A systematic approach to determination of permeation enhancer action efficacy and sites: Molecular mechanism investigated by quantitative structure−activity relationship

Yang, Degong; Liu, Chao; Quan, Peng; Fang, Liang

doi:10.1016/j.jconrel.2020.03.014

Cited by 59 publications

(36 citation statements)

References 38 publications

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“…Furthermore, only CP 90 and POCC could significantly disrupt the skin barrier for Gla penetration from the hydrogel (Figure 6d). β R/P values >1 indicate that the enhancers mainly facilitated the drug release process while β R/P values <1 indicate that the enhancement action site was mainly skin [17]. The results (Table 3) showed that the β R/P values of PG were 2.28 and 1.63 for the LicA-CP and Gla-CP systems, respectively, which proves that the site of action of the enhancement was mainly the CP matrix for PG.…”

Section: In Vitro Skin Permeation and Drug Retention Of Drug Hydrogelmentioning

confidence: 91%

“…ER com = P hydrogel with enhancer P hydrogel without enhancer (3) β R/P was calculated to evaluate the sites of action of the enhancers [17]:…”

Section: In Vitro Skin Permeation Of Drug Solution and Hydrogelmentioning

confidence: 99%

“…After enhancers were added, they could occupy the site of drug-skin interaction and link with the skin, leading to better compatibility between the enhancers and skin. Thus, a lower E mix value is indicative of better enhancers-skin interaction and higher drug permeation [17]. Next, multivariate linear regression analysis was conducted to confirm the correlation between the P solution , RE solution , and physicochemical parameters of enhancers and the regression equations are expressed as follows: P solution (LicA) = 1.90 + 7.59 × log P (R 2 = 0.88)…”

Section: Molecular Modeling and Correlation Analysismentioning

confidence: 99%

“…It was found that hydrophilic enhancers including Transcutol ® P (TP) and propylene glycol (PG) had a better miscibility with matrix carboxyl PSA, indicating their ability to facilitate a higher drug release. In contrast, hydrophobic enhancers including POCC and SP linked with SC lipids more easily, disrupting the lipid arrangement, and thereby improving drug permeation [17]. As a result, demonstrating the molecular interaction of drug-enhancers-CP and drug-enhancers-skin systems is significant, thus shedding new light on the reasonable utilization of enhancers in pharmaceutical and cosmetic preparations.…”

Section: Introductionmentioning

confidence: 99%

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Quantitative Structure-Activity Relationship of Enhancers of Licochalcone A and Glabridin Release and Permeation Enhancement from Carbomer Hydrogel

et al. 2022

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This study aimed to systematically compare licochalcone A (LicA) and glabridin (Gla) (whitening agents) release and permeation from Carbomer 940 (CP) hydrogels with different enhancers, and evaluate the relationship between the quantitative enhancement efficacy and structures of the enhancers. An in vitro release study and an in vitro permeation experiment in solution and hydrogels using porcine skin were performed. We found that the Gla–CP hydrogel showed a higher drug release and skin retention amount than LicA–CP due to the higher solubility in medium and better miscibility with the skin of Gla than that of LicA. Enhancers with a higher molecular weight (MW) and lower polarizability showed a higher release enhancement effect (ERrelease) for both LicA and Gla. The Van der Waals forces in the drug–enhancers–CP system were negatively correlated with the drug release percent. Moreover, enhancers with a higher log P and polarizability displayed a higher retention enhancement effect in solution (ERsolution retention) for LicA and Gla. Enhancers decreased the whole intermolecular forces indrug–enhancers-skin system, which had a linear inhibitory effect on the drug retention. Moreover, C=O of ceramide acted asthe enhancement site for drug permeation. Consequently, Transcutol® P (TP) and propylene glycol (PG), seven enhancers showed a higher retention enhancement effect in hydrogel (ERhydrogel retention) for LicA and Gla. Taken together, the conclusions provide a strategy for reasonable utilization of enhancers and formulation optimization in topical hydrogel whitening.

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Section: In Vitro Skin Permeation and Drug Retention Of Drug Hydrogelmentioning

confidence: 91%

“…ER com = P hydrogel with enhancer P hydrogel without enhancer (3) β R/P was calculated to evaluate the sites of action of the enhancers [17]:…”

Section: In Vitro Skin Permeation Of Drug Solution and Hydrogelmentioning

confidence: 99%

Section: Molecular Modeling and Correlation Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Quantitative Structure-Activity Relationship of Enhancers of Licochalcone A and Glabridin Release and Permeation Enhancement from Carbomer Hydrogel

et al. 2022

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“…6 The transdermal penetration enhancers have good penetration enhancing effect was well recognized. 7,8 The mechanism of penetration enhancing effect of enhancers was also widely investigated. As a functional excipient included in the patch formulation, previous studies.…”

Section: Introductionmentioning

confidence: 99%

A Systematic Quantitative Evaluation of Permeation Enhancement Window: Transdermal Permeation Enhancing Dynamics Establishment and Molecular Mechanisms Characterization of Permeation Enhancer

Ruan

Zhong

Zhang

et al. 2022

Journal of Pharmaceutical Sciences

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At present, transdermal permeation enhancing dynamics studies on permeation enhancers are still limited. In this study, these dynamics were established based on the content of enhancer Plurol Oleique CC in skin (C POCC ) and the increment of drug permeation amount (DQ). A new concept deemed "permeation enhancement window" (DC POCC ), comprised of a threshold dose (C thr ), maximal dose (C max ) and permeation enhancement efficiency (Eff) was used to evaluate the enhancement effect of POCC for different drugs. According to results of FT-IR, ATR-FTIR and DSC analyses, the higher CPOCC of patches containing acidic drugs vs. basic drugs resulted from their stronger interaction with pressure-sensitive adhesives, leading to more free POCC and a greater disturbing effect on stratum corneum (SC) lipids. Below C thr , a longer lag phase for acidic drugs resulted from more POCC required to compete with ceramide. When CPOCC exceeded C max by about 400 mg/g, plateau phases for all drugs were reached due to the upper limit of SC lipid fluidity, as confirmed by SAXS and Raman imaging. In summary, the differences in the permeation enhancement window for the test drugs resulted from the varied interaction strengths among POCC, drugs and adhesives, as well as changeable SC lipid fluidity.

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Comparison of percutaneous permeation profiles of flurbiprofen enantiomers

et al. 2022

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Flurbiprofen is clinically effective for the treatment of acute or long‐term rheumatoid arthritis and osteoarthritis. Studies showed that S‐flurbiprofen had better anti‐inflammatory effect than R‐flurbiprofen. As flurbiprofen racemates are usually used in the form of transdermal preparations, such as Flurbiprofen Cataplasms (Zepolas), it is of great significance to investigate the percutaneous permeation profiles of flurbiprofen enantiomers for considering whether it is necessary to develop the transdermal preparation with single optical enantiomer. Taking the economy into consideration, the flurbiprofen enantiomers as the mode drug and the CHIRALPAKAAGP column we had as instrument were used to perform the following experiments. On the basis of experiences provided by predecessors, we made some improvements to the analytical conditions, and method validation was developed to verify the feasibility of the method. The results showed that the established method could be used to analyze the percutaneous permeation profiles of flurbiprofen enantiomers in the flurbiprofen cataplasms accurately and effectively, and the percutaneous permeation profiles of flurbiprofen enantiomers had no significantly difference no matter under what conditions (P > 0.05).

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A systematic approach to determination of permeation enhancer action efficacy and sites: Molecular mechanism investigated by quantitative structure−activity relationship

Cited by 59 publications

References 38 publications

Quantitative Structure-Activity Relationship of Enhancers of Licochalcone A and Glabridin Release and Permeation Enhancement from Carbomer Hydrogel

Quantitative Structure-Activity Relationship of Enhancers of Licochalcone A and Glabridin Release and Permeation Enhancement from Carbomer Hydrogel

A Systematic Quantitative Evaluation of Permeation Enhancement Window: Transdermal Permeation Enhancing Dynamics Establishment and Molecular Mechanisms Characterization of Permeation Enhancer

Comparison of percutaneous permeation profiles of flurbiprofen enantiomers

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