Enhancement of dissolution and oral bioavailability of lacidipine via pluronic P123/F127 mixed polymeric micelles: formulation, optimization using central composite design and in vivo bioavailability study

Figures & data

Table 1. Independent variables and respective levels in the 3² CCFD for LCDP polymeric micelles preparation, model summary statistics of quadratic model, constrains for optimization and factors levels for optimized LCDP polymeric micelles formula and their predicted and observed values.

		Levels of variables
Factors (independent variables)		Low (−1)	Medium (0)	High (+1)		Optimized level
A: Pluronic to drug ratio^a		10	30	50		45
B: P123 percentage (% w/w)		10	50	90		80
Responses	r^2	Adjusted r^2	Prediction r^2	Constrains	Predicted	Observed	95% prediction interval
Y1: Entrapment efficiency (%)	0.9162	0.8900	0.8247 (0.8311)^b	Maximize	100	99.23	81.06–123.26
Y2: Particle size (nm)	0.8650	0.8229	0.7200	Minimize	19.88	21.08	9.74–30.02
Y3: PDI	0.9053	0.8757	0.8257 (0.8366)^b	Minimize	0.097	0.11	0.039–0.160

^a The levels of variable (A) are 10:1, 30:1 and 50:1. Since the drug is always designated in the ratio as “1”, so the levels of variable (A) were written as 10, 30 and 50.

^b Reduced model prediction r².

Table 2. Composition of the 3² CCFD and the average EE%, PS and PDI for the prepared LCDP polymeric micelles.

	Factors levels in actual values
Formula	Pluronic to drug ratio	P123 percentage (%)	EE% + SD (%)^a	PS + SD (nm)^a	PDI + SD^a
M1	10	10	7.27 ± 0.47	58.73 ± 1.56	0.23 ± 0.01
M2	50	10	98.72 ± 0.72	26.34 ± 0.09	0.14 ± 0.01
M3	10	90	79.22 ± 1.00	26.83 ± 0.96	0.29 ± 0.03
M4	50	90	99.55 ± 0.18	20.03 ± 0.21	0.08 ± 0.02
M5	10	50	64.28 ± 0.98	26.07 ± 1.07	0.32 ± 0.04
M6	50	50	96.69 ± 0.77	23.46 ± 0.29	0.14 ± 0.02
M7	30	10	97.35 ± 0.25	29.93 ± 0.76	0.18 ± 0.01
M8	30	90	98.15 ± 0.89	20.65 ± 0.20	0.15 ± 0.01
M9	30	50	97.75 ± 0.16	23.13 ± 0.16	0.15 ± 0.03
M10	30	50	97.23 ± 0.41	23.12 ± 0.53	0.14 ± 0.01
M11	30	50	99.43 ± 0.73	23.74 ± 0.95	0.13 ± 0.03

^a All measurements are done in triplicates.

Figure 1. Response surface plot for the effect of Pluronic to drug ratio and P123 percentage on: (a) EE%, (b) PS and (c) PDI.

Figure 2. (a) TEM of optimum LCDP polymeric micelles formula, (b) and (c) SEM of optimum LCDP lyophilized polymeric micelles formula, magnification 200× and 500×, respectively.

Figure 3. (a) Optimum Pluronic P123/F127 mixed polymeric micelles CMC determination by I₂ UV spectroscopy method (b) In vitro dissolution rate profile of LCDP polymeric micelles in 0.1 M HCl (pH = 1.2) at 37 °C in comparison to raw LCDP and (c) The mean plasma concentration time curve after the administration of LCDP polymeric micelles and LCDP oral suspension to six albino rabbits.

Table 3. Mean pharmacokinetic parameters of LCDP following the administration of optimum LCDP polymeric micelles formula and LCDP oral suspension to six albino rabbits.

PK parameter	LCDP polymeric micelles	LCDP oral suspension	Statistical test
Cmax (ng/ml)	230.68 ± 20.21	3.72 ± 1.55	p = .000
tmax (h)^a	0.5	8	p = .000
AUC(0–72) (ng h/ml)	493.22 ± 67.28	69.59 ± 28.38	p = .000
AUC(0–∞) (ng h/ml)	498.87 ± 66.38	72.75 ± 26.97	p = .000
λz (h^−1)	0.05 ± 0.01	0.05 ± 0.01	p = .791
t1/2 (h)	14.92 ± 3.21	15.02 ± 5.61	p = .976

^a Median.