Rapid disintegrating tablets of simvastatin dispersions in polyoxyethylene–polypropylene block copolymer for maximized disintegration and dissolution

Figures & data

Table 1 Composition of different simvastatin solid dispersions and physical mixtures

Formulation code	Drug:poloxamer 188 (w/w)
SD1	1:4
SD2	1:2
SD3	1:1
SD4	1:0.5
PM1	1:4
PM2	1:2
PM3	1:1
PM4	1:0.5

Abbreviations: PM, physical mixture; SD, solid dispersion.

Table 2 3² full-factorial design layout of simvastatin RDTs

Formulation #	Variables		Responses*
	Croscarmellose sodium (%) X1	Hardness (kP) X2	Disintegration time (seconds)	Q15min§	Q30min§	Water absorption ratio
1	1	1	6.43	26.52	40.94	129.1
2	1	3	52.45	30.2	39.47	84.5
3	1	5	63.72	29.54	43.76	69.2
4	2	1	4.98	40.85	48.51	124.8
5	2	3	45.65	39.45	52.47	75.8
6	2	5	52.23	36.47	48.96	72.3
7	3	1	5.06	48.12	59.74	139.5
8	3	3	39.19	45.98	56.19	102.7
9	3	5	47.43	42.51	57.57	83.6
Check point	2.4	1	5.82	25.64	51.61	124.7

Notes:

* Standard deviation values of the responses did not exceed 5% of the measured values.

§ Q_15min and Q_30min are percentages of drug dissolved after 15 and 30 minutes, respectively.

Abbreviation: RDT, rapid disintegrating tablet.

Figure 1 Effect of increasing concentration of poloxamer 188 on the solubility of simvastatin.

Note: Standard deviations did not exceed 3% of the plotted values.

Figure 2 Dissolution profiles and parameters of raw simvastatin powder and its SDs and PMs with poloxamer 188 (n=3).

Note: DE10 and DE60 are percentage dissolution efficiencies after 10 and 60 minutes, respectively.
Abbreviations: PM, physical mixture; SD, solid dispersion.

Figure 3 FTIR spectra of raw simvastatin, poloxamer 188 powders as well as their SDs and PMs.

Abbreviations: FTIR, Fourier transform infrared spectroscopy; PM, physical mixture; SD, solid dispersion.

Figure 4 DSC thermograms (A) and XRD diffractograms (B) of raw simvastatin, poloxamer 188 powders as well as their SDs and PMs.

Abbreviations: DSC, differential scanning calorimetry; PM, physical mixture; SD, solid dispersion; XRD, X-ray diffraction.

Table 3 Evaluation of RDTs incorporating simvastatin solid dispersion

Batch #	Mean weight (mg) ± standarddeviation	Mean diameter(mm) ± standarddeviation	Mean thickness(mm) ± standarddeviation	% drug content± standarddeviation	% friability ±standarddeviation	Breaking strength(kP) ± standarddeviation
1	220.2±0.58	9.9±0.02	2.1±0.02	100.9±0.21	0.43±0.28	1.1±0.34
2	218.5±0.85	10.2±0.01	2.1±0.01	101.2±0.53	0.25±0.17	3.1±0.75
3	220.5±0.42	10.1±0.03	2.2±0.03	100.2±1.43	0.43±0.43	5.0±0.93
4	220.6±0.52	10.2±0.02	2.1±0.01	99.9±1.04	0.52±0.11	2.9±0.72
5	220.3±0.54	10.8±0.02	2.2±0.02	99.3±0.83	0.32±0.33	2.9±0.45
6	219.3±0.40	10.3±0.01	2.1±0.01	98.7±0.93	0.28±0.27	5.1±0.42
7	222.8±0.84	10.1±0.01	2.3±0.03	99.2±1.73	0.39±0.68	1.2±0.60
8	219.1±0.21	10.1±0.02	2.2±0.01	100.2±0.92	0.37±0.37	3.1±0.52
9	220.5±0.25	10.2±0.01	2.1±0.03	98.6±1.36	0.51±0.51	2.1±0.61

Abbreviation: RDT, rapid disintegrating tablet.

Table 4 Results of multiple regression analysis and analysis of variance for testing the model in portions

Multiple regression analysis
Response	A	y1	y2	y3	y4	y5
Disintegration time (seconds)	18.39	−5.15	12.24	−1.87	1.43	−3.95
P-value	0.0043	0.0065	<.0001	0.0277	0.3566	0.0012
Q15min*	24.69	8.39	−0.58	−1.08	−1.78	−0.30
P-value	0.0005	0.0004	0.0931	0.0345	0.1206	0.2401
Q30min*	32.90	8.22	0.09	−0.62	−0.37	0.13
P-value	0.0018	0.0039	0.8673	0.3869	0.8465	0.7788
Water absorption ratio	108.43	7.17	−14.03	0.50	10.47	3.85
P-value	0.0004	0.039	0.0008	0.7154	0.0593	0.0222
Analysis of variance
	Degrees of freedom	Sum of squares	Mean square	P > F	R^2
Disintegration time	5	4,314.70	862.94	0.0004	0.9976
Q15min*	5	458.48	91.70	0.0028	0.9911
Q30min*	5	412.85	82.57	0.0286	0.9575
Water absorption ratio	5	5,727.43	1,145.49	0.0049	0.9871

Note:

* Q_15min and Q_30min are percentages of drug released after 15 and 30 minutes, respectively.

Figure 5 Response surface and contour plots showing the effect of Ac-Di-Sol amount (X₁) and hardness (X₂) on the dependent factors of simvastatin SD-loaded RDTs.

Note: Q_15min and Q_30min are percentages of simvastatin released after 15 and 30 minutes, respectively.
Abbreviations: RDTs, rapid disintegrating tablets; SD, solid dispersion.

Figure 6 Quantile–quantile plots for predicting the investigated the responses of simvastatin RDT.

Note: Q_15min and Q_30min are percentages of drug released after 15 and 30 minutes, respectively.
Abbreviation: RDT, rapid disintegrating tablet.

Figure 7 Interaction plots and Pareto charts showing the colinear effects of interactions between the independent factors on the disintegration time, Q_15min, Q_30min, and water absorption ratio.