title: Prednisolone Delivery Platforms: Capsules and Beads Combination for a Right Timing Therapy.
abstract: In this work, a platform of alginate beads loaded with Prednisolone in hypromellose/gellan gum capsules (F6/Cps) able to delay steroidal anti-inflammatory drug (SAID) release as needed for chronotherapy of rheumatoid arthritis is proposed. Rheumatoid arthritis, showing a worsening in symptoms in the morning upon waking, is a pathology that can benefit from chronotherapy. With the aim to maximize prednisolone therapeutic action allowing the right timing of glucocorticoid therapy, different engineered microparticles (gel-beads) were manufactured using prilling (laminar jet break-up) as micro-encapsulation technique and Zn-alginate as gastroresistant carrier. Starting from various feed solutions and process parameters, the effect of the variables on particles size, morphology, solid state properties and drug release was studied. The optimization of operative and prilling/ionotropic gelation variables led to microspheres with almost spherical shape and a narrow dimensional range. The feed solution with the highest alginate (2.5% w/v) amount and drug/polymer ratio (1:5 w/w) gave rise to the highest encapsulation efficiency (78.5%) as in F6 formulation. As to drug release, F6 exhibited an interesting dissolution profile, releasing about 24% of the drug in simulated gastric fluid followed by a more sustained profile in simulated intestinal fluid. #F6, acting as a gastro-resistant and delayed release formulation, was selected for in vivo studies on male Wistar rats by means of a carrageenan-induced oedema model. Finally, this efficacious formulation was used as core material for the development of a final dosage form: F6/Cps allowed to significantly reduce prednisolone release in simulated gastric fluid (12.6%) and delayed drug release up to about 390 minutes.
authors.affiliation: Department of Pharmacy, University of Salerno, Fisciano, Italy.|PhD Program in Drug Discovery and Development, University of Salerno, Fisciano, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Cerciello
authors.affiliation: Department of Pharmacy, University of Salerno, Fisciano, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Auriemma
authors.affiliation: Department of Pharmacy, University of Salerno, Fisciano, Italy.
authors.forename: Silvana
authors.initials: S
authors.lastname: Morello
authors.affiliation: Department of Pharmacy, University of Salerno, Fisciano, Italy.
authors.forename: Rita P
authors.initials: RP
authors.lastname: Aquino
authors.affiliation: Department of Pharmacy, University of Salerno, Fisciano, Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Del Gaudio
authors.affiliation: Department of Pharmacy, University of Salerno, Fisciano, Italy.
authors.forename: Paola
authors.identifier: http://orcid.org/0000-0002-4362-4388
authors.initials: P
authors.lastname: Russo
mesh_terms: D000464:Alginates / Q000737:chemistry*; D000818:Animals; D002152:Calorimetry, Differential Scanning; D004304:Dosage Forms; D004334:Drug Administration Schedule; D004337:Drug Carriers; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D008297:Male; D008855:Microscopy, Electron, Scanning; D011239:Prednisolone / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D013055:Spectrophotometry, Infrared
chemical_list: D000464:Alginates; D004304:Dosage Forms; D004337:Drug Carriers; D006603:Hexuronic Acids; D020723:Glucuronic Acid; D011239:Prednisolone