The co-drug of conjugated hydroquinone and azelaic acid to enhance topical skin targeting and decrease penetration through the skin

Pei Wen Hsieh, Saleh A. Al-Suwayeh, Chia Lang Fang, Chwan Fwu Lin, Chun Che Chen, Jia You Fang

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

A co-drug of hydroquinone (HQ) and azelaic acid (AA), bis(4-hydroxyphenyl) nonanedioate (BHN), was synthesized and investigated as a topical prodrug with the aim of improving the dermal delivery of the parent drugs. Physicochemical parameters were ascertained, and the enzymatic hydrolysis was examined. Skin permeation of HQ, AA, and BHN was studied by determining the skin deposition and flux across nude mouse skin under equivalent doses with the same thermodynamic activity. The partition coefficient (log P) of the co-drug increased by up to 5.0 with HQ and AA conjugation, which had respective log P values of 0.5 and 1.4. In the skin absorption experiment, BHN in ethanol/pH 7 buffer resulted in a 2-fold enhancement of skin deposition compared to both HQ and AA. With permeation using polyethylene glycol 400/pH 7 buffer as the vehicle, the co-drug, respectively, exhibited 8.1- and 1.4-fold enhancements of skin uptake compared to HQ and AA alone. The transdermal flux from BHN was negligible compared to those with HQ and AA treatments. The results of a preliminary safety evaluation showed no signs of stratum corneum disruption or erythema by BHN application within 24 h. The co-drug approach provides a viable option for the treatment of skin hyperpigmentation of HQ and AA.

Original languageEnglish
Pages (from-to)369-378
Number of pages10
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Volume81
Issue number2
DOIs
Publication statusPublished - Jun 2012

Fingerprint

Skin
Pharmaceutical Preparations
Buffers
Skin Absorption
Hyperpigmentation
Prodrugs
Erythema
azelaic acid
hydroquinone
Thermodynamics
Nude Mice
Cornea
Hydrolysis
Ethanol
Safety

Keywords

  • Azelaic acid
  • Co-drug
  • Hydroquinone
  • Prodrug
  • Skin delivery

ASJC Scopus subject areas

  • Biotechnology
  • Pharmaceutical Science

Cite this

The co-drug of conjugated hydroquinone and azelaic acid to enhance topical skin targeting and decrease penetration through the skin. / Hsieh, Pei Wen; Al-Suwayeh, Saleh A.; Fang, Chia Lang; Lin, Chwan Fwu; Chen, Chun Che; Fang, Jia You.

In: European Journal of Pharmaceutics and Biopharmaceutics, Vol. 81, No. 2, 06.2012, p. 369-378.

Research output: Contribution to journalArticle

@article{b9e376167546475ab95add38b5de477f,
title = "The co-drug of conjugated hydroquinone and azelaic acid to enhance topical skin targeting and decrease penetration through the skin",
abstract = "A co-drug of hydroquinone (HQ) and azelaic acid (AA), bis(4-hydroxyphenyl) nonanedioate (BHN), was synthesized and investigated as a topical prodrug with the aim of improving the dermal delivery of the parent drugs. Physicochemical parameters were ascertained, and the enzymatic hydrolysis was examined. Skin permeation of HQ, AA, and BHN was studied by determining the skin deposition and flux across nude mouse skin under equivalent doses with the same thermodynamic activity. The partition coefficient (log P) of the co-drug increased by up to 5.0 with HQ and AA conjugation, which had respective log P values of 0.5 and 1.4. In the skin absorption experiment, BHN in ethanol/pH 7 buffer resulted in a 2-fold enhancement of skin deposition compared to both HQ and AA. With permeation using polyethylene glycol 400/pH 7 buffer as the vehicle, the co-drug, respectively, exhibited 8.1- and 1.4-fold enhancements of skin uptake compared to HQ and AA alone. The transdermal flux from BHN was negligible compared to those with HQ and AA treatments. The results of a preliminary safety evaluation showed no signs of stratum corneum disruption or erythema by BHN application within 24 h. The co-drug approach provides a viable option for the treatment of skin hyperpigmentation of HQ and AA.",
keywords = "Azelaic acid, Co-drug, Hydroquinone, Prodrug, Skin delivery",
author = "Hsieh, {Pei Wen} and Al-Suwayeh, {Saleh A.} and Fang, {Chia Lang} and Lin, {Chwan Fwu} and Chen, {Chun Che} and Fang, {Jia You}",
year = "2012",
month = "6",
doi = "10.1016/j.ejpb.2012.03.006",
language = "English",
volume = "81",
pages = "369--378",
journal = "European Journal of Pharmaceutics and Biopharmaceutics",
issn = "0939-6411",
publisher = "Elsevier",
number = "2",

}

TY - JOUR

T1 - The co-drug of conjugated hydroquinone and azelaic acid to enhance topical skin targeting and decrease penetration through the skin

AU - Hsieh, Pei Wen

AU - Al-Suwayeh, Saleh A.

AU - Fang, Chia Lang

AU - Lin, Chwan Fwu

AU - Chen, Chun Che

AU - Fang, Jia You

PY - 2012/6

Y1 - 2012/6

N2 - A co-drug of hydroquinone (HQ) and azelaic acid (AA), bis(4-hydroxyphenyl) nonanedioate (BHN), was synthesized and investigated as a topical prodrug with the aim of improving the dermal delivery of the parent drugs. Physicochemical parameters were ascertained, and the enzymatic hydrolysis was examined. Skin permeation of HQ, AA, and BHN was studied by determining the skin deposition and flux across nude mouse skin under equivalent doses with the same thermodynamic activity. The partition coefficient (log P) of the co-drug increased by up to 5.0 with HQ and AA conjugation, which had respective log P values of 0.5 and 1.4. In the skin absorption experiment, BHN in ethanol/pH 7 buffer resulted in a 2-fold enhancement of skin deposition compared to both HQ and AA. With permeation using polyethylene glycol 400/pH 7 buffer as the vehicle, the co-drug, respectively, exhibited 8.1- and 1.4-fold enhancements of skin uptake compared to HQ and AA alone. The transdermal flux from BHN was negligible compared to those with HQ and AA treatments. The results of a preliminary safety evaluation showed no signs of stratum corneum disruption or erythema by BHN application within 24 h. The co-drug approach provides a viable option for the treatment of skin hyperpigmentation of HQ and AA.

AB - A co-drug of hydroquinone (HQ) and azelaic acid (AA), bis(4-hydroxyphenyl) nonanedioate (BHN), was synthesized and investigated as a topical prodrug with the aim of improving the dermal delivery of the parent drugs. Physicochemical parameters were ascertained, and the enzymatic hydrolysis was examined. Skin permeation of HQ, AA, and BHN was studied by determining the skin deposition and flux across nude mouse skin under equivalent doses with the same thermodynamic activity. The partition coefficient (log P) of the co-drug increased by up to 5.0 with HQ and AA conjugation, which had respective log P values of 0.5 and 1.4. In the skin absorption experiment, BHN in ethanol/pH 7 buffer resulted in a 2-fold enhancement of skin deposition compared to both HQ and AA. With permeation using polyethylene glycol 400/pH 7 buffer as the vehicle, the co-drug, respectively, exhibited 8.1- and 1.4-fold enhancements of skin uptake compared to HQ and AA alone. The transdermal flux from BHN was negligible compared to those with HQ and AA treatments. The results of a preliminary safety evaluation showed no signs of stratum corneum disruption or erythema by BHN application within 24 h. The co-drug approach provides a viable option for the treatment of skin hyperpigmentation of HQ and AA.

KW - Azelaic acid

KW - Co-drug

KW - Hydroquinone

KW - Prodrug

KW - Skin delivery

UR - http://www.scopus.com/inward/record.url?scp=84861608854&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84861608854&partnerID=8YFLogxK

U2 - 10.1016/j.ejpb.2012.03.006

DO - 10.1016/j.ejpb.2012.03.006

M3 - Article

C2 - 22469554

AN - SCOPUS:84861608854

VL - 81

SP - 369

EP - 378

JO - European Journal of Pharmaceutics and Biopharmaceutics

JF - European Journal of Pharmaceutics and Biopharmaceutics

SN - 0939-6411

IS - 2

ER -