Design and in vitro evaluation of formulations with pH and transit time controlled sigmoidal release profile for colon-specific delivery

Figures & data

Table 1.  Composition, physical characterization, and release rate kinetics of polycarbophil-based formulations.

Batches	Composition#			Physical characterization					Power law correlation
	Drug (mg)	PCP (mg)	EC (mg)	Drug content (mg/tablet)	Weight variation^a (%)	Crushing strength^b (kg)	Friability^c (%)	Thickness^d (mm)	Correlation time span	r^e	K^f (%/h^n)	n^g	t10%^h	t90%^i
Effect of PCP only
IPCP10	75	7.5	—	69.9	±3.9	4.3 (±0.3)	0.1%	1.76 (±0.02)	2–10 h	0.9791	4.201	1.46	2.0	8.2
IPCP20	75	15	—	70.1	±4.0	4.6 (±0.2)	0.4%	2.11 (±0.01)	2–8 h	0.9808	11.114	1.03	1.1	7.6
IPCP50	75	37.5	—	72.7	±4.3	4.3 (±0.1)	0.3%	2.16 (±0.02)	2–8 h	0.9703	20.710	0.78	0.3	6.7
Effect of EC on PCP matrix
IPCP10EC5	75	7.5	3.75	70.2	±4.6	4.6 (±0.6)	0.4%	1.86 (±0.01)	2–14 h	0.9968	1.281	1.59	3.8	14.5
IPCP10EC10	75	7.5	7.5	74.1	±1.0	4.7 (±0.3)	0.2%	1.72 (±0.02)	2–14 h	0.9978	1.067	1.65	3.9	14.7
IPCP10EC20	75	7.5	15	78.3	±3.0	4.7 (±0.2)	0.1%	2.06 (±0.01)	4–14 h	0.9834	1.145	1.55	4.6	16.7
IPCP10EC40	75	7.5	30	70.2	±4.1	4.9 (±0.1)	0.4%	2.08 (±0.01)	6–14 h	0.9975	4.260	1.02	5.9	19.9
IPCP20EC5	75	15	3.75	72.8	±2.3	4.4 (±0.3)	0.1%	2.06 (±0.02)	2–10 h	0.9974	7.495	1.21	1.6	7.8
IPCP20EC10	75	15	7.5	77.3	±4.6	4.1 (±0.1)	0.4%	2.07 (±0.01)	2–10 h	0.9874	5.959	1.33	1.8	7.7
IPCP20EC20	75	15	15	72.2	±3.8	4.1 (±0.4)	0.2%	2.08 (±0.02)	2–10 h	0.9874	3.035	1.64	2.2	7.9
IPCP20EC40	75	15	30	70.4	±4.6	4.2 (±0.3)	0.4%	2.12 (±0.02)	2–14 h	0.9882	0.484	2.11	3.8	11.9
Effect of simulated GI fluid pH (without enzymes)
IPCP10EC5	75	7.5	3.75	70.3	±4.6	4.6 (±0.8)	0.4%	1.82 (±0.01)	6–14 h	0.9836	0.250	2.1	4.5	16.5
IPCP20EC20	75	15	15	72.8	±2.3	4.1 (±0.4)	0.2%	2.11 (±0.01)	6–14 h	0.9870	0.399	1.95	8.3	16.1
IPCP10EC10	75	7.5	7.5	70.4	±4.6	4.7 (±0.3)	0.2%	1.69 (±0.02)	6–14 h	0.9982	0.152	2.20	9.2	18.2

# Also contains 1% w/w talc and 0.5% w/w magnesium stearate as formulation additives.

^a SD from the mean value (n = 20); ^b mean SD (n = 10); ^c mean of 10 tablets; ^d mean SD (n = 5); ^e Correlation coefficient; ^f Release rate constant; ^g Diffusional exponent indicative of the release mechanism; ^h Time for 10% of the drug release (in h); ⁱ the predicted or calculated time for 90% of the drug release (in h from equation 2).

The diameter of the tablets was 0.70 ± 0.01 cm.

Table 2.  Composition, physical characterization, and release rate kinetics of carbopol-based formulations.

Batches	Composition#			Physical characterization					Power law correlation
	Drug (mg)	CP (mg)	EC (mg)	Drug content (mg/ tablet)	Weight variation^a(%)	Crushing strength^b(kg)	Friability^c (%)	Thickness^d (mm)	Correlation time span	r^e	K^f (%/h^n)	n^g	t10%^h	t90%^i
Effect of CP only
ICP10	75	7.5	—	71.5	±5.0	4.4 (±0.3)	0.1%	1.79 (±0.01)	2–14 h	0.9721	5.411	0.74	1.0	*
ICP20	75	15	—	73.1	±2.3	4.8 (±0.2)	0.2%	2.03 (±0.02)	2–14 h	0.9736	6.382	0.62	1.0	*
ICP50	75	37.5	—	75.7	±5.0	4.0 (±0.3)	0.5%	2.16 (±0.02)	2–14 h	0.9802	4.966	0.37	4.2	*
Effect of EC on CP matrix
ICP10EC5	75	7.5	3.75	69.7	±2.0	4.1 (±0.1)	0.3%	1.85 (±0.01)	2–14 h	0.9823	2.714	1.26	4.2	16.1
ICP10EC10	75	7.5	7.5	76.5	±3.2	4.2 (±0.4)	0.4%	1.69 (±0.02)	2–14 h	0.9931	2.155	1.34	5.0	16.2
ICP10EC20	75	7.5	15	70.6	±2.5	4.6 (±0.2)	0.5%	2.07 (±0.01)	2–14 h	0.9918	1.473	1.48	5.5	16.1
ICP10EC40	75	7.5	30	78.1	±4.6	4.9 (±0.3)	0.4%	2.09 (±0.01)	2–14 h	0.9892	1.497	1.25	6.8	26.5
ICP20EC5	75	15	3.75	71.8	±5.0	4.0 (±0.1)	0.5%	2.05 (±0.02)	2–14 h	0.9860	0.396	1.87	4.7	18.2
ICP20EC10	75	15	7.5	74.9	±2.5	4.8 (±0.2)	0.5%	2.07 (±0.01)	2–14 h	0.9835	0.267	1.94	5.5	20.1
ICP20EC20	75	15	15	70.5	±5.0	4.8 (±0.5)	0.4%	2.08 (±0.02)	2–14 h	0.9993	1.043	1.44	6.1	22.1
ICP20EC40	75	15	30	74.3	±3.4	4.0 (±0.4)	0.5%	2.12 (±0.02)	2–14 h	0.9772	1.355	1.23	7.2	30.3
Effect of simulated GI fluid pH (without enzymes)
ICP10EC5	75	7.5	3.75	72.2	±3.4	4.1 (±0.1)	0.3%	1.80 (±0.01)	4–14 h	0.9884	0.032	2.84	5.4	16.3
ICP20EC5	75	15	3.75	74.8	±2.5	4.0 (±0.1)	0.5%	2.08 (±0.01)	4–14 h	0.9884	0.134	2.10	4.3	22.2

# Also contains 1% w/w talc and 0.5% w/w magnesium stearate as formulation additives.

^a SD from the mean value (n = 20); ^b mean SD (n = 10); ^c mean of 10 tablets; ^d mean SD (n = 5); ^e Correlation coefficient; ^f Release rate constant; ^g Diffusional exponent indicative of the release mechanism; ^h Time for 10% of the drug release (in h); ⁱ the predicted or calculated time for 90% of the drug release (in h from equation 2).

* Not determined as release rate was very slow.

The diameter of the tablets was 0.70 ± 0.01 cm.

Figure 1.  Release profile of indomethacin from matrix tablets with varying proportion of PCP. Each data point is expressed as mean  ± SD (n = 6).

Figure 2.  Release profile of indomethacin from matrix tablets with varying proportion of CP. Each data point is expressed as mean ± SD (n = 6).

Figure 3.  Release profile of indomethacin from matrix tablet showing effect of varying proportion of EC on 10% PCP. Each data point is expressed as mean ± SD (n = 6). The dotted trend line represents the predicted release profile for each formulation beyond 14 h till 24 h.

Figure 4.  Release profile of indomethacin from matrix tablet showing effect of varying proportion of EC on 20% PCP. Each data point is expressed as mean ± SD (n = 6). The dotted trend line represents the predicted release profile for each formulation beyond 14 h till 24 h.

Figure 5.  Release profile of indomethacin from matrix tablet showing effect of varying proportion of EC on 10% CP. Each data point is expressed as mean ± SD (n = 6). The dotted trend line represents the predicted release profile for each formulation beyond 14 h till 24 h.

Figure 6.  Release profile of indomethacin from matrix tablet showing effect of varying proportion of EC on 20% CP. Each data point is expressed as mean ± SD (n = 6). The dotted trend line represents the predicted release profile for each formulation beyond 14 h till 24 h.

Figure 7.  Release profile of indomethacin from selected formulations in simulated GI fluid pH (without enzymes). Each data point is expressed as mean ± SD (n = 6).The dotted trend line represents the predicted release profile for each formulation beyond 14 h till 24 h.