The present disclosure relates generally to pharmaceutical compositions. More specifically, the disclosure is directed to a pharmaceutical microemulsion composition for skin disorders comprising Urtica pilulifera. The disclosure also provides a process of manufacturing the composition.
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] Urtica pilulifera L. (Urticaceae) is an annual herb with a tough, creeping branched rhizome and an erect, square leafy stem. All parts of the plant bristle with stinging hair and it flowers from May to August. Various studies had been carried out to know the chemical constituents of this plant. It has been found that the primary constituents of this plant are alkaloids, polyphenols, flavonoids viz., kaempferol, isorhamnetin, chlorogenic acid and quercetin. Therefore, the whole plant extract of Urtica pilulifera has anti-asthmatic, antidandruff, astringent, depurative, diuretic, galactogogue, haemostatic, hypoglycemic and stimulating tonic activity. It also has great potential in treatment of anemia, excessive menstruation, hemorrhoids, arthritis, rheumatism and skin disorders, especially eczema. However, phytoconstituents in whole plant extract of Urtica pilulifera have certain limitations like poor aqueous solubility and permeability issues and therefore, tends to impart lesser therapeutic activity.
[0004] Micro-emulsions are fascinating and relatively potential compositions owing to superior solubilization capacity, thermodynamic stability, high rate of diffusion as well as absorption, transparency, and simplicity in production. [0005] Thus, there is a need to develop improved compositions of Urtica pilulifera for pharmaceutical applications that overcome its solubility and permeability limitations. The inventors of the present disclosure provide a

pharmaceutical microemulsion composition of Urtica pilulif era that is stable and enhances skin permeability of the phytoconstituents of Urtica pilulif era.
OBJECTS OF THE INVENTION
[0006] An object of the present disclosure is to provide a pharmaceutical composition for Urticapilulifera that improves its solubility and permeability. [0007] An object of the present disclosure is to provide a pharmaceutical microemulsion composition for skin disorders comprising Urtica pilulifera. [0008] Another object of the present disclosure is to provide a pharmaceutical microemulsion composition comprising Urtica pilulifera having optimum viscosity and globule size.
[0009] Yet another object of the present disclosure is to provide a process of manufacturing a pharmaceutical microemulsion composition comprising Urtica pilulifera.
SUMMARY OF THE INVENTION
[0010] This summary is provided to introduce a selection of concepts in a
simplified form that are further described below in 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.
[0011] Aspects of the present disclosure provide development of microemulsion
system of Urtica pilulifera by ultra-sonication technique to enhance skin
permeability potential of phytoconstituents for the purpose of getting improved
potential in treatment of skin disorders.
[0012] In an aspect, the present disclosure provides a pharmaceutical
microemulsion composition for skin disorders comprising Urtica pilulifera,
polysorbate, polyethylene glycol, sunflower seed oil and distilled water.
[0013] In an embodiment, the composition may comprise whole of Urtica
pilulifera, a part of Urtica pilulifera, or an extract of Urtica pilulifera.

[0014] In an embodiment, the part or extract may be obtained from the group
comprising of root, leaves, shoot, fruits, rhizome, seed, stem, barks, flower, sap,
bud or combinations thereof of Urtica pilulifera. In a preferred embodiment, the
composition comprises an extract of whole of Urtica pilulifera, including the
stem, leaves and shoot of Urtica pilulifera. In an embodiment, the Urtica
pilulifera may be present in a range of about 5%w/v to about 15% w/v of the
composition.
[0015] In an embodiment, the polysorbate may be selected from polyoxyethylene
(20) sorbitan monolaurate (polysorbate 20), polyoxyethylene (20) sorbitan
monopalmitate (polysorbate 40), polyoxyethylene (20) sorbitan monostearate
(polysorbate 60), or polyoxyethylene (20) sorbitan monooleate (polysorbate 80).
[0016] In an embodiment, the polysorbate may be present in a range of about
5%v/v to about 20% v/v of the composition.
[0017] In an embodiment, the polyethylene glycol may be polyethylene glycol-
600 that may be present in a range of about l%v/v to about 10% v/v of the
composition.
[0018] In an embodiment, the ratio of polysorbate (surfactant) to polyethylene
glycol (co-surfactant) maybe 3:1.
[0019] In an embodiment, the sunflower seed oil may be present in a range of
about l%v/v to about 10% v/v of the composition.
[0020] In an embodiment, the distilled water provides the aqueous phase and may
be present in a range of about 60%v/v to about 80% v/v of the composition.
[0021] In an aspect, the present disclosure provides a pharmaceutical
microemulgel formulation for skin disorders comprising Urtica pilulifera,
polysorbate, polyethylene glycol, sunflower seed oil, distilled water, and one or
more additive(s).
[0022] In an embodiment, the additive may be selected from triethnaolamine; a
gelling agent such as but not limited to, polyacrylic acid polymer, poloxamer 407,
tragacanth, pectin, starch, sodium alginate, gelatin, or cellulose derivatives; or
combinations thereof. In an embodiment, the additive(s) may be present in a range
of about l%w/v to about 2%w/v of the formulation.

[0023] In an aspect, the present disclosure provides a medicament comprising the pharmaceutical microemulsion composition.
[0024] In another aspect, the present disclosure provides a process of manufacturing a pharmaceutical microemulsion composition, wherein the process comprises the steps of: (a) dissolving an extract of Urtica pilulifera in sunflower seed oil to generate an oil phase; (b) dissolving polysorbate and polyethylene glycol in distilled water to generate an aqueous phase; (c) adding the oil phase slowly into the aqueous phase with continuous homogenization to produce a macroemulsion; and (d) ultrasonicating the macroemulsion to give the microemulsion composition.
[0025] Other aspects of the invention will be set forth in the description which follows, and in part will be apparent from the description, or may be learnt by the practice of the invention.
BRIEF DESCRIPTION OF THE DRAWINGS
[0026] The following drawings form 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.
[0027] Figure 1 provides Contour plots (2D) (Figures 1(a) and 1 (c)) and corresponding response surface plots (3D) (Figures 1(b) and 1 (d)) showing the effect of independent variables (sonication time (minutes), tween® 80(%v/v) and sunflower seed oil (%v/v)) on globule size (um) (Yl) of the microemulsion composition as per an embodiment of the present disclosure. [0028] Figure 2 provides Contour plots (2D) (Figures 2(a) and 2(c)) and corresponding response surface plots (3D) (Figures 2(b) and 2(d)) showing the effect of independent variables (sonication time (minutes), tween® 80(%v/v) and sunflower seed oil (%v/v)) on viscosity (centipoises) (Y2) of the microemulsion composition as per an embodiment of the present disclosure. [0029] Figure 3 provides the Contour plot (2D) (Figure 3(a)) and corresponding response surface plot (3D) (Figure 3(b)) showing the effect of independent

variables (sonication time (minutes) and tween 80(%v/v)) on desirability value of the microemulsion composition as per an embodiment of the present disclosure.
DETAILED DESCRIPTION OF THE INVENTION
[0030] 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 as defined by the appended claims.
[0031] 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. [0032] 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.
[0033] In some embodiments, numbers have been used for quantifying amounts, 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. [0034] 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.
[0035] 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. [0036] 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."
[0037] 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. [0038] 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.

[0039] 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.
[0040] 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.
[0041] 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. [0042] The headings and abstract of the invention provided herein are for convenience only and do not interpret the scope or meaning of the embodiments. [0043] 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.
[0044] As described herein, the term 'therapeutically effective amount' refers to the amount of the composition or formulation required to bring about a change or improvement in a subject without side effects or overdosing.

[0045] The term, "subject" as used herein refers to an animal, preferably a
mammal, and most preferably a human. The term "mammal" used herein refers to
warm-blooded vertebrate animals of the class 'mammalia' , including humans,
characterized by a covering of hair on the skin and, in the female, milk-producing
mammary glands for nourishing the young, the term mammal includes animals
such as cat, dog, rabbit, bear, fox, wolf, monkey, deer, mouse, pig and human.
[0046] The term, 'management', or 'treatment' as used herein refers to alleviate,
slow the progression, attenuation, prophylaxis or as such treat the existing disease
or condition. Treatment also includes treating, preventing development of, or
alleviating to some extent, one or more of the symptoms of the diseases or
condition.
[0047] Aspects of the present disclosure provide an optimized composition of
Urtica pilulifera through Central Composite Design optimization methodology to
produce transparent microemulsion with optimum viscosity and least globule size
which augments absorption and permeability potential of the phytoconstituents of
Urtica pilulifera.
[0048] In an embodiment, the present disclosure provides a pharmaceutical
microemulsion composition comprising Urtica pilulifera.
[0049] In an embodiment, the present disclosure provides a pharmaceutical
microemulsion composition for skin disorders comprising Urtica pilulifera,
polysorbate, polyethylene glycol, sunflower seed oil and distilled water.
[0050] In an embodiment, the composition may comprise whole of Urtica
pilulifera, a part of Urtica pilulifera, or an extract of Urtica pilulifera.
[0051] In an embodiment, the part or extract may be obtained from the group
comprising of root, leaves, shoot, fruits, rhizome, seed, stem, barks, flower, sap,
bud or combinations thereof of Urtica pilulifera.
[0052] In a preferred embodiment, the composition comprises an extract of whole
plant, including leaves, shoot, and stem, of Urtica pilulifera.
[0053] In an embodiment, the extract of Urtica pilulifera may be an aqueous
extract or an alcoholic extract, such as an ethanolic or methanolic extract. In a

preferred embodiment, the extract is an ethanolic extract of whole plant of Urtica pilulifera.
[0054] In an embodiment, the Urtica pilulifera may be present in a range of about 5%w/v to about 15% w/v of the composition. In a preferred embodiment, the Urtica pilulifera may be present in a range of about 6%w/v to about 12% w/v of the composition. In a preferred embodiment, the extract of Urtica pilulifera may be present in 10% w/v of the composition.
[0055] In an embodiment, the polysorbate acts as a surfactant, emulsifier and absorption enhancer. In an embodiment, the polysorbate may be selected from polyoxyethylene (20) sorbitan monolaurate (polysorbate 20), polyoxyethylene (20) sorbitan monopalmitate (polysorbate 40), polyoxyethylene (20) sorbitan monostearate (polysorbate 60), or polyoxyethylene (20) sorbitan monooleate (polysorbate 80). In a preferred embodiment, the polysorbate may be polysorbate 80 or polyoxyethylene (20) sorbitan monooleate.
[0056] In an embodiment, the polysorbate may be present in a range of about 5%v/v to about 20% v/v of the composition. In a preferred embodiment, the polysorbate may be present in a range of about 10%v/v to about 15% v/v of the composition. In a preferred embodiment, the polysorbate 80 may be present in 15%) v/v of the composition.
[0057] In an embodiment, the polyethylene glycol (PEG) may act as a co-surfactant. The molecular weight of PEG may range from 200 to 600. In a preferred embodiment, the polyethylene glycol is polyethylene glycol -600. [0058] In an embodiment, the polyethylene glycol may be present in a range of about l%v/v to about 10% v/v of the composition. In a preferred embodiment, the polyethylene glycol may be present in a range of about 3%v/v to about 6% v/v of the composition. In a preferred embodiment, the polyethylene glycol-600 may be present in 5% v/v of the composition.
[0059] In an embodiment, the ratio of polysorbate (surfactant) to polyethylene glycol (co-surfactant) maybe kept as 3:1.
[0060] In an embodiment, the sunflower seed oil acts as the oil phase. In an embodiment, the sunflower seed oil may be present in a range of about l%v/v to

about 10% v/v of the composition. In a preferred embodiment, the sunflower seed
oil may be present in a range of about 2%v/v to about 5% v/v of the composition.
In a preferred embodiment, the sunflower seed oil may be present in 3% v/v of the
composition.
[0061] In an embodiment, the distilled water provides the aqueous phase and may
be present in a range of about 60%v/v to about 80% v/v of the composition. In a
preferred embodiment, the distilled water may be present in 67% v/v of the
composition or in quantity sufficient.
[0062] The microemulsion composition of the present disclosure has the optimum
globule size and viscosity for improving the solubility and penetration of the
composition into the skin.
[0063] The microemulsion composition synergistically helps overcome the low
permeability and weak solubility of the phytoconstituents of Urtica pilulifera by
providing the optimum globule size and viscosity which the extract of Urtica
pilulifera alone does not possess. In some embodiments, the composition shows
increase in solubility of upto 16 folds compared to ordinary aqueous
compositions.
[0064] In an embodiment, the present disclosure provides a pharmaceutical
microemulgel formulation for skin disorders comprising Urtica pilulifera,
polysorbate, polyethylene glycol, sunflower seed oil, distilled water, and one or
more additive(s).
[0065] In an embodiment, the formulation is suitable for topical applications for
skin disorders.
[0066] In an embodiment, the additive may be selected from triethanolamine, a
gelling agent such as but not limited to, polyacrylic acid polymer, tragacanth,
pectin, starch, sodium alginate, gelatin, cellulose derivatives, or poloxamer 407;
or combinations thereof.
[0067] In an embodiment, the additive may be present in a range of about l%w/v
to about 2%w/v of the formulation.
[0068] The formulation is aesthetically acceptable, pleasant to touch, stable and
homogenous without any indications of phase separation. In some embodiments,

the spreadability time for the formulation maybe 11±3 seconds with application of
very small shear stress. In some embodiments, pH of the formulation maybe
6.6±0.5 which ensures that it can be employed for skin disorders with low risk of
skin irritation since topical dosage forms should have a pH range of 6-7 in order
to prevent skin pH alteration.
[0069] The formulation also shows physical stability with no phase separation and
increase in permeability. In some embodiments, the formulation shows increase in
permeability of upto 24 folds compared to ordinary gel formulations.
[0070] In another embodiment, the present disclosure provides a process of
manufacturing a pharmaceutical microemulsion composition, wherein the process
comprises the steps of: (a) dissolving an extract of Urtica pilulifera in sunflower
seed oil to generate an oil phase; (b) dissolving polysorbate and polyethylene
glycol in distilled water to generate an aqueous phase; (c) adding the oil phase
slowly into the aqueous phase with continuous homogenization to produce a
macroemulsion; and (d) ultrasonicating the macroemulsion to give the
microemulsion composition.
[0071] In an embodiment, the oil phase may be added to aqueous phase at about
37±2°C temperature and the homogenization may be performed at about 500 rpm
for about 10 minutes.
[0072] In an embodiment, the present disclosure provides a method of treatment,
amelioration or prophylaxis of one or more skin disorder(s) in a subject by
administering a therapeutically effective amount of the composition as recited
above.
[0073] In an embodiment, the skin disorders may include, but is not limited to,
eczema, psoriasis, acne, rosacea, ichthyosis, vitiligo, hives, or seborrheic
dermatitis.
[0074] In an embodiment, the present disclosure provides a medicament for
treating, or managing one or more skin disorder(s) as defined above.
[0075] While the foregoing describes various embodiments of the disclosure,
other and further embodiments of the disclosure may be devised without departing
from the basic scope thereof. The scope of the invention is determined by the

claims that follow. The invention is not limited to the described embodiments, versions or examples, which are included to enable a person having ordinary skill in the art to make and use the invention when combined with information and knowledge available to the person having ordinary skill in the art. EXAMPLES
[0076] The present invention is further explained in the form of following examples. However, it is to be understood that the following examples are merely illustrative and are not to be taken as limitations upon the scope of the invention. [0077] Materials and methods: Urtica pilulifera was obtained from Har-Veer Herbal Pharma, Ludhiana and Urtica pilulifera extracts were prepared by soxhlet extraction procedure using soxhlet apparatus.
[0078] Example 1: Composition of Urtica pilulifera microemulsion [0079] The composition of micro-emulsion includes Urtica pilulifera extracts (10%w/v), Tween® 80 as emulsifier and absorption enhancer; polyethylene glycol 600 (PEG 600) as co-surfactant, sunflower seed oil as an oil phase and distilled water (aqueous phase) quantity sufficient up to 100 ml. The percentages of oil and surfactant used during microemulsion production and sonication time are depicted in Table 1. The ratio of surfactant: co-surfactant (Smix) was kept at 3:1. Twenty batches of microemulsion compositions were fabricated as per Central Composite Design layout (Table 2). Response variables evaluated for microemulsion compositions include globule size (um) (Yl), and viscosity (centipoises) (Y2). Constraints criterion set for response variables was to minimize their values. [0080] Preparation of the composition by ultra-sonication: Urtica pilulifera plant extract (10 % w/v) was dissolved in sunflower seed oil to generate oil phase. The aqueous phase was prepared by dissolving surfactant and co-surfactant in distilled water. The oil phase was transferred drop-wise to aqueous phase with continuous homogenization at 37±2°C temperature and 500 rpm for 10 minutes to produce macroemulsion. Macroemulsion were further converted into microemulsion using an ultrasonicator [PCI (Probe sonicator-Advanced model) 20 kHz] at different sonication time as mentioned in Table 2. The mild heat

generated during sonication was monitored by positioning the composition in ice filled container.
Table 1: Levels of independent variables for microemulsion composition

Independent variables -1.68 (axial) -1
(Low) 0 (Medium) +1 (High) +1.68 (axial)
Xl= Sunflower seed oil (%
v/v) 0.96 3 6 9 11.04
X2 = Tween®80(%v/v) 1.6 5 10 15 18.4
X3 = Sonication time (minutes) 1.32 2 3 4 4.68
Table 2: Central composite design layout for the microemulsion
composition

Run Sunflower seed oil (% v/v) (XI) Tween 80 (% v/v) (X2) Sonication time (minutes) (X3)
1 3 5 2
2 9 5 2
3 3 15 2
4 9 15 2
5 3 5 4
6 9 5 4
7 3 15 4
8 9 15 4
9 0.96 10 3
10 11.04 10 3
11 6 1.6 3
12 6 18.4 3
13 6 10 1.32
14 6 10 4.68
15 6 10 3
16 6 10 3
17 6 10 3
18 6 10 3

19 6 10 3
20 6 10 3
[0081] Determination of response variables of Urtica pilulifera microemulsion:_Optical microscope was used for determination of globule size (um) (Yl) of microemulsion. Measurements were executed in triplicate (n = 3) to obtain average globule size. The viscosities (centipoises) (Y2) of micro-emulsions were estimated through Brookfield rotational digital viscometer model at rotating-spindle using LV-spindle-64 at 37±2°C.
[0082] a) Response surface analysis of globule size (um) (Yl): Independent factors affecting globule size (um) of Urtica pilulifera microemulsion were tween® 80 (% v/v) (X2) and sonication time (minutes) (X3) (p < 0.05) which impart antagonistic effect on globule size (um) which can be elucidated by following polynomial quadratic equation and the results have been depicted in Figure 1 in terms of contour plots and response surface plots for effect of %v/v of tween® 80, sonication time and %v/v of sunflower seed oil.
Yl = 155.28 + 6.42 XI -10.55 X2 - 22.42 X3 - 1.52 X1X2 + 5.42 X1X3 + 3.11
X2X3 - 22.08 XI2 - 12.8 X22 - 8.75 X32 Eq. (1)
[0083] The negative and positive coefficients before independent variables pinpoint negative and positive effect on response variables, respectively. The model F-value of 24.44 (*p<0.05) implies that model is significant. The non-significant lack of fit F-value of 5 (p>0.05) implies that there is least signal to noise ratio (Table 3).
Table 3: ANOVA for quadratic model for globule size (urn) (Yl)

Source Sum of Squares df Mean Square F-value p-value
Model 18376.66 9 2041.85 24.44 < 0.0001 Significant
XI 561.91 1 561.91 6.73 0.0268 Not significant
X2 1517.88 1 1517.88 18.17 0.0017 Significant
X3 6861.53 1 6861.53 82.13 < 0.0001 Significant
X1X2 18.48 1 18.48 0.2212 0.6482 Not

significant
X1X3 235.44 1 235.44 2.82 0.1241 Not significant
X2X3 77.25 1 77.25 0.9247 0.3589 Not significant
XP 7004.51 1 7004.51 83.84 < 0.0001 Significant
X22 2351.84 1 2351.84 28.15 0.0003 Significant
X32 1098.69 1 1098.69 13.15 0.0046 Significant
Lack of Fit 244.17 5 638.36 5 127.67 Not significant
[0084] b) Response surface analysis of viscosity (centipoises) (Y2): Design-Expert software developed quadratic model for Y2. Therefore, second order polynomial model was generated by multiple regression analysis using Design-Expert software. Independent factors affecting viscosity (centipoises) of Urtica pilulifera microemulsion composition were tween® 80 (% v/v) (X2) and sonication time (minutes) (X3) (p < 0.05) which can be elucidated by following polynomial quadratic equation and the results have been depicted in Figure 2 in terms of contour plots and response surface plots for effect of %v/v of tween® 80, sonication time and %v/v of sunflower seed oil.
Y2 = 194.27 + 5.05 XI - 8.4 X2 - 17.95 X3 - 1.76 X1X2 + 4.23 X1X3 + 1.83
X2X3 - 16.61 XI2 - 10.04 X22 - 6.36 X32 Eq. (2)
[0085] The negative and positive coefficients before independent variables pinpoint negative and positive effect on response variables, respectively. The model F-value of 26.86 (*p < 0.05) implies the model is significant. The non-significant lack of fit F-value of 2.86 (p>0.05) implies that there is least signal to noise ratio (Table 4).
Table 4: ANOVA for quadratic model for viscosity (centipoises) (Y2)

Source Sum of Squares df Mean Square F-value p-value
Model 11125.12 9 1236.12 26.86 < 0.0001 Significant
XI 348.02 1 348.02 7.56 0.0205 Not significant
X2 963.66 1 963.66 20.94 0.0010 Significant

X3 4396.58 4396.58 95.52 < 0.0001 Significant
X1X2 24.78 24.78 0.5384 0.4799 Not significant
X1X3 143.48 143.48 3.12 0.1079 Not significant
X2X3 26.79 26.79 0.5821 0.4631 Not significant
XP 3965.06 3965.06 86.15 < 0.0001 Significant
X22 1448.42 1448.42 31.47 0.0002 Significant
X32 581.72 581.72 12.64 0.0052 Significant
Lack of Fit 335.30 5 67.06 2.68 0.1513 Not significant
[0086] Values of variables for optimized microemulsion and the composition of optimized Urtica pilulifera microemulsion are provided in Table 5 and Table 6, respectively.
Table 5 Values of variables for production of optimized microemulsion composition of Urtica pilulifera

Independent variables Criteria Value Desirability function
Xl= Sunflower seed oil (% v/v) In range 3 -
X2 = Tween 80 (% v/v) In range 15

X3 = Sonication time (minutes) In range 4

Response variables
Yl = Globule Size (um) Minimize 71.47 0.907
Y2 = Viscosity (mPa.s) Minimize 129.19

Table 6 Final optimized microemulsion composition of Urtica pilulifera

Formulation components Amount
Urtica pilulifera extract 10 %w/v
Sunflower seed oil 3 % v/v
Tween 80 15 %v/v
PEG 600 5 % v/v
Distilled water 67 % v/v

[0087] The required sonication time for production of optimized microemulsion
was found to be 4 minutes.
[0088] Solubility study: Urtica pilulifera extract was added in excess to two
different systems; one part was added in to the microemulsion composition as in
Table 6 and second part was added to distilled water. After continuous stirring for
24 h in orbital shaker at room temperature, the samples were withdrawn and
centrifuged for 5 minutes at 6000 rpm. Subsequently, samples were analyzed at
270 nm using UV spectrophotometer and concentration of gallic acid solubilized
from Urtica pilulifera extract {Urtica pilulifera is rich in gallic acid) in
microemulsion system and distilled water was calculated using appropriate
regression equation. It was found that solubility of Urtica pilulifera extract (gallic
acid equivalent) in microemulsion was 160.6 mg/ml while in distilled water;
concentration was 14.6 mg/ml. This indicated that development of microemulsion
system brings upon 16-fold solubility enhancement of Urtica pilulifera extract in
comparison to solubility in distilled water.
Example 2: Production of microemulgel of optimized Urtica pilulifera
microemulsion
[0089] Carbopol 940 (cross-linked polyacrylic acid polymer) (1% w/v) was
consistently mixed into optimized Urtica pilulifera microemulsion composition of
Example 1 with continuous magnetic stirring to produce a homogenous
dispersion. Then, triethanolamine was transferred to polymeric dispersion which
generated microemulgel of optimized Urtica pilulifera microemulsion.
[0090] Physical appearance: Microemulgel of optimized Urtica pilulifera
microemulsion composition was inspected for color and homogeneity.
Homogeneity was estimated via rubbing the little quantity of microemulgel
among index and thumb finger. The microemulgel emerged aesthetically
acceptable, pleasant to touch and homogenous without any indications of phase
separation.
[0091] Spreadability: Spreadability was determined by placing one gram of
microemulgel of optimized Urtica pilulifera microemulsion composition among
two horizontal glass plates and applying standard weight of twenty five grams for

sixty seconds over upper glass plate. The spreadability time was 11±3 seconds with application of very small shear stress.
[0092] pH: Small quantity of microemulgel of optimized Urtica pilulifera microemulsion composition was dispersed in distilled water and then estimated pH using a previously calibrated pH meter. The pH of the formulation was found to be 6.6±0.5 which ensures that it could be indicated for skin disorders with low risk of skin irritation since topical dosage forms should have a pH range of 6-7 in order to prevent skin pH alteration.
[0093] Viscosity: Microemulgel of optimized Urtica pilulifera microemulsion composition was examined for rheological characteristics using Brookfield rotational digital viscometer model at rotating-spindle using LV-spindle-62 at 37±2°C at different shear rates. All measurements were taken in triplicate and are represented as mean ± SD. The viscosity of Urtica pilulifera microemulgel was found to be 290 centipoises.
[0094] Thermodynamic stability: Centrifuge stress test and freeze-thaw testing were performed to examine the thermal stability of Urtica pilulifera microemulgel. During centrifugation stress test, microemulgel was centrifuged around 3000 rpm for 20 minutes and subsequently examined for phase separation. In freeze-thaw period testing, microemulgel was exposed to freeze-thaw intervals i.e. 24 hrs at 25°C and next 24 hours at -5°C. There was no phase separation after thermodynamic testing which demonstrated physical stability of microemulgel. [0095] In-vitro drug permeation study: In-vitro drug permeation was investigated using Franz diffusion cell at 37±0.5°C. Dialysis membrane having 12,000-14,000 Da molecular weights with 2.54 cm2 surface area was fixed between donor and acceptor compartments. The acceptor chamber was filled with 20 mL phosphate buffer, pH 6.8. Urtica pilulifera microemulgel formulation was applied over dialysis membrane towards donor compartment. Approximately 0.5 mL sample was taken out from acceptor compartment after 2 hour and concentration of drug was analyzed at 270 nm (Xmax for gallic acid) using spectrophotometer. Another experiment was executed for plain Urtica pilulifera gel formulation by similar procedure. It was found that concentration of bioactive

(gallic acid) permeated through dialysis membrane into acceptor compartment from Urtica pilulifera microemulgel was 3864 ug/ml while concentration permeated from plain Urtica pilulifera gel formulation was 161 ug/ml. This showed that development of microemulsion system brings a 24-fold permeability enhancement of Urtica pilulifera extract through dialysis membrane in comparison to plain Urtica pilulifera gel formulation.
[0096] 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.
ADVANTAGES OF THE PRESENT INVENTION
[0097] The present disclosure provides a pharmaceutical microemulsion composition of Urtica pilulifera that has low viscosity and globule size. [0098] The present disclosure provides a composition that synergistically improves the solubility and permeability of Urtica pilulifera.

We Claim:

1. A pharmaceutical microemulsion composition for skin disorders comprising Urtica pilulifera, polysorbate, polyethylene glycol, sunflower seed oil and distilled water.
2. The composition as claimed in claim 1, wherein the composition comprises whole of Urtica pilulifera, a part of Urtica pilulifera, or an extract of Urtica pilulifera.

3. The composition as claimed in claim 2, wherein the part or extract is obtained from the group comprising of root, leaves, shoot, fruits, rhizome, seed, stem, barks, flower, sap, bud or combinations thereof of Urtica pilulifera.
4. The composition as claimed in claim 1, wherein Urtica pilulifera is an ethanolic extract of whole plant of Urtica pilulifera.
5. The composition as claimed in claim 1, wherein the Urtica pilulifera is present in a range of 5%w/v to 15% w/v of the composition.
6. The composition as claimed in claim 1, wherein the polysorbate is selected from polyoxyethylene (20) sorbitan monolaurate (polysorbate 20), polyoxyethylene (20) sorbitan monopalmitate (polysorbate 40), polyoxyethylene (20) sorbitan monostearate (polysorbate 60), or polyoxyethylene (20) sorbitan monooleate (polysorbate 80).
7. The composition as claimed in claim 1, wherein the polysorbate is present in a range of 5%v/v to 20% v/v of the composition.
8. The composition as claimed in claim 1, wherein the polyethylene glycol is polyethylene glycol 600.
9. The composition as claimed in claim 1, wherein the polyethylene glycol is present in a range of P/ov/v to 10% v/v of the composition.

10. The composition as claimed in claim 1, wherein the polysorbate and the polyethylene glycol are present in a ratio of 3:1.
11. The composition as claimed in claim 1, wherein the sunflower seed oil is present in a range of P/ov/v to 10% v/v of the composition.

12. The composition as claimed in claim 1, wherein the distilled water is present in a range of 60%v/v to 80% v/v of the composition.
13. A pharmaceutical microemulgel formulation for skin disorders comprising Urtica pilulifera, polysorbate, polyethylene glycol, sunflower seed oil, distilled water, and one or more additive(s).
14. A process of manufacturing a pharmaceutical microemulsion composition, wherein the process comprises the steps of: (a) dissolving an extract of Urtica pilulifera in sunflower seed oil to generate an oil phase; (b) dissolving polysorbate and polyethylene glycol in distilled water to generate an aqueous phase; (c) adding the oil phase slowly into the aqueous phase with continuous homogenization to produce a macroemulsion; and (d) ultrasonicating the macroemulsion to give the microemulsion composition.