QbD-based carbopol transgel formulation: characterization, pharmacokinetic assessment and therapeutic efficacy in diabetes

Figures & data

Table 1. Observed and predicted response in the Box–Behnken design for pioglitazone proniosomal formulation.

Code				Particle Size Y1 (nm)		Entrapment Y2 (%)		Flux Y3 (µg/cm^2/h)
S.No	A	B	C	Actual	Predicted	Actual	Predicted	Actual	Predicted
1	120	40	30	413.87 ± 6.77	412.55	54.28 ± 11.87	54.07	29.31 ± 24.65	30.99
2	160	40	30	477.24 ± 6.81	478.95	69.76 ± 13.27	70.91	40.78 ± 19.73	40.11
3	120	80	30	437.22 ± 7.87	435.51	63.65 ± 10.54	62.50	20.27 ± 20.74	20.94
4	160	80	30	578.27 ± 6.29	579.59	83.38 ± 9.65	83.59	25.41 ± 28.94	24.72
5	120	60	15	416.65 ± 8.43	418.65	42.27 ± 11.28	43.11	36.87 ± 23.54	36.38
6	160	60	15	517.79 ± 7.76	516.75	71.54 ± 8.54	71.02	37.67 ± 19.77	38.54
7	120	60	45	437.12 ± 4.51	438.16	54.37 ± 6.98	54.89	19.82 ± 26.65	18.41
8	160	60	45	552.54 ± 5.65	550.54	65.76 ± 8.39	64.92	29.66 ± 32.78	30.15
9	140	40	15	417.26 ± 9.98	416.59	71.99 ± 7.54	71.36	43.24 ± 30.83	43.04
10	140	80	15	498.69 ± 12.67	498.41	81.32 ± 11.28	81.63	21.28 ± 35.86	21.10
11	140	40	45	462.97 ± 8.49	463.26	74.23 ± 9.44	73.92	19.68 ± 29.56	20.16
12	140	80	45	504.37 ± 5.87	505.04	84.13 ± 8.53	84.75	17.44 ± 19.66	17.64
13	140	60	30	393.41 ± 6.76	392.46	90.59 ± 10.39	90.65	41.23 ± 23.64	40.61
14	140	60	30	392.22 ± 10.12	392.46	91.42 ± 7.43	90.65	40.28 ± 27.78	40.61
15	140	60	30	391.76 ± 9.13	392.46	89.95 ± 13.44	90.65	40.32 ± 25.87	40.61
16	Hydroethanolic Solution							13.67 ± 4.54

A = Tween80 (mg), B = Phospholipid (mg), C = Cholesterol (mg); Y₁ = Particle size (nm); Y₂ = Entrapment efficiency (%); Y₃ = Flux (µg/cm²/h).

Figure 1. (a) Response surface analysis: a response surface graph representing the effect of independent variables on size, (b) response surface graph representing the effect of independent variables on % encapsulation efficiency and (c) response surface graph representing the effect of independent variables on flux.

Table 2. Summary of results of regression analysis for responses Y₁, Y₂ and Y_3..

Model	R^2	Adjusted R^2	Predicted R^2	SD	% CV	Remark
Response (Y1)
Linear	0.6215	0.5183	0.4557	41.57
2F1	0.6606	0.4060	0.3115	46.16
Quadratic	0.9996	0.9988	0.9934	2.1	0.46	Suggested
Response (Y2)
Linear	0.3162	0.1297	0.1426	13.73
2F1	0.3441	0.1478	0.1401	15.76
Quadratic	0.9978	0.9937	0.9691	1.16	1.6	Suggested
Response (Y3)
Linear	0.5758	0.4601	0.3112	7.05
2F1	0.6744	0.4302	0.19	7.25
Quadratic	0.9965	0.9901	0.9498	0.95	3.09	Suggested

Figure 2. Regression line of actual versus predicted value: (a) particle size, (b) entrapment efficiency and (c) flux.

Figure 3. Particle size graph (a) and TEM image of proniosome (b).

Figure 4. Confocal laser microscopy of control (a) and proniosome (b).

Figure 5. In vitro drug release from POPF gel and control formulation.

Table 3. Pharmacokinetic parameters of pioglitazone in rats (mean ± SD, n = 6).

Parameters	Tablet	POPF-TTS
Tmax^a (h)	2 ± 0.23	8 ± 0.76
Cmax^b (ng/mL)	54.52 ± 29.41	41.19 ± 27.27
AUC0–48^c (ng/ml/h)	427.82 ± 57.59	868.53 ± 61.1
AUC0–∞^d (ng/ml/h)	481.36 ± 69.67	1113.92 ± 84.27
t1/2^e (h)	2.41 ± 0.41	10.14 ± 1.63
F%^f	–	2.26

^aTime of peak concentration.

^bPeak of maximum plasma concentration.

^cArea under concentration time profile curve until last observation.

^dArea under concentration time profile curve from time 0 to infinity.

^eElimination half-life.

^fRelative bioavailability.

Table 4. Influence of formulations of pioglitazone on mean Blood sugar level (BS) in STZ-induced diabetic rats (mean ± SD, n = 6).

Mean Blood glucose level (mg/dl)
Group	0 h	1 h	3 h	6 h	9 h	12 h	24 h	36 h	48 h	percentage reduction in BS^a
Group I^b	89.7 ± 7.32	87.7 ± 9.14	91.7 ± 11.34	88.7 ± 7.66	87.7 ± 8.84	85.7 ± 9.91	92.7 ± 10.28	93.7 ± 8.16	90.7 ± 7.75	–
Group II^c	245.5 ± 10.82	243.7 ± 8.79	238.5 ± 9.43	233.5 ± 10.35	241.6 ± 8.66	246.3 ± 9.57	253.5 ± 1.59	238.2 ± 2.41	241.2 ± 7.83	–
Group III	238.4 ± 9.23	217.8 ± 11.33	178.9 ± 8.74	157.8 ± 10.65	131.65 ± 9.29	125.5 ± 7.28	111.5 ± 8.48	122.2 ± 11.27	136.3 ± 9.68	44.49
Group IV	237.6 ± 9.84	205.4 ± 8.25	151.6 ± 10.79	133.3 ± 12.21	165.2 ± 10.29	181.7 ± 8.27	211.2 ± 9.26	223.2 ± 7.21	219.7 ± 9.17	8.91

Group I – Control, Group II – Diabetic Control, Group III – POPF-TTS, Group IV – Oral formulation.

^aPercentage reduction in BS at 48-h time point.

^bControl rats without diabetes induced and no further treatment.

^cDiabetes was induced with STZ, and no treatment was given.