Probucol Release from Novel Multicompartmental Microcapsules for the Oral Targeted Delivery in Type 2 Diabetes

Abstract

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.

Novel chenodeoxycholic acid–sodium alginate matrix in the microencapsulation of the potential antidiabetic drug, probucol. Anin vitrostudy

“…The micro-CT analysis (Figure 1c and g) shows more dense microcapsules in the presence of CDCA, which is distributed evenly throughout the microcapsules. The surface elemental analysis (Figure 1d and h) shows that PB was deposited on the surface of both PB-SA and PB-CDCA-SA microencapsulated formulations, although less deposition of PB was noted on the surface of PB-CDCA-SA microcapsules, which is in line with recently published work (Mooranian et al, 2014c(Mooranian et al, , 2015. Examination of crystal depositions on the microcapsule surfaces showed high levels of sulphur atoms present as small crystals on the surface of PB-SA, and to a lesser extent on PB-CDCA-SA microcapsules.…”

Electrokinetic potential-stabilization by bile acid-microencapsulating formulation of pancreatic β-cells cultured in high ratio poly-L-ornithine-gel hydrogel colloidal dispersion: applications in cell-biomaterials, tissue engineering and biotechnological applications

“…Microencapsulation methods used were based on our well-established Buchi-concentric system. In brief, concentric nozzle system was incorporated with voltage of 800 V and vibrational frequency of 2000 Hz, followed by gelation bath of 2% Cacl 2 [4][5][6]8,11,13,14,[29][30][31][32][33][34][35]. Microcapsule incubation was carried out using set protocols as per Biotechnology and Drug Development Research Laboratory systems [29][30][31][32][33][34].…”

“…In brief, concentric nozzle system was incorporated with voltage of 800 V and vibrational frequency of 2000 Hz, followed by gelation bath of 2% Cacl 2 [4][5][6]8,11,13,14,[29][30][31][32][33][34][35]. Microcapsule incubation was carried out using set protocols as per Biotechnology and Drug Development Research Laboratory systems [29][30][31][32][33][34]. Vibrational jet flow technology was used to form microspheres containing high load cells with spherical shape and thin surface-parameters based on calculated cell-cell electric resistance and pressure flow properties, using established methods [6,9,10,13].…”

Biological Assessments of Encapsulated Pancreatic β-Cells: Their Potential Transplantation in Diabetes

“…22,23,28,29,34 Incorporation of specific bile acids in second-generation microcapsules demonstrated membrane-stabilising as well as potential synergistic antidiabetic properties. 25,26,33,35,37 Our second generation microcapsules also showed excellent elasticity, rheological parameters and excipient-biocompatibility.…”