Indian Patents. 233620:" A COMPOSITION FOR USE AS A CARRIER IN TRANSDERMAL DRUG DELIVERY "

Title of Invention	" A COMPOSITION FOR USE AS A CARRIER IN TRANSDERMAL DRUG DELIVERY "
Abstract	A composition for use as a carrier in transdermal drug delivery such as nitroglycerin consisting of 43-52% w/w surfactant such as lecithin and co-surfactant such as lower alcohol (normal propanol) mixed together in the ratio of 18-22:25-30%, 30-38% w/w water and 19-25% w/w of oil in he form of microemulsion.

Full Text	This invention relates to a composition for use as a carrier in transdermal drug delivery for example nitroglycerin and a process for the preparation thereof. The transdermal drug delivery is as such known in the art for delivering the drug continuously into the body of a patient at a programmed rate through the intact skin. Drug administration by conventional means often has harmful side effects and one of the major problems in using the transdermal drug delivery is the selective barrier property of the skin. The greatest obstacle is the stratum corneum, the thin outermost and least permeable layer of the skin. A number of carriers/drug penetration enhancers are as such known in the art to reduce the barrier property of the stratum comeum. The known penetration enhancers are 1) Silicon oil, 2) Platicized poly (vinyl) pyrrolidon poly vinyl alcohol and drug mixture, 3) Mixed isobutalene 4) Cross linked silicon rubber, 5) Plasticized poly vinyl chloride, for the nitroglycerin. There are disadvantages associated with the earlier enhancer as such known in the art. One of the main disadvantages is that the conventional transdermal patches for nitroglycerin have long on set time of the drug action as well as it requires a high dose/concentration of drug. In the known art an enhancer together with the drug (nitroglycerin) is mixed together to form the ointment and patches of this drug are applied over the skin of the patient. Another disadvantage is that the known compositions as an enhancer for nitroglycerin are not transparent. Still another disadvantage is that the known compositions do not posses low viscosity and they have poor spreadability for applying the same to the large surface of the skin. Therefore, the main object of this invention is to propose an isotropic and biocompatible formulation, which acts as an effective penetration enhancer and a better reservoir to solublize, the nitroglycerin, which is safe to the skin also. Another object of this invention is to propose a composition for use as a carrier in transdermal drug delivery for example nitroglycerin and a process for the preparation thereof, which can be used on the skin of the patient easily for administering the drug into the body of the patient. Yet another object of this invention is to propose a composition for use as a carrier in transdermal drug delivery for example nitroglycerin and a process for the preparation thereof, which is an isotropic and thermodynamic stable composition. Still another object of this invention is to propose a composition for use as a carrier in transdermal drug delivery for example nitroglycerin and a process for the preparation thereof, which reduces onset time of the drug action remarkably. A further object of this invention is to propose a composition for use as a carrier in transdermal drug delivery for example nitroglycerin and a process for the preparation thereof, which provide high skin flux of drug at even low doses of the nitroglycerin. According to this invention there is provided a process for preparing a composition for use as a carrier in transdermal drug delivery for example nitroglycerin comprising in the steps of mixing 43-52% w/w surfactant such as lecithin and co-surfactant such as lower alcohol (normal propanol), 30-38% w/w water and 19-25% w/w of oil mixed together in the form of microemultion. Further according to this invention there is provided a composition for use as a carrier in transdermal drug delivery for example nitroglycerin comprising 43-52% w/w surfactant such as lecithin and co-surfactant such as lower alcohol (normal propanol), 30-38% w/w water and 19-25% w/w of oil mixed together in the form of microemultion. In accordance with this invention 43-52% w/w of surfactant and co-surfactant is mixed with 30-38% w/w of water and 19-25% w/w of oil (isopropyl myristate) in order to prepare a microemulsion. The surfactant and co-surfactant comprises lecithin and lower alcohol (normal propanol) respectively. The oil used for the preparation of the above composition is biocompatible oil for example isopropyl myristate. Further in accordance with the process of this invention the surfactant (lecithin) and co-surfactant (normal propane) are mixed together in the ratio of 18-22:25-30% w/w respectively. 19-25% w/w of an oil e.g. isopropyl myristate is added to said mixture at room temperature, 30-38% w/w water is then added under sonication to said mixture upto one hour to get the microemulsion as the carrier. The composition exhibits synergism. A composition for use as a carrier in transdermal drug delivery for example nitroglycerin is herein described and illustrated herein with reference to the following examples: EXAMPLE 1. 12 gen lacithin was mixed with 15 gm normal propanol and the mixture was dissolved in 14 gms isopropyl myristate oil at room temperature. 12 gm Mater Mas added to said solution under sonication in a period of 30 minutes to get the carrier micro-emulsion. To this carrier composition 400 mg of nitro glycerine (10% nitroglycerin in lactose) Mas added after dissolving the same in the above quantity of Mater being addes under sonication. A. The drug formulation so obtained Mas tested in- vitro on mice skin for the transdermal permiation of the drug (nitroglycerin) at 37°C. The skin flux Mas found to o be 154 B. The above drug formulation Mas also tested on in- vivo experiment an rabit. The permiation of drug Mas determined by measuring fall in blood pressure of thw rabit. It was found that on set time Mas 4—5 minute* and attain zero order release within 15 minutes of application of the formulation. The average fall in blood pressure was 15% within the above time. From preliminary toxicological studies, it has been found that drug formulation is safe to the akin. EXAMPLE 2 8 gm lacithin was mixed with 9 gm normal propanol and the mixture was dissolved in 22 gms isopropyl myristate oil at room temperature. 8 gm water was added to naid solution under sonication in a period of 3B minuten to get the carrier micro-emulsion. To this carrier composition 250 mg of nitro glycerine (1(9% nitroglycerin in lactose) was added after dissolving the same in the above quantity of water being addes under sonication. A. The drug formulation so obtained was tested in— vitro on mice skin for the transdermal permiation of the drug (nitroglycerin) at 37°C. The skin flux was found to 2 be 11^0.6 microgram/cm 7hr. B. The above drug formulation was also tested on in— vivo experiment on rabit. The permiation of drug was determined by measuring fall in blood pressure of the rabit. It was found that on set time was 4-5 minutes and attain zero order release within 15 minutes of application of the formulation. The average fall in blood pressure was 12X with the above time from preliminary. It has been found from preliminary toxicological studies that drug formulation is safe to the skin. WE CLAIM: 1. A composition for use as a carrier in transdermal drug delivery such as nitroglycerin consisting of 43-52% w/w surfactant such as lecithin and co-surfactant such as lower alcohol (normal propanol) mixed together in the ratio of 18-22:25-30%, 30-38% w/w water and 19-25% w/w of oil in the form of microemulsion. 2. A composition as claimed in claim 1 wherein said oil comprises biocompatible oil such as isopropyl myristate oil. 3. A composition for use a carrier in transdermal drug delivery substantially as herein described and illustrated.

Full Text

This invention relates to a composition for use as a carrier in transdermal drug delivery for example nitroglycerin and a process for the preparation thereof.
The transdermal drug delivery is as such known in the art for delivering the drug continuously into the body of a patient at a programmed rate through the intact skin. Drug administration by conventional means often has harmful side effects and one of the major problems in using the transdermal drug delivery is the selective barrier property of the skin. The greatest obstacle is the stratum corneum, the thin outermost and least permeable layer of the skin. A number of carriers/drug penetration enhancers are as such known in the art to reduce the barrier property of the stratum comeum. The known penetration enhancers are 1) Silicon oil, 2) Platicized poly (vinyl) pyrrolidon poly vinyl alcohol and drug mixture, 3) Mixed isobutalene 4) Cross linked silicon rubber, 5) Plasticized poly vinyl chloride, for the nitroglycerin.
There are disadvantages associated with the earlier enhancer as such known in the art. One of the main disadvantages is that the conventional transdermal patches for nitroglycerin have long on set time of the drug action as well as it requires a high dose/concentration of drug. In the known art an enhancer together with the drug (nitroglycerin) is mixed together to form the ointment and patches of this drug are applied over the skin of the patient.
Another disadvantage is that the known compositions as an enhancer for nitroglycerin are not transparent.
Still another disadvantage is that the known compositions do not posses low viscosity and they have poor spreadability for applying the same to the large surface of the skin.
Therefore, the main object of this invention is to propose an isotropic and biocompatible formulation, which acts as an effective penetration enhancer and a better reservoir to solublize, the nitroglycerin, which is safe to the skin also.
Another object of this invention is to propose a composition for use as a carrier in transdermal drug delivery for example nitroglycerin and a process for the preparation thereof, which can be used on the skin of the patient easily for administering the drug into the body of the patient.
Yet another object of this invention is to propose a composition for use as a carrier in transdermal drug delivery for example nitroglycerin and a process for the preparation thereof, which is an isotropic and thermodynamic stable composition.
Still another object of this invention is to propose a composition for use as a carrier in transdermal drug delivery for example nitroglycerin and a process for the preparation thereof, which reduces onset time of the drug action remarkably.
A further object of this invention is to propose a composition for use as a carrier in transdermal drug delivery for example nitroglycerin and a process for the preparation thereof, which provide high skin flux of drug at even low doses of the nitroglycerin.
According to this invention there is provided a process for preparing a composition for use as a carrier in transdermal drug delivery for example nitroglycerin comprising in the steps of mixing 43-52% w/w surfactant such as lecithin and co-surfactant such as lower alcohol (normal propanol), 30-38% w/w water and 19-25% w/w of oil mixed together in the form of microemultion.
Further according to this invention there is provided a composition for use as a carrier in transdermal drug delivery for example nitroglycerin comprising 43-52% w/w surfactant such as lecithin and co-surfactant such as lower alcohol (normal propanol), 30-38% w/w water and 19-25% w/w of oil mixed together in the form of microemultion.
In accordance with this invention 43-52% w/w of surfactant and co-surfactant is mixed with 30-38% w/w of water and 19-25% w/w of oil (isopropyl myristate) in order to prepare a microemulsion. The surfactant and co-surfactant comprises lecithin and lower alcohol (normal propanol) respectively. The oil used for the preparation of the above composition is biocompatible oil for example isopropyl myristate.
Further in accordance with the process of this invention the surfactant (lecithin) and co-surfactant (normal propane) are mixed together in the ratio of 18-22:25-30% w/w respectively. 19-25% w/w of an oil e.g. isopropyl myristate is added to said mixture at room temperature, 30-38% w/w water is then added under sonication to said mixture upto one hour to get the microemulsion as the carrier.
The composition exhibits synergism.
A composition for use as a carrier in transdermal drug
delivery for example nitroglycerin is herein described
and illustrated herein with reference to the following
examples:
EXAMPLE 1.
12 gen lacithin was mixed with 15 gm normal propanol and
the mixture was dissolved in 14 gms isopropyl myristate
oil at room temperature. 12 gm Mater Mas added to said
solution under sonication in a period of 30 minutes to
get the carrier micro-emulsion.
To this carrier composition 400 mg of nitro glycerine
(10% nitroglycerin in lactose) Mas added after
dissolving the same in the above quantity of Mater being
addes under sonication.
A. The drug formulation so obtained Mas tested in-
vitro on mice skin for the transdermal permiation of the
drug (nitroglycerin) at 37°C. The skin flux Mas found to
o be 154 B. The above drug formulation Mas also tested on in-
vivo experiment an rabit. The permiation of drug Mas
determined by measuring fall in blood pressure of thw rabit. It was found that on set time Mas 4—5 minute* and attain zero order release within 15 minutes of application of the formulation. The average fall in blood pressure was 15% within the above time. From preliminary toxicological studies, it has been found that drug formulation is safe to the akin.
EXAMPLE 2
8 gm lacithin was mixed with 9 gm normal propanol and the mixture was dissolved in 22 gms isopropyl myristate oil at room temperature. 8 gm water was added to naid solution under sonication in a period of 3B minuten to get the carrier micro-emulsion.
To this carrier composition 250 mg of nitro glycerine (1(9% nitroglycerin in lactose) was added after dissolving the same in the above quantity of water being addes under sonication.
A. The drug formulation so obtained was tested in— vitro on mice skin for the transdermal permiation of the
drug (nitroglycerin) at 37°C. The skin flux was found to
2 be 11^0.6 microgram/cm 7hr.
B. The above drug formulation was also tested on in— vivo experiment on rabit. The permiation of drug was determined by measuring fall in blood pressure of the rabit. It was found that on set time was 4-5 minutes and attain zero order release within 15 minutes of application of the formulation. The average fall in blood pressure was 12X with the above time from preliminary. It has been found from preliminary toxicological studies that drug formulation is safe to the skin.

WE CLAIM:
1. A composition for use as a carrier in transdermal drug delivery such as nitroglycerin consisting of 43-52% w/w surfactant such as lecithin and co-surfactant such as lower alcohol (normal propanol) mixed together in the ratio of 18-22:25-30%, 30-38% w/w water and 19-25% w/w of oil in the form of microemulsion.
2. A composition as claimed in claim 1 wherein said oil comprises biocompatible oil such as isopropyl myristate oil.
3. A composition for use a carrier in transdermal drug delivery substantially as herein described and illustrated.

Documents:

820-DEL-2003-Abstract-(27-03-2009).pdf

820-DEL-2003-Abstract-16-01-2008.pdf

820-del-2003-abstract.pdf

820-DEL-2003-Claims-(27-03-2009).pdf

820-DEL-2003-Claims-16-01-2008.pdf

820-del-2003-claims.pdf

820-del-2003-complete specification (granted).pdf

820-DEL-2003-Correspondence-Others-16-01-2008.pdf

820-del-2003-correspondence-others.pdf

820-del-2003-description (complete)-(27-03-2009).pdf

820-del-2003-description (complete).pdf

820-DEL-2003-Description (Complete)16-01-2008.pdf

820-DEL-2003-Form-1-(27-03-2009).pdf

820-del-2003-form-1.pdf

820-del-2003-form-18.pdf

820-DEL-2003-Form-2-16-01-2008.pdf

820-del-2003-form-2.pdf

820-DEL-2003-Form-3-16-01-2008.pdf

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Patent Number

233620

Indian Patent Application Number

820/DEL/2003

PG Journal Number

18/2009

Publication Date

01-May-2009

Grant Date

31-Mar-2009

Date of Filing

19-Jun-2003

Name of Patentee

JAMIA HAMDARD ( HAMDARD UNIVERSITY)

Applicant Address

HAMDARD NAGAR, NEW DELHI-110062, INDIA.

Inventors:

#	Inventor's Name	Inventor's Address
1	MANOJ VARSHNEY	DEPARTMENT OF CHEMISTRY, FACULTY OF SCIENCE, HAMDARD UNIVERSITY, HAMDARD NAGAR, NEW DELHI-110062, INDIA.
2	MOHD. CHANGEZ	DEPARTMENT OF CHEMISTRY, FACULTY OF SCIENCE, HAMDARD UNIVERSITY, HAMDARD NAGAR, NEW DELHI-110062, INDIA.

PCT International Classification Number

A61K 47/00

PCT International Application Number

N/A

PCT International Filing date

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1			NA