Design, formulation and optimization of novel soft nano-carriers for transdermal olmesartan medoxomil delivery: In vitro characterization and in vivo pharmacokinetic assessment

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• 作者：Mohd. Kamran^a ; Abdul Ahad^b ; ^{abdulahad20@yahoo.com" class="auth_mail" title="E-mail the corresponding author} ; ^{aahad@ksu.edu.sa" class="auth_mail" title="E-mail the corresponding author} ; Mohd. Aqil^a ; ^{aqilmalik@yahoo.com" class="auth_mail" title="E-mail the corresponding author} ; Syed Sarim Imam^c ; Yasmin Sultana^a ; Asgar Ali^a
• 关键词：Acetonitrile (PubChem CID ; 6342) ; Carbopol 934 (PubChem CID ; 6581) ; Chloroform (PubChem CID ; 6212) ; Ethanol (PubChem CID ; 702) ; Ethylenediaminetetraacetic acid (PubChem CID ; 6049) ; Isopropyl alcohol (PubChem CID ; 3776) ; Methanol (PubChem CID ; 887) ; Olmesartan medoxomil (PubChem CID ; 130881) ; Phosphotungstic acid (PubChem CID ; 16212977) ; Polyethylene glycol-400 (PubChem CID ; 174) ; Potassium dihydrogen phosphate (PubChem CID ; 516951) ; Rhodamine B (PubChem CID ; 6694) ; Sodium hydroxide (PubChem CID
• 刊名：International Journal of Pharmaceutics
• 出版年：2016
• 出版时间：30 May 2016
• 年：2016
• 卷：505
• 期：1-2
• 页码：147-158
• 全文大小：2644 K

文摘

Olmesartan is a hydrophobic antihypertensive drug with a short biological half-life, and low bioavailability, presents a challenge with respect to its oral administration. The objective of the work was to formulate, optimize and evaluate the transdermal potential of novel vesicular nano-invasomes, containing above anti-hypertensive agent. To achieve the above purpose, soft carriers (viz. nano-invasomes) of olmesartan with β-citronellene as potential permeation enhancer were developed and optimized using Box-Behnken design. The physicochemical characteristics e.g., vesicle size, shape, entrapment efficiency and skin permeability of the nano-invasomes formulations were evaluated. The optimized formulation was further evaluated for in vitro drug release, confocal microscopy and in vivo pharmacokinetic study. The optimum nano-invasomes formulation showed vesicles size of 83.35 ± 3.25 nm, entrapment efficiency of 65.21 ± 2.25% and transdermal flux of 32.78 ± 0.703 (μg/cm²/h) which were found in agreement with the predicted value generated by Box-Behnken design. Confocal laser microscopy of rat skin showed that optimized formulation was eventually distributed and permeated deep into the skin. The pharmacokinetic study presented that transdermal nano-invasomes formulation showed 1.15 times improvement in bioavailability of olmesartan with respect to the control formulation in Wistar rats. It was concluded that the response surfaces estimated by Design Expert^® illustrated obvious relationship between formulation factors and response variables and nano-invasomes were found to be a proficient carrier system for transdermal delivery of olmesartan.