Development, Optimization, and Evaluation of Carvedilol-Loaded Solid Lipid Nanoparticles for Intranasal Drug Delivery

Abstract

Abstract. Carvedilol, a beta-adrenergic blocker, suffers from poor systemic availability (25%) due to firstpass metabolism. The aim of this work was to improve carvedilol bioavailability through developing carvedilol-loaded solid lipid nanoparticles (SLNs) for nasal administration. SLNs were prepared by emulsion/solvent evaporation method. A 2 3 factorial design was employed with lipid type (Compritol or Precirol), surfactant (1 or 2% w/v poloxamer 188), and co-surfactant (0.25 or 0.5% w/v lecithin) concentrations as independent variables, while entrapment efficiency (EE%), particle size, and amount of carvedilol permeated/unit area in 24 h (Q 24 ) were the dependent variables. Regression analysis was performed to identify the optimum formulation conditions. The in vivo behavior was evaluated in rabbits comparing the bioavailability of carvedilol after intravenous, nasal, and oral administration. The results revealed high drug EE% ranging from 68 to 87.62%. Carvedilol-loaded SLNs showed a spherical shape with an enriched core drug loading pattern having a particle size in the range of 66 to 352 nm. The developed SLNs exhibited significant high amounts of carvedilol permeated through the nasal mucosa as confirmed by confocal laser scanning microscopy. The in vivo pharmacokinetic study revealed that the absolute bioavailability of the optimized intranasal SLNs (50.63%) was significantly higher than oral carvedilol formulation (24.11%). Hence, we conclude that our developed SLNs represent a promising carrier for the nasal delivery of carvedilol.

Preparation and evaluation of carvedilol-loaded solid lipid nanoparticles for targeted drug delivery

“…The stability studies revealed the physical stability of SLN after 3 months storage and there was no significant change observed in the data. Zeta potential is a key Factor used for the evaluation of the stability of colloidal dispersions [5,20]. As observed from the results F3 formulation was negatively charged, indicating a relatively good stability and quality.…”

“…Although CL is well absorbed in the gastrointestinal tract, it is extensively metabolized in the liver leading to decreased bioavailability of about 25 % [5]. The oral bioavailability remains low because of significant first-pass hepatic metabolism by cytochrome P450 and also because of its short plasma halflife [6].…”

“…As a way of improving the bioavailability of orally administered CL, drug-loaded solid lipid nanoparticles were developed using trimyristin as lipid and polyethylene glycol sorbitan monooleate as surfactant. It has also been shown to be nontoxic for human use and officially recognized as a pharmaceutical excipient [5]. In this study, carvedilol-loaded SLNs were prepared using hot homogenization and ultra-sonication method, and studied.…”

Preparation and Optimization of Buccal Propranolol Hydrochloride Nanoethosomal Gel: A Novel Approach for Enhancement of Bioavailability

“…The sample was prepared by placing a drop of PHCL loaded ethosomes that was previously diluted 50 fold with double-distilled water onto a 400-mesh copper grid coated with carbon film and followed by negative staining with 1% phosphotungstic acid. The sample was dried in the air before TEM observation [25].…”

Sustained release biodegradable solid lipid microparticles: Formulation, evaluation and statistical optimization by response surface methodology

“…Compatibility of β-blockers with lipid excipients has been established (7) and some β-blockers such as propranolol (8), atenolol, metoprolol (8)(9), pindolol, labetolol (7) and carvedilol (9) have been encapsulated in solid lipid based polymers for oral (8,10), topical (11), intranasal (12) and ophthalmic (13) routes of administration. β-blockers have also been formulated in the form of mucoadhesive tablets containing propranolol loaded chitosan-gelatin microparticles (14)(15).…”