Mini-Tablets versus Nanoparticles for Controlling the Release of Amoxicillin: In vitro/In vivo Study

Figures & data

Figure 1 Chemical structure of Amoxicillin.

Table 1 Composition and Physical Character of AMX-MTs Formulation, Each Dose of Tablets Contain 250 Mg of AMX

*Formula Code	Compitrol (mg)	GMS (mg)	Chitosan (mg)	Average Hardness (Kg/cm^2)	Average Friability (%)	Content Uniformity (%)
AMX-MT1	50	-	200	8.25±0.57	0.29±0.12	100.41± 1.25
AMX-MT2	75	-	200	8.16±0.62	0.31±0.24	99.62± 2.24
AMX-MT3	100	-	200	8.05±0.82	0.15±0.11	98.60±0.95
AMX-MT 4	125	-	200	8.23±0.26	0.35±0.21	99.6±1.24
AMX-MT 5	150	-	200	8.00±0.35	0.24±0.42	101.24±1.02
AMX-MT 6	200	-	200	7.95±0.54	0.40±0.33	100.54±1.25
AMX-MT 7	-	-	200	8.24±0.68	0.36±0.41	99.68±0.95
AMX-MT 8	-	50	200	8.43±0.46	0.28±0.32	101.2±1.23
AMX-MT 9	-	75	200	8.24±0.52	0.31±0.11	100.23±1.45
AMX-MT 10	-	100	200	8.10±0.25	0.42±0.05	99.5±2.35
AMX-MT 11	-	125	200	8.32±0.74	0.35±0.21	101.5±1.35
AMX-MT 12	-	150	200	8.45±0.22	0.42±0.15	100.7±1.85

Notes: *All floating matrix tablets contain 1% talc, and 2% magnesium stearate as a lubricant.

Table 2 Formulation Code, Drug:Lipid Ratio and Chitosan (CN) Solution Concentration (mg/mL), PI, ZP %EE and % DL of AMX-LPN Formulations

Formulations	AMX:Lipid Ratio (Cr) (w:w)	Chitosan Solution (CN) Concentration (mg/mL)	PI	ZP (+ mV)	% EE	% DL
AMX-LPN 1	1:0.5	0.5	0.211±0.015	21.5 ±0.2	54.1±2.3	38.1±1.3
AMX-LPN 2		1	0.235±0.02	22.1±0.9	59.5±2.6	32.2±1.1
AMX-LPN 3		2	0.225±0.014	23.3 ±0.2	62.2±1.2	28.5±0.9
AMX-LPN 4	1:1	0.5	0.264±0.014	19.8±0.3	64.1±2.5	41.2±2.3
AMX-LPN 5		1	0.229±0.09	20.1±0.7	69.7±1.5	39.1±0.5
AMX-LPN 6		2	0.301±0.015	20.9±0.1	71.1±1.8	36.3±1.6
AMX-LPN 7	1:2	0.5	0.251±0.011	17.8±0.2	73.7±1.5	40.1±1.7
AMX-LPN 8		1	0.33±0.023	18.2±0.4	76.2±2.4	35.4±1.2
AMX-LPN 9		2	0.311±0.023	18.8±0.8	77.9±1.4	33.1±0.3
AMX-LPN 10	1:3	0.5	0.221±0.014	16.6±0.8	84.1±1.1	40.1±2.3
AMX-LPN 11		1	0.261±0.013	17.01±0.6	86.4±1.4	40.3±1.1
AMX-LPN 12		2	0.301±0.003	17.3±0.8	86.9±0.5	39.2±0.6

Notes: PI, ZP, %EE, and % DL Data are mean value ± SD (n = 3).

Figure 2 TEM image of optimized AMX-LPNs formula.

Figure 3 DSC thermograms of AMX, AMX-LPN1, AMX-LPN4, AMX-LPN7, and AMX-LPN10.

Figure 4 FTIR spectra of AMX, AMX-LPN1, AMX-LPN4, AMX-LPN7, and AMX-LPN10.

Figure 5 (A, B) In vitro dissolution profiles of AMX from Mini-tablets formulations (A) for MT1-MT-6, (B) for MT-7-MT-12 in 0.1N HCl. Each point is a mean value of three tablets.

Figure 6 (A-D). In vitro dissolution profiles of AMX from LPNs formulations for (A) LPN1-3, (B) LPN4-6, (C) LPN7-9, (D) LPN10-12 in 0.1N HCl. Each point is a mean value of three trials.

Table 3 Study of in vitro Release Kinetics Data for AMX from Selected Mini-Tablets and Lipid/Polymer Nanolipid Systems

Formulation	Zero Order R^2	First Order R^2	Higuchi Model R^2	Korsmeyer–Peppas Model R^2 n		Hixson Crowel R^2
MT6	0.881	0.670	0.891	0.978	0.40	0.376
LPN11	0.616	0.714	0.970	0.988	0.43	0.412

Abbreviations: R², regression coefficient; n, release exponent.

Table 4 %EE, PS, ZP of AMX-LPN11 Under Different Storage Conditions for 45 Days

Storage Temperature (^oC)	Time of Testing (days)	%EE	PS (nm)	ZP(+ mV)
4	15	87.1±0.4	385 ± 18	17.11±1.6
	30	86.1±1.1	386 ± 22	18.21±0.9
	45	86.3±1.6	385 ± 20	17.88±1.8
25	15	85.8±0.9	386 ± 8	16.61±1.26
	30	85.9±1.1	388 ± 10	17.21±1.5
	45	86.0±0.4	390 ± 11	16.88±0.6
40	15	85.8±1.3	400 ± 28	10.51±2.1
	30	86.1±0.5	411 ± 11	10.09±0.6
	45	85.6±1.7	425 ± 25	9.01±1.4

Table 5 Mean Results ±SD for Microbiological Tests of Selected AMX-PLN Formula

Test	AMX-LPN11	AMX-MT10	Control (Commercial Product)
Inhibition zone (mm)	34.1±1.3	33.2±2.5	28.5±1.8
MIC (µg/mL)	15±3.2	16±3.2	32±2.6

Table 6 Pharmacokinetic Parameters of AMX After Oral Administration of AMX-LPN11 and Commercial Tablets in Rats

Pharmacokinetic Parameter	AMX-LPN11	AMX-MT10	Commercial Tablets
Cmax, µg/mL	1.94±0.3	1.88±0.1	1.79±0.7
Tmax, hr	2.1±0.1	2.0±0.05	2.0 ±0.2
AUC0-24, µgml^−1hr	43.68 ± 4.3	42.49 ± 4.0	23.61 ± 3.20
MRT, hr	12.1	11.9	10.5
Rel F	1.85	1.80

Figure 7 AMX plasma concentration (mean ± SE) time profiles in rats after oral administrations MT6, AMX-LPN11, and commercial tablets.

Figure 8 In vitro/in vivo correlation between drug released in 0.1 N HCl (pH1.2) and plasma drug concentration in rats using MT6, LPN11, and market tablet.