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

Abstract

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±3.25nm, entrapment efficiency of 65.21±2.25% and transdermal flux of 32.78±0.703 (μg/cm(2)/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.

Keywords: Acetonitrile (PubChem CID: 6342); Box-Behnken design; 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); Nano-invasomes; Olmesartan; Olmesartan medoxomil (PubChem CID: 130881); Pharmacokinetics; 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: 14798); Transdermal; Triethanolamine (PubChem CID: 7618); β-citronellene (PubChem CID: 10887985).