Unlock instant, AI-driven research and patent intelligence for your innovation.

Skin Penetration Enhancing Systems for Polar Drugs

Inactive Publication Date: 2011-08-11
ACTION MEDICINES SL
View PDF5 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0006]In certain embodiments, the present invention relates to a topical pharmaceutical skin penetration enhancing system, comprising an active pharmaceutical agent, an occlusive agent; and a stabilizer, wherein the active pharmaceutical agent is polar or ionic and wherein at least 0.1% of the app

Problems solved by technology

Drugs that insufficiently penetrate the skin may be only partially effective in resolving such skin diseases, such as, for example, actinic keratosis, basal cell and squamous cell carcinomas, melanomas, psoriasis, atopic dermatitis, rosacea, hemangiomas, scars and queloids.
Topical administration of ionic or polar drugs therefore poses challenges in that the charged or ionizable nature of an ionic or polar drug typically acts as a barrier to penetration of the skin.
However, the amount of polar drug, for example, a pharmaceutically acceptable salt form of a drug, which is capable of penetrating skin from such topically applied formulations, is generally low.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Skin Penetration Enhancing Systems for Polar Drugs
  • Skin Penetration Enhancing Systems for Polar Drugs
  • Skin Penetration Enhancing Systems for Polar Drugs

Examples

Experimental program
Comparison scheme
Effect test

example 1

In Vitro Percutaneous Absorption of 2,5-Dihydroxybenzenesulfonate from Various Formulations

Methods

[0162]An in vitro percutaneous absorption study evaluated tissue permeation and penetration of 2,5-dihydroxybenzenesulfonate from various formulations along with controls 10% Calcium Dobesilate in DMSO and Doxiproct® Ointment (4% Calcium Dobesilate). The composition of the formulations evaluated in this study is summarized below.

Formulations:

[0163]A. ID: 2567-20A (Calcium Dobesilate, 10% in DMSO). DMSO is known to provide the maximum skin permeability of many pharmaceutical ingredients.

B. ID: Doxiproct® Ointment (4% Calcium Dobesilate, Lot# OM Portuguesa, S.A. 151065) PEG (polyethylene glycol) Base ointment. Commercially available for the treatment of hemorrhoids.

C. ID: 2567-19B (Cream, 5% Potassium 2,5-dihydroxybenzenesulfonate). The active pharmaceutical ingredient (API) is introduced to the base formulation via spatulation.

Formulations D-F: Propylene glycol, transcutol and a combinat...

example 2

In Vitro Percutaneous Absorption of Potassium 2,5-Dihydroxybenzenesulfonate from Various Formulations

[0174]Formulations were tested that differ in the approach used for physically stabilizing Formulation 2567-95 (shown in Table 4 below). The in vitro percutaneous absorption of 2,5-dihydroxybenzenesulfonate was characterized from eight formulations at 10% potassium 2,5-dihydroxybenzenesulfonate and one reference formulation (Formulation 2567-95, 5% potassium 2,5-dihydroxybenzenesulfonate) following topical application to excised human skin from elective surgery.

Methods

[0175]This in vitro percutaneous absorption study evaluated tissue permeation and penetration of 2,5-dihydroxybenzenesulfonate from various formulations. The composition of each of the formulations evaluated in this study is summarized in Table 4.

TABLE 4Formulation Compositions123456789Lot # 2567-958689879190929394IngredientsControlIn SolutionSuspendedPotassium Dobesilate51010101010101010Cetyl Alcohol2.50.50.50.50.50.50...

example 3

Formulation Preparation Methods

[0184]A formulation of the invention may be prepared using the non-limiting methods disclosed below, which are intended to illustrate certain embodiments of the invention.

[0185]Preparation of formulation # 2567-87, a solution, discussed above may be carried out as follows.

Formulation #2567-87

[0186]

Ingredients% w / wA.DI Water31.4100 mM Acetate10.0Buffer (pH 4.0)Sodium Thiosulfate,0.1PenatahydrateB.Potassium 2,5-10.0dihydroxybenzenesulfonateC.Benzyl Alcohol0.5D.Cetyl Alcohol0.5Stearyl Alcohol2.5White Petrolatum20.0Mineral Oil20.0Brij 721.0Brij 7214.0

[0187]Procedure:

[0188]1. Combine ingredients in phase A in an appropriate size beaker and propeller mix until a solution is achieved (approximately 30 minutes).

[0189]2. In a laminar flow hood, add API in phase B to step 1. Once API is properly wetted, remove from hood and propeller mix until solution is achieved (approximately a few hours). Add heat (water bath) if necessary to speed up disillusion process. He...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
Temperatureaaaaaaaaaa
Fractionaaaaaaaaaa
Fractionaaaaaaaaaa
Login to View More

Abstract

The invention relates to pharmaceutical compositions and related methods for the topical administration of polar drugs. In a particular embodiment, the invention relates to a pharmaceutical composition comprising an active pharmaceutical agent that is a polar drug, such as potassium 2,5-dihydroxybenzenesulfonate, at least one occlusive agent, and at least one stabilizer.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims the benefit of priority of U.S. Provisional Application Ser. No. 61 / 029,231, filed Feb. 15, 2008, which is hereby incorporated by reference in its entirety.BACKGROUND OF THE INVENTION[0002]The composition of a formulation for topical application of a drug can play a vital role in the bioavailability and the efficacy of the drug on its targeted site of action. A key parameter for any drug product is its efficacy, which may require systemic uptake of the drug in an individual in order to be efficacious in the individual that is in need of treatment with the drug. Particularly in diseases of the skin, penetration into deep layers of the skin (e.g., the dermis and the deep layers of the epidermis) is important for the treatment of diseases located at these levels of the skin. Drugs that insufficiently penetrate the skin may be only partially effective in resolving such skin diseases, such as, for example, actinic kerat...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): A61K31/185C07C309/42A61P17/00
CPCA61K9/0014A61K31/185A61K47/38A61K47/10A61K47/26A61K47/06A61P17/00
Inventor OSBORNE, DAVIDSARPOTDAR, PRAMOD P.ANGEL, ARTURO J.SAENZ DE TEJADA, INIGOKRAUEL, MARIA LUISA
Owner ACTION MEDICINES SL