The present invention relates to a self-emulsifying drug delivery system that comprises an oil phase, surfactant mixture and the active pharmaceutical ingredients. Specifically, the present invention relates to a combination of a standard antihypertensive drug telmisartan and a dietary supplement trans-resveratrol, the solubility of both the compounds is improved in the form of self-emulsifying drug delivery system.
BACKGROUND OF THE INVENTION
[0002] Background description includes information that may be useful in
understanding the present invention. It is not an admission that any of the
information provided herein is prior art or relevant to the presently claimed
invention, or that any publication specifically or implicitly referenced is prior art.
[0003] Telmisartan is an angiotensin II receptor blocker intended to treat
hypertension and cardiovascular manifestations associated with diabetes.
[0004] Crystalline telmisartan (4'-[2-n-propyl-4-methyl-6-(l-
methylbenzimidazol-2-yl) benzimidazol-1-ylmethyl] biphenyl-2-carboxylic acid) exists in two polymorphic forms i.e. A and B. Both polymorphic forms have poor aqueous solubility of approximately 0.078 mg/mL and low solubility at the physiological pH range of 1 to 7. It has been reported in patent EP2203158A2 that telmisartan is sparingly soluble in strong acids but insoluble in hydrochloric acid and soluble in strong bases. The solubility of drug is a critical attribute to determine the efficient drug absorption. As a consequence, telmisartan formulations suffer from limited absorption profile and erratic bioavailability.
[0005] Resveratrol (3,4',5-trihydroxystilbene) is a stilbenoid polyphenol compound and having antioxidant property commonly found in grapes, berries, nuts, red and white wines. It is also reported with anti-inflammatory, free radical scavenger, lowers blood glucose and anti-cancer therapeutic properties. [0006] Resveratrol is known to increase the nitric oxide production which further leads to vasodilation. The release of potent vasodilator nitric oxide from the endothelium layer of smooth muscles leads to decrease the peripheral resistance

which has a direct impact on arterial pressure and controls blood pressure. This stilbene flavanoid compound shows isomerism and has two isoform, -cis and -trans forms. Out of the two isoforms -trans resveratrol is more stable. The low oral bioavailability of this compound is due to its low aqueous solubility. Resveratrol is insoluble in water particularly at low pH whereas at higher pH particularly at 7.0 it shows saturated aqueous solubility of around 0.015ug/mL. Therefore, increased water solubility is required for better bioavailability, therapeutic efficacy and commercial utility.
[0007] The combination of resveratrol with standard drug (telmisartan) for hypertension in single dosage form is sufficient to control blood pressure without any additional standard anti-hypertensive drug.
[0008] Further, there is a need for additional, preferably less complex, self-emulsifying and micellar dispersion forming formulations, particularly those that are more stable, faster acting (i.e., have a faster onset of action), avoid or reduce hepatic first-pass metabolism, deliver more of the active ingredient(s) to the lymphatic system, or increase oral bioavailability for treating a variety of conditions. There also remains a need for more effective compositions for treating pain, inflammation and inflammatory diseases, including autoimmune inflammatory diseases such as MS, and other diseases, conditions, and pathologies. There is still a further need for composition comprising a lipophilic agent that disperses rapidly in aqueous medium and forms a transparent emulsion or micellar dispersion. The present invention addresses these needs by providing improved formulations, including rapid dispersing formulations, for use in a variety of conditions including pain, inflammation and inflammatory diseases, including autoimmune inflammatory diseases such as MS, nausea and vomiting, and other diseases or conditions.
[0009] Self-Emulsifying Drug Delivery System (SEDDS) is a solid or liquid dosage form comprising an oil phase, a surfactant and a cosurfactant. When SEDDS enters the gastrointestinal tract, it is firstly self-emulsified as emulsion droplets and rapidly dispersed throughout the gastrointestinal tract, and thus reducing the irritation caused by the direct contact of the drug with the mucous membrane of the

gastrointestinal tract. In the gastrointestinal tract, the structure of the emulsion microparticulates will be changed or destroyed. The thus-formed microparticulates of micrometer or nanometer level can penetrate into the mucous membrane of the gastrointestinal tract, and the digested oil droplets enter the blood circulation, thereby significantly improving the bioavailability of the drug. The SEDDS is predominantly employed with respect to lipid-soluble and less water-soluble drugs. It can increase the stability and the bioavailability of the drugs. [0010] The present invention is intended to develop self-emulsifying drug delivery system for poorly aqueous soluble drugs, telmisartan and trans- resveratrol combination, having improved solubility and dissolution profile with the aim of improving the solubility and bioavailability of the said drugs. [0011] The present invention tries to alleviate the existing problems associated with the dissolution properties of the poorly aqueous soluble drugs and to improve the solubility and bioavailability of the said drugs.
[0012] The present invention satisfies the existing needs, as well as others, and generally overcomes the deficiencies found in the prior art.
OBJECTS OF THE INVENTION
[0013] An obj ect of the present invention is to provide a SEDDS for improving
the solubility and bioavailability of poorly aqueous soluble drugs.
[0014] An object of the present invention is to provide a SEDDS for delivering
poorly aqueous soluble drugs in a single dosage form.
[0015] Another object of the invention was to develop a SEDDS for delivering
telmisartan and trans- resveratrol a single dosage form that has improved solubility
and dissolution profile.
[0016] Another object of the invention was to develop a SEDDS comprising
cinnamon as oil phaser for delivering telmisartan and trans- resveratrol a single
dosage form, wherein cinnamon oil acts as an adjunct therapy to synergise the
antihypertensive effect of said drug combination.

[0017] Another object of the invention was to develop a drug loaded SEDDS
comprising telmisartan and trans-resveratrol; cinnamon oil; propylene glycol
surfactant; and Tween 20 surfactant.
[0018] Another object of the invention was to develop a method for producing
drug loaded SEDDS-based pharmaceutical composition comprising telmisartan and
trans-resveratrol; cinnamon oil; propylene glycol surfactant; and Tween 20
surfactant, by dissolving the telmisartan and trans-resveratrol in cinnamon oil and
surfactant mixture comprising Tween 20 and propylene glycol.
[0019] Yet another object of the invention was to produce a drug loaded
SEDDS comprising pharmaceutical^ active drugs; vegetable oil; surfactant
mixture, which forms either nano size emulsion (SENDDS) or micro size emulsion
(SMEDDS) when comes in contact with the gastrointestinal fluid medium of
varying pH and in-vitro simulated aqueous medium.
[0020] Yet another object of the invention was to develop a drug loaded
SEDDS comprising telmisartan and trans-resveratrol; cinnamon oil; propylene
glycol surfactant; and Tween 20 surfactant, which forms either nano size emulsion
(SENDDS) or micro size emulsion (SMEDDS) when comes in contact with the
gastrointestinal fluid medium of varying pH and in-vitro simulated aqueous
medium.
SUMMARY OF THE INVENTION
[0021] This summary is provided to introduce a selection of concepts in a
simplified form that is further described below in the detailed description section.
This summary is not intended to identify key features or essential features of the
claimed subject matter, nor is it intended to be used as an aid in determining the
scope of the claimed subject matter.
[0022] The present invention relates to a SEDDS for improving the solubility
and bioavailability of poorly aqueous soluble drugs.
[0023] In an aspect, the present invention relates to a SEDDS for delivering
poorly aqueous soluble drugs in a single dosage form

[0024] In an aspect, the present invention relates to a drug loaded SEDDS
comprising pharmaceutical^ active drugs; vegetable oil; surfactant mixture, which
forms either nano size emulsion (SENDDS) or micro size emulsion (SMEDDS)
when comes in contact with the gastrointestinal fluid medium of varying pH and
in-vitro simulated aqueous medium.
[0025] In a particular aspect, the present invention relates to a SEDDS for
delivering telmisartan and trans- resveratrol a single dosage form that has improved
solubility and dissolution profile.
[0026] In one aspect, the present invention relates to a SEDDS comprising
cinnamon as oil phaser for delivering telmisartan and trans- resveratrol a single
dosage form, wherein cinnamon oil acts as an adjunct therapy to synergise the
antihypertensive effect of said drug combination..
[0027] In another aspect, the present invention relates to a drug loaded SEDDS
comprising telmisartan and trans-resveratrol; cinnamon oil; propylene glycol
surfactant; and Tween 20 surfactant.
[0028] In yet another aspect, the present invention relates to a method for
producing drug loaded SEDDS-based pharmaceutical composition comprising
telmisartan and trans-resveratrol; cinnamon oil; propylene glycol surfactant; and
Tween 20 surfactant, by dissolving the telmisartan and trans-resveratrol in
cinnamon oil and surfactant mixture comprising Tween 20 and propylene glycol.
[0029] Various objects, features, aspects and advantages of the inventive
subject matter will become more apparent from the following detailed description
of preferred embodiments
BRIEF DESCRIPTION OF THE DRAWINGS
[0030] FIG. 1A represents the ternary phase diagram of the drug loaded SEDDS composition comprising cinnamon:Tween 20/Propylene glycol(l/l):water. [0031] FIG. IB represents the ternary phase diagram of the drug loaded SEDDS composition comprising cinnamon:Tween 20/Propylene glycol(2/l):water. [0032] FIG. 1C represents the ternary phase diagram of the drug loaded SEDDS composition comprising cinnamon:Tween 20/Propylene glycol(4/l):water.

[0033] FIG. ID represents the ternary phase diagram of the drug loaded
SEDDS composition comprising cinnamon:Tween 20/Propylene glycol(l/2).
[0034] FIG. 2 represents the size distribution of nano size emulsion.
[0035] FIG. 3 represents the transmission electron microscope (TEM) image
of nano size O/W emulsion.
[0036] FIG. 4 represents the percentage cummulative release of telmisartan
from SEDDS.
[0037] FIG. 5 represents the percentage cummulative release of trans-
resveratrol from SEDDS.
DETAILED DESCRIPTION OF THE INVENTION
[0038] The following is a detailed description of embodiments of the disclosure. The embodiments are in such detail as to clearly communicate the disclosure. However, the amount of detail offered is not intended to limit the anticipated variations of embodiments; on the contrary, the intention is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the present disclosure.
[0039] All publications herein are incorporated by reference to the same extent as if each individual publication or patent application were specifically and individually indicated to be incorporated by reference. Where a definition or use of a term in an incorporated reference is inconsistent or contrary to the definition of that term provided herein, the definition of that term provided herein applies and the definition of that term in the reference does not apply.
[0040] Reference throughout this specification to "one embodiment" or "an embodiment" means that a particular feature, structure or characteristic described in connection with the embodiment is included in at least one embodiment. Thus, the appearances of the phrases "in one embodiment" or "in an embodiment" in various places throughout this specification are not necessarily all referring to the same embodiment. Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments.

[0041] In some embodiments, numbers have been used for quantifying weight percentages, ratios, and so forth, to describe and claim certain embodiments of the invention and are to be understood as being modified in some instances by the term "about." Accordingly, in some embodiments, the numerical parameters set forth in the written description and attached claims are approximations that can vary depending upon the desired properties sought to be obtained by a particular embodiment. In some embodiments, the numerical parameters should be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. Notwithstanding that the numerical ranges and parameters setting forth the broad scope of some embodiments of the invention are approximations, the numerical values set forth in the specific examples are reported as precisely as practicable. The numerical values presented in some embodiments of the invention may contain certain errors necessarily resulting from the standard deviation found in their respective testing measurements.
[0042] Various terms as used herein are shown below. To the extent a term used in a claim is not defined below, it should be given the broadest definition persons in the pertinent art have given that term as reflected in printed publications and issued patents at the time of filing.
[0043] As used in the description herein and throughout the claims that follow, the meaning of "a," "an," and "the" includes plural reference unless the context clearly dictates otherwise. Also, as used in the description herein, the meaning of "in" includes "in" and "on" unless the context clearly dictates otherwise. [0044] Unless the context requires otherwise, throughout the specification which follow, the word "comprise" and variations thereof, such as, "comprises" and "comprising" are to be construed in an open, inclusive sense that is as "including, but not limited to."
[0045] The recitation of ranges of values herein is merely intended to serve as a shorthand method of referring individually to each separate value falling within the range. Unless otherwise indicated herein, each individual value is incorporated into the specification as if it were individually recited herein.

[0046] All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (e.g. "such as") provided with respect to certain embodiments herein is intended merely to better illuminate the invention and does not pose a limitation on the scope of the invention otherwise claimed. No language in the specification should be construed as indicating any non-claimed element essential to the practice of the invention. [0047] Groupings of alternative elements or embodiments of the invention disclosed herein are not to be construed as limitations. Each group member can be referred to and claimed individually or in any combination with other members of the group or other elements found herein. One or more members of a group can be included in, or deleted from, a group for reasons of convenience and/or patentability. When any such inclusion or deletion occurs, the specification is herein deemed to contain the group as modified.
[0048] The description that follows, and the embodiments described therein, is provided by way of illustration of an example, or examples, of particular embodiments of the principles and aspects of the present disclosure. These examples are provided for the purposes of explanation, and not of limitation, of those principles and of the disclosure.
[0049] It should also be appreciated that the present disclosure can be implemented in numerous ways, including as a system, a method or a device. In this specification, these implementations, or any other form that the invention may take, may be referred to as processes. In general, the order of the steps of the disclosed processes may be altered within the scope of the invention. [0050] The headings and abstract of the invention provided herein are for convenience only and do not interpret the scope or meaning of the embodiments. [0051] The following discussion provides many example embodiments of the inventive subject matter. Although each embodiment represents a single combination of inventive elements, the inventive subject matter is considered to include all possible combinations of the disclosed elements. Thus if one embodiment comprises elements a, b, and c, and a second embodiment comprises

elements b and d, then the inventive subject matter is also considered to include
other remaining combinations of a, b, c, or d, even if not explicitly disclosed.
[0052] While a particular form of the invention has been illustrated and
described, it will be apparent that various modifications can be made without
departing from the spirit and scope of the invention.
[0053] The present invention provides a self-emulsifying drug delivery system
(SEDDS) comprising comprises an oil phase, surfactant mixture and the active
pharmaceutical ingredients.
[0054] In some embodiments of the present invention, the active
pharmaceutical ingredients are poorly aqueous soluble drugs.
[0055] In some embodiments of the present invention, the poorly aqueous
soluble drugs are anti-hypertensive active agents.
[0056] In preferred embodiments of the present invention, the poorly aqueous
soluble drug is selected from telmisartan or trans-resveratrol or combinations
thereof.
[0057] In preferred embodiments of the present invention, the delivery system
is self-emulsifying nano drug delivery system (SENDDS) or self-microemulsifying
drug delivery system (SMEDDS) or combinations thereof.
[0058] In some embodiments of the present invention, the SEDDS
formulations distribute readily in the gastrointestinal tract. The aqueous contents of
the stomach and the digestive motility of the intestines provide the required
environment and sufficient agitation for the spontaneous formation of nano sizes
emulsions when comes in contact with gastrointestinal fluid.
[0059] In some embodiments of the present invention, the oil phase is selected
from but not limited to edible plant oils including but not limited to angelica oil,
anise oil, arnica oil, aurantiiaetheroleum, valerian oil, bergamot oil, savory oil,
camphor, cardamom oil, cassia oil, chenopodium oil, chrysanthemum oil, citronella
oil, lemon oil, citrus oil, costus oil, curcuma oil, carlina oil, elemi oil, tarragon oil,
eucalyptus oil, fennel oil, pine needle oil, pine oil, galbanum oil, geranium oil,
guaiac wood oil, hazelwort oil, iris oil, hypericum oil, calamus oil, camomile oil,
fir needle oil, garlic oil, coriander oil, carraway oil, lavender oil, lemon grass oil,

lovage oil, bay oil, mace oil, marjoram oil, mandarine oil, melissa oil, menthol, mint oil, clary oil, nutmeg oil, spikenard oil, clove oil, neroli oil, olibanum oil, opopranax oil, orange oil, oregano oil, orthosiphon oil, patchouli oil, parsley oil, petit-grain oil, peppermint oil, tansy oil, rosewood oil, rose oil, rosemary oil, rue oil, sabinaeaetheroleum, saffron oil, sage oil, sandalwood oil, sassafras oil, celery oil, mustard oil, immortelle oil, fir oil, teatree oil, terpentine oil, thyme oil, juniper oil, frankincense oil, hyssop oil, cedar wood oil, cinnamon oil, cypress oil, sesame oil, corn oil, peanut oil, soybean oil, almond oil, peach kernel oil, cotton seed oil, sunflower seed oil, and olive oil, or the combinations thereof. Most preferably cinnamon oil.
[0060] In preferred embodiment, the cinnamon oil used in the present invention has cholesterol lowering and antioxidant effects.
[0061] In some embodiments of the present invention, the surfactant mixture is selected from propylene glycol, polyethylene glycol (PEG), PEG 15 hydroxystearate (Solutol HS15), polyoxyl-10-Oleyl Ether (BRIJ® 97), polyethylene glycol 25 hydrogenated castor oil, polyethylene glycol (PEG) 40 hydrogenated castor oil (Kolliphor RH40, Cremophor RH40), polyethylene-polypropylene glycol (poloxamer 124), PEG 8 caprylic/capric glycerides (Labrasol), PEG 300 oleic glycerides (Labrafil M 1944), diethylene glycol monoethyl ether (Transcutol), lauroylmacrogol32 glycerides (GELUCIRE® 44/14), polyethylene glycol 400 (PEG 400), propylene glycol laurate (Lauroglycol FCC), D-a-Tocopherol polyethylene glycol 1000 succinate (TPGS), polyethylene-polypropylene glycol (poloxamer 188), polyethylene-polypropylene glycol (poloxamer 407), polyvinyl pyrrolidone (e.g., Mw 28-34 kDa, Mw 44-54 kDa (e.g., Kollidon 30), or 1-1.5M kDa (e.g., Kollidon 90), Iota Carrageenan, Xanthan gum, locust Bean gum, Kelcogel LT100, acacia gum, guar gum, gamma-Cyclodextrin, Tracacanth gum, hydroxypropyl methylcellulose (HPMC), carboxymethyl cellulose (CMC), microcrystalline cellulose (MCC), lecithin, polyethylene-polypropylene glycol (poloxamer 124), polyethylene glycol sorbitanmonolaurate (polysorbate 20, TWEEN 20), polyethylene glycol sorbitanmonopalmitate (polysorbate 40, TWEEN 40), polyethylene glycol sorbitanmonostearate

(polysorbate 60, TWEEN 60), polyethylene glycol sorbitantristearate (polysorbate 65, TWEEN 65), polyethylene glycol sorbitanmonooleate (polysorbate 80, TWEEN 80), polyethylene glycol sorbitantrioleate (polysorbate 85, TWEEN 85), polyethylene glycol sorbitanhexaoleate, polyethylene glycol sorbitantetraoleate, sorbitanmonolaurate (Span 20), sorbitanmonopalmitate (Span 40), sorbitanmonostearate (Span 60), sorbitantri stearate (Span 65), sorbitanemonooleate (Span 80), sorbitantrioleate (Span 85), sucrose laurate, sucrose palmitate, sucrose stearate, gamma-cyclodextrin, beta-cyclodextrin (e.g., CAPTISOL) pectin, whey protein, caseinates, quillaia/quillaj a saponins, quillaia extract, PEG 8 stearate, PEG 40 stearate, or a combination thereof. Most preferably the surfactant mixture comprises Tween 20 and propylene glycol.
[0062] In some embodiments of the present invention, the surfactant mixture is in an amount selected from: at least 5 wt %, at least 10 wt %, at least 15 wt %, at least 20 wt %, at least 25 wt %, at least 30 wt %, at least 35 wt %, at least 40 wt %, at least 50 wt %, at least 55 wt %, at least 60 wt %, at least 65 wt %, at least 70 wt %, at least 75 wt %, at least 80 wt %, at least 85 wt %, at least 90 wt %, at least 95 wt %, at least 97 wt %, 0-2.5 wt %, 2.5-5 wt %, 5-10 wt %, 10-15 wt %, 15-20 wt %, 20-25 wt %, 25-30 wt %, 30-35 wt %, 35-40 wt %, 40-45 wt %, 45-50 wt %, 45-55 wt %, 45-65 wt %, 46-65 wt %, 47-65 wt %, 48-65 wt %, 49-65 wt %, 50-65 wt %, 51-65 wt %, 52-65 wt %, 53-65 wt %, 54-65 wt %, 55-65 wt %, 50-55 wt %, 55-60 wt %, 60-65 wt %, 65-70 wt %, 70-75 wt %, 75-80 wt %, 80-85 wt %, 85-90 wt %, 90-95 wt %, or 95-97 wt % surfactant.
[0063] In some embodiments of the present invention, the SEDDS composition comprises an active pharmaceutical ingredient, telmisartan, at least 40%, at least 45%, at least 50 wt %, at least 55 wt %, at least 60 wt %, at least 65 wt %, at least 70 wt %, at least 75 wt %, at least 80 wt %, at least 85 wt %, at least 90 wt %, at least 95 wt %, or at least 97 wt %, 35-40 wt %, 40-45 wt %, 45-50 wt %, 45-55 wt %, 45-65 wt %, 46-65 wt %, 47-65 wt %, 48-65 wt %, 49-65 wt %, 50-65 wt %, 51-65 wt %, 52-65 wt %, 53-65 wt %, 54-65 wt %, 55-65 wt %, 50-55 wt %, 55-60 wt %, 60-65 wt %, 65-70 wt %, or 70-75 wt %. Most preferably 10-40 wt%.

[0064] In some embodiments of the present invention, the SEDDS composition comprises an active pharmaceutical ingredient, trans-resveratrol, at least 40%, at least 45%, at least 50 wt %, at least 55 wt %, at least 60 wt %, at least 65 wt %, at least 70 wt %, at least 75 wt %, at least 80 wt %, at least 85 wt %, at least 90 wt %, at least 95 wt %, or at least 97 wt %, 35-40 wt %, 40-45 wt %, 45-50 wt %, 45-55 wt %, 45-65 wt %, 46-65 wt %, 47-65 wt %, 48-65 wt %, 49-65 wt %, 50-65 wt %, 51-65 wt %, 52-65 wt %, 53-65 wt %, 54-65 wt %, 55-65 wt %, 50-55 wt %, 55-60 wt %, 60-65 wt %, 65-70 wt %, or 70-75 wt %. Most preferably 10-40 wt%. [0065] In some embodiments of the present invention, the SEDDS composition comprises cinnamon oil, at least 40%, at least 45%, at least 50 wt %, at least 55 wt %, at least 60 wt %, at least 65 wt %, at least 70 wt %, at least 75 wt %, at least 80 wt %, at least 85 wt %, at least 90 wt %, at least 95 wt %, or at least 97 wt %, 35-40 wt %, 40-45 wt %, 45-50 wt %, 45-55 wt %, 45-65 wt %, 46-65 wt %, 47-65 wt %, 48-65 wt %, 49-65 wt %, 50-65 wt %, 51-65 wt %, 52-65 wt %, 53-65 wt %, 54-65 wt %, 55-65 wt %, 50-55 wt %, 55-60 wt %, 60-65 wt %, 65-70 wt %, or 70-75 wt %. Most preferably 10-50 wt%.
[0066] In some embodiments of the present invention, the SENDDS have sizes ranging in the nanometer scale. However, many modified nanoparticles have wider ranges of sizes. In some embodiments, the nanoparticles may have a diameter of at least about 1 nm, 10 nm, 50 nm, 100 nm, 200 nm, 300 nm, 400 nm, 500 nm, 600 nm, 700 nm, 800 nm, 900 nm, 1000 nm, 1100 nm, 1200 nm, 1300 nm, 1400 nm, 1500 nm, 1600 nm, 1700 nm, 1800 nm, 1900 nm, 2000 nm, 2500 nm, 3000 nm, 4000 nm, 5000 nm, 6000 nm, 7000 nm, 8000 nm, or at least 9000 nm. In some embodiments, the nanoparticles may have a diameter of less than 10,000 nm, 9000 nm, 8000 nm, 7000 nm, 6000 nm, 5000 nm, 4500 nm, 4000 nm, 3500 nm, 3000 nm, 2500 nm, 2000 nm, 1900 nm, 1800 nm, 1700 nm, 1600 nm, 1500 nm, 1400 nm, 1300 nm, 1200 nm, 1100 nm, 1000 nm, 900 nm, 800 nm, 700 nm, 600 nm, 500 nm, 250 nm, or less than 100 nm. The diameter of nanoparticles can range from any of the minimum values described above to any of the maximum values described above, for example from 1 nm to 10,000 nm, 50 nm to 5,000 nm, 100 nm to 2500 nm, 200 nm to 2000 nm, or 500 nm to 1000 nm. Most preferably 400nm to 700 nm.

[0067] In some embodiments of the present invention, the drug loaded SEDDS formulated as a pharmaceutical composition.
[0068] In another embodiment, the drug loaded SEDDS-based pharmaceutical composition is an oral dosage form, e.g., a liquid, a solid or a semi-solid oral dosage form.
[0069] In some embodiments of the present invention, the drug loaded SEDDS comprising the active agents and excipients are appropriate for corresponding dosage forms, such as tablets, soft capsules, granules, hard capsules and oral liquids for self-emulsifying drug delivery.
[0070] In preferred embodiments of the present invention, the drug loaded SEDDS is either filled into the hard gelatin capsules or soft gelatin capsules. [0071] In some embodiments of the present invention, the drug loaded SEDDS is formulated as tablets (including delayed capsules, and controlled release tablets), capsules (including delayed, and controlled release capsules), granules and the like, can be obtained by incorporating excipients as required by the oral solid formulations, such as disintegrants, binders, flavorings, and/or polymeric scaffold materials, and the like, to the aforementioned self-emulsifying drug delivery system, resulting in solid powders or granules of a self-emulsifying feature by conventional techniques.
[0072] In some embodiments of the present invention, the soft capsule can be produced by conventional processes for the preparation of soft capsules, such as the manual compression moulding method, the rotary compression moulding method or the dropping method.
[0073] In some embodiments of the present invention, the drug loaded SEDDS-based pharmaceutical composition may further comprise additional active ingredient(s) selected from one or more of group consisting of: ace-inhibitors, anti-Alzheimer's agents, antianginal drugs, anti-arrhythmias, anti-asthmatics, anti-cholesterolemics, analgesics, anesthetics, anti-convulsants, anti-depressants, anti¬diabetic agents, anti-diarrhea preparations, antidotes, anti-emetics, anti-histamines, anti-hypertensive drugs, anti-inflammatory agents, anti-lipid agents, anti-manics, anti-migraines, anti-nauseants, anti-stroke agents, anti-thyroid preparations, anti-

tumor drugs, anti-viral agents, acne drugs, alkaloids, amino acid preparations, anti-tussives, anti-uricemic drugs, anti-viral drugs, anabolic preparations, systemic and non-systemic anti-infective agents, anti-neoplasties, anti-parkinsonian agents, anti-rheumatic agents, anxiolytics, anti-psychotics, appetite stimulants, biological response modifiers, blood modifiers, bone metabolism regulators, bronchodilators, cardiovascular agents, central nervous system stimulates, cholinesterase inhibitors, contraceptives, decongestants, dietary supplements, dopamine receptor agonists, endometriosis management agents, enzymes, erectile dysfunction agents, fertility agents, gastrointestinal agents, H2-antagonists, homeopathic remedies, hormones, hypercalcemia and hypocalcemia management agents, immunomodulators, immunosuppressives, migraine preparations, motion sickness treatments, muscle relaxants, non-steroidal anti-inflammatories (NSAID's), obesity management agents, osteoporosis preparations, oxytocics, parasympatholytics, parasympathomimetics, prostaglandins, psychotherapeutic agents, respiratory agents, sedatives, serotonin 5-HT3 receptor antagonists, smoking cessation aids, sympatholytics, tremor preparations, urinary tract agents, vasodilators, laxatives, antacids, ion exchange resins, anti-pyretics, appetite suppressants, expectorants, anti-anxiety agents, anti-ulcer agents, anti-inflammatory substances, coronary dilators, cerebral dilators, peripheral vasodilators, psycho-tropics, stimulants, anti-hypertensive drugs, vasoconstrictors, migraine treatments, antibiotics, tranquilizers, anti-psychotics, anti-tumor drugs, anti-coagulants, anti-thrombotic drugs, hypnotics, anti-emetics, anti-nauseants, anti-convulsants, neuromuscular drugs, hyper- and hypo-glycemic agents, thyroid and anti-thyroid preparations, diuretics, anti-spasmodics, anti-obesity drugs, erythropoietic drugs, anti¬asthmatics, cough suppressants, mucolytics, DNA and genetic modifying drugs, and combinations thereof.
[0074] In one embodiment of the present invention, the drug loaded SEDDS-based pharmaceutical composition comprises telmisartan and trans-resveratrol; a vegetable oil; a first surfactant; and a second surfactant, wherein the second surfactant is different from that of the first surfactant.

[0075] In particular embodiment of the present invention, the drug loaded SEDDS-based pharmaceutical composition comprises telmisartan and trans-resveratrol; cinnamon oil; propylene glycol surfactant; and Tween 20 surfactant. [0076] In particular embodiment of the present invention, the cinnamon oil present in the drug loaded SEDDS-based pharmaceutical composition comprising telmisartan and trans-resveratrol is an adjunct therapy to synergise the antihypertensive effect of the said drugs.
[0077] In one embodiment of the present invention, the drug loaded SEDDS-based pharmaceutical composition comprisingtelmisaltan and trans-resveratrol; cinnamon oil; propylene glycol surfactant; and Tween 20 surfactant is prepared by dissolving the telmisartan and trans-resveratrol in cinnamon oil and surfactant mixture (Tween 20:propylene glycol).
[0078] In one embodiment of the present invention, the surfactant mixture is prepared in the ratio of 1:2 Tween 20 and propylene glycol, respectively. [0079] In one embodiment of the present invention, the pre-concentrate means the system loaded with active pharmaceutical ingredients does not contain water. [0080] In an embodiment, the drug loaded SEDDS-based pharmaceutical composition of the present invention maybe used in any manner known to a person skilled in the art. EXAMPLES
[0081] The present disclosure is further explained in the form of following examples. However, it is to be understood that the foregoing examples are merely illustrative and are not to be taken as limitations upon the scope of the invention. Various changes and modifications to the disclosed embodiments will be apparent to those skilled in the art. Such changes and modifications may be made without departing from the scope of the invention.
[0082] Example 1. Preparation of SEDDS comprising telmisartan and trans-resveratrol
The appropriate combinations were selected from the ternary phase diagram and active pharmaceutical ingredients (telmisartan and resveratrol) were dissolved in an oil (cinnamon) and surfactant mixture (Tween 20:propylene glycol:: 1:2). Herein,

the active pharmaceutical ingredients dissolved in oil and surfactant mixture is referred as pre-concentrate which means the system loaded with active pharmaceutical ingredients does not contain water. The range of amount of active pharmaceutical ingredients to be loaded in developed self emulsifying drug delivery system was 10 to 40 mg for telmi saltan and 10 to 40 mg for trans-resveratrol.
Table 1: Self emulsifying drug delivery system - Formulation 1

Ingredients Category Quantity
Telmisartan Active pharmaceutical ingredient 30 mg
Trans-Resveratrol Active pharmaceutical ingredient 30 mg
Cinnamon oil Oil phase 500 uL
Tween 20 Surfactant 133.3 uL
Propylene glycol Co-surfactant 266.6 uL
Table 1: Self emulsifying drug delivery system - Formulation 2

Ingredients Category Quantity
Telmisartan Active pharmaceutical ingredient 35 mg
Trans-Resveratrol Active pharmaceutical ingredient 35 mg
Cinnamon oil Oil phase 500 uL
Tween 20 Surfactant 133.3 uL
Propylene glycol Co-surfactant 266.6 uL
Table 1: Self emulsifying drug delivery system - Formulation 3

Ingredients Category Quantity
Telmisartan Active pharmaceutical ingredient 35 mg

Trans-Resveratrol Active pharmaceutical ingredient 35 mg
Cinnamon oil Oil phase 500 uL
Tween 20 Surfactant 133.3 uL
Propylene glycol Co-surfactant 266.6 uL
The above mentioned compositions are exemplary and those of skill in the art will
be able to define and alter the compositions appropriately to justify the present
invention. Those skilled in the art will be able to understand the ratio of oil to
surfactant, ratio of surfactant mixture, composition of each component may vary.
[0083] Example 2. Size analysis of the drug-loaded SEDDS prepared from
Example 1
The emulsion preconcentrate was diluted 500 times and subjected to size analysis
through differential laser spectroscopy.
FIG. 2 shows the size is observed to be within the range of nanometers with uniform
polydispersity
[0084] Example 3. Structural morphology analysis of the drug-loaded
SEDDS prepared from Example 1
The emulsion preconcentrate was diluted to 500 times with distilled water and
observed under transmission electron microscope (TEM) after negative staining.
The small dark globules as shown in FIG. 3 represents the nano size in situ formed
emulsified oil globules.
[0085] Example 4. Dissolution profile of the drug-loaded SEDDS prepared
from Example 1
The emulsion preconcentrate was dissolved in dissolution media of pH 1.2 and 6.8.
FIG. 4 and 5 represents almost 100% drug release for both the drugs (telmisartan
and trans-resveratrol) within 60 minutes from developed formulation in both
dissolution media of pH 1.2 and 6.8.

We Claim:

1. A self-emulsifying drug delivery system(SEDDS)for improving the solubility
and bioavailability of pharmaceutical^ active poorly aqueous soluble drugs
in a single dosage form, wherein the SEDDS comprises,
a. a poorly aqueous solubledrug combination, wherein the drugs are
loaded in the SEDDS;
b. an oil phase;
c. a mixture of surfactants.
2. The SEDDS as claimed in claim 1, wherein the poorly aqueous solubledrug combination is a combination of telmisartan and trans-resveratrol.
3. The SEDDS as claimed in claim 1, wherein the oil phase is cinnamon oil.
4. The SEDDS as claimed in claim 1, wherein the surfactant is a mixture of Tween 20 and propylene glycol in 1:2 ratio.
5. The SEDDS as claimed in claim 4, wherein the cinnamon oil cinnamon oil acts as an adjunct therapy to synergise the antihypertensive effect of telmisartan and trans-resveratrol combination.
6. The SEDDS as claimed in claim 1, wherein the drug loaded SEDDS forms nano size emulsion (SENDDS) or micro size emulsion (SMEDDS) when comes in contact with gastrointestinal fluid medium of varying pH and in-vitro simulated aqueous medium.
7. A SEDDS for delivering poorly aqueous soluble drugs in a single dosage form comprises,
a. telmisartan and trans-resveratrol combination, wherein the amount
of telmisartan in the combination ranges from about 10 to about 40
wt% and the the amount of trans-resveratol in the combination
ranges from about 10 to about 40 wt%.
b. cinnamon oil ranging from about 10% to about 50 wt%;
c. propylene glycol surfactant; and
d. Tween 20 surfactant.
8. A pharmaceutical composition comprising SEDDS as claimed in claim 8.

9. The pharmaceutical composition as claimed in claim 9, wherein the composition is formulated as tablets, soft capsules, granules, hard capsules, oral liquids, and the like.
10. A method for producing drug loaded SEDDS-based pharmaceutical composition comprising telmisartan and trans-resveratrol; cinnamon oil; propylene glycol; and Tween 20, comprises the steps of:
a. dissolving the telmisartan and trans-resveratrol in cinnamon oil and surfactant mixture, comprising Tween 20 and propylene glycol in the proportion of 1:2.