title: Preliminary investigation on the design of biodegradable microparticles for ivermectin delivery: set up of formulation parameters.
abstract: The aim was to design sterile biodegradable microparticulate drug delivery systems based on poly(dl-lactide) (PLA) and poly(ε-caprolactone) (PCL) and containing ivermectin (IVM), an antiparasitic drug, for subcutaneous administration in dogs. The drug delivery system should: (i) ensure a full 12-month protection upon single dose administration; (ii) be safe with particular attention regarding IVM dosage and its release, in order to prevent over dosage side effects. This preliminary work involves: polymer selection, evaluation of the effects of γ-irradiation on the polymers and IVM, investigation and set up of suitable microparticle preparation process and parameters, IVM-loaded microparticles in vitro release evaluation. Results of gel permeation chromatography analysis on the irradiated polymers and IVM mixtures showed that combination of IVM with the antioxidant α-tocopherol (TCP) reduces the damage extent induced by irradiation treatment, independently on the polymer type. Solvent evaporation process was successfully used for the preparation of PLA microparticles and appropriately modified; it was recognized as suitable for the preparation of PCL microparticles. Good process yields were achieved ranging from 76.08% to 94.72%; encapsulation efficiency was between 85.76% and 91.25%, independently from the polymer used. The type of polymer and the consequent preparation process parameters affected microparticle size that was bigger for PCL microparticles (480-800 µm) and solvent residual that was >500 ppm for PLA microparticles. In vitro release test showed significantly faster IVM release rates from PCL microparticles, with respect to PLA microparticles, suggesting that a combination of the polymers could be used to obtain the suitable drug release rate.
authors.affiliation: Department of Drug Sciences, University of Pavia , Pavia , Italy.
authors.forename: Rosella
authors.initials: R
authors.lastname: Dorati
authors.forename: Ida
authors.initials: I
authors.lastname: Genta
authors.forename: Barbara
authors.initials: B
authors.lastname: Colzani
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tripodo
authors.forename: Bice
authors.initials: B
authors.lastname: Conti
mesh_terms: D000818:Animals; D000977:Antiparasitic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003692:Delayed-Action Preparations; D004283:Dog Diseases / Q000517:prevention & control; D004285:Dogs; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000662:veterinary*; D007559:Ivermectin / Q000008:administration & dosage* / Q000009:adverse effects; D008863:Microspheres; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry; D012997:Solvents / Q000737:chemistry
chemical_list: D000977:Antiparasitic Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011091:Polyesters; D012997:Solvents; C016240:polycaprolactone; C033616:poly(lactide); D007559:Ivermectin
keywords: Biodegradable polymers; ionizing irradiation; ivermectin; microspheres; poly(dl-lactide); poly(ε-caprolactone)