title: Probucol release from novel multicompartmental microcapsules for the oral targeted delivery in type 2 diabetes.
abstract: In previous studies, we developed and characterised multicompartmental microcapsules as a platform for the targeted oral delivery of lipophilic drugs in type 2 diabetes (T2D). We also designed a new microencapsulated formulation of probucol-sodium alginate (PB-SA), with good structural properties and excipient compatibility. The aim of this study was to examine the stability and pH-dependent targeted release of the microcapsules at various pH values and different temperatures. Microencapsulation was carried out using a Büchi-based microencapsulating system developed in our laboratory. Using SA polymer, two formulations were prepared: empty SA microcapsules (SA, control) and loaded SA microcapsules (PB-SA, test), at a constant ratio (1:30), respectively. Microcapsules were examined for drug content, zeta potential, size, morphology and swelling characteristics and PB release characteristics at pH 1.5, 3, 6 and 7.8. The production yield and microencapsulation efficiency were also determined. PB-SA microcapsules had 2.6 ± 0.25% PB content, and zeta potential of -66 ± 1.6%, suggesting good stability. They showed spherical and uniform morphology and significantly higher swelling at pH 7.8 at both 25 and 37°C (p < 0.05). The microcapsules showed multiphasic release properties at pH 7.8. The production yield and microencapsulation efficiency were high (85 ± 5 and 92 ± 2%, respectively). The PB-SA microcapsules exhibited distal gastrointestinal tract targeted delivery with a multiphasic release pattern and with good stability and uniformity. However, the release of PB from the microcapsules was not controlled, suggesting uneven distribution of the drug within the microcapsules.
authors.affiliation: Biotechnology and Drug Development Research Laboratory, School of Pharmacy, Curtin Health Innovation Research Institute, Biosciences Research Precinct, Curtin University, Perth, WA, Australia.
authors.forename: Armin
authors.initials: A
authors.lastname: Mooranian
authors.forename: Rebecca
authors.initials: R
authors.lastname: Negrulj
authors.forename: Hesham S
authors.initials: HS
authors.lastname: Al-Sallami
authors.forename: Zhongxiang
authors.initials: Z
authors.lastname: Fang
authors.forename: Momir
authors.initials: M
authors.lastname: Mikov
authors.forename: Svetlana
authors.initials: S
authors.lastname: Golocorbin-Kon
authors.forename: Marc
authors.initials: M
authors.lastname: Fakhoury
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Watts
authors.forename: Vance
authors.initials: V
authors.lastname: Matthews
authors.forename: Frank
authors.initials: F
authors.lastname: Arfuso
authors.forename: Amanda
authors.initials: A
authors.lastname: Lambros
authors.forename: Hani
authors.initials: H
authors.lastname: Al-Salami
mesh_terms: D000284:Administration, Oral; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000737:chemistry; D001826:Body Fluids / Q000737:chemistry; D002214:Capsules / Q000008:administration & dosage / Q000138:chemical synthesis*; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000138:chemical synthesis*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004058:Diffusion; D004339:Drug Compounding / Q000379:methods; D004355:Drug Stability; D006801:Humans; D006863:Hydrogen-Ion Concentration; D011341:Probucol / Q000008:administration & dosage* / Q000737:chemistry*; D013696:Temperature
chemical_list: D000924:Anticholesteremic Agents; D002214:Capsules; D003692:Delayed-Action Preparations; D011341:Probucol