Development of enzyme-controlled colonic drug delivery using amylose and hydroxypropyl methylcellulose: Optimization by factorial design

Figures & data

Table 1.  Formulation of core tablets.

Sr. No.	Ingredients	Qty/tablet (mg)
1	Diclofenac sodium IP	50
2	Sodium Starch Glycolate	10
3	Microcrystalline cellulose	4
4	Talc	5
5	Magnesium stearate	10
6	Lactose monohydrate	121

Table 2.  Physical properties of Diclofenac core tablet compression coated with Amylose–HPMC K100LV.

Code	Weight (mg)	Crushing strength (kg/cm^2)	Thickness (mm)	Friability (%)
Core	200 ± 1.98	2–3	3.71 ± 0.04	0.18
R1	450 ± 1.24	4–5	5.90 ± 0.04	0.08
R2	475 ± 1.75	4–5	5.89 ± 0.05	0.09
R3	500 ± 2.10	4–5	5.94 ± 0.04	0.10
R4	425 ± 1.56	4–5	5.88 ± 0.03	0.09
R5	450 ± 1.12	4–5	5.90 ± 0.05	0.10
R6	475 ± 1.72	4–5	5.92 ± 0.03	0.08
R7	400 ± 1.34	4–5	5.87 ± 0.04	0.09
R8	425 ± 1.52	4–5	5.89 ± 0.04	0.09
R9	450 ± 1.45	4–5	5.89 ± 0.03	0.10

Table 3.  Experimental design: Factors and responses.

Factors (independent variables)	Levels used			Responses (dependent variables)
	−1	0	1
X1 = Amylose (mg)	325	300	275	Y1 = % release in lag time
X2 = HPMC K100 LV(mg)	125	150	175	Y2 = T90% drug release

Table 4.  Composition of experimental formulations (runs).

Code	Variable factors
	X1 = Amylose (mg)	X2 = HPMC K100 LV (mg)
R1	325	125
R2	325	150
R3	325	175
R4	300	125
R5	300	150
R6	300	175
R7	275	125
R8	275	150
R9	275	175

Table 5.  Experimental runs and observed results of Release after 5h (Y ₁) and T90% (Y ₂).

Run	Responses
	Y1	Y2
R1	12.10	6.5
R2	7.46	8
R3	3.21	8
R4	14.63	6.5
R5	8.10	7.5
R6	5.42	8
R7	15.12	6
R8	10.13	7
R9	6.21	7.5

Table 6.  Composition of observed and predicted response parameters.

Formulation code	Formulation composition Amylose:HPMC K100LV	Response property	Experimental value	Predicted value	Residual error
A1	275:150	% release in lag time	11.20	10.23	0.97
		T90% drug release	7.00	7.057	−0.057
A2	280:150	% release in lag time	10.78	9.85	0.93
		T90% drug release	7.15	7.17	−0.02
A3	285:150	% release in lag time	9.53	9.48	0.044
		T90% drug release	7.30	7.27	0.0219

Table 7.  Analysis of variance (ANOVA) of dependent variables.

Source of variation	Sum of squares	Degree of freedom	Mean square	F ratio	p-value
Y1
Regression	158.07	5	31.61	129.17	0.0011
Residuals	0.73	3	0.24
Total	158.81	8
R^2	0.9954
Y2
Regression	5.51	5	1.10	67.97	0.0028
Residuals	0.049	3	0.016
Total	5.56	8
R^2	0.9912

Figure 1.  Response surface plot of release after 5 h from compression-coated tablet formulation containing amylose and HPMC in different proportions.

Figure 2.  Response surface plot of time required for 90% release from compression-coated tablet formulation containing amylose and HPMC in different proportions.

Figure 3.  Dissolution profiles of all formulations R1–R9 (Table 4). Mean (± SD) percentage of diclofenac released from compression-coated tablet formulation (n = 3) containing amylose and HPMC in different proportions with amylase enzyme added in dissolution media after stage II.

Figure 4.  Dissolution profile diclofenac sodium tablet coated with amylose and HPMC (285:150) in the presence of enzyme (B1) and without enzyme in dissolution media (B2).

Figure 5.  Dissolution profile of diclofenac sodium tablet coated with amylose and HPMC (285:150) in different pH media.

Figure 6.  Dissolution profile of diclofenac tablet coated with amylose and HPMC (285:150) with (F1) and without superdisintegrant (F2).

Table 8.  The position of the tablets throughout the gastrointestinal tract in the subjects at certain points in time. Subjects 1 and 2 ingested tablets with superdisintegrant and subjects 3 and 4 ingested tablets without superdisintegrant, both coated with optimized amylose and HPMC compression coat.

Subject	2 h	3.30 h	3.45 h	6.30 h
1	Compression coating with disintegrant
	Stomach	Ileo-cecal region	Disintegrated	—
2	Small intestine	cecum	Disintegrated	—
	Compression coating without disintegrant
3	Stomach	Small intestine	Ileo-cecal region	Ascending colon (non-disintegrated)
4	Stomach	Small intestine	Ileo-cecal region	Ascending colon (non-disintegrated)

Figure 7.  Radiograph of the tablet after specified time interval indicating the position and status of tablet. Subjects 1 and 2 ingested tablets with superdisintegrant and subjects 3 and 4 ingested tablets without superdisintegrant, both coated with optimized amylose and HPMC compression coat.