Triacetin as a transdermal penetration enhancer

A technology of triacetin and patch, which is applied in anesthetics, drug combinations, cardiovascular system diseases, etc., and can solve the problems of poor bioavailability, low importance, and short half-life of drugs

Inactive Publication Date: 2008-03-12
WATSON LAB INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] Currently available oral drug delivery methods are unsatisfactory for many reasons
First, drugs with short half-lives require frequent dosing (2 to 4 times daily), which leads to poor patient compliance
Second, the drug's short plasma half-life and frequent dosing will create "peaks" and "troughs" in the plasma concentration profile, which will lead to increased potential for side effects with peak concentrations and loss of therapeutic effect near the end of the dosing interval
Third, the hepatic first-pass metabolism associated with oral administration will result in poor bioavailability of the drug
Increasing the amount of triacetin in the enhancer formulation with a corresponding decrease in the amount of linoleic acid will decrease the amount absorbed and prolong the penetration lag time of the drug oxymorphone, suggesting the importance of triacetin in the enhancer formulation. Relatively low

Method used

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  • Triacetin as a transdermal penetration enhancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0052] Oxybutynin free base (pK a = 10.3) is a strong basic drug for transdermal administration for antispasmodic and anticholinergic therapy. Matrix patches containing varying amounts of oxybutynin free base and penetration enhancer were prepared and tested as described above. The matrix system consists of 5-20% by weight oxybutynin free base and 0-20% by weight accelerator contained in a pharmaceutical grade acrylic copolymer binder.

[0053] Matrix formulations were prepared as follows. First, the solids content of the binder was determined by weighing a small amount of the binder solution in a weighed aluminum pan. The solvent was evaporated by drying in a convection oven at 80°C overnight, and the weight of the residue (dry binder) and the percent solid binder in solution were determined. After the solids content has been determined, a known weight of the acrylic copolymer adhesive solution is weighed in a glass bottle. The amount of binder in the solution was calcula...

Embodiment 2

[0067] According to the method of Example 1, various known accelerators were evaluated for their activity in promoting the transdermal absorption of oxybutynin free base, except that triacetin was replaced by these accelerators. The results of the in vitro skin absorption test are listed in Table 4.

[0068] Table 4

Accelerator

formula a

A / D / E(%W / W)

Q t (t = 24 hours)

(μg / cm 2 / t) b

J ss

(μg / cm 2 / hr) b

none

80 / 20 / 0

47.05±21.01

2.03±0.95

Sorbitan Monooleate

70 / 20 / 10

42.47±21.63

1.92±0.98

N-Methylpyrrolidone

60 / 20 / 20

54.36±1.98

2.42±0.97

lauryl alcohol

70 / 20 / 10

24.29±8.73

1.25±0.41

Isopropyl myristate

70 / 20 / 10

48.26±13.08

2.05±0.54

glyceryl monooleate

70 / 20 / 10

52.78±8.25

2.25±0.32

[0069] a A = binder = TSR; D = drug = oxybutynin free base; E = accelerator = t...

Embodiment 3

[0073] Yantong Xikang is a weak alkaline anti-inflammatory, analgesic and antipyretic agent, its pK a is 6.3. According to the method of Example 1, the activity of triacetin in promoting the percutaneous absorption of piroxicam was evaluated, except that oxybutynin was replaced by piroxicam. The results are listed in Table 5.

[0074] table 5

Example number

formula a A / D / E(%W / W)

Q t (t=24 hours) (μg / cm 2 / t) b

1

99.75 / 0.25 / 0

0.56±0.30

99.25 / 0.25 / 0.5

0.58±0.07

[0075] 97.75 / 0.25 / 2.0

0.32±0.08

95.75 / 0.25 / 4.0

0.45±0.17

2

99.75 / 0.25 / 0

0.55±0.31

99.25 / 0.25 / 0.5

0.27±0.15

97.75 / 0.25 / 2.0

0.03±0.02

95.75 / 0.25 / 4.0

0.18±0.04

3

99.75 / 0.25 / 0

0.60±0.20

99.25 / 0.25 / 0.5

0.36±0.14

97.75 / 0.25 / 2.0

0.42±0.09

95.75 / 0.25 / 4.0

0.31±0.14

[0076] a A = Ad...

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Abstract

A composition and method for enhancing transdermal penetration of a basic drug are described. The composition comprises a matrix patch comprising an effective amount of a basic drug, preferably having a pKa of about 8.0 or greater, an effective amount of penetration enhancer consisting essentially of triacetin, and a polymer later preferably comprising a pressure-sensitive adhesive. A preferred basic drug is oxybutynin and acid addition salts thereof. The method for enhancing transdermal penetration comprises applying the matrix patch to a selected area of skin.

Description

[0001] This application is a divisional application of the patent application filed on February 5, 2004, the invention title is "Transdermal Accelerator Triacetin", and the application number of said application is 200410039211.2. technical field [0002] The present invention relates generally to compositions and methods for promoting the release of biologically active substances through biological membranes, including skin and mucous membranes, and more particularly to triacetin-promoted pK a Use of transmembrane or transmucosal release of basic drugs such as oxybutynin of about 8.0 or greater. Background technique [0003] Presently used forms of oral administration of drugs are unsatisfactory for a number of reasons. First, drugs with a short half-life require frequent dosing (2 to 4 times a day), which will lead to poor patient compliance. Second, the drug's short plasma half-life and frequent dosing will create "peaks" and "troughs" in the plasma concentration profile...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K45/00A61K47/14A61K9/70A61K9/00A61K31/137A61K31/138A61K31/167A61K31/216A61K31/404A61K31/4458A61K31/46A61K31/485A61K31/5415A61K31/55A61K47/10A61K47/30A61K47/32A61P9/00A61P9/06A61P21/02A61P23/02A61P25/04A61P25/24A61P25/26A61P27/02
CPCY10S514/946A61K47/14A61K9/7069A61K9/7061A61K9/7053A61K9/0014A61P13/02A61P21/02A61P23/02A61P25/04A61P25/24A61P25/26A61P27/02A61P9/00A61P9/06A61F13/00
Inventor 全丹毅N·A·德什潘戴S·温卡特什瓦仁C·D·埃伯特
Owner WATSON LAB INC
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