Engineering of solidified glyburide nanocrystals for tablet formulation via loading of carriers: downstream processing, characterization, and bioavailability

Figures & data

Figure 1 Schematic diagram of the downstream solidification process.

Table 1 Composition of GBD tablets

Component	Formulations (mg)
	GBD–MCC–MIC	GBD–MCC–NANO	GBD–LAC–MIC	GBD–LAC–NANO
GBD	2.5	2.5	2.5	2.5
MCC	185.6	185.6	–	–
Lactose monohydrate	–	–	185.6	185.6
Poloxamer 188	0.5	0.5	0.5	0.5
Polyplasdone XL10	10	10	10	10
Aerosil 200	0.4	0.4	0.4	0.4
Magnesium stearate	1	1	1	1

Abbreviations: GBD, glyburide; GBD–LAC–NANO, formulation of GBD nanocrystals and lactose; GBD–MCC–NANO, formulation of GBD nanocrystals and microcrystalline cellulose; LAC, lactose monohydrate; MCC, microcrystalline cellulose; MIC, micronized drug.

Figure 2 SEM micrograph of unprocessed GBD particles.

Abbreviations: GBD, glyburide; SEM, scanning electron microscopy.

Figure 3 Size distribution of GBD particles. (A) Unprocessed GBD. (B) GBD after precipitation. (C) GBD after HPH.

Abbreviations: GBD, glyburide; HPH, high-pressure homogenization.

Figure 4 SEM micrographs of (A) MCC, (B) lactose, (C) MCC at a larger magnification, (D) lactose at a larger magnification, (E) GBD–MCC, and (F) GBD–lactose particles.

Note: Scales in A, B, C, D, E, and F are 50, 40, 10, 10, 2, and 2 μm, respectively.

Abbreviations: GBD, glyburide; MCC, microcrystalline cellulose; SEM, scanning electron microscopy.

Figure 5 Size distribution after redispersion. (A) GBD–lactose. (B) GBD–MCC. (C) MCC alone.

Abbreviations: GBD, glyburide; MCC, microcrystalline cellulose.

Figure 6 Powder X-ray diffraction patterns of GBD, MCC, lactose, and GBD-loaded carriers.

Abbreviations: GBD, glyburide; MCC, microcrystalline cellulose.

Figure 7 DSC characterization of GBD, plain carriers, and GBD-loaded carriers.

Abbreviations: DSC, differential scanning calorimetry; GBD, glyburide; MCC, microcrystalline cellulose.

Table 2 Powder flowability characteristics

Powder	Lactose, mean ± SD	GBD–lactose, mean ± SD	MCC, mean ± SD	GBD–MCC, mean ± SD
Bulk density (g/cm^3)	0.42±0.063	0.50±0.050	0.29±0.003	0.32±0.007
Tapped density (g/cm^3)	0.66±0.045	0.71±0.03	0.40±0.016	0.38±0.006
Hausner ratio	1.60±0.147	1.43±0.141	1.36±0.063	1.10±0.017
Carr’s index	37.50±1.178	30.00±1.440	26.47±1.475	9.67±1.364

Abbreviations: GBD, glyburide; MCC, microcrystalline cellulose.

Table 3 Tablet characterization

Parameters	GBD–MCC–MIC	GBD–MCC–NANO	GBD–LAC–MIC	GBD–LAC–NANO
Hardness (kg/cm^2), mean ± SD	5.6±0.80	5.8±0.53	5.7±0.48	5.9±0.42
Disintegration time (seconds)	<10	<10	<10	<10
Friability %, mean ± SD	0.298±0.005	0.340±0.027	0.280±0.019	0.335±0.022
Assay %, mean ± SD	95.2±2.5	95.4±3.8	96.1±2.7	95.3±1.8

Abbreviations: GBD, glyburide; GBD–LAC–NANO, formulation of GBD nanocrystals and lactose; GBD–MCC–NANO, formulation of GBD nanocrystals and microcrystalline cellulose; LAC, lactose monohydrate; MCC, microcrystalline cellulose; MIC, micronized drug.

Figure 8 Comparative dissolution profiles of different GBD formulations. (A) GBD–lactose. (B) GBD–MCC.

Abbreviations: COM, commercial formulation; GBD, glyburide; GBD–LAC–NANO, formulation of GBD nanocrystals and lactose; GBD–MCC–NANO, formulation of GBD nanocrystals and microcrystalline cellulose; LAC, lactose monohydrate; MCC, microcrystalline cellulose; MIC, micronized drug; RAW, unprocessed drug.

Table 4 Pharmacokinetic parameters of GBD formulations after oral administration

Pharmacokinetic parameters	GBD–COM	GBD–MCC–NANO	GBD–LAC–NANO
Cmax (µg/mL)	0.39±0.10	2.03±0.06	2.21±0.18
Tmax (hours)	2±0.00	1±0.00	1±0.00
AUC0–24 h (µg hours/mL)	4.58±0.62	9.05±0.41	10.27±0.50
F %	100.00	197.60	224.23

Abbreviations: AUC_{0–24 h}, area under the plasma concentration–time curve in the first 24 h; COM, commercial formulation; GBD, glyburide; GBD–LAC–NANO, formulation of GBD nanocrystals and lactose; GBD–MCC–NANO, formulation of GBD nanocrystals and microcrystalline cellulose; LAC, lactose monohydrate; MCC, microcrystalline cellulose.

Figure 9 Plasma concentration of GBD vs time curve after oral administration.

Abbreviations: COM, commercial formulation; GBD, glyburide; GBD–LAC– NANO, formulation of GBD nanocrystals and lactose; GBD–MCC–NANO, formulation of GBD nanocrystals and microcrystalline cellulose; LAC, lactose monohydrate; MCC, microcrystalline cellulose.