Non-Absorbable Oral Gentamicin Sulphate: Biopharmaceutical and Dosage Form Evaluation

Figure 1

Figure 2

Formula for the production of different batches of gentamicin sulphate oral capsules_

	Quantity (mg)
Ingredients	Batch A	Batch B	Batch C
Gentamicin sulphate	250	250	250
Carb-o-sil®	15	15	15
N-starch	30	30	30
Ac-di-sol®	5	5	5
PEG 4000	50	---	---
PVP	---	50	---
Gelatine powder	---	---	50

Inhibition zone diameters (IZDs) of some bacteria for selection for the in vitro permeability study_

Time (h)
	0.5	1	2	3
Organism		IZD (mm)
B. subtilis	13.3±0.6	7.0±0.0	10.0±0.0	3.6±0.6
K. pneumonia	8.0±0.0	5.0±0.0	2.0±0.0	0.0±0.0
S. aureus*	20.0±0.0	14.0±0.0	15.7±0.6	4.0±0.0
E. coli	6.0±0.0	4.0±0.0	3.3±0.6	0.0±0.0
S. typhi	8.0±0.0	3.0±0.0	3.0±0.0	0.0±0.0

Average inhibition zone diameter (IZD) (mm) of gentamicin sulphate after 6 h of oral administration at different concentrations_

	Dose (mg/kg)
Microorganism	500	14.28	10.71	7.14	3.57
E. coli	12.0±0.8	6.3±0.5	6.0±0.0	4.3±0.5	0.0±0.0
S. typhi	13.3±0.5	6.0±0.0	6.3±0.5	4.0±0.0	0.0±0.0
K. pneumonia	15.0±0.8	8.0±0.8	10.0±0.0	8.3±0.5	0.0±0.0
S. aureus	14.3±0.5	10.0±0.8	7.0±0.8	6.3±0.5	0.0±0.0

Baseline gentamicin sulphate dose level using inhibition zone diameter (IZDs) (mm) produced by serum drug level of oral gentamicin sulphate against Staphylococcus aureus_

	Dose (mg/kg)
Time (h)	400	500	1,000
0.0	0.0	0.0	0.0
0.5	0.0	7.3±0.6	10.3±0.6
1.0	0.0	8.7±1.2	11.3±0.6
2.0	0.0	8.2±1.2	12.3±0.6
3.0	0.0	7.3±0.6	13.0±0.0

Inhibition zone diameter (IZDs) (mm) produced by serum drug level of orally co-administered gentamicin sulphate with permeation enhancers against Staphylococcus aureus_

			IZD	(mm)
Drug/P. enhancera	((mg/kg)/%)	0 h	0.5 h	1 h	2 h	3 h
Drug	400500	0.0±0.00.0±0.0	0.0±0.00.0±0.0	0.0±0.08.0±0.0	0.0±0.08.7±0.6	0.0±0.08.0±0.0
Drug/PEG 4000	400/30500/30	0.0±0.00.0±0.0	0.0±0.06.7±0.6	0.0±0.07.6±0.6	0.0±0.06.7±0.6	0.0±0.06.7±0.6
Drug/Tween® 80	400/15500/15	0.0±0.00.0±0.0	0.0±0.06.7±0.6	0.0±0.06.7±0.6	0.0±0.06.7±0.6	0.0±0.07.0±1.0
Drug/Kolliphor® 188	400/1.0500/1.0	0.0±0.00.0±0.0	0.0±0.08.7±0.6	0.0±0.08.7±0.6	0.0±0.09.0±0.0	0.0±0.09.0±0.0
Drug/Glycerine	400/1.5500/1.5	0.0±0.00.0±0.0	0.0±0.07.7±0.6	0.0±0.08.3±0.6	0.0±0.08.0±0.0	0.0±0.07.0±1.0
Drug/SLS	400/2500/2	0.0±0.00.0±0.0	0.0±0.00.0±0.0	0.0±0.09.0±0.0	0.0±0.01 0.0±0.0	0.0±0.09.3±0.6
Drug/Citric acid	400/2500/2	0.0±0.00.0±0.0	0.0±0.09.0±0.0	0.0±0.08.7±0.6	0.0±0.08.3±0.6	0.0±0.08.3±0.6
Drug/Oleic acid	400/2500/2	0.0±0.00.0±0.0	0.0±0.07.7±0.6	0.0±0.08.0±0.0	0.0±0.07.3±0.6	0.0±0.06.3±0.6
aP. enhancer =	Permeation	enhancer,	SLS =	Sodium	lauryl	sulphate

Duration of GIT local activity of orally administered gentamicin sulphate_

Time (h)	E. coli	S. typhi	K. pneumonia	S. aureus
0	0.0±0.0	0.0±0.0	0.0±0.0	0.0±0.0
4	2.5±0.7	0.0±0.0	0.0±0.0	2.0±0.0
6	3.5±0.7	4.0±0.0	2.0±0.0	6.0±0.0
8b	6.0±0.0	4.0±0.0	4.0±0.0	8.0±0.0
10	3.5±0.7	0.0±0.0	0.0±0.0	4.0±0.0
12	0.0±0.0	0.0±0.0	0.0±0.0	0.0±0.0
14	0.0±0.0	0.0±0.0	0.0±0.0	0.0±0.0
16	0.0±0.0	0.0±0.0	0.0±0.0	0.0±0.0
18	0.0±0.0	0.0±0.0	0.0±0.0	0.0±0.0