Formulation of sitagliptin-loaded oral polymeric nano scaffold: process parameters evaluation and enhanced anti-diabetic performance

Figures & data

Table 1. Process variables and their levels for experimental design.

	Level used, actual coded
Factor	Low (−1)	Medium (0)	High (+1)
Independent variables
A = Eudragit (%)	2	3.5	5
B = Tween 80 (%)	2	4.5	7
C = Sonication time (minute)	3	5	7
Dependent variables	Goals
Y1= Particle size (nm)	Minimize
Y2 = Drug loading (%)	Maximize
Y3 = Drug release (%)	Maximize

Table 2. Experimental runs obtained from Box–Behnken design and their observed value of particle size (Y₁), drug loading (Y₂) and %drug release (Y₃).

				Dependent variables
	Independent variables			Y1		Y2		Y3
Run	A	B	C	Actual	Predicted	Actual	Predicted	Actual	Predicted
1	5	4.5	3	169.46	168.58	7.17	7.18	70.12	70.44
2	3.5	7	3	158.56	159.40	6.55	6.57	64.56	64.13
3	3.5	7	7	181.27	180.7	6.84	6.86	67.55	67.03
4	3.5	2	7	171.11	170.27	7.32	7.31	69.23	69.66
5	2	2	5	135.86	135.82	8.48	8.52	82.45	82.34
6	5	2	5	168.33	168.64	6.55	6.56	63.54	62.70
7	3.5	4.5	5	138.56	139.63	8.66	8.72	83.76	84.21
8	3.5	4.5	5	140.22	139.57	8.75	8.72	84.65	84.21
9	2	4.5	7	167.48	168.36	7.71	7.70	75.87	75.55
10	3.5	4.5	5	140.11	139.63	8.76	8.72	84.23	84.21
11	2	4.5	3	126.98	126.45	7.81	7.79	77.97	77.56
12	2	7	5	157.87	157.56	6.36	6.35	61.45	62.29
13	5	7	5	193.45	193.49	6.54	6.51	62.22	62.33
14	3.5	2	3	122.66	123.24	8.37	8.35	81.41	81.93
15	5	4.5	7	194.45	194.98	6.49	6.51	62.65	63.06

A: Eudragit (%); B: tween 80 (%); C: Sonication time (min.); Y₁: size (nm); Y₂: drug loading (%); Y₃: drug release (%)

Table 3. Summary of regression analysis for responses [Y₁ = particle size (nm), Y₂ = drug loading (%), and Y₃ = drug release (%)] for fitting to different kinetic models.

Model	R^2	Adjusted R^2	Predicted R^2	SD	%CV
Response (Y1)
Linear	0.7877	0.7298	0.6790	11.90	–
2FI	0.8188	0.6829	0.5970	12.90	–
Quadratic	0.9992	0.9977	0.9899	1.11	0.70
Response (Y2)
Linear	0.3656	0.1926	0.0539	0.83	–
2FI	0.5031	0.1304	0.3732	0.86	–
Quadratic	0.9991	0.9974	0.9919	0.047	0.63
Response (Y3)
Linear	0.3903	0.2240	0.0368	7.95	–
2FI	0.5321	0.1812	0.0520	8.16	–
Quadratic	0.9971	0.9919	0.9587	0.81	1.11

Figure 1. (A–D) 3D-response surface plots and 2D contour plot showing the influence of independent variables [eudragit (%), tween 80 (%), and sonication time (minutes)] on particle size (nm) for the SIT-NPs.

Figure 2. (A–D) 3D-response surface plots and 2D contour plot showing the influence of independent variables [eudragit (%), tween 80 (%), and sonication time (minutes)] on drug loading (%) for the SIT-NPs.

Figure 3. (A–D) 3D-response surface plots and 2D contour plot showing the influence of independent variables [eudragit (%), tween 80 (%), and sonication time (minutes)] on drug release (%) for the SIT-NPs.

Figure 4. Predicted vs. actual plot showing the influence of independent variables [eudragit (%), tween 80 (%), and sonication time (minutes)] on dependent variables [particle size (nm), drug loading (%) and drug release (%)] for the SIT-NPs.

Table 4. Experimentally optimized value of formulation SIT-NPopt.

Particle size	Drug loading	Drug release	Encapsulation efficiency	PDI	Enhancement ratio	Release kinetics	Shelf life
135.29 ± 5.12 nm	8.78 ± 1.11%	84.81 ± 6.23%	82.34 ± 3.27%	0.287	3.11 times	Higuchi’s (R^2= 0.925)	583 d

Figure 5. (A–D) Images of SIT-NPopt: (A) Particle size distribution image; (B) Transmission electron micrograph; (C) Scanning electron micrograph; (D) Atomic force microscopy.

Figure 6. Comparative in-vitro drug release profile of SIT-NPopt and SIT-Fs.

Table 5. In vitro release kinetics data to different mathematical models for SIT-NPopt and SIT-fs.

Release kinetics	Equation	X axis	Y axis	SIT-NPopt (R^2)	SIT-FS (R^2)
Zero order release	Mt = M0 + k0 t	Fraction of drug released	Time	0.891	0.823
First order release	ln Mt = ln M0 + k1 t	Log % drug remaining	Time	0.911	0.817
Korsmeyer–Peppas	Mt/M∞ = Ktn	Log fraction of drug released	Log time	0.873	0.723
Higuchi	Mt = M0 + kH t1/2	Fraction of drug released	√time	0.925	0.711

M₀: initial amount of drug; M_t: remaining amount of drug at time t; k₀: zero order release constant; k1: first order release constant; Mt/M∞: fraction of drug released at time t; K: release rate constant; n: release exponent; Higuchi dissolution constant.

Figure 7. Comparative In-vivo antidiabetic activity profile of different treated groups on animal model.

Figure 8. (A–D) Effect of different temperature with humidity on the stability study data of SIT-NPopt.