Back to Search
Start Over
Sustained release ivermectin-loaded solid lipid dispersion for subcutaneous delivery: in vitro and in vivo evaluation
- Source :
- Drug Delivery, Vol 24, Iss 1, Pp 622-631 (2017)
- Publication Year :
- 2017
- Publisher :
- Taylor & Francis Group, 2017.
-
Abstract
- This work aimed to develop a sustained release solid dispersion of ivermectin (IVM-SD) in a lipid matrix (hydrogenated castor oil, HCO) for subcutaneous delivery. Solvent-melting technology was employed to prepare IVM-SDs using HCO. The physicochemical properties of the IVM-SDs were evaluated by scanning electron microscopy (SEM), X-ray powder diffraction (XRPD), and Fourier transform infrared spectroscopy (FTIR). The release of IVM from IVM-SDs was evaluated with HPLC in vitro. Pharmacokinetics of IVM was studied in rabbits following a single subcutaneous administration of IVM-SD formulations. The efficacy of IVM-SD against the ear mange mite was evaluated in rabbits. IVM was completely dispersed in HCO in an amorphous state at a drug:carrier ratio lower than 1:3. No chemical interactions between drug and carrier were found besides hydrogen bonding for the amorphous IVM-SDs. The amorphous IVM-SDs formulations exhibited a sustained release of IVM versus physical mixtures (PMs) of IVM and HCO. The drug release decreased as the drug:carrier ratios decreased, and the release kinetics of IVM were controlled via diffusion. Cytotoxicity of IVM-SD to MDCK cells was lower than native IVM. The IVM plasma concentration of SD1:3 remained above 1 ng/mL for 49 d. Higher AUC, MRT, and Tmax values were obtained at a SD1:3 relative to the IVM group. The IVM-SD improved almost 1.1-fold bioavailability of drug compared with IVM in rabbits. IVM-SD could provide longer persistence against rabbit’s ear mites than a commercial IVM injection. This study shows that these solid lipid dispersions are a promising approach for the development of subcutaneous IVM formulations.
Details
- Language :
- English
- ISSN :
- 10717544 and 15210464
- Volume :
- 24
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- Drug Delivery
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.5228d5b378e4170a3921450738fb566
- Document Type :
- article
- Full Text :
- https://doi.org/10.1080/10717544.2017.1284945