A comprehensive study of novel microcapsules incorporating gliclazide and a permeation enhancing bile acid: hypoglycemic effect in an animal model of Type-1 diabetes

Figures & data

Figure 1. Study design of animal work.

Figure 2. Light microscopy of G–SA microcapsule (a); G–TCA–SA microcapsule (c); SEM image of G–SA microcapsule (b) and SEM image of G–TCA–SA microcapsule (d) at 100 µm scale, 20 µm scale, 10 µm scale, and 1 µm scale.

Figure 3. EDXR of G–SA microcapsules and the corresponding elemental analysis.

Figure 4. EDXR of G–TCA–SA microcapsules and the corresponding analysis.

Table 1. Viscosities and related rheological parameter of both microencapsulated formulations: G–SA and G–TCA–SA.

Formula Code	Set speed	RPM	Viscosity (m Pa s)	Shear rate (s^−1)	Torque (m Nm)	Shear stress (Pa)
G–SA	1	20	UD	22 ± 1	UD	UD
	2	35	UD	43 ± 2	UD	UD
	3	61	30.4 ± 3.0	74 ± 4	UD	UD
	4	107	27 ± 1.0	120 ± 6	0.03 ± 0.0	UD
	5	187	25 ± 0.4	225 ± 15	0.05 ± 0.01	1.7 ± 0.01
	6	327	17 ± 0.3	374 ± 16	0.1 ± 0.03	2.3 ± 0.01
	7	572	8 ± 0.2	623 ± 22	0.2 ± 0.03	4.8 ± 0.03
	8	1000	7 ± 0.1	1161 ± 38	0.4 ± 0.07	7.9 ± 0.10
G–TCA–SA	1	20	UD	UD	UD	UD
	2	35	UD	UD	UD	UD
	3	61	11 ± 3	33 ± 3	UD	UD
	4	107	17 ± 2	60 ± 10	UD	UD
	5	187	12 ± 0.3	112 ± 16	0.06 ± 0.01	3.0 ± 0.02
	6	327	10 ± 0.3	370 ± 12	0.10 ± 0.02	4.4 ± 0.04
	7	572	6 ± 0.2	677 ± 13	0.14 ± 0.03	5.0 ± 0.03
	8	1000	4 ± 0.1	1163 ± 33	0.34 ± 0.05	7.4 ± 0.07

Values expressed as mean ± SD, n = 3. UD: undetected (below the instrument limit of detection).

Figure 5. Fourier Transform Infrared spectra of (a) TCA powder, (b) G powder, (c) G–TCA–SA microcapsule, (d) G–SA microcapsule, (e) G–TCA–SA powder, and (f) SA powder.

Table 2. Dominant peaks measured by DSC analysis.

Compound name	Dominant peak (s)
SA powder	231 °C
G powder	176 °C
TCA powder	223 °C
G–SA microcapsule	219 °C
G–TCA–SA microcapsule	169 °C and 207 °C
G–TCA–SA powder	170 °C and 204 °C

Table 3. Drug contents (%), production yield (%), microencapsulation efficiency (%), Zeta-potential and mean particle size.

Formulation code	Formula	Drug content (%)	Production yield (%)	Encapsulation efficiency (%)	Zeta-potential (mV)	Mean particle size (µm)
G–SA	Gliclazide–sodium alginate microcapsules	7 ± 0.5	86 ± 7	90 ± 3	−69 ± 2	950 ± 55
G–TCA–SA	Gliclazide–taurocholic acid–sodium  alginate microcapsules	4 ± 0.3**	88 ± 8	86 ± 8	−50 ± 2.0**	988 ± 50

Data are mean ± SD, n = 3. **p < 0.01.

Figure 6. In vitro G-dissolution from G–SA and G–TCA–SA microcapsules at pH of 1.5 and 3.0 (a), and 6.0 and 7.8 (b). Average ± SD (n = 3).

Figure 7. Swelling index at 25 °C and at (a) pH 1.5 and 3.0, and (b) pH 6.0 and 7.8. Data are mean ± SD, n = 3.

Figure 8. Swelling index at 37 °C and at (a) pH 1.5 and 3.0, and (b) pH 6.0 and 7.8. Data are mean ± SD, n = 3.

Figure 9. Mechanical index of both, G–SA and G–TCA–SA microcapsules. Data expressed as mean ± SD and n = 3. **p < 0.01.

Figure 10. Blood glucose measurements (a), and Gliclazide serum concentration (b). Data are expressed as mean ± SD; n = 8 and each sample analyzed in triplicates.

Figure 11. Cell viability at three glucose concentrations, 24 hours post exposure (a), and media-glucose concentrations at 24 (b), 48 (c), and 72 hours (d) post exposure to 5.5 mM glucose, and three different formulations of untreated (1), G–SA (2), and G–TCA–SA (3) microcapsules. Values are mean ± SD, n = 3.