Fabrication of Nanosuspension Directly Loaded Fast-Dissolving Films for Enhanced Oral Bioavailability of Olmesartan Medoxomil: In Vitro Characterization and Pharmacokinetic Evaluation in Healthy Human Volunteers

Abstract

Olmesartan medoxomil (OM) is an antihypertensive drug with poor water solubility and low oral bioavailability (28.6%). Accordingly, this study aimed to formulate and evaluate OM nanosuspension incorporated into oral fast-dissolving films (FDFs) for bioavailability enhancement. OM nanosuspension was prepared by antisolvent-precipitation-ultrasonication method and characterized regarding particle size (122.67 ± 5.03 nm), span value (1.40 ± 0.51), and zeta potential (- 46.56 ± 1.20 mV). Transmission electron microscopy (TEM) of the nanosuspension showed spherical non-aggregating nanoparticles. The nanosuspension was then directly loaded into FDFs by solvent casting technique. A full factorial design (2 × 3) was implemented for optimization of the FDFs using Design-Expert® software. Physical and mechanical characteristics in addition to dissolution profiles of the FDFs were investigated. The optimum formula (FDF1) showed 0.43 ± 0.02 kg/mm tensile strength, 20.50 ± 2.12 s disintegration time, and 87.53 ± 2.50 and 95.99 ± 0.25% OM dissolved after 6 and 10 min, respectively. Accelerated and long-term shelf stability studies confirmed the stability of FDF1. More than 75% OM was dissolved within 10 min from FDF1 compared with 9.80 and 47.80% for films prepared using coarse drug powder and market tablet, respectively. Relative bioavailability of FDF1 compared to market tablet was assessed in healthy human volunteers. The C value increased significantly from 66.62 ± 14.95 to 179.28 ± 23.96 ng/mL for market tablet and FDF1, respectively. Similarly, the AUC value significantly increased from 498.36 ± 217.46 to 1083.67 ± 246.32 ng h/mL for market tablet and FDF1, respectively. Relative bioavailability of FDF1 was 209.28%. The highlighted results verified the effectiveness of OM nanosuspension-loaded FDFs in improving OM bioavailability.

<p>Use of transethosomes for enhancing the transdermal delivery of olmesartan medoxomil: in vitro, ex vivo, and in vivo evaluation</p>

“…An isocratic reversed-phase validated HPLC method was used for detection and quantification of OLM. 4 The apparatus used was an Agilent 1260 infinity LC system equipped with a quaternary pump, an auto-sampler unit, and a UV detector (Shimadzu Corp.). The stationary phase was Thermo ® C 18 (150×4.6 mm) column packed with a 5 µm size adsorbent.…”

“…The efficacy of OLM has been shown to be much higher or at least equivalent to many other prescribed antihypertensive agents. 4 An alternative technique to oral delivery of OLM is to integrate the drug into submicroscopic vesicles and give it through transdermal route, thereby obscuring the drug molecule and delivering it to systemic circulation in a controlled manner which subsequently avoids the first-pass metabolism.…”

Formulation, characterization, optimization, and in-vivo performance of febuxostat self-nano-emulsifying system loaded sublingual films

“…Sublingual films were inspected visually for any defects, color, and transparency. The weight of each film was found using electric balance (Sartorius C224, Göttingen, Germany) (Alsofany et al, 2018 ).…”

“…The film was pulled apart by the clamps at a rate of 32 mm/min until breakage. The force and elongation at the point of its break were computed (Alsofany et al, 2018). Each parameter of mechanical properties whether measured by texture analyzer or manually was tested in triplicate on three different films and results were represented as mean ± SD.…”

Enhancing the Sunscreen Efficacy of Bemotrizinol Micropigment by Using O/W Nanoemulsion Topical Preparations

“…In vitro release study of BEMT nanoemulsion formulae and coarse BEMT powder as control [20] were performed using a USP dissolution apparatus II (Hanson research, USA) with slight modification in 300 ml sweat simulated solution (pH=5.5) containing 1% tween 80 to maintain the sink condition [10] kept at 37±0.5 °Ϲ. The stirring rate was 100 rpm.…”