 1 2 4 Particle 192. 226. 234. 181. 182. 183. 197. 184. 198. Size 169.1 185 186 7 1 2 9 4 2 9 5 6 4 Stability Data of Formulation Example 37 at Accelerated Conditions (40⁰C & 75%RH) for up to 6 months: Time Particle Size Diclofenac pH 10 15

[0016] Particle size distribution data (by Malvern Zetasizer) of above Examples 33 to 69. S. No. Example No. Particle size (in nm) *PDI 19 Example 53 102.0 0.151 5 Effect of Concentration of Surfactant and Water (in primary dispersion) on Particle size (in nm) of Formulation (Example 34, Optimization): Figures 1 and 2 show the TEM image of Diclofenac Diethylamine, Methyl salicylate and Menthol Nano-dispersion formulation of Example 34, which shows well defined spherical nanoparticles with particle size below 300nm. The stability data at accelerated conditions (40°C & 75% RH) demonstrates that the nano- dispersion formulation remains remarkably stable over a period of 6 months. Despite some reduction in viscosity and drug entrapment efficiency, the formulation retains its integrity, showcasing minimal variations in critical parameters like particle size distribution and drug content. The data also suggests that the nano-dispersion is capable of maintaining a prolonged shelf-life at less aggressive storage conditions (ICH Conditions), with assay values remaining above 90% even at 12 months under 25°C & 60% RH, further supporting its stability. This robust profile emphasizes the formulation's potential for commercial viability as a stable and effective topical composition with enhanced skin penetration, fast onset of action, and reduced systemic side effects compared to conventional formulations. The simplicity of its manufacturing process adds further value, positioning it as an economical option for large-scale production.

Claims

Claims:

1. A topical nano-dispersion composition, comprising: - a dispersed phase comprising one or more drug selected from non- steroidal anti-inflammatory drugs (NSAIDs) or salts thereof, muscle relaxants, local anaesthetics, analgesics, gabapentinoids, or combinations thereof, one or more lipid and / or polymer, one or more surfactant with a combined hydrophilic-lipophilic balance (HLB) ranging from 3 to 25, one or more amphiphilic penetration enhancer, and one or more solvent with a dielectric constant ranging from 2 to 38; and - an aqueous phase comprising water, wherein the surfactant to water weight ratio in the nano-dispersion composition ranges from 1:6 to 1:

36.

2. A topical gel nano-dispersion composition, comprising: - a dispersed phase comprising one or more drug selected from Non- steroidal anti-inflammatory drugs (NSAIDs) or salts thereof, muscle relaxants, local anaesthetics, analgesics, gabapentinoids, or combinations thereof, one or more lipids and / or polymers, one or more surfactants with a combined hydrophilic-lipophilic balance (HLB) ranging from 3 to 25, one or more amphiphilic penetration enhancer, and one or more solvent with a dielectric constant ranging from 2 to 38; - an aqueous phase comprising water, a gelling agent, and an alkali / buffering agent, wherein the surfactant to water weight ratio in the gel nano-dispersion composition ranges from 1:6 to 1:36.

3. The composition of Claim 1 or 2, wherein the dispersed phase has a particle size of below 300 nm and a polydispersity index (PDI) of less than 0.5 with a unimodal particle size distribution.

4. The composition of Claim 1 or 2, wherein the aqueous phase further comprises one or more chelating agents, stabilizers or antioxidants, or alkali / buffering agents.

5. The composition of any one of Claims 1-4, wherein the lipid is selected from medium-chain and long-chain triglycerides (MCT / LCT), esters of fatty acids with C1-C36, alkanols such as isopropyl myristate, oleic acid decyl ester, ethyl oleate, C6-C12 alkanoic acid esters, C12-C18 saturated and unsaturated fatty alcohols, oils, phospholipids, phosphatidylcholines (PC) and its derivatives, or lecithins.

6. The composition of any one of Claims 1-5, wherein the lipid concentration is between about 1% w / w and about 30% w / w of the total composition.

7. The composition of any one of Claims 1-6, wherein the surfactant is selected from fatty esters of sorbitan (polyol esters / span series), polyoxyethylene esters / polysorbates, D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), sucrose esters, polyoxyl hydrogenated castor oil surfactants, fatty acid esters of glycerol, polyglycerol esters, propylene glycol fatty esters, sulfate surfactants, sulfonate surfactants, docusate sodium, cetyltrimethylammonium bromide (CTAB), sodium lauryl sulfate, and poloxamers or pluronic block copolymers.

8. The composition of any one of Claims 1-7, wherein the dispersed phase further comprises water, and wherein the surfactant to water weight ratio in the dispersed phase ranges from 1:0.1 to 1:1.5 for considerable particle size reduction.

9. The composition of any one of Claims 1-8, wherein the surfactant is present in an amount of more than about 1.0% w / w of the dispersed phase.

10. The composition of any one of Claims 1-9, wherein the solvent is an amphipathic solvent with a dielectric constant ranging from 2 to 38.

11. The composition of any one of Claims 1-10, wherein the solvent is selected from unsaturated and saturated fatty alcohols, dipolar aprotic solvents with a chain length of C5 to C20, such as pentanol, dodecanol, octadecanol (stearyl alcohol / oleyl alcohol), octyldodecanol, or methyl pyrrolidone (NMP).

12. The composition of any one of Claims 1-11, wherein the solvent concentration is up to 12% w / w of the total composition.

13. The composition of any one of Claims 1-12, wherein the amphiphilic penetration enhancer is selected from fatty acids such as caprylic acid, capric acid, lauric acid, myristic acid, palmitic acid, oleic acid, stearic acid, linolenic acid, arachidonic acid, cetylpyridinium chloride, sodium deoxycholate, sodium caprate, sodium hydroxy benzoyl amino caprylate, dodecyl dimethyl amino propionate, triacetin, glycerol esters, glyceryl oleate, glyceryl monostearate, cocoyl caprylocaprate, terpenes (limonene or others), or their mixtures.

14. The composition of any one of Claims 1-13, wherein the amphiphilic penetration enhancer is present in a concentration between about 0.1% and about 20% w / w of the total composition.

15. The composition of any one of Claims 2-14, wherein the gelling agent is selected from cellulose derivatives, carbomers, pectins, gelatin, starches, alginates, polyvinyl alcohol, povidones, hypromellose, natural gums (xanthan gum), carrageenans (kappa, iota, and lambda), gellan gum, chitosan, polyacrylamides, polyethylene glycol-based gelling agents, or silica-based gelling agents; the alkali / buffering agent is selected from sodium hydroxide or triethanolamine solution.

16. The composition of any one of Claims 1-15, wherein the polymer is selected from polyvinylpyrrolidones (PVPs), polyethylene glycols (PEGs), polyvinyl alcohols (PVAs), polylysine, polyglycine, cellulose and its derivatives, hyaluronate derivatives, or natural polymers.

17. The composition of any one of Claims 1-16, wherein one or more NSAIDs and salts thereof is selected from Diclofenac, flurbiprofen, ibuprofen, naproxen, fenoprofen, pirprofen, carprofen, oxaprozin, tiaprofenic acid, acetylsalicylic acid, diflunisal, etodolac, etofenamate, ketoprofen, flufenamic acid, indomethacin, ketorolac, meclofenamate, mefenamic acid, nabumetone, oxyphenbutazone, phenylbutazone, piroxicam, meloxicam, salsalate, sodium salicylate, sulindac, tenoxicam, tolmetin, celecoxib, methyl salicylate, aceclofenac, bromfenac, loxoprofen, acemetacin, nimesulide, etoricoxib, O-ethoxy benzamide, choline salicylate, benorylate, benzydamine, nefopam, dexketoprofen, nepafenac, gatifloxacin, dexibuprofen, zaltoprofen, or parecoxib.

18. The composition of any one of Claims 1-17, wherein the analgesic is selected from non-narcotic and narcotic analgesics.

19. The composition of Claim 18, wherein the non-narcotic analgesic is selected from fenoverine or tapentadol, and the narcotic analgesic is selected from buprenorphine hydrochloride, butorphanol tartrate, remifentanil hydrochloride, or tramadol.

20. The composition of any one of Claims 1-19, wherein the local anesthetic is selected from lidocaine, ropivacaine, benzocaine, tetracaine, prilocaine, pramoxine, dibucaine, oxybuprocaine, proxymetacaine, ketamine, or menthol.

21. The composition of any one of Claims 1-20, wherein the muscle relaxant is selected from capsaicin, thiocolchicoside, metaxalone, tizanidine, methocarbamol, carisoprodol, orphenadrine, dantrolene, cyclobenzaprine, idrocilamide, tolperisone, eperisone, piperidinoethoxy, phenyramidol, iso- dihydro-ethaverine chloride, chlormezanone, phenprobamate, pancuronium bromide, mebeverine, flavoxate hydrochloride, atracurium besylate, vecuronium bromide, pipecuronium bromide, or rocuronium bromide.

22. The composition of any one of Claims 1-21, wherein the gabapentinoid is selected from gabapentin, pregabalin, mirogabalin, baclofen, or phenibut.

23. The composition of any one of Claims 1-22, wherein the composition is in the form of a gel, lotion, emulgel, cream, ointment, spray, or liquid.

24. The composition of any one of Claims 1-23, wherein the one or more drug is entrapped in a lipidic / polymeric carrier.

25. The composition of any one of Claims 1-24, wherein the composition comprises: - About 1.0% to about 6.0% by weight of drug; - From about 0.1% to about 15.0% by weight of methyl salicylate; - From about 0.1% to about 10.0% by weight of menthol; - Up to about 12% by weight of solvent; - From about 1% to about 12% by weight of surfactant; - From about 1% to about 30% by weight of lipid; - From about 0.1% to about 10% by weight of amphiphilic penetration enhancer; - from about 0.01% to about 1.0% by weight of antioxidants; - wherein the formulation contains water q.s. to 100% along with chelating agents and buffering agents.

26. The composition of any one of Claims 1-24, wherein the chelating agent is selected from Ethylenediaminetetraacetic acid (EDTA), disodium EDTA, calcium disodium EDTA, or salts thereof.

27. The composition of any one of Claims 1-25, wherein the stabilizer or antioxidant is selected from alpha-tocopherol, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), ascorbic acid, or sodium metabisulfite.

28. The composition of any one of Claims 1-27, wherein the amphiphilic penetration enhancer is used in combination with a hydrophilic penetrationenhancer selected from propylene glycol, polyethylene glycol, or N-methyl pyrrolidone.

29. The composition of any one of Claims 1-28, wherein the pH of the composition is adjusted to a range of about 4 to 10.

30. The composition of any one of Claims 1-29, wherein the composition is formulated into a dosage form selected from transdermal patches, impregnated dressings, or topical sprays.

31. The composition of any one of Claims 1-30, wherein the drug is encapsulated within a lipidic carrier selected from nanoemulsions, nanodispersions, solid lipid nanoparticles, nanostructured lipid carriers, polymeric nanoparticles, or lipidic-polymeric nanoparticles.

32. The composition of any one of Claims 1-31, wherein the composition further comprises a preservative selected from parabens, benzyl alcohol, phenoxyethanol, or sorbic acid or its salts.

33. The composition of any one of Claims 1-32, wherein the composition has a shelf life of at least 2 years under recommended ICH storage conditions.

34. The composition of any one of Claims 1-33, wherein the entrapped drug concentration in the composition is proportional to the total drug concentration in the composition, such that for 1%, 2%, 4%, or 6% drug concentration in the composition, the entrapped drug will be at least 60%, 50%, 45%, or 40%, respectively, of the total drug concentration.

35. The composition of any one of Claims 1-34, wherein the composition is used once or twice a day.

36. The composition of any one of Claims 1-35, wherein the composition is prepared without the use of nanonization machines or equipment.

37. The composition of any one of Claims 1-36, wherein the composition is used in combination with oral or systemic administration of NSAIDs, analgesics, local anesthetics, muscle relaxants, or gabapentinoids for enhanced therapeutic efficacy.

38. A topical nano-dispersion composition comprising: - i) From about 1% to about 6% by weight of Diclofenac or its salts; - ii) From about 0.1% to about 15.0% by weight of methyl salicylate; - iii) From about 0.1% to about 10% by weight of menthol; - iv) Up to about 12% by weight of oleyl alcohol; - v) From about 1.0% to about 30% by weight of MCT oil; - vi) From about 0.1% to about 10% by weight of oleic acid or octyldodecanol; - vii) Up to about 2% by weight of carbomer, xanthan gum, or gelling agent; - viii) From about 1.0% to about 12% by weight of polyoxyl 40 hydrogenated castor oil or polysorbate 80; - ix) From about 0.01% to about 1.0% by weight of BHT or alpha- tocopherol; - wherein the formulation contains water q.s. to 100% of the total formulation.

39. A topical nano-dispersion composition comprising:- i) From about 1% to about 5% by weight of Diclofenac or its salts; - ii) Up to about 10% by weight of oleyl alcohol or N-methyl pyrrolidone (NMP); - iii) From about 1.0% to about 30% by weight of MCT oil or oleic acid; - iv) From about 0.1% to about 10% by weight of octyldodecanol or limonene; - v) Up to about 2% by weight of carbomer, xanthan gum, or gelling agent; - vi) From about 1.0% to about 12% by weight of polyoxyl 40 hydrogenated castor oil or polysorbate 80; - vii) From about 0.01% to about 1.0% by weight of BHT or alpha- tocopherol; - wherein the formulation contains water q.s. to 100% of the total formulation.

40. A topical nano-dispersion composition comprising: - One or more NSAIDs, local anaesthetics, gabapentinoids, and / or muscle relaxants, selected from the group consisting of Ketoprofen, Ibuprofen, Capsaicin, Thiocolchicoside, Etofenamate, Lidocaine HCl, Gabapentin, and Methyl salicylate; - From about 0.1% to about 5% by weight of Menthol; - An antioxidant selected from the group consisting of BHT and Alpha- Tocopherol in a concentration from about 0.1% to about 0.7% by weight; - A penetration enhancer, lipid, solvent and a surfactant selected from the group consisting of Isopropyl myristate, MCT Oil, Oleic acid, Oleyl alcohol, Polyoxyl 40 hydrogenated castor oil, and Octyldodecanol in a concentration of 1-30%; - Up to 2% by weight Carbomer 980 or other gelling agent, - and Purified water q.s.

41. The topical nano-dispersion composition of Claim 38-40, wherein the aqueous phase comprises one or more of 0.01% to 0.5% of disodium EDTA, sodium metabisulfite, alkali / buffering agents.

42. A topical nano-dispersion composition comprising: - A dispersed phase comprising: - One or more NSAIDs and / or muscle relaxants, selected from the group consisting of Ketoprofen, Ibuprofen, Capsaicin, Thiocolchicoside, Etofenamate, Lidocaine HCl, Gabapentin, and Methyl salicylate; - From about 0.1% to about 10% by weight of Menthol; - An antioxidant selected from the group consisting of BHT and Alpha- Tocopherol in a concentration from about 0.1% to about 0.3% by weight; - A penetration enhancer selected from the group consisting of Isopropyl myristate, MCT Oil, Oleic acid, Oleyl alcohol, Polyoxyl 40 hydrogenated castor oil, and Octyldodecanol in a concentration of 1-30%; - An aqueous phase comprising 0.01% to 0.5% by weight: - Disodium EDTA, - Sodium metabisulphite, - Purified water; and - A gel component comprising: - Up to 2.0% by weight Carbomer 980 or other gelling agent, - Sodium hydroxide to neutralize, - Purified water.

43. The topical composition of Claim 42, wherein the NSAID is ketoprofen or ibuprofen in an amount ranging from 1.0% to 2.0% w / w.

44. The topical composition of Claim 42, wherein the muscle relaxant is Thiocolchicoside / capsaicin in an amount of 0.25% w / w.

45. The topical composition of Claim 42, wherein Methyl salicylate is present in an amount ranging from 10% to 15% w / w.

46. The topical composition of Claim 42, wherein Lidocaine HCl is present in an amount ranging from 1% to 2% w / w.

47. A process for preparing the topical nano-dispersion composition, comprising the steps of: - i) preparing a primary dispersion, wherein one or more drug is dissolved in one or more lipids and / or polymers, one or more surfactant with a combined HLB ranging from 3 to 25, one or more amphiphilic penetration enhancers, and one or more solvents with dielectric constant ranging from 2 to 38 to form an oily nano-dispersion concentrate, to which water is added under controlled conditions of temperature and stirring rate for considerable particle size reduction, wherein the weight ratio of surfactant to water ranges from 1:0.1 to 1:1.5, - ii) adding the primary dispersion into an aqueous phase under stirring, followed by homogenization to obtain the topical nano-dispersion composition.

48. A process of producing a gel nano-dispersion composition comprising the steps of: - i) preparing a primary dispersion, wherein one or more drug is dissolved in one or more lipids and / or polymers, one or more surfactant with a combined HLB ranging from 3 to 25, one or more amphiphilic penetration enhancers,and one or more solvents with dielectric constant ranging from 2 to 38 to form an oily nano-dispersion concentrate, to which water is added under controlled conditions of temperature and stirring rate for considerable particle size reduction, wherein the weight ratio of surfactant to water ranges from 1:0.1 to 1:1.5, - ii) adding the primary dispersion into an aqueous phase under stirring, followed by homogenization to obtain the topical nano-dispersion product, - iii) preparing a gel component, wherein a gelling agent is dispersed in purified water using a high-shear disperser and is neutralized using an alkali / buffering agent, - iv) adding the gel component slowly to the topical nano-dispersion product of step (ii) while stirring, followed by continuous homogenization to obtain a gel nano-dispersion composition.

49. The process of any one of Claims 47-48, wherein alkali, buffering agents, surfactants, polyols, sugars, amino acids, hydrophilic solvents, or their combinations are added to the water in step i).

50. The process as claimed in claim 47 to 49, wherein: (a) the aqueous phase further comprises one or more chelating agents, stabilizers or antioxidants, or alkali / buffering agents; and / or (b) the drug concentration is between about 1.0% to about 6.0% w / w of the total composition; and / or (c) the lipid concentration is between about 1% w / w and about 30% w / w of the total composition; and / or (d) the surfactant is present in an amount of more than about 1.0% w / w of the primary dispersion; and / or(e) the amphiphilic penetration enhancer concentration is between about 0.1% and about 20% w / w of the total composition; and / or (f) the solvent concentration is up to 12% w / w of the total composition.

51. The process as claimed in claims 47 to 50, wherein: (a) the chelating agent is selected from Ethylenediaminetetraacetic acid (EDTA), disodium EDTA, calcium disodium EDTA, or salts thereof; the stabilizer or antioxidant is selected from alpha-tocopherol, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), ascorbic acid, or sodium metabisulfite; alkali / buffering agent is selected from sodium hydroxide or triethanolamine solution; and / or (b) the drug is selected from Non-steroidal anti-inflammatory drugs (NSAIDs) or salts thereof, muscle relaxants, local anaesthetics, analgesics, gabapentinoids, or combinations thereof, wherein the NSAIDs and salts thereof is selected from Diclofenac, flurbiprofen, ibuprofen, naproxen, fenoprofen, pirprofen, carprofen, oxaprozin, tiaprofenic acid, acetylsalicylic acid, diflunisal, etodolac, etofenamate, ketoprofen, flufenamic acid, indomethacin, ketorolac, meclofenamate, mefenamic acid, nabumetone, oxyphenbutazone, phenylbutazone, piroxicam, meloxicam, salsalate, sodium salicylate, sulindac, tenoxicam, tolmetin, celecoxib, methyl salicylate, aceclofenac, bromfenac, loxoprofen, acemetacin, nimesulide, etoricoxib, O- ethoxy benzamide, choline salicylate, benorylate, benzydamine, nefopam, dexketoprofen, nepafenac, gatifloxacin, dexibuprofen, zaltoprofen, or parecoxib; the muscle relaxant is selected from capsaicin, thiocolchicoside, metaxalone, tizanidine, methocarbamol, carisoprodol, orphenadrine, dantrolene, cyclobenzaprine, idrocilamide, tolperisone, eperisone, piperidinoethoxy, phenyramidol, iso-dihydro-ethaverine chloride, chlormezanone, phenprobamate, pancuronium bromide, mebeverine,flavoxate hydrochloride, atracurium besylate, vecuronium bromide, pipecuronium bromide, or rocuronium bromide; the local anesthetic is selected from lidocaine, ropivacaine, benzocaine, tetracaine, prilocaine, pramoxine, dibucaine, oxybuprocaine, proxymetacaine, ketamine, or menthol; the analgesic is selected from non-narcotic and narcotic analgesics, wherein the non-narcotic analgesic is selected from fenoverine or tapentadol, and the narcotic analgesic is selected from buprenorphine hydrochloride, butorphanol tartrate, remifentanil hydrochloride, or tramadol; the gabapentinoid is selected from gabapentin, pregabalin, mirogabalin, baclofen, or phenibut; and / or (c) the lipid is selected from medium-chain and long-chain triglycerides (MCT / LCT), esters of fatty acids with C1-C36, alkanols such as isopropyl myristate, oleic acid decyl ester, ethyl oleate, C6-C12 alkanoic acid esters, C12-C18 saturated and unsaturated fatty alcohols, oils, phospholipids, phosphatidylcholines (PC) and its derivatives, or lecithins; and / or (d) the surfactant is selected from fatty esters of sorbitan (polyol esters / span series), polyoxyethylene esters / polysorbates, D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), sucrose esters, polyoxyl hydrogenated castor oil surfactants, fatty acid esters of glycerol, polyglycerol esters, propylene glycol fatty esters, sulfate surfactants, sulfonate surfactants, docusate sodium, cetyltrimethylammonium bromide (CTAB), sodium lauryl sulfate, and poloxamers or pluronic block copolymers; and / or (e) the amphiphilic penetration enhancer is selected from fatty acids such as caprylic acid, capric acid, lauric acid, myristic acid, palmitic acid, oleic acid, stearic acid, linolenic acid, arachidonic acid, cetylpyridinium chloride, sodium deoxycholate, sodium caprate, sodium hydroxy benzoyl amino caprylate, dodecyl dimethyl amino propionate, triacetin, glycerol esters, glyceryl oleate,glyceryl monostearate, cocoyl caprylocaprate, terpenes (limonene or others), or their mixtures; and / or (f) the solvent is selected from unsaturated and saturated fatty alcohols, dipolar aprotic solvents with a chain length of C5 to C20, such as pentanol, dodecanol, octadecanol (stearyl alcohol / oleyl alcohol), octyldodecanol, or methyl pyrrolidone (NMP).

52. A method of treating inflammation, pain, or muscle spasms comprising administering a therapeutically effective amount of the composition of any one of Claims 1-46 to a patient in need thereof.

53. The method of Claim 52, wherein the composition is applied to an affected area of the skin of the patient.

54. The method of any one of Claims 52-53, wherein the composition is used for the treatment and management of pain and inflammation associated with musculoskeletal, joint, and soft tissue disorders, and management of neuropathic pain.

55. The method of any one of Claims 52-54, wherein the composition is used for the treatment and management of acute and chronic pain associated with inflammatory conditions, especially those involving the musculoskeletal system, including osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis.

56. The method of any one of Claims 52-55, wherein the composition is used for the acute treatment of migraine attacks and primary dysmenorrhea.

57. The method of any one of Claims 52-56, wherein the composition is used for the treatment and management of acute pain due to minor strains, sprains, and contusions.

58. A method of applying the topical nano-dispersion composition of any one of Claims 1-46, comprising applying the composition to an affected area of the skin of a patient in need of treatment for pain, inflammation, or muscle spasms.

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