Title of Invention

"POLYMERIC DIFFUSIN MATRIX CONTAINING A POTASSIUM CHANNEL OPENER"

Abstract This invention relates to polymeric diffusion matrix containing a potassium channel opener for sustained and controlled release of a potassium channel opener in order to transdermally deliver said potassium channel opener to a patient and provide said patient with an antihypertensive effect, said matrix comprising 0% to 10% by weight of a plasticizer selected from dibutylphthalate and polyethylene glycol, 20% to 80% by weight of a polymer solution prepared from PVPK-30, polyvinyl acetate eudragit RL PO, eudragit RS PO, eudragit E-100, eduragit RL30D, ethyl cellulose, cellulose acetate, eudragit RL PM, and eudragit RS PM present singularly or in any combination, 5% to 10% by weight of a penetration promoter selected from dimethylsulfoxide and d-limonene and a pharmaceutically effective amount of pinacidil monohydrate to provide a sustained and controlled release of said pinacidil over a prolonged period.
Full Text FIELD OF INVENTION
The present invention relates to a polymeric diffusion matrix containing a potassium channel opener. More specifically, the invention relates to a polymeric diffusion matrix containing pinacidil monohydrate characterized by a controlled and sustained release of pinacidil.
PRIOR ART
Polymeric diffusion matrices containing active ingredient have been described many times in the literature and in patents. These matrices can be differentiated for example according to their composition and construction. These matrices are usually constructed by homogenous dispersion of active ingredient in a polymer blend or gel matrix. In this case, the polymer matrix or gel matrix ideally has self-adhesive properties so that there is no need of fixing the matrix on the skin by additional application of an adhesive layer. The active ingredient is usually blended homogenously in the polymer matrix or gel matrix by dissolving, dispersing, suspending extruding, kneading, mixing or similar processes, in some cases at elevated temperature.
U.S. Patent 4,291,014 describes a polymeric diffusion matrix for the sustained release of estradiol diacetate by delivery to a patient requiring uterine wall maintenance or other types of estrogen therapy wherein the matrix comprises a polar plasticizer, polyvinylalcohal, polyvinylpyrrolidine and a pharmaceutically effective amount of estradiol diacetate to provide a sustained release of estradiol for the treatment and prevention of diseases associated with estradiol deficiency.
U.S. Patent 4,921,015 claims a self supporting polymeric diffusion matrix containing a vasoliator for sustained release of vasodilator e.g. trinitroglycerol. The matrix composed of about equal parts of water and glycerol, about 7% by weight polyvinylalcohol having a moiecular weight of about 1.15000, about 5% by weight polyvinylpyrrolidone having a molecular weight of about 40000 and a pharmaceutically effective amount of trinitroglycerol.
U.S. Patent 4,292,301 mentions a self supporting polymeric diffusion matrix for the sustained release of ephedrine in order to transdermally deliver said ephedrine to a patient for decongestant effect, the matrix comprising from about 2 to about 60% of a polar plasticizer, from about 6 to about 20% by weight polyvinylalcohol, from about 2 to about 10% by weight polyvinylpyrrolidone and a pharmaceutically effective amount of ephedrine to be provided a sustained release of the drug over a prolonged period.
U.S. Patent 4,29,2302 proposes a self supporting polymeric diffusion matrix for the sustained release of terbutaline in order to transdermally deliver terbutaline to a patient for bronchodilator effect, the matrix comprising from about 2 to about 60% of a polar plasticizer, from about 6 to about 20% by weight polyvinyl alcohol, from about 2 to 10% by weight polyvinylpyrrolidone and a pharmaceutically effective amount of terbutaline to provide a sustained release of the drug over a prolonged period.
U.S. Patent 4. 29,2303 discloses a self supporting polymeric diffusion matrix for sustained release of clonidine in order to transdermally deliver clonidine to a patient and to provide the said patient with an antihypertersive effect, the said matrix comprising from about 2 to about 60% of a polar plasticizer from about 6 to about 20% by weight polyvinylalcohol, from about 2 to 10% by weight polyvinylpyrrolodone, and a pharmaceutically effective amount of clonidine to provide a sustained release of said clonidine over a prolonged period. The polar plasticizer is glycerol.
However, we could not find under the patents granted and patents applications currently filed in India or abroad and in the prior art literature, any claims of polymeric diffusion matrix containing a potassium channel opener with the polymers comprising of eudragit RL100 and Eudragit RS100 for transdermal delivery of potassium channel opener e.g. pinacidil for management of hypertension over a prolonged period.
OBJECTS OF THE INVENTION
The main object of this invention is to propose formulation and preparation of polymeric diffusion matrix containing a potassium channel opener e.g. pinacidil for sustained and controlled delivery of pinacidil for the management of hypertension over a prolonged period.
Another object of this invention is to propose formulation and preparation of polymeric diffusion matrix containing a potassium channel opener e.g. pinacidil for sustained and controlled delivery of pinacidil for the management of hypertension over a prolonged period which provides improved bioavailability of the drug and better management of hypertension and would improve patient compliance.
DETAILED DESCRIPTION OF THE INVENTION
The present invention relates to a polymeric diffusion matrix containing a potassium channel opener e.g. pinacidil characterized by a sustained and controlled release of pinacidil monohydrate.
A self supporting polymeric diffusion matrix is provided for the sustained and controlled release of pinacidil monohydrate in order to transdermally deliver said pinacidil to a patient and provide said patient with an antihypertensive effect, said matrix comprising from 0 to 10% by weight of plasticizer, 20% to 80% by weight eudragit RL100; 20% to 80% by weight eudragit RS100 above 5% to above 10% of a penetration promoter and a pharmaceutically effective amount of pinacidil monohydrate to provide sustained and controlled release of pinacidil over a prolonged period.
In one embodiment, the plasticizer is dibutylphthalate in an amount of 0 to 10% by weight. In another embodiment, the plasticizer is polyethylene glycol 400 present in an amount from 0 to 10% by weight.
The self supporting polymeric diffusion matrix generally contains a mixture of eudragit RL100 and eudragit RS100 although it will be assumed that other polymeric mixtures may be used provided they yield the desired sustained and controlled release effect.
The amount by weight of the ingredients other than the plasticizer and penetration promoter generally should be in the following ranges: Eudragit RL100 is generally present in an amount from 20% to 80% by weight, with 80% being a preferred embodiment, Eudragit RS100 is present generally in an amount from 20 to 80% with preferred embodiment being 20%. The amount by weight of pinacidil monohydrate present is from 5% to 20% with 10% being the preferred embodiment.
The polymers can be replaced (in addition to eudragit RL100 and eudragit RS100) with PVPK-30, polyvinyl acetate eudragit RL PO, eudragit RS PO, eudragit E-100, eduragit RL30D, ethyl cellulose, cellulose acetate, eudragit RL PM, and eudragit RS PM.

Polyalkylene glycol such as polyethylene glycol may replace all or part of the dibutyl phthalate. The above matrix can also be formed without the addition of any plasticizer.
It is understood that pinacidil may be added to the above formulation not only in the form of the pure chemical compound, but also in combination with other drugs that may be transdermally applied or with other ingredients which are not incompatible with the desired objective of transdermally administering the drug to a patient. Thus, pharmacologically acceptable derivatives of drugs such as ethers, esters, amides, acetals, salts and the like may be used with same drugs, such derivatives may actually be preferred.
The following methods may be used for preparing the diffusion matrix of the present invention.
The matrix is prepared by solvent evaporation technique in a fabricated stainless steel apparatus. The apparatus consists of a wooden block of 14x14x2 cm dimensions over which a stainless steel plate (of 9x9x1 cm dimensions having a cylindrical cup of 4 cm diameter) can be fixed by screwing (fig. 1).
For casting polymeric films, first a thick aluminium foil is placed between the wooden block and the steel plate and the apparatus is screwed. The polymeric solution 10% weight by volume containing eudragit RL100, eudragit RS100, pinacidil monohydrate and plasticizer e.g. dibutylphthalate and a penetration promoter e.g. di-limonene in a mixture of dichloromethane (80% by volume) and isopropyl alcohol (20% by volume), is poured on the aluminium foil placed at the bottom of the cylindrical cup of the above apparatus and the solvent is allowed to evaporate at ambient conditions for 24 hours. This diffusion matrix is then cut into pieces with a total surface area suitable for administration of a pharmaceutically effect amount of pinacidil.
The present drug delivery system comprises the drug containing diffusion matrix and means for fastening the matrix to the skin of a patient. Such means can take various forms, as an occlusive backing layer to forming a type of "bandage" with the diffusion matrix being held against the skin of a patient being treated. It can also take the form of an elastic a band, such as a cloth band, a rubber band or other material. Here the diffusion matrix is placed directly on the skin of the arm, wrist or chest of the patient. An adhesive layer can also be rolled over the backing film with protruding flanges for easy sticking.






WE CLAIM:
1. Polymeric diffusion matrix containing a potassium channel opener
for sustained and controlled release of a potassium channel opener
in order to transdermally deliver said potassium channel opener to
a patient and provide said patient with an antihypertensive effect,
said matrix comprising 0% to 10% by weight of a plasticizer
selected from dibutylphthalate and polyethylene glycol, 20% to
80% by weight of a polymer solution prepared from PVPK-30,
polyvinyl acetate eudragit RL PO, eudragit RS PO, eudragit E-100,
eduragit RL30D, ethyl cellulose, cellulose acetate, eudragit RL PM,
and eudragit RS PM present singularly or in any combination, 5%
to 10% by weight of a penetration promoter selected from
dimethylsulfoxide and d-limonene and a pharmaceutically effective
amount of pinacidil monohydrate to provide a sustained and
controlled release of said pinacidil over a prolonged period.
2. The polymeric diffusion matrix as claimed in claim 1 wherein said
potassium channel opener is pinacidil monohydrate.
3. The polymeric diffusion matrix as claimed in claim 1 wherein said
potassium channel opener is present in an amount of 5% to 20%
by weight.

Documents:

2390-DEL-2004-Abstract-(07-12-2010).pdf

2390-del-2004-abstract.pdf

2390-del-2004-claims-(30-11-2004).pdf

2390-del-2004-claims.pdf

2390-DEL-2004-Correspondence-Others-(07-12-2010).pdf

2390-DEL-2004-Correspondence-Others-(09-12-2010).pdf

2390-DEL-2004-Correspondence-Others-(10-01-2011).pdf

2390-del-2004-correspondence-others.pdf

2390-del-2004-correspondence-po.pdf

2390-DEL-2004-Description (Complete)-(07-12-2010).pdf

2390-del-2004-description (complete)-(30-11-2004).pdf

2390-del-2004-description (complete).pdf

2390-del-2004-form-1.pdf

2390-del-2004-form-18.pdf

2390-del-2004-form-2-(30-11-2004).pdf

2390-del-2004-form-2.pdf

2390-DEL-2004-GPA-(09-12-2010).pdf

2390-DEL-2004-GPA-(10-01-2011).pdf

2390-del-2004-gpa.pdf


Patent Number 249119
Indian Patent Application Number 2390/DEL/2004
PG Journal Number 40/2011
Publication Date 07-Oct-2011
Grant Date 30-Sep-2011
Date of Filing 30-Nov-2004
Name of Patentee JAMIA HAMDARD
Applicant Address HAMDARD NAGAR, NEW DELHI-110062, IDNIA.
Inventors:
# Inventor's Name Inventor's Address
1 M. AQIL DEPARTMENT OF PHARMACEUTICS, FACULTY OF PHARMACY, HAMDARD UNIVERSITY, HAMDARD NAGAR, NEW DELHI-110062, INDIA.
2 YASMIN SULTANA DEPARTMENT OF PHARMACEUTICS, FACULTY OF PHARMACY, HAMDARD UNIVERSITY, HAMDARD NAGAR, NEW DELHI-110062, INDIA.
3 ASGAR ALI DEPARTMENT OF PHARMACEUTICS, FACULTY OF PHARMACY, HAMDARD UNIVERSITY, HAMDARD NAGAR, NEW DELHI-110062, INDIA.
4 FARHAN J. AHMAD DEPARTMENT OF PHARMACEUTICS, FACULTY OF PHARMACY, HAMDARD UNIVERSITY, HAMDARD NAGAR, NEW DELHI-110062, INDIA.
PCT International Classification Number A61K 9/70
PCT International Application Number N/A
PCT International Filing date
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 NA