EP1711146A1 - Administration transdermique d'oxybutynine dans des formulations de gel - Google Patents

Administration transdermique d'oxybutynine dans des formulations de gel

Info

Publication number
EP1711146A1
EP1711146A1 EP04782917A EP04782917A EP1711146A1 EP 1711146 A1 EP1711146 A1 EP 1711146A1 EP 04782917 A EP04782917 A EP 04782917A EP 04782917 A EP04782917 A EP 04782917A EP 1711146 A1 EP1711146 A1 EP 1711146A1
Authority
EP
European Patent Office
Prior art keywords
oxybutynin
gel formulation
topical gel
gel formulations
propylene glycol
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP04782917A
Other languages
German (de)
English (en)
Inventor
Chiang Chin-Chin
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Orient Europharma Co Ltd
Original Assignee
Orient Europharma Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from US10/770,088 external-priority patent/US20050064037A1/en
Application filed by Orient Europharma Co Ltd filed Critical Orient Europharma Co Ltd
Publication of EP1711146A1 publication Critical patent/EP1711146A1/fr
Withdrawn legal-status Critical Current

Links

Definitions

  • the invention relates generally to the transdermal delivery of oxybutynin. More specifically, the invention provides the compositions and methods of use for gel formulations of oxybutynin therapeutic for topical administration, and the method of preparing the gel formulation and the products.
  • Oxybutynin is used for treating various forms of overactive bladder and urinary incontinence. Particularly, oxybutynin effectively treats neurogenically caused bladder disorders. Relief from such disorders is attributed to the anticholinergic and antispasmodic action which oxybutynin imparts to the parasympathetic nervous system and the urinary bladder detrusor muscle.
  • Oral and transdermal oxybutynin administrations are currently used for treating various forms of overactive bladder and urinary incontinence.
  • the bioavailability of the oral delivery is rather low, and the majority of the actives can not reach the systemic circulation.
  • the adverse side effects caused by the active metabolites can be significant.
  • the oral dosage forms are particularly inconvenient for the elders and the patients with swallowing difficulties. Bue-t ⁇ various' disadvantages" ⁇ ! -oral dosage forms, transdermal adhesive matrix patches have been developed.
  • U.S. Pat. Nos. 6,555,129 and 6,562,368, and European Pat. No. 1174132 A 1 have demonstrated the transdermal therapies of oxybutynin.
  • the transdermal delivery of oxybutynin can avoid the first-pass hepatic effect by directly introducing the drug into blood stream, and consequently enhance the bioavailability.
  • the dose can be reduced and the adverse side effects can also be minimized by transdermal delivery of oxybutynin.
  • the skin irritations caused by the transdermal adhesive matrix patches remain to be a problem. Sometimes, the irritation may discourage patients to discontinue the treatment, particularly for the long-term users.
  • the present invention provides the compositions and methods of use for topical gel formulations of oxybutynin.
  • the gel formulation comprises 0.5-5% (w/w) oxybutynin chloride salt, 10- 80% (w/w) short chain alcohols, and 0.2-2.0% of gelling agents.
  • the gel formulation comprises the permeation enhancers in order to increase the rate at which oxybutynin penetrates through the skin.
  • Chemical enhancers are compounds that are administered along with the drug in order to increase the permeability of the stratum corneum, and thereby provide for enhanced penetration of the drug through the skin.
  • such chemical permeation enhancers are compounds that are innocuous and serve merely to facilitate diffusion of the drug through the stratum corneum.
  • the topical gel formulations of oxybutynin in the present invention have advantages including the following aspects.
  • FIG. 1 illustrates the plasma concentrations of oxybutynin vs. time following the transdermal delivery of 1% topical gel formulation and 3% topical gel formulation.
  • the present invention provides the compositions of topical gel formulation of oxybutynin, which exhibits reduced adverse side effects and minimal skin irritation.
  • Such topical gel formulation of oxybutynin is delivered by topical administration to systemic circulation.
  • the gel formulation comprises 0.5-5% (w/w) oxybutynin chloride salt, 10- 80% (w/w) short chain alcohols, and 0.2-2.0% of gelling agents.
  • the preferred short chain alcohols are ethanol and isopropanol.
  • the preferred gelling agents include Carbomer (a synthetic compound comprised of a cross-linked polymer of acrylic acid with a high molecular weight, including various products such as Carbopol ETD 2020 et al.) and Pemulen TR-1NF (a cross- linked copolymer of acrylic acid and C1 0 - 30 alkyl acrylate).
  • the gel formulation comprises the permeation enhancers in a range of 0.5-5.0%) (w/w).
  • the suitable permeation enhancers include propylene glycol, propylene glycol laurate, isopropyl myristate, and methyl lactate, and preferably with the use of isopropyl myristate.
  • moisturizers can be added in the formulation, such as propylene glycol.
  • Example 1 The following examples of the gel formulations of oxybutynin are provided to further explain the invention.
  • Example 1 The following examples of the gel formulations of oxybutynin are provided to further explain the invention.
  • Example 1 The following examples of the gel formulations of oxybutynin are provided to further explain the invention.
  • a gel formulation of oxybutynin was prepared by the following representative procedure.
  • step 6 Adjust pH of the solution in step 5 to 6.5 - 7.5 using a base (such as 2-amine-2-methyl-l- isopropanol, or diisopropanolamine).
  • a base such as 2-amine-2-methyl-l- isopropanol, or diisopropanolamine.
  • the skin permeation rates were measured for various gel formulations of oxybutynin as shown in Table 1.
  • the blood concentration of oxybutynin is at a similar level in gel formulations of the present invention as in a conventional oral formulation. Since the topical gel formulation of oxybutynin in the present invention is delivered transdermally into blood stream, it avoids the first-pass hepatic effect. Consequently, the adverse side effects induced by the active metabolite of oxybutynin from an oral delivery can be minimized. The gel formulations also reduced the skin irritation comparing to the conventional adhesive matrix patch.

Landscapes

  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention concerne une formulation de gel topique d'oxybutynine qui présente une biodisponibilité accrue, entraîne des effets indésirables réduits et des irritations cutanées limitées et améliore l'observance thérapeutique comparativement aux formulations d'oxybutynine orales et transdermiques existantes.
EP04782917A 2004-02-02 2004-09-02 Administration transdermique d'oxybutynine dans des formulations de gel Withdrawn EP1711146A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US10/770,088 US20050064037A1 (en) 2003-09-18 2004-02-02 Transdermal delivery of oxybutynin in gel formulations
PCT/US2004/028520 WO2005032441A1 (fr) 2003-09-18 2004-09-02 Administration transdermique d'oxybutynine dans des formulations de gel

Publications (1)

Publication Number Publication Date
EP1711146A1 true EP1711146A1 (fr) 2006-10-18

Family

ID=36968265

Family Applications (1)

Application Number Title Priority Date Filing Date
EP04782917A Withdrawn EP1711146A1 (fr) 2004-02-02 2004-09-02 Administration transdermique d'oxybutynine dans des formulations de gel

Country Status (1)

Country Link
EP (1) EP1711146A1 (fr)

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2005032441A1 *

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