Mechanistic insights of the controlled release capacity of polar functional group in transdermal drug delivery system: the relationship of hydrogen bonding strength and controlled release capacity.,Acta Pharmaceutica Sinica B

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Mechanistic insights of the controlled release capacity of polar functional group in transdermal drug delivery system: the relationship of hydrogen bonding strength and controlled release capacity.
Acta Pharmaceutica Sinica B ( IF 14.7 ) Pub Date : 2019-11-29 , DOI: 10.1016/j.apsb.2019.11.014
Zheng Luo ₁ , Chao Liu ₁ , Peng Quan ₁ , Degong Yang ₁ , Hanqing Zhao ₁ , Xiaocao Wan ₁ , Liang Fang ₁

Affiliation

Background

Hydrogen bonding interaction was considered to play a critical role in controlling drug release from transdermal patch. However, the quantitative evaluation of hydrogen bonding strength between drug and polar functional group was rarely reported, and the relationship between hydrogen bonding strength and controlled release capacity of pressure sensitive adhesive (PSA) was not well understood. The present study shed light on this relationship.

Methods

Acrylate PSAs with amide group were synthesized by a free radical-initiated solution polymerization. Six drugs, i.e., etodolac, ketoprofen, gemfibrozil, zolmitriptan, propranolol and lidocaine, were selected as model drugs. In vitro drug release and skin permeation experiments and in vivo pharmacokinetic experiment were performed. Partial correlation analysis, fourier-transform infrared spectroscopy and molecular simulation were conducted to provide molecular details of drug-PSA interactions. Mechanical test, rheology study, and modulated differential scanning calorimetry study were performed to scrutinize the free volume and molecular mobility of PSAs.

Results

Release rate of all six drugs from amide PSAs decreased with the increase of amide group concentrations; however, only zolmitriptan and propranolol showed decreased skin permeation rate. It was found that drug release was controlled by amide group through hydrogen bonding, and controlled release extent was positively correlated with hydrogen bonding strength.

Conclusion

From these results, we concluded that drugs with strong hydrogen bond forming ability and high skin permeation were suitable to use amide PSAs to regulate their release rate from patch.

中文翻译：

透皮给药系统中极性官能团控释能力的机理见解：氢键强度与控释能力的关系。

背景

氢键相互作用被认为在控制透皮贴剂药物释放方面发挥着关键作用。然而，药物与极性官能团之间氢键强度的定量评价鲜有报道，且氢键强度与压敏胶（PSA）控释能力之间的关系尚不清楚。目前的研究阐明了这种关系。

方法

通过自由基引发的溶液聚合合成了带有酰胺基团的丙烯酸酯压敏胶。选择依托度酸、酮洛芬、吉非贝齐、佐米曲普坦、普萘洛尔和利多卡因6种药物作为模型药物。进行了体外药物释放和皮肤渗透实验以及体内药代动力学实验。进行偏相关分析、傅里叶变换红外光谱和分子模拟，以提供药物-PSA 相互作用的分子细节。进行机械测试、流变学研究和调制差示扫描量热研究来检查 PSA 的自由体积和分子迁移率。