Design, Characterization, and Application of a pH-Triggered In Situ Gel for Ocular Delivery of Vinpocetine
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Research Article Theme: Formulation and Delivery of Natural Products Guest Editors: Harsh Chauhan, Abhijit Date and Sonali Dhindwal
Design, Characterization, and Application of a pH-Triggered In Situ Gel for Ocular Delivery of Vinpocetine Qun Ma,1 Rui Luo,1 Huimin Zhang,1 Manman Dai,1 Luyu Bai,1 Qingsong Fei,1 Fang Lei,1 and Ning He1,2,3,4,5
Received 16 March 2020; accepted 18 August 2020 Abstract.
We developed a pH-triggered in situ gel (ISG) for ocular delivery of vinpocetine to achieve systemic absorption and a brain-targeting effect in rats. Carbopol acted as a gelling agent combined with hydroxypropyl methylcellulose (HPMC) as a viscosity-enhancing agent. The concentration of Carbopol (0.2%, w/v) and HPMC (1.5%, w/v) was optimized for the ISG system. The optimized formulation was evaluated for studies on release in vitro, rheology, differential scanning calorimetry, ocular irritation, residence time, and in vivo pharmacokinetics. The vinpocetine ISG stayed longer in rabbit eyes than vinpocetine ointment. In vivo pharmacokinetics showed that compared with vinpocetine ointment, vinpocetine ISG attained a peak plasma concentration and area under the curve that was 1–2 folds greater in rat plasma. The Drug Targeting Index (DTI) was 1.06 and 1.26 for vinpocetine ointment and vinpocetine ISG, respectively, after ocular administration, showing that vinpocetine ISG had better distribution in rat brain. These results revealed that a pHtriggered ISG system via ocular administration could be an alternative approach compared with traditional ophthalmic formulations.
KEY WORDS: in situ gel; vinpocetine; ocular delivery system; pharmacokinetics.
INTRODUCTION Vinpocetine is a vasoactive vinca alkaloid used for treatment of cerebrovascular diseases (1). It is a white crystalline powder, odorless and tasteless, soluble in chloroform or 96% ethanol, and almost insoluble in water. Vinpocetine is highly lipophilic, absorbed readily by tissues, distributed widely, and can pass the blood–brain barrier. It is an alkaline substance extracted from plants of the oleander species and is a weakly basic drug (pKa = 7.31). Vinpocetine active pharmaceutical ingredient is relatively stable under acid, alkali, oxidant, heat, and light conditions. Pharmacokinetic experiments have revealed an obvious first-pass effect, resulting in the oral bioavailability of Guest Editors: Harsh Chauhan, Abhijit Date and Sonali Dhindwal 1
Department of Pharmaceutics, College of Pharmacy, Anhui University of Chinese Medicine, No. 1, QianJiang Road, Hefei, AnHui, People’s Republic of China. 2 Institute of Pharmaceutics, Anhui Academy of Chinese Medical Sciences, Hefei, China. 3 Engineering Technology Research Center of Modernized Pharmaceutics, Hefei, Anhui Province, China. 4 Key Laboratory of Chinese Medicinal Formula, Hefei, Anhui Province, China. 5 To whom correspondence should be addressed. (e–mail: [email protected])
vinpocetine being low (~ 7%). Its short elimination half-life results in frequent drug dosing, which hinders patient compliance (2). Th
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