An optimized probucol microencapsulated formulation integrating a secondary bile acid (deoxycholic acid) as a permeation enhancer

Abstract

The authors have previously designed, developed, and characterized a novel microencapsulated formulation as a platform for the targeted delivery of therapeutics in an animal model of type 2 diabetes, using the drug probucol (PB). The aim of this study was to optimize PB microcapsules by incorporating the bile acid deoxycholic acid (DCA), which has good permeation-enhancing properties, and to examine its effect on microcapsules' morphology, rheology, structural and surface characteristics, and excipients' chemical and thermal compatibilities. Microencapsulation was carried out using a BÜCHI-based microencapsulating system established in the authors' laboratory. Using the polymer sodium alginate (SA), two microencapsulated formulations were prepared: PB-SA (control) and PB-DCA-SA (test) at a constant ratio (1:30 and 1:3:30, respectively). Complete characterization of the microcapsules was carried out. The incorporation of DCA resulted in better structural and surface characteristics, uniform morphology, and stable chemical and thermal profiles, while size and rheological parameters remained similar to control. In addition, PB-DCA-SA microcapsules showed good excipients' compatibilities, which were supported by data from differential scanning calorimetry, Fourier transform infrared spectroscopy, scanning electron microscopy, and energy dispersive X-ray studies, suggesting microcapsule stability. Hence, PB-DCA-SA microcapsules have good rheological and compatibility characteristics and may be suitable for the oral delivery of PB in type 2 diabetes.

Keywords: BÜCHI B390; anti-inflammatory; antioxidant; artificial cell microencapsulation; bile acids; diabetes; probucol.

Figure 1

Optical microscopy of PB-SA and PB-DCA-SA microcapsules. Notes: (A) PB-SA microcapsules. (B) PB-DCA-SA microcapsules. Abbreviations: DCA, deoxycholic acid; L1, outer membrane thickness; L2, horizontal diameter; L3, vertical diameter; PB, probucol; SA, sodium alginate.

Figure 2

Scanning electron micrographs of a PB-SA microcapsule. Notes: (A) 200 μm scale. (B) Surface morphology at 10 μm scale. (C) 200 nm scale. (D) 1 μm scale. Abbreviations: PB, probucol; SA, sodium alginate.

Figure 3

Scanning electron micrographs of a PB-DCA-SA microcapsule. Notes: (A) 100 μm scale. (B–D) Surface morphology from different angles at 10 μm scale. Abbreviations: DCA, deoxycholic acid; PB, probucol; SA, sodium alginate.

Figure 4

Energy dispersive X-ray spectra of PB-SA microcapsules. Notes: (A and B) PB deposition (indicated by 1) with corresponding analysis. (C and D) Surface composition (indicated by 2) with corresponding analysis. Abbreviations: PB, probucol; SA, sodium alginate.

Figure 5

Energy dispersive X-ray spectra of PB-DCA-SA microcapsules. Notes: (A and B) PB deposition (indicated by 1) with corresponding analysis. (C and D) Surface composition (indicated by 2) with corresponding analysis. Abbreviations: DCA, deoxycholic acid; PB, probucol; SA, sodium alginate.

Figure 6

Differential scanning calorimetric thermograms of the individual powders, mixed powder containing all the ingredients, and microcapsules. Notes: (A) PB powder. (B) DCA powder. (C) SA powder. (D) PB-DCA-SA powder. (E) PB-SA microcapsules. (F) PB-DCA-SA microcapsules. Abbreviations: DCA, deoxycholic acid; PB, probucol; SA, sodium alginate.

Figure 7

Fourier transform infrared spectra of the individual powders, mixed powder containing all the ingredients, and microcapsules. Notes: (A) PB powder. (B) DCA powder. (C) SA powder. (D) PB-DCA-SA powder. (E) PB-SA microcapsules. (F) PB-DCA-SA microcapsules. Abbreviations: DCA, deoxycholic acid; PB, probucol; T, transmitted light; SA, sodium alginate.