Ethylcellulose Inserts of an Orphan Drug for Periodontitis: Preparation, In Vitro, and Clinical Studies

Figures & data

TABLE 1 Composition and physicochemical characterization of the prepared inserts

Batch code	Niridazole (mg/insert)	Ethylcellulose (mg/cm^2)	Weight (mg ± S.D.)	Drug content (mg ± S.D.)	Thickness (mg ± S.D.)
EN1	0.25	30	4.0 ± 0.74	0.25 ± 0.02	0.28 ± 0.03
EN2	0.50	30	4.13 ± 0.42	0.51 ± 0.03	0.26 ± 0.03
EN3	1.0	30	4.04 ± 0.46	0.92 ± 0.05	0.35 ± 0.04
EN4	0.45	65	8.42 ± 0.38	0.44 ± 0.05	0.77 ± 0.05
EN5	0.45	75	8.90 ± 0.54	0.47 ± 0.04	0.79 ± 0.05
EN6	0.60	55	7.53 ± 0.88	0.57 ± 0.05	0.75 ± 0.07
EN7	0.60	55	8.0 ± 0.40	0.61 ± 0.08	0.78 ± 0.05

All inserts were fabricated in chloroform as solvent containing 40% w/v dibutyl phthalate as plasticizer. Batch EN6 and EN7 were prepared by casting and spraying, respectively.

FIG. 1 Effect of niridazole loading on release rate.

FIG. 2 Effect of ethylcellulose concentration on release rate.

TABLE 2 Drug release kinetics from the fabricated inserts

	r
Batch	Zero order	Higuchi equation	First order	n	k
EN1	0.9604 ± 0.02	0.9941 ± 0.01	0.990 ± 0.02	0.5439	0.0552 ± 0.06
EN2	0.9768 ± 0.01	0.9985 ± 0.02	0.9837 ± 0.01	0.5765	0.0278 ± 0.001
EN3	0.9985 ± 0.04	0.9920 ± 0.03	0.9443 ± 0.03	0.6649	0.0090 ± 0.002
EN4	0.7698 ± 0.02	0.8917 ± 0.04	0.9803 ± 0.02	0.4352	0.0674 ± 0.005
EN5	0.7308 ± 0.01	0.8284 ± 0.01	0.9155 ± 0.01	0.5950	0.0958 ± 0.003
EN6	0.9834 ± 0.05	0.9953 ± 0.04	0.9772 ± 0.05	0.6034	0.0229 ± 0.004
EN7	0.9796 ± 0.02	0.9986 ± 0.03	0.9886 ± 0.03	0.5582	0.0203 ± 0.001

FIG. 3 Method of fabrication on drug release (EN6-casting; EN7-spraying method).

TABLE 3 Full scale clinical evaluation of niridazole insert (Batch EN3) in patients for 6 months.

	Scores
Clinical indices	Prescaling	Day 0	Day 7	Day 14	Day 21	Day 28	1.5 M	2 M	3 M	6 M
CC	1.57 ± 0.05	B	−0.46 ± 0.08	−0.58 ± 0.12	−0.75 ± 0.09	−0.77 ± 0.11	−0.80 ± 0.15	−0.87 ± 0.17	−0.79 ± 0.11	−0.57 ± 0.09
	(0.53 ± 0.11)	A	(−0.50 ± 0.18)	(−0.67 ± 0.23)	(−0.58 ± 0.30)	(−0.43 ± 0.03)	−0.50 ± 0.18)	(−0.55 ± 0.19)	(−0.51 ± 0.16)	(−0.61 ± 0.6)
PI	1.06 ± 0.07	S	−0.48 ± 0.07	−0.59 ± 0.05	−0.67 ± 0.10	−0.42 ± 0.09	−0.64 ± 0.09	−0.28 ± 0.18	−0.33 ± 0.11	−0.23 ± 0.15
	(0.28 ± 0.12)	E	(−0.18 ± 0.11)	(−0.12 ± 0.09)	(−0.40 ± 0.17)	(−0.50 ± 0.13)	(−0.13 ± 0.07)	(+0.22 ± 0.05)	(+0.27 ± 0.17)	(−0.11 ± 0.76)
GI	0.55 ± 0.06	L	−0.85 ± 0.18	−1.44 ± 0.07	−1.49 ± 0.10	−1.57 ± 0.08	−1.48 ± 0.09	−1.29 ± 0.17	−1.61 ± 0.07	−1.36 ± 0.11
	(0.11 ± 0.02)	I	(−0.55 ± 0.21)	(−0.89 ± 0.18)	(−0.58 ± 0.29)	(−1.0 ± 0.09)	(−0.90 ± 0.06)	(−0.89 ± 0.07)	(−1.0 ± 0.16)	(−0.38 ± 0.22)
BI	0.72 ± 0.04	N	−0.74 ± 0.04	−1.08 ± 0.07	−1.39 ± 0.07	−1.36 ± 0.09	−1.62 ± 0.08	−1.32 ± 0.13	−1.42 ± 0.10	−1.26 ± 0.13
	(0.13 ± 0.01)	E	(−0.82 ± 0.13)	(−0.75 ± 0.17)	(−0.94 ± 0.18)	(−1.07 ± 0.2)	(−0.60 ± 0.17)	(−1.0 ± 0.18)	(−1.38 ± 0.26)	(−0.14 ± 0.29)
PD	0.008 ± 0.001		−0.23 ± 0.10	−0.26 ± 0.13	−0.28 ± 0.11	−0.43 ± 0.12	−0.67 ± 0.11	−0.83 ± 0.12	−0.83 ± 0.12	−2.59 ± 0.37
	(0.01 ± 0.008)		(−0.14 ± 0.15)	(−0.43 ± 0.13)	(−0.41 ± 0.14)	(−0.45 ± 0.14)	(−0.41 ± 0.19)	(−0.50 ± 0.24)	(−0.45 ± 0.25)	(−0.29 ± 0.27)

Values in parenthesis are of control group.

CC = calculus criteria; PI = plaque index; GI = gingival index; BI = bleeding index; PD = pocket depth (in mm).

TABLE 4 Total bacterial count of gingival crevical fluid pre- and postdevice insertion

	Treatment group				Control group
Periodontal site	Day 0	Day 7	Day 28	Periodontal site	Day 0	Day 7	Day 28
1	2.4 × 10^7	1.3 × 10^3	2.83 × 10^6	2	1.48 × 10^7	0.99 × 10^2	1.02 × 10^6
3	2.36 × 10^7	1.89 × 10^7	1.94 × 10^7	4	3.65 × 10^6	2.12 × 10^6	1.89 × 10^7
5	3.73 × 10^6	1.08 × 10^2	2.98 × 10^5	6	1.13 × 10^7	0.63 × 10^3	7.80 × 10^4
7	3.98 × 10^6	2.12 × 10^5	5.43 × 10^6	8	5.04 × 10^6	2.89 × 10^6	0.04 × 10^6
9	2.32 × 10^7	3.99 × 10^2	1.08 × 10^5	10	2.46 × 10^6	1.08 × 10^2	2.32 × 10^6
11	7.45 × 10^6	3.42 × 10^5	5.09 × 10^6	12	2.49 × 10^6	3.12 × 10^5	2.13 × 10^6