Diclofenac sodium ion exchange resin complex loaded melt cast films for sustained release ocular delivery

Figures & data

Table 1. Composition of various formulations of Diclofenac sodium (DFS) used for ocular disposition studies.

Formulations	Formulation #1	Formulation #2	Formulation #3	Formulation #4
Ingredients	0.1% DFS ophthalmic solution	DFSfree+DFS:IR(1:1)(3 + 1) suspension	DFSfree film	DFSfree+DFS:IR(1:1) (3 + 1) film
Diclofenac sodium	10 mg	120 mg	1.6 mg	1.2 mg
DFS-IR::1:1 complex	–	80 mg	–	0.8 mg
Boric acid	√	–	–	–
Edetate Disodium	10 mg	–	–	–
Polyxyl 35 Castor Oil	√	–	–	–
Sorbic acid	20 mg	–	–	–
Tromethamine	√	–	–	–
Mannitol	–	450 mg	–	–
HPMC	–	10 mg	–	–
PEO N10	–	–	6.4 mg	6 mg
Water	10 mL	10 mL	–	–

Figure 1. FTIR spectra of DFS, Duolite^TM AP 143/1083 (IR) and DFS:IR complex.

Figure 2. SEM of PEO N10, DFS_free and DFS_free+DFS:IR_1:1(3 + 1) films at 25×, 70× and 300× magnification.

Figure 3. Percentage release of DFS up to 24 h form various ion exchange resin formulations and marketed ophthalmic solution.

Table 2. Model parameters obtained from fitting DFS release data to zero order, first order, Higuchi and Boyd models.

Formulation	Rate order	Zero	First	Higuchi	Boyd
DFS:IR(1:1) Suspension	Kinetic constant	2.0547	0.012	10.891	0.1195
	Coefficient correlation	0.9273	0.9688	0.9894	0.9903
DFSfree+DFS:IR(1:1)(1 + 1) Suspension	Kinetic constant	3.0905	0.0237	16.681	0.1393
	Coefficient correlation	0.8874	0.9671	0.9871	0.9959
DFS:IR(1:1) Film	Kinetic constant	2.1577	0.013	11.639	0.119
	Coefficient correlation	0.8973	0.9573	0.9913	0.9949
DFSfree+DFS:IR(1:1)(1 + 1) Film	Kinetic constant	2.8066	0.0227	15.879	0.1294
	Coefficient correlation	0.7871	0.9424	0.9567	0.9751
0.1% w/v ophthalmic solution	Kinetic constant	3.9885	0.0961	23.449	0.1864
	Coefficient correlation	0.6748	0.9895	0.8857	0.9687

Table 3. Ocular tissue DFS concentration (μg/g of tissue) obtained from various topical formulations of DFS.

Formulations (#)	Time (h) post instillation	Group #	Cornea	AH	IC	RC	Sclera
0.1%w/v DFS solution (#1)	4	1	NA	0.18 ± 0.06	0.93 ± 0.4	NA	NA
1.6%w/v DFSfree+DFS:IR(1:1)(3 + 1) suspension (#2)	8	2	1.3 ± 1.0	0.18 ± 0.07	0.43 ± 0.19	ND	8.4 ± 1.7
20%w/w DFSfree Film (#3)	4	3	NA	2.6 ± 0.2*	2.7 ± 1.1^b	NA	NA
	8	4	7.5 ± 3.4	0.7 ± 0.06^b	0.78 ± 0.35^c	ND	14.6 ± 4.8
20%w/w DFSfree+DFS:IR(1:1)(3 + 1) Film (#4)	4	5	NA	0.9 ± 0.2*	1.02 ± 0.05	NA	NA
	8	6	2.3 ± 1.4	0.36 ± 0.06^a	0.66 ± 0.15^c	0.09 ± 0.02	7.02 ± 4.03

AH - Aqueous humor, IC - Iris ciliary bodies, RC - Retina-choroid. NA - not analyzed, ND - below detection limit. Statistical significance was calculated using Tukey HSD (IBM SPSS 23). *Significantly different from all groups, ^aSignificantly different from group #5, ^bSignificantly different from all groups except group #5, ^cSignificantly different from group #3.