Claims:CLAIMS
I/We Claim,
1. A pharmaceutical composition (310) for penetration of water-insoluble boswellia saratta extracts (410) into skin comprising:
0.1% (w/w) of boswellia sarrata extracts (410) as an anti-inflammatory agent;
0.005% (w/w) of capsaicin (420) as a warming agent imparting warmth;
5% (w/w) of phosphotidyl choline (430) as a bio-lubricant;
5% (w/w) of isopropyl myristate (440) as a topical enhancer;
10% (w/w) of glycerine (450) as a moisturizing agent;
15% (w/w) of polyethylene glycol (460) as a plasticizer;
65% (w/w) of ethyl alcohol (470) as a diluting agent; and
0.01% (w/w) of simethicone (480) as a non-sticky agent,
wherein the phosphotidyl choline (430) reduces the particle size of the boswellia saratta extracts (410) in presence of the isopropyl myristate (440) on sonicating resulting the penetration of water-insoluble boswellia saratta extracts (410) into skin.
2. The pharmaceutical composition of claim 2, wherein the sonication is carried out at 50000 watts to obtain nano-scale sized particles of the boswellia sarrata extracts and the topical enhancer, bio-lubricants and other ingredients of the pharmaceutical composition makes the boswellia sarrata extracts soluble and gets infused when administered topically.
3. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition further comprises a therapeutic drug along with supplementary agents for topical administration.
4. A method (201) of preparing a pharmaceutical composition (310) for transdermal drug delivery comprising:
taking boswellia serrata extracts (210) as anti-inflammatory agent;
adding capsaicin (220) as a warming agent;
adding phosphotidyl choline (230) as a bio-lubricant;
adding isopropyl myristate (240) as a topical enhancer;
adding a mixture (250) of glycerine, ethyl alcohol and polyethylene glycol;
incorporating simethicone (260) as a non-sticky agent; and
sonicating (270) the mixture to obtain a clear solution, wherein the boswellia saratta extract penetrates through the skin when the composition (310) is sprayed and adhered onto a topical surface of the skin.
5. A method, system, device and apparatus comprising one or more features described in one or more sections of the specification.

Date: 05-10-2018 Signature………………………
, Description:Form 2
The Patent Act 1970
(39 of 1970)
AND
Patent Rules 2003
Complete Specification
(Sec 10 and Rule 13)

Title A Method and Composition for Transdermal Drug Delivery in Animals for Osteoarthritis
Applicant(s) Stabicon Life Sciences Pvt Ltd
Nationality India
Address #28, Bommasandra Industrial Area (Sub Layout), 4th Phase, Jigani Hobli, Anekal Taluk, Bengaluru – 560100, Karnataka, India

The following specification, particularly describes the invention and the manner in which it is to be performed.

DESCRIPTION
FIELD OF INVENTION
[0001] Embodiments of the present disclosure relate to a pharmaceutical composition and in particular relates to a method and composition for transdermal drug delivery in animals.
RELATED ART
[0002] A variety of anti-inflammatory and other therapeutic drugs are available in the prior art which are being used for reducing osteoarthritis and muscular pains in animals through transdermal drug delivery methods. The skin acts as a barrier for the drug to penetrate thereby limiting topical and transdermal bioavailability. Skin penetration enhancement techniques have been developed to improve bioavailability of a drug as the topical and transdermal drug delivery is a viable option.
[0003] In animals the thickness of the skin is more when compared to human beings which takes more time for the drug to reach a desired site of action through topical administration. Further, it is harmful to a caretaker from the animal as it may not allow the caretaker to touch the inflammatory region for topical administration of the drug.
[0004] Conventionally, Boswellia extracts are one of the active ingredient being used in a variety of therapeutic drugs due to its anti-inflammatory and analgesic properties. However, the Boswellia extracts are insoluble in water and other commonly used solvents in pharmaceutical industry which leads to poor therapeutic actions and less bioavailability to act at the desired site of action.
[0005] The prior art EP2149378 discloses topical formulations for the symptomatic treatment of musculoskeletal disorders, US20160030498 discloses herbal compositions for treating pain and skin disorders, US9795631 discloses a composition and method to alleviate joint pain using low molecular weight hyaluronic acid and astaxanthin.
[0006] Further, the patent WO2011030021 discloses animal or human health food supplement for relieving and supporting joints, WO2008036932 discloses compositions and methods comprising boswellia species and the patent US20160243057 discloses methods of stabilizing the extracellular matrix and compositions therefor.
[0007] Hence, a pharmaceutical composition with solubilized Boswellia extracts providing increased therapeutic efficacy of the drug through transdermal delivery in animals is required.
SUMMARY
[0008] According to an aspect of the present disclosure, a pharmaceutical composition (310) for penetration of water-insoluble boswellia saratta extracts (410) into skin comprising 0.1% (w/w) of boswellia sarrata extracts (410) as an anti-inflammatory agent, 0.005% (w/w) of capsaicin (420) as a warming agent imparting warmth, 5% (w/w) of phosphotidyl choline (430) as a bio-lubricant, 5% (w/w) of isopropyl myristate (440) as a topical enhancer, 10% (w/w) of glycerine (450) as a moisturizing agent, 15% (w/w) of polyethylene glycol (460) as a plasticizer, 65% (w/w) of ethyl alcohol (470) as a diluting agent, and 0.01% (w/w) of simethicone (480) as a non-sticky agent, wherein the phosphotidyl choline (430) reduces the particle size of the boswellia saratta extracts (410) in presence of the isopropyl myristate (440) on sonicating resulting the penetration of water-insoluble boswellia saratta extracts (410) into skin.
[0009] In an embodiment, a method (201) of preparing a pharmaceutical composition (310) for transdermal drug delivery comprising taking boswellia serrata extracts (210) as anti-inflammatory agent, adding capsaicin (220) as a warming agent, adding phosphotidyl choline (230) as a bio-lubricant, adding isopropyl myristate (240) as a topical enhancer, adding a mixture (250) of glycerine, ethyl alcohol and polyethylene glycol, incorporating simethicone (260) as a non-sticky agent and sonicating (270) the mixture to obtain a clear solution, wherein the boswellia saratta extract penetrates through the skin when the composition (310) is sprayed and adhered onto a topical surface of the skin.
[0010] Several aspects are described below, with reference to diagrams. It should be understood that numerous specific details, relationships, and methods are set forth to provide full understanding of the present disclosure. Skilled personnel in the relevant art, however, will readily recognize that the present disclosure can be practiced without one or more of the specific details, or with other methods, etc. In other instances, well-known structures or operations are not shown in detail to avoid obscuring the features of the present disclosure.
BRIEF DESCRIPTION OF DRAWINGS
[0011] FIG. 1A through 1C are the block diagrams illustrating conventional transdermal drug delivery system in an example.
[0012] FIG. 1D is a diagram illustrating osteoarthritis in an example.
[0013] FIG. 2 is a flowchart illustrating the steps involved in preparing a pharmaceutical composition for topical administration in animals in an embodiment of the present disclosure.
[0014] FIG. 3A and 3B are the diagrams illustrating the transdermal application of the pharmaceutical composition of the present disclosure.
[0015] FIG. 4 is a table illustrating the components present in the pharmaceutical composition of the present disclosure in an example.
DETAILED DESCRIPTION OF THE PREFERRED EXAMPLES
[0016] FIG. 1A through 1C are the block diagrams illustrating conventional transdermal drug delivery system in an example. FIG. 1A is a diagram illustrating the routes of administering a drug through skin in an example. As shown there, the drug may be administered into the body intercellularly (102) through sweat pores on the skin in an example. In another example, the drug may be penetrated through the follicular spaces (104) present on the skin which makes the drug to allow inside the body through epidermis (106). In yet another example, the drug may be administered through transcellular mechanism (108) (intracellular) i.e., passing through the cells present in the epidermis.
[0017] FIG. 1B is a diagram illustrating conventional drugs that are used in transdermal drug delivery in an example. As shown there, 110 represents a transdermal patch that is embedded with a desired drug which gradually releases over a period of time. The conventionally available patches are water resistant and may be applied onto the skin for at least 48 hours to achieve a sustained release of drug into the body. The active components i.e., the drug present in the patch slowly enters the blood stream through skin. Similar to the patches, a variety of topical drug formulations have been developed by the researchers which comprises a semisolid therapeutic paste like substance (112), an aqueous oil (114) and a semisolid gel (116) that are applied topically onto the skin. In an example, conventional topical drugs need to be spread over the affected area in order to get immediate relief from the inflammation.
[0018] FIG. 1C is a block diagram illustrating the passage of the drug through skin barrier into blood stream in an example. As shown there, the drug is administered onto the skin 101 by using any conventional topical drug formulation (as shown in 110 through 116). Once the drug is administered onto the skin 101, it starts penetrating into the body either intercellular or intracellular mechanism but not limited to the follicular spaces as discussed in the FIG. 1A in various routes 118. The drug thus enters into the blood stream through epidermis 106 and reaches the site of action to perform the desired action. However, the penetration of drug through skin barrier is difficult as the drug formulation affects the lubrication and passage into the body through epidermis 106. Further, all conventional drugs are not soluble in majority of the solvents that are being used in the drug formulations which hinders the application of topical drug administration. Hence, a pharmaceutical composition is disclosed in the present disclosure which enhances solubility and in turn topical absorption of the drug or active components in the composition.
[0019] FIG. 1D is a diagram illustrating osteoarthritis in an example. As shown there, cartilage (122) which is a hard and slippery tissue at joints on tip of the bones (120A and 120B) gets damaged over a period of time due to various factors but not limited to aging, injury and the like. The cartilage further disrupted into fragments progressively with the movement of bones (120A and 120B). Conventionally, this disruption due to movement of bones is reduced by surgical procedures or medicaments through oral administration and conventional drug delivery methods. However, the topical administration of drug especially for osteoarthritis is not efficient as the drugs such as Boswellia serrata extracts are insoluble not able to reach the site of action when topically administered. Hence, a pharmaceutical composition that makes the insoluble drugs such as Boswellia serrata extracts gets solubilized and reach the site of action by penetrating through the skin is disclosed in the present disclosure.
[0020] FIG. 2 is a flowchart illustrating the steps involved in preparing a pharmaceutical composition for topical administration of a drug in animals in an embodiment of the present disclosure. In step 210, Boswellia serrata extracts are taken and used as a therapeutic drug for the topical administration in animals. The Boswellia serrata extracts are insoluble in water and majority of the solvents used in drug formulations resulting in poor absorption through topical administration due to its poor solubility. In an embodiment, the Boswellia extracts are procured commercially and diluted using a solvent for example, ethyl alcohol to obtain 0.1% w/w Boswellia extracts. In another example, any water insoluble drug may be incorporated into the pharmaceutical composition of the present disclosure but not limited to a single active ingredient.
[0021] In step 220, capsaicin is added to the diluted Boswellia extracts and mixed vigorously to obtain a uniform mixture. In an embodiment, 90% of capsaicin is used which is extracted from capsicum. The capsaicin is soluble in alcohol and becomes warm when applied onto the skin. This warmth helps in penetration of drug into skin along with a topical enhancer in transdermal drug delivery.
[0022] In step 230, Phosphotidyl choline is added to the mixture of boswellia extracts and the capsaicin. The phosphotidyl choline is a liposome that acts as a bio-lubricant due to the combination of phosphor and lipid components in it. In an embodiment, 5% phosphotidyl choline is prepared using ethyl alcohol and is used as the bio-lubricant around the joints for topical administration of Boswellia extracts in animals.
[0023] In step 240, isopropyl myristate is added and incubated for a predetermined period of time at room temperature. In an embodiment, isopropyl myristate acts as the topical enhancer making the Boswellia extracts solubilise so that it is able to penetrate through the skin.
[0024] In step 250, a homogenous mixture is prepared and added to the composition obtained from the step 240. The homogenous mixture is prepared by mixing glycerine, ethyl alcohol and polyethylene glycol (PEG 1500). This homogenous mixture is then added to the composition obtained from the step 240. In an embodiment, 10% glycerine is used as a moisturizer to prevent the composition getting dried besides decreasing itchiness and flaking if any when applied on the skin. Further, 65% ethyl alcohol and 15% PEG 1500 acts as an adherent as well as plasticizer for forming a film when applied onto the skin of an animal.
[0025] In step 260, simethicone is added to the mixture to obtain a uniform and smooth fluid like solution. In an embodiment, the 0.01% simethicone is used which acts as a lubricant and non-sticky agent. Simethicone makes the composition smoother and non-sticky.
[0026] In step 270, the mixture is finally sonicated with all the components using a conventional sonicating device. In an embodiment, the sonication is performed up to 50000 watts at regular intervals of time in a sequence of 10 seconds and 30 seconds repetitively until 50000 watts is achieved. Sonication of the mixture reduces the particle size of the Boswellia extracts in the mixture into nano-scale sized particles. This enables the Boswellia extracts to get solubilized and penetrate easily into the skin when applied onto the animal skin topically.
[0027] In step 280, the sonicated mixture is then cooled to room temperature and incubated for a predetermined period of time. This mixture is then further centrifuged to obtain a clear transparent solution which is used as the pharmaceutical composition of the present disclosure.
[0028] FIG. 3A and 3B are the diagrams illustrating the transdermal application of the pharmaceutical composition of the present disclosure. As shown in the figure, the pharmaceutical composition 310 of the present disclosure is canned into a bottle or a container 320 after the sonication process similar to the method as discussed in FIG. 2. The pharmaceutical composition may comprise plurality of active ingredients besides the Boswellia extracts and isopropyl myristate. This solution may be sprayed onto the skin 330 of an animal at the site of action such that the Boswellia extracts and other active ingredients gets absorbed into the skin 330 through transdermal routes of administration as discussed in the FIG. 1A. As the smearing or spreading is not required after spraying the pharmaceutical composition, there is no change in the comfort levels of the animal causing harm to the caretaker. After spraying the pharmaceutical composition onto the skin, it gets dried and adhered onto the skin immediately due to the PEG 1500 used in the composition. As the composition is adhered to the skin, the drug i.e., Boswellia extracts slowly penetrates the skin of animal to act at the site of action. FIG. 3B is a diagram illustrating the cartilage (340) disruption due to the movements of bone is reduced by incorporating the pharmaceutical composition of the present disclosure. The nanoparticle sized Boswellia extracts and other components in the pharmaceutical composition 310 gets penetrated into the skin and enters the cartilage area in a joint as shown in the figure. The pharmaceutical composition 310 acts as a bio-lubricant and reduces a friction generated between the bones 350A and 350B. Thus, the pharmaceutical composition enables the transdermal delivery of Boswellia extracts for osteoarthritis in animals.
[0029] FIG. 4 is a table illustrating the components present in the pharmaceutical composition of the present disclosure in an example. The pharmaceutical composition of the present disclosure comprises 0.1% (w/w) of Boswellia serrata extracts as active ingredient of therapeutic drug, 0.005% (w/w) of capsaicin as a warming agent, 5% (w/w) of phosphotidyl choline as a bio-lubricant, 5% (w/w) of isopropyl myristate as a topical enhancer, 10% (w/w) glycerine, 15% (w/w) PEG 1500, 65% (w/w) ethyl alcohol and 0.01% (w/w) simethicone. In an embodiment, conventional anti-inflammatory agents with analgesic properties may be added as a therapeutically active ingredient in the pharmaceutical composition of the present disclosure. The pharmaceutical composition comprising the solubilized Boswellia extracts increases therapeutic efficacy of the drug through transdermal delivery in animals.
[0030] While various embodiments of the present disclosure have been described above, it should be understood that they have been presented by way of example only, and not limitation. Thus, the breadth and scope of the present disclosure should not be limited by any of the above-discussed embodiments but should be defined only in accordance with the following claims and their equivalents.
CLAIMS
I/We Claim,
1. A pharmaceutical composition (310) for penetration of water-insoluble boswellia saratta extracts (410) into skin comprising:
0.1% (w/w) of boswellia sarrata extracts (410) as an anti-inflammatory agent;
0.005% (w/w) of capsaicin (420) as a warming agent imparting warmth;
5% (w/w) of phosphotidyl choline (430) as a bio-lubricant;
5% (w/w) of isopropyl myristate (440) as a topical enhancer;
10% (w/w) of glycerine (450) as a moisturizing agent;
15% (w/w) of polyethylene glycol (460) as a plasticizer;
65% (w/w) of ethyl alcohol (470) as a diluting agent; and
0.01% (w/w) of simethicone (480) as a non-sticky agent,
wherein the phosphotidyl choline (430) reduces the particle size of the boswellia saratta extracts (410) in presence of the isopropyl myristate (440) on sonicating resulting the penetration of water-insoluble boswellia saratta extracts (410) into skin.
2. The pharmaceutical composition of claim 2, wherein the sonication is carried out at 50000 watts to obtain nano-scale sized particles of the boswellia sarrata extracts and the topical enhancer, bio-lubricants and other ingredients of the pharmaceutical composition makes the boswellia sarrata extracts soluble and gets infused when administered topically.
3. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition further comprises a therapeutic drug along with supplementary agents for topical administration.
4. A method (201) of preparing a pharmaceutical composition (310) for transdermal drug delivery comprising:
taking boswellia serrata extracts (210) as anti-inflammatory agent;
adding capsaicin (220) as a warming agent;
adding phosphotidyl choline (230) as a bio-lubricant;
adding isopropyl myristate (240) as a topical enhancer;
adding a mixture (250) of glycerine, ethyl alcohol and polyethylene glycol;
incorporating simethicone (260) as a non-sticky agent; and
sonicating (270) the mixture to obtain a clear solution, wherein the boswellia saratta extract penetrates through the skin when the composition (310) is sprayed and adhered onto a topical surface of the skin.
5. A method, system, device and apparatus comprising one or more features described in one or more sections of the specification.

Date: 05-10-2018 Signature………………………
A METHOD AND COMPOSITION FOR TRANSDERMAL DRUG DELIVERY IN ANIMALS FOR OSTEOARTHRITIS
ABSTRACT
A pharmaceutical composition (310) for penetration of water-insoluble boswellia saratta extracts (410) into skin comprising 0.1% (w/w) of boswellia sarrata extracts (410) as an anti-inflammatory agent, 0.005% (w/w) of capsaicin (420) as a warming agent imparting warmth, 5% (w/w) of phosphotidyl choline (430) as a bio-lubricant, 5% (w/w) of isopropyl myristate (440) as a topical enhancer, 10% (w/w) of glycerine (450) as a moisturizing agent, 15% (w/w) of polyethylene glycol (460) as a plasticizer, 65% (w/w) of ethyl alcohol (470) as a diluting agent, and 0.01% (w/w) of simethicone (480) as a non-sticky agent, wherein the phosphotidyl choline (430) reduces the particle size of the boswellia saratta extracts (410) in presence of the isopropyl myristate (440) on sonicating resulting the penetration of water-insoluble boswellia saratta extracts (410) into skin.