title: Formulation and characterization of ORMOSIL particles loaded with budesonide for local colonic delivery.
abstract: In this study, hybrid silica xerogel particles were developed as carriers of budesonide (BDS) for efficient local treatment of inflammatory bowel diseases (IBD). Organically modified silica particles (ORMOSILs) were prepared by co-condensation of 3-aminopropyltriethoxysilane (APTES) and tetraethyl orthosilicate (TEOS) by an ambient temperature acid catalysed sol-gel process followed by spray-drying. Formulation for preparation of BDS-loaded particles was optimized and their physicochemical parameters and drug release profiles were evaluated in vitro. Optimal formulation had a small particle size (mean diameter of 1.45±0.02μm) with unimodal narrow size distribution and high encapsulation efficiency (98.0 ± 1.85%). Due to the positive surface charge originated from amino group of APTES, ORMOSILs showed excessive mucoadhesiveness in comparison to native TEOS particles. The drug release decreased with increasing pH from 2.0 to 7.4. In order to avoid undesirable erroneous performance in the upper GI tract, particles were additionally coated with Eudragit(®) FS 30D, as a barrier to the drug release at pH range from 2.0 to 7.0. After Eudragit(®) FS 30D coating, the release of BDS in acidic media was sustained, while no significant differences in drug release were observed at pH 7.4. In conclusion, pH-responsive ORMOSILs showed great potential for efficient BDS delivery to the colon region.
authors.affiliation: Institute of Pharmaceutical Technology, Center for Pharmaceutical Nanotechnology, Faculty of Pharmacy, University Ss. Cyril and Methodius, Majka Tereza 47, 1000 Skopje, Macedonia; Research & Development, Alkaloid AD-Skopje, Blv. Aleksandar Makedonski 12, 1000 Skopje, Macedonia.
authors.forename: Vesna
authors.initials: V
authors.lastname: Petrovska-Jovanovska
authors.affiliation: Institute of Pharmaceutical Technology, Center for Pharmaceutical Nanotechnology, Faculty of Pharmacy, University Ss. Cyril and Methodius, Majka Tereza 47, 1000 Skopje, Macedonia.
authors.forename: Nikola
authors.initials: N
authors.lastname: Geskovski
authors.affiliation: Institute of Pharmaceutical Technology, Center for Pharmaceutical Nanotechnology, Faculty of Pharmacy, University Ss. Cyril and Methodius, Majka Tereza 47, 1000 Skopje, Macedonia.
authors.forename: Maja Simonoska
authors.initials: MS
authors.lastname: Crcarevska
authors.affiliation: Institute of Pharmaceutical Technology, Center for Pharmaceutical Nanotechnology, Faculty of Pharmacy, University Ss. Cyril and Methodius, Majka Tereza 47, 1000 Skopje, Macedonia; Research & Development, Alkaloid AD-Skopje, Blv. Aleksandar Makedonski 12, 1000 Skopje, Macedonia.
authors.forename: Oya
authors.initials: O
authors.lastname: Memed
authors.affiliation: Research & Development, Alkaloid AD-Skopje, Blv. Aleksandar Makedonski 12, 1000 Skopje, Macedonia.
authors.forename: Gjorgji
authors.initials: G
authors.lastname: Petruševski
authors.affiliation: Research & Development, Alkaloid AD-Skopje, Blv. Aleksandar Makedonski 12, 1000 Skopje, Macedonia.
authors.forename: Marina
authors.initials: M
authors.lastname: Chachorovska
authors.affiliation: Institute of Preclinical and Clinical Pharmacology and Toxicology, Faculty of Medicine, University Ss. Cyril and Methodius, 50 Divizija 6, 1000 Skopje, Macedonia.
authors.forename: Marija
authors.initials: M
authors.lastname: Petrusevska
authors.affiliation: Institute of Applied Chemistry and Pharmaceutical Analyses, Faculty of Pharmacy, University Ss. Cyril and Methodius, Majka Tereza 47, 1000 Skopje, Macedonia.
authors.forename: Ana
authors.initials: A
authors.lastname: Poceva-Panovska
authors.affiliation: Institute of Pharmaceutical Technology, Center for Pharmaceutical Nanotechnology, Faculty of Pharmacy, University Ss. Cyril and Methodius, Majka Tereza 47, 1000 Skopje, Macedonia.
authors.forename: Kristina
authors.initials: K
authors.lastname: Mladenovska
authors.affiliation: Research & Development, Alkaloid AD-Skopje, Blv. Aleksandar Makedonski 12, 1000 Skopje, Macedonia.
authors.forename: Sonja
authors.initials: S
authors.lastname: Ugarkovic
authors.affiliation: Institute of Pharmaceutical Technology, Center for Pharmaceutical Nanotechnology, Faculty of Pharmacy, University Ss. Cyril and Methodius, Majka Tereza 47, 1000 Skopje, Macedonia. Electronic address: magl@ff.ukim.edu.mk.
authors.forename: Marija
authors.initials: M
authors.lastname: Glavas-Dodov
mesh_terms: D000818:Animals; D019819:Budesonide / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D012833:Siloxanes / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*
chemical_list: D012833:Siloxanes; C510784:ormosil; D019819:Budesonide
keywords: Budesonide; Colonic delivery; Organically modified silica particles; Sol–gel processes