羟丙基-β-环糊精对 pH 诱导型黏附性水凝胶中地塞米松眼部生物利用度的影响。

Effect of hydroxypropyl-β-cyclodextrin on the ocular bioavailability of dexamethasone from a pH-induced mucoadhesive hydrogel.

机构信息

Department of Pharmaceutics, Institute of Technology, Banaras Hindu University, Varanasi, Uttar Pradesh, India.

出版信息

Curr Eye Res. 2011 Oct;36(10):918-29. doi: 10.3109/02713683.2011.593728.

DOI:10.3109/02713683.2011.593728

PMID:21950697

Abstract

PURPOSE

Dexamethasone (DXN) is an effective anti-inflammatory drug in the treatment of acute and chronic eye disease such as uveitis. It is relatively lipophilic and permeates biological membranes quite easily. However, its low aqueous solubility limits its clinical usefulness. To circumvent this problem Hydroxypropyl-β-cyclodextrin (HP-β-CD) was used as solubilizer and penetration enhancer for DXN. The purpose of this study was to develop HP-β-CD based pH-induced mucoadhesive hydrogel for ophthalmic delivery of DXN to treat uveitis.

MATERIALS AND METHODS

The formation of inclusion complex of DXN with HP-β-CD was characterized in solution and solid states by phase solubility, X-ray diffractometry and IR spectrum analyses. To improve ocular retention and sustained action Carbopol 980 NF and sodium carboxymethylcellulose (NaCMC) were added to the formulations as phase transition and mucoadhesive agents, respectively.

RESULTS

The HP-β-CD-based hydrogel system enhanced the solubility of DXN and the apparent stability constant (k') of the DXN-HP-β-CD inclusion complex was found to be 258.62 M(-1). The optimum concentrations of Carbopol 980NF and NaCMC for the mucoadhesive hydrogel were 0.2% (w/v) and 0.4% (w/v), respectively. This mucoadhesive hydrogel could flow freely under non-physiological condition and showed the character of pseudoplastic fluid under both physiological and non-physiological conditions. In vitro release of DXN from the HP-β-CD complex in simulated tear fluid (STF, pH- 7.4), was influenced significantly by the properties and concentration of Carbopol and NaCMC. In vivo studies in rabbit eye showed a marked improvement in anti-inflammatory activity of mucoadhesive hydrogel-treated eye compared with a marketed solution formulation in a uveitis-induced rabbit eye model.

CONCLUSION

The developed HP-β-CD-based mucoadhesive system is a viable alternative to conventional eye drops of DXN due to its ability to enhance bioavailability through its longer precorneal residence time and ability to sustain the release of the drug.

摘要

目的

地塞米松（DXN）是一种有效的抗炎药物，可用于治疗急性和慢性眼部疾病，如葡萄膜炎。它具有一定的亲脂性，很容易穿透生物膜。然而，其低水溶性限制了它的临床应用。为了解决这个问题，羟丙基-β-环糊精（HP-β-CD）被用作 DXN 的增溶剂和渗透增强剂。本研究的目的是开发基于 HP-β-CD 的 pH 诱导型黏附性水凝胶，用于眼部递送 DXN 以治疗葡萄膜炎。

材料和方法

通过相溶解度、X 射线衍射和 IR 光谱分析，在溶液和固态中对 DXN 与 HP-β-CD 的包合复合物的形成进行了表征。为了提高眼部滞留时间和持续作用，Carbopol 980NF 和羧甲基纤维素钠（NaCMC）分别作为相转变和黏附性赋形剂添加到制剂中。

结果

HP-β-CD 基水凝胶系统提高了 DXN 的溶解度，并且发现 DXN-HP-β-CD 包合复合物的表观稳定常数（k'）为 258.62M(-1)。Carbopol 980NF 和 NaCMC 的最佳浓度分别为 0.2%（w/v）和 0.4%（w/v），用于黏附性水凝胶。这种黏附性水凝胶在非生理条件下可以自由流动，在生理和非生理条件下均表现出假塑性流体的特性。在模拟泪液（STF，pH-7.4）中，DXN 从 HP-β-CD 配合物中的体外释放受到 Carbopol 和 NaCMC 的性质和浓度的显著影响。在兔眼体内研究中，与市售滴眼剂相比，黏附性水凝胶治疗的兔眼在葡萄膜炎诱导兔眼模型中显示出抗炎活性的显著改善。