Development and evaluation of isradipine via rutin-loaded coated solid–lipid nanoparticles

Abstract

The objective was to develop a stable and non-compliance coated solid–lipid nanoparticles (coated SLN) using polymer (Eudragit L100) and lipoid (glycerol monostearate: soya lecithin) for partial dose reduction of isradipine [ISR; 2.5 mg by combination of bioenhancing agent (rutin; Ru) in equivalent ratio]. The physicochemical characterizations were performed by FT-IR and DSC of elected model drug (ISR), drug mixer with Ru/polymer and coated SLN with Ru (ONbp); the resulted distinctive peaks demonstrated that no chemical interaction and incompatibility found between them. The plasma samples of formulation (ONbp) were analyzed by liquid chromatography (HPLC) using UV-spectrometer. Data were integrated and analyzed with the help of a computer-designed program “Kinetica Software” (Thermo Scientific Kinetica, PK/PD Analysis, version 5.0, Philadelphia, PA). The pharmacokinetic study showed 3.2- to 4.7-folds enhancement in oral bioavailability of coated SLN of ISR with Ru (ONbp) when compared to a coated formulation of ISR without Ru (ONps) and conventional drug suspension. In vivo studies were revealed significantly at greater extent in (drug stability and solubility) oral absorption, which has shown potential entrapment efficiency (97.85% ± 1.02%) to improve biological activity against hypertension. Hence, nano-system of ISR against hypertension is achieved with consequent dose reduction with enhanced systemic bioavailability.

Solid Lipid Nanoparticles for Drug Delivery: Pharmacological and Biopharmaceutical Aspects

“…The group of calcium channel blockers derived from dihydropyridine, for example, is characterized by its low oral BA due to its low water solubility and high rate of firstpass metabolism. Administered as lipid-based nanosystems, significant increases in the oral relative BA was observed for isradipine [4.5-fold, (Kumar et al, 2018)], nisolpine [2.5-fold, (Dudhipala et al, 2018)], felodipine [3.2-fold, (He et al, 2020)], and cilnidipine [2.4-folds, (Diwan et al, 2020)]. These are very promising results taking into consideration that, when administered as conventional formulations, the oral BA of these four drugs is in the range of 5-20% (Wishart et al, 2018).…”

Therapeutic benefits of rutin and its nanoformulations

“…The enhanced oral bioavailability of coated SLN of ISR with Ru (ONbp) was observed (3.2‐ to 4.7‐folds) relative to a coated formulation of ISR without Ru (ONps) and conventional drug suspension. Moreover, in vivo experiments showed improved biological activity against hypertension (Kumar et al, 2018).…”

Nanoparticle-Based Therapies in Hypertension

“…Nanoformulation plasma concentrations remained relatively steady even 12 hours postadministration, whereas blood levels in isradipine solution rats declined rapidly-nearly zero by 12 hours. 22 Another CCB intriguing for improved formulations is lercanidipine due to its poor bioavailability (≈10%), erratic absorption, food-dependent dosing, and short elimination half-life, resulting in poor patient compliance. 23 To improve lercanidipine's profile, numerous formulations of lercanidipine-hydroxypropylmethyl cellulose nanoparticles were developed and oral bioavailability was evaluated in rats.…”

“…Nanoformulation plasma concentrations remained relatively steady even 12 hours postadministration, whereas blood levels in isradipine solution rats declined rapidly—nearly zero by 12 hours. 22…”