CLIAMS:We Claim

1. A pharmaceutical composition for the topical treatment of acne comprising an antibiotic of the lincomycin family entrapped in microsponges, wherein said composition provides sustained release of said antibiotic at the area to be treated for up to 9 hours.

2. The pharmaceutical composition as claimed in claim 1, wherein said antibiotic is present in said composition in an amount in the range of 0.01 to 5.0 wt. % of said composition.

3. The pharmaceutical composition as claimed in claim 1, wherein said antibiotic is lincomycin hydrochloride.

4. The pharmaceutical composition as claimed in claim 1, wherein said composition has a pH in the range of 4.6 to 5.7.

5. The pharmaceutical composition as claimed in claim 1, wherein said composition further comprises one or more active ingredient selected from the group consisting of emollient, essential oil, sunscreen agent, antioxidant, antibacterial agent, bacteriostatic agent, antimicrobial agent, antifungal agent, anti-infective agent, antiseptic agent and anti-inflammatory agent.

6. The pharmaceutical composition as claimed in claim 1, wherein said composition is in a form selected from the group consisting of gel, cream, lotion, suspension, emulsion and ointment.

7. The pharmaceutical composition as claimed in claim 1, wherein said composition comprises 0.1 to 2.0 wt. % of a polymeric microsponge system.

8. The pharmaceutical composition as claimed in claim 7, wherein said polymeric microsponge system comprises a styrene and divinyl benzene system.

9. The pharmaceutical composition as claimed in claim 7, wherein said polymeric microsponge system comprises a methyl methacrylate and ethylene glycol dimethacrylate system.

10. The pharmaceutical composition as claimed in claim 1, wherein said composition further comprises 0.1 to 15 wt % of a gelling agent.

11. The pharmaceutical composition as claimed in claim 10, wherein said gelling agent is selected from a group consisting of microcrystalline cellulose, colloidal magnesium silicate, hydroxypropyl methyl cellulose, hydroxylated vinylic polymer, carbomer, and mixtures thereof.

12. The pharmaceutical composition as claimed in claim 11, wherein said gelling agent is carbomer.

13. The pharmaceutical composition as claimed in claim 5, wherein said composition comprises an antimicrobial agent in an amount in the range of 0.075 to 1.0 wt% of said composition.

14. The pharmaceutical composition as claimed in claim 13, wherein said antimicrobial agent is chlorocresol.

15. The pharmaceutical composition as claimed in claim 1, wherein said composition further comprises a vehicle selected from a group consisting of purified water, propylene glycol, glycerin, stearyl alcohol, cetyl alcohol, cetyl-stearyl alcohol, and mixtures thereof.

16. The pharmaceutical composition as claimed in claim 1, wherein said composition further comprises a surface-active agent selected from a group consisting of esters of polyols and sugars, products of condensation of ethylene oxide with fatty acids, fatty alcohols, long-chain alkylphenols, long-chain mercaptans or long-chain amides, polyethers of polyhydroxylated fatty alcohols and alkylpolyglycol ethers, and mixtures thereof.

17. A method for preparing a gel for the topical treatment of acne, said method comprising the steps of:
dissolving chlorocresol in glycerin at a temperature between 50 – 60 ºC;
mixing carbomer and the dissolved chlorocresol in purified water to obtain a carbomer chlorocresol slurry;
filtering the carbomer chlorocresol slurry to obtain a filtered carbomer chlorocresol slurry;
dispersing Microsponge in glycerin;
adding the dispersion of Microsponge and glycerin to the filtered carbomer chlorocresol slurry to obtain a carbomer, Microsponge glycerin slurry;
adding propylene glycol solvent to the carbomer, Microsponge glycerin slurry to obtain carbomer, Microsponge glycerin, propylene glycol slurry;
preparing a solution of lincomycin hydrochloride in purified water;
adding the solution to the carbomer, Microsponge glycerin, propylene glycol slurry to obtain carbomer slurry and lincomycin hydrochloride Microsponges; and
adding sodium hydroxide to neutralize the carbomer slurry and lincomycin hydrochloride Microsponges to obtain said gel.

,TagSPECI:FIELD OF THE INVENTION
The present invention relates to a pharmaceutical composition for the topical treatment of acne. More particularly, the present invention relates to a pharmaceutical composition for the topical treatment of acne vulgaris with antibiotics of the lincomycin family.

BACKGROUND OF THE INVENTION
Acne vulgaris is a common inflammatory disorder of the skin found to be caused due to the interaction of interrelated processes: an increased excretion of the sebum, a ductal cornification, an abnormal number and function of P. acnes and C. acnes, and the production of inflammatory mediators. In its milder form, acne vulgaris is a superficial disorder evidenced by slight, spotty irritations, which can be treated satisfactorily by ordinary skin hygiene. However, pilosebaceous follicles may occur and result in the formation of pustules, infected cysts and, in extreme cases, canalizing inflamed and infected sacs, which may become extensive and leave permanent scars.

Generally, a topical treatment of benzoyl peroxide or hexachlorophene to kill bacteria, salicylic acid to help unclog follicles, or sulfur to unclog follicles and help break down blackheads and whiteheads, may be used. Also, Vitamin A derivatives, called retinoids, may be used topically to speed up the shedding of skin, to help unclog follicles. Systemic antibiotics such as tetracycline and clindamycin are usually more effective but are reserved for severe cases of acne. It has been known that the systemic treatment of acne is not preferred because of the side effects resulting from saturation of the entire body with antibiotics and the fact that only the affected skin needs to be treated. However, despite a long-felt need for a topical treatment for acne, antibiotics generally have been used only systemically to treat acne as it was not believed that antibiotics could be used effectively in the topical formulations.

Ideally, the topical formulations for the treatment of acne should contain very little or no oil in the formulation, so as to not leave any oil film on the skin which can further aggravate the condition. However, most anti-acne agents are insoluble in water, and thus are difficult to incorporate into an aqueous system. The typical gels are usually formed from low molecular weight polymers and therefore do not allow high loading of the anti-acne agent. As a result, many known topical acne formulations have an oil-based vehicle, typically in the form of lotions or creams.

Another major disadvantage of the known topical anti-acne formulations in the form of lotions or creams, is that the lotion or cream needs to be applied multiple times in a day during the treatment period. This can be a hassle and quite expensive. Repeat applications are inconvenient, and there’s a probability of missing the dose. Still another major drawback of the known topical anti-acne formulations is that they can cause skin irritation, dryness, redness or inflammation, which may discourage the use.

Several efforts have been made in the past to provide topical formulations containing antibiotics. One such currently available product, Cleocin T® by Pharmacia & Upjohn Company is a topical solution containing 1% clindamycin. Cleocin T®, however, has several noted drawbacks. The formulation may cause excessive drying and irritation to the skin. In addition, the formulation lacks the necessary stability for extended storage at room temperature.

Another, currently available product BenzaClin® is a topical gel containing 1% clindamycin and 5% benzoyl peroxide. BenzaClin®, however, also has several noted drawbacks. For example, the product lacks the stability necessary for extended storage at room temperature, and the product can only be stored for up to three months. The product requires compounding of benzoyl peroxide gel and clindamycin powder, which may cause variability issues as a result of partially dissolved or undissolved aggregates, and which may exacerbate the inflammation and irritation problem due to skin abrasion.

Another known composition for the topical treatment of acne is disclosed in the US Patent No. 5446028. The patent discloses a composition comprising a peroxide and an antibiotic of the lincomycin family, which is substantially stable at a temperature of 50 °C for a period of thirty days.

Still another known composition for the topical treatment of acne is disclosed in the US Patent No. 6013637. The patent discloses a composition comprising a peroxide and an antibiotic of the lincomycin family, having pH between 4.6 and 5.7 and being free of sun filter.

These known formulations may have several adverse effects. Clindamycin, which is well absorbed through the skin, may have side-effects such as diarrhea. Likewise, benzoyl peroxide is a known skin-irritant. Accordingly, there is a need to reduce the potential side effects of these prior known compositions.

There is therefore felt a need to provide an improved composition for topical treatment of acne which overcomes at least partially the above-mentioned drawbacks in the prior art.

SUMMARY OF THE INVENTION
Accordingly, an object of the present invention is to provide a pharmaceutical composition containing an antibiotic of the lincomycin family for the topical treatment of acne.

Another object of the present invention is to provide a pharmaceutical composition for the topical treatment of acne which gives increased residence time at the site of infection and sustained release of the drug such that the therapeutic outcome of the drug is enhanced.

Yet another object of the present invention is to provide a pharmaceutical composition for the topical treatment of acne which prevents the undesirable side effects, maintains skin moisture and absorbs skin secretions.

Still another object of the present invention is to provide a pharmaceutical composition for the topical treatment of acne which has a soft feel and enhanced spreadability.

One more object of the present invention is to provide a pharmaceutical composition for the topical treatment of acne which is stable for extended storage at room temperature.

An additional object of the present invention is to provide a pharmaceutical composition for the topical treatment of acne which is cost-effective.

Other objects, aspects and advantages of the present invention will be more apparent from the following description.

The present invention discloses a pharmaceutical composition for the topical treatment of acne comprising an antibiotic of the lincomycin family entrapped in microsponges, wherein said composition provides sustained release of said antibiotic at the area to be treated for up to 9 hours.

The said antibiotic is typically present in said composition in an amount in the range of 0.01 to 5.0 wt. % of said composition. The antibiotic is preferably lincomycin hydrochloride. The composition has a pH in the range of 4.6 to 5.7.

The composition further comprises one or more active ingredient selected from the group consisting of emollient, essential oil, sunscreen agent, antioxidant, antibacterial agent, bacteriostatic agent, antimicrobial agent, antifungal agent, anti-infective agent, antiseptic agent and anti-inflammatory agent.
The composition preferably comprises an antimicrobial agent in an amount in the range of 0.075 to 1.0 wt% of said composition. More preferably, the antimicrobial agent is chlorocresol.

The composition can be in a form selected from the group consisting of gel, cream, lotion, suspension, emulsion and ointment.

The composition comprises 0.1 to 2.0 wt. % of a polymeric microsponge system. The polymeric microsponge system preferably comprises a styrene and divinyl benzene system or methyl methacrylate and ethylene glycol dimethacrylate system.

The composition typically comprises 0.1 to 15 wt % of a gelling agent. The gelling agent is preferably selected from a group consisting of microcrystalline cellulose, colloidal magnesium silicate, hydroxypropyl methyl cellulose, hydroxylated vinylic polymer, carbomer, and mixtures thereof. More preferably, the gelling agent is carbomer.

The composition further comprises a vehicle selected from a group consisting of purified water, propylene glycol, glycerin, stearyl alcohol, cetyl alcohol, cetyl-stearyl alcohol, and mixtures thereof.

The composition additionally comprises a surface-active agent selected from a group consisting of esters of polyols and sugars, products of condensation of ethylene oxide with fatty acids, fatty alcohols, long-chain alkylphenols, long-chain mercaptans or long-chain amides, polyethers of polyhydroxylated fatty alcohols and alkylpolyglycol ethers, and mixtures thereof.

The present invention further discloses a preferred method for preparing a gel for the topical treatment of acne, said method comprising the steps of:
dissolving chlorocresol in glycerin at a temperature between 50 – 60 ºC;
mixing carbomer and the dissolved chlorocresol in purified water to obtain a carbomer chlorocresol slurry;
filtering the carbomer chlorocresol slurry to obtain a filtered carbomer chlorocresol slurry;
dispersing Microsponge in glycerin;
adding the dispersion of Microsponge and glycerin to the filtered carbomer chlorocresol slurry to obtain a carbomer, Microsponge glycerin slurry;
adding propylene glycol solvent to the carbomer, Microsponge glycerin slurry to obtain carbomer, Microsponge glycerin, propylene glycol slurry;
preparing a solution of lincomycin hydrochloride in purified water;
adding the solution to the carbomer, Microsponge glycerin, propylene glycol slurry to obtain carbomer slurry and lincomycin hydrochloride Microsponges; and
adding sodium hydroxide to neutralize the carbomer slurry and lincomycin hydrochloride Microsponges to obtain said gel.

DETAILED DESCRIPTION OF THE INVENTION
The embodiments herein and the various features and advantageous details thereof are explained with reference to the non-limiting examples in the following description. The examples used herein are intended merely to facilitate an understanding of the ways in which the embodiments herein may be practiced and to further enable those of skill in the art to practice the embodiments herein. Accordingly, the examples should not be construed as limiting the scope of the embodiments herein.

The description herein after, of the specific embodiments will so fully reveal the general nature of the embodiments herein that others can, by applying current knowledge, readily modify and/or adapt for various applications such specific embodiments without departing from the generic concept, and, therefore, such adaptations and modifications should and are intended to be comprehended within the meaning and range of equivalents of the disclosed embodiments. It is to be understood that the phraseology or terminology employed herein is for the purpose of description and not of limitation. Therefore, while the embodiments herein have been described in terms of preferred embodiments, those skilled in the art will recognize that the embodiments herein can be practiced with modification within the spirit and scope of the embodiments as described herein.

The present invention envisages a pharmaceutical composition for the topical treatment of acne. The pharmaceutical composition comprises an antibiotic of the lincomycin family. The antibiotic is entrapped in microsponges to obtain a controlled and sustained release of the drug at the area of treatment. The composition of the present invention is adapted to provide a sustained and controlled release of the drug at the area of application for up to 9 hours, thereby increasing the therapeutic outcome of the drug. The pH of the composition is such as to stabilize the antibiotic over the period during storage. The composition typically has a pH in the range of about 4.6 to about 5.7, more preferably in the range of about 5.2 to about 5.5. The composition prevents undesirable side effects, maintains skin moisture and absorbs excess skin secretions. Also, the composition has a soft feel and enhanced spreadability, and is stable for an extended storage over a broad temperature range.

In an exemplary embodiment of the present invention the antibiotic is lincomycin hydrochloride. The antibiotic is present in an amount in the range of about 0.01 to about 5.0 wt % of the composition. The composition may further comprise one or more secondary active ingredient selected from the group consisting of emollient, essential oil, sunscreen agent, antioxidant, antibacterial agent, bacteriostatic agent, antimicrobial agent, antifungal agent, anti-infective agent, antiseptic agent and anti-inflammatory agent. Preferably, the composition comprises an antimicrobial agent in an amount in the range of about 0.075 to about 1 wt. % of the composition, preferably in the range of about 0.075 to about 0.2 wt. %. The antimicrobial agent is preferably chlorocresol.

The composition of the present invention includes a microsponge delivery system. Microsponge are polymeric delivery system composed of porous microspheres having myriad interconnected voids of particle size in the range of 5 – 300 µm. These porous microspheres can adsorb or load active ingredients in the voids. When applied to the skin, the microsponge drug delivery system releases the drug from the microspheres in a controlled manner for an extended period. The microsponges also absorb skin secretions, thereby reducing oiliness and shine of the skin.

The polymer forming the microsponge system or the polymeric microsponge system is typically present in an amount in the range of about 0.1 to about 2.0 wt. % of the composition, and more preferably in the range of about 0.1 to about 0.5 wt. %. The concentration can be varied depending on the desired composition viscosity. Examples of preferred polymer systems are styrene and divinyl benzene or methyl methacrylate and ethylene glycol dimethacrylate. Polymeric microsponge delivery system available by the brand name “Microsponge 5647 glycerin” is preferably used.

The composition comprises a gelling agent in an amount in the range of about 0.1 to about 15 wt. % of the composition, and more preferably in the range of about 0.5 to about 3 wt%. The gelling agent can be selected from microcrystalline cellulose, colloidal magnesium silicate, hydroxypropyl methyl cellulose, hydroxylated vinylic polymer, carbomer, or mixtures thereof. The carbomer or hydroxylated vinylic polymer are more preferred and can be described generally as interpolymers prepared from a monomeric mixture comprising a mono-olefinic acrylic acid and about 0.1% to about 10 wt. % of the other monomers in the monomeric mixture of polyether of an oligosaccharide having hydroxyl groups which are etherified with allyl groups. The oligosaccharide contains at least two allyl groups per oligosaccharide molecule. Commercially available interpolymers of this type are marketed under the trademark Carbopols®. These are described as being polymers of acrylic acid cross-linked with about 1% of a polyalkyl ether of sucrose having an average of about 5.8 alkyl groups for each sucrose molecule. These polymers have molecular weight in the order of 5. The gelling agent used in the preferred composition may be selected to give products of magnitude of 1,000,000. Such polymers are available under such trademarks as Carbopol® 934, Carbopol® 940 and Carbopol® 941. Closely related copolymers, such as Carbopol® 1342 may be used.

The composition further comprises a pH stabilizing agent in an amount in the range of about 0.1 to about 1.5 wt. % of the composition, and more preferably in the range of about 0.1 to about 0.5 wt. %. A preferred pH stabilizing agent is sodium hydroxide. The pH of the composition is such as to prevent skin irritation and provide improved thermal, physical and chemical stability of the composition.

The composition further comprises a vehicle in an amount in the range of about 5 to about 80 wt. % of the composition. Examples of preferred vehicles include purified water, propylene glycol, glycerin, stearyl alcohol, cetyl alcohol, cetyl-stearyl alcohol, or mixtures thereof, depending on the form of the composition. The composition can be a gel, cream, lotion, suspension, emulsion or ointment.

The composition may further comprise a surface-active agent selected from esters of polyols and sugars, products of condensation of ethylene oxide with fatty acids, fatty alcohols, long-chain alkylphenols, long-chain mercaptans or long-chain amides, polyethers of polyhydroxylated fatty alcohols and alkylpolyglycol ethers, or mixtures thereof. Examples of suitable surface-active agent include dioctyl sodium sulfosuccinate, PEG-100 stearate, cocamidopropyl betaine, lauryl glucoside, and the like.

The composition may further comprise preservatives, essential oils, fragrance, flavoring agent, coloring agent, and the like.

The present invention will now be described with respect to the following non-limiting examples. The examples should not be construed as limiting the scope of the embodiment herein.

Example 1: A gel containing lincomycin hydrochloride antibiotic was prepared in accordance with the present invention.

The antimicrobial agent chlorocresol was dissolved in glycerin at a temperature between 50 – 60 ºC. Carbopol® 934P and the dissolved chlorocresol were mixed together in purified water to obtain carbomer chlorocresol slurry. The carbomer chlorocresol slurry was filtered through sieve size 60 to obtain filtered carbomer chlorocresol slurry. Microsponge 5647 glycerin was dispersed in glycerin. The dispersion of the Microsponge in glycerin was added to filtered carbomer chlorocresol slurry to obtain a carbomer, Microsponge glycerin slurry. Propylene glycol solvent was added to the carbomer, Microsponge glycerin slurry to obtain carbomer, Microsponge glycerin, propylene glycol slurry. A solution of lincomycin hydrochloride was prepared in purified water. The lincomycin hydrochloride solution was added to the carbomer, Microsponge glycerin, propylene glycol slurry to obtain carbomer slurry and lincomycin hydrochloride Microsponges. Finally, sodium hydroxide solution was added to neutralize the carbomer slurry and lincomycin hydrochloride Microsponges and obtain the gel. The composition and characteristics of the gel of Example 1 are given below in Table 1 & 2. The gel so obtained was a soft, translucent and homogenous gel with enhanced viscosity which gave easy applicability.

Table 1: Gel Composition

Sr. No. Ingredient Wt. %
1. Lincomycin Hydrochloride 2.0
2. Carbopol® 934P 2.5
3. Propylene Glycol 10
4. Chlorocresol 0.075
5. Glycerin 15.0
6. Microspore 5647glycerin 0.75
7. Sodium hydroxide 0.1
8. Purified water q.s

Figure 1 of the accompanying drawings illustrates the % drug diffusion with respect to time (in hrs) comparing a typical Lincomycin Hydrochloride gel and the Lincomycin Hydrochloride gel of the Example 1. It is observed that the gel of the present invention provides a controlled drug release over an extended period as compared to a typical Lincomycin Hydrochloride gel. Also, the drug release is sustained for up to 9 hrs.

Table 2: Characteristics of the gel

Sr. No. Characteristic Result
1. pH 5.3 – 5.8
2. Viscosity 1200000 – 1300000 cps
3. Extrudability 15.163 – 18.427 N
4. Spreadability 23 – 32 g cm/sec
5. Drug content 98.5 – 100 %
6. Drug Diffusion Not less than 75% for up to 9 hrs.

From the above analysis, it is observed that the composition of the present invention has enhanced extrudability, spreadability and homogeneity. Also, the composition provides a sustained release of not less than 75% of the drug in a controlled manner for up to 9 hours. The mild composition prevent any undesirable side-effects, skin rashes, skin irritation or skin redness by avoiding over-exposure to the drug, thereby making the composition suitable for daily use even on a sensitive skin.

Further, stability of the composition of the present invention was studied over wide range of temperatures and humidity conditions. The results are enumerated in table 3.

Table 3: Results of stability analysis of the gel

A] At 25 ºC and 60 % RH (relative humidity) -

Parameter Initial 1 month 2 months 3 months 6 months
Active concentration (% w/w) 2.01 2.00 1.99 1.98 1.98
pH 5.89 5.85 5.85 5.83 5.83
Total aerobic count (cfu/g) Less than 10 Less than 10 Less than 10 Less than 10 10
Total fungal count (cfu/g) Less than 10 Less than 10 Less than 10 Less than 10 Less than 10
Microorganisms absent absent absent absent absent
* (Test for Microoganisms includes test for Escherichia coli, Salmonella, Pseudomonas aeruginosa and Staphylococcus aureus)

B] At 30 ºC and 65 % RH -
Parameter Initial 1 month 2 months 3 months 6 months
Active concentration (% w/w) 2.01 2.00 1.99 1.98 1.96
pH 5.89 5.85 5.83 5.83 5.79
Total aerobic count (cfu/g) Less than 10 Less than 10 Less than 10 Less than 10 10
Total fungal count (cfu/g) Less than 10 Less than 10 Less than 10 Less than 10 Less than 10
Microorganisms absent absent absent absent absent

C] At 40 ºC and 75 % RH -
Parameter Initial 1 month 2 months 3 months 6 months
Active concentration (% w/w) 2.01 2.01 2.00 1.98 1.95
pH 5.85 5.85 5.83 5.80 5.76
Total aerobic count (cfu/g) Less than 10 Less than 10 Less than 10 10 10
Total fungal count (cfu/g) Less than 10 Less than 10 Less than 10 Less than 10 Less than 10
Microorganisms absent absent absent absent absent

Example 2: A gel containing lincomycin hydrochloride antibiotic and a cream was prepared in accordance with the present invention. The gel was prepared as explained above in Example 1. The formulation of the cream is given in Table 4.

Table 4: Formulation of cream
Sr. No Ingredient w/w (%)
1. Stearyl alcohol (and) Ceteareth-20 11
2. Cetyl-stearyl alcohol 1.25
3. Alcohol benzoate 5
4. Butylated hydroxyanisole 0.01
5. PEG-100 stearate 0.85
6. Water, deionized or distilled 64
7. Propylene glycol 3
8. Benzoyl peroxide 5
9. Acetone 10
10. Dioctyl Sodium Sulfosuccinate 0.1

The gel composition and the cream formulation may be packed together in two separate containers such that for every approximately 3 cc of the gel approximately 20 grams of cream is dispensed, which composition shall be mixed thoroughly prior to application.

Likewise, a lotion can be used. The formulation of the lotion is given in Table 5.
Table 5: Formulation of lotion

Sr. No. Ingredient w/w (%)
1. Stearyl alcohol (and) Ceteareth-20 5.5
2. Cetyl-stearyl alcohol 0.75
3. Alcohol benzoate 5
4. Butylated hydroxyanisole 0.1
5. PEG-100 stearate 0.25
6. Water, deionized or distilled 70.3
7. Propylene glycol 3.0
8. Benzoyl peroxide 5
9. Acetone 10
10. Dioctyl sodium sulfosuccinate 0.1

The gel composition and the lotion formulation may be packed together in two separate containers such that for every approximately 3 cc of the gel approximately 20 grams of lotion is dispensed, which composition shall be mixed thoroughly prior to application. Alternatively, the composition and the lotion can be applied in a step-wise manner to obtain mixing of the ingredients on the skin.

Throughout this specification the word “comprise”, or variations such as “comprises” or “comprising”, will be understood to imply the inclusion of a stated element, integer or step, or group of elements, integers or steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps.

The use of the expression “at least” or “at least one” suggests the use of one or more elements or ingredients or quantities, as the use may be in the embodiment of the invention to achieve one or more of the desired objects or results.

Any discussion of documents, acts, materials, devices, articles or the like that has been included in this specification is solely for the purpose of providing a context for the invention. It is not to be taken as an admission that any or all of these matters form part of the prior art base or were common general knowledge in the field relevant to the invention as it existed anywhere before the priority date of this application.

The numerical values mentioned for the various physical parameters, dimensions or quantities are only approximations and it is envisaged that the values higher/lower than the numerical values assigned to the parameters, dimensions or quantities fall within the scope of the invention, unless there is a statement in the specification specific to the contrary.

Embodiment of the present invention is applicable over a wide number of uses and other embodiments may be developed beyond the embodiment discussed heretofore. Only the most preferred embodiments and their uses have been described herein for purpose of example, illustrating the advantages over the prior art obtained through the present invention; the invention is not limited to these specific embodiments or their specified uses. Thus, the forms of the invention described herein are to be taken as illustrative only and other embodiments may be selected without departing from the scope of the present invention. It should also be understood that additional changes and modifications, within the scope of the invention, will be apparent to one skilled in the art and that various modifications to the composition described herein may fall within the scope of the invention.