Formulation in vitro and in vivo evaluation of SRMS-based heterolipid-templated homolipid delivery system for diclofenac sodium

Figures & data

Table 1. Quantities of material used for SLM formulation.

Batch	Tween-80 (g)	Sorbic acid (%)	DicNa (mg)	Lipid matrix (g)	Distilled water q.s. (% w/w)
SLM-0	0.50	0.005	–	5.0	100
SLM-1	0.50	0.005	25	5.0	100
SLM-2	0.50	0.005	50	5.0	100
SLM-3	0.50	0.005	75	5.0	100
SLM-4	0.50	0.005	100	5.0	100

Qs = quantity sufficient.

Table 2. Properties of the SLMs formulation.

					Encapsulation efficiency (%)
Batch	PDI	ZP (mV)	PS (µm)	% Yield	1 week	After 8 months of storage
SLM-0	0.61 ± 0.80	−43.00 ± 0.20	73.00 ± 0.40	94.0	–	–
SLM-1	0.61 ± 0.40	−64.70 ± 0.10	86.00 ± 0.10	93.3	88.0 ± 0.1	83.1 ± 0.1
SLM-2	0.61 ± 0.10	−53.10 ± 1.00	81.00 ± 0.20	96.1	92.0 ± 0.1	87.8 ± 0.4
SLM-3	0.62 ± 0.20	−59.40 ± 0.02	82.00 ± 0.60	97.8	89.0 ± 0.1	86.2 ± 0.0
SLM-4	0.63 ± 0.90	−63.20 ± 0.20	79.00 ± 1.10	95.8	95.0 ± 0.3	89.1 ± 0.3

PS = particles size, ZP = zeta potential.

SLM-0, SLM-1, SLM-2, SLM-3 and SLM-4 containing the same quantity of ingredient, apart from SLM-0, others contain 25, 50, 75 and 100 mg of diclofenac sodium, respectively.

Table 3. Anti-inflammatory activity and time-resolved pH analysis.

		Percentage inhibition of inflammation					pH values
Batch	(Time h)	1	2	4	6	8	24 h	2 weeks	8 weeks
SLM-0		00.0 ± 0.1	00.0 ± 0.2	2.8 ± 0.5	4.0 ± 0.1	5.3 ± 0.2	8.5 ± 0.1	7.9 ± 0.7	7.3 ± 0.1
SLM-1		12.2 ± 0.3	31.4 ± 0.1	33.3 ± 0.4	49.1 ± 0.1	55.9 ± 1	7.8 ± 0.2	6.8 ± 0.4	6.7 ± 0.1
SLM-2		26.1 ± 0.1	30.9 ± 0.1	35.2 ± 0.1	63.2 ± 0.6	85.2 ± 0.2	7.9 ± 0.1	6.5 ± 0.1	6.9 ± 0.3
SLM-3		11.6 ± 0.2	21.1 ± 0.4	25.6 ± 0.2	49.0 ± 0.5	71.3 ± 0.1	8.8 ± 0.0	8.8 ± 0.0	8.7 ± 0.1
SLM-4		10.0 ± 0.4	19.9 ± 0.1	35.1 ± 0.3	63.2 ± 0.1	85.1 ± 0.0	6.9 ± 0.3	6.8 ± 0.1	6.7 ± 0.8
PS		14.0 ± 0.0	25.3 ± 0.0	35.6 ± 0.2	51.6 ± 0.5	47.2 ± 0.1	7.4 ± 0.2	7.5 ± 0.1	7.4 ± 0.3

SLM-0 to SLM-4 containing 0, 25, 50, 75 and 100 mg of diclofenac sodium, respectively. PS = pure sample of diclofenac sodium. Values are mean ± SEM (n = 5). Significant p < 0.05 as compared to control.

Figure 1. Photomicrographs of SLM-0 (0 mg DicNa) SLM-1 (25 mg DicNa), SLM-2 (50 mg DicNa), SLM-3 (75 mg DicNa) and SLM-4 (100 mg DicNa) after 2 weeks of preparation. Bar represents 65.0 μm.

Figure 2. Particle-size distribution of formulations a SLM-1 to SLM-4 containing 25, 50, 75 and 100 mg of diclofenac sodium, respectively. SLM-0 is the unloaded formulation.

Figure 3. In vitro release profile of DicNa from SLM formulated in phosphate buffer (pH 7.4) system. SLM-1 to SLM-4 contains 25, 50, 75 and 100 mg of DicNa, respectively.

Figure 4. Mean ulcer index (±SD) of SLM-0 to SLM-4 containing 0, 25, 50, 75 and 100 mg of DicNa, respectively. PS represent the pure sample (diclofenac sodium) as a positive control.

Figure 5. Percentage GI protection of SLM-0 to SLM-4 containing 0, 25, 50, 75 and 100 mg of DicNa, respectively. PS represent the pure drug sample as a positive control.

Figure 6. Plasma concentration versus time plotting of DicNa after oral administration of SLM-4, PS and MKT-S within 18 h (mean ± SD, n = 3). DicNa = diclofenac sodium, SLM-4 = batch 4 of the diclofenac sodium-loaded SLMs, PS = pure drug and MKT-S = market sample of diclofenac sodium.

Table 4. Pharmacokinetic parameters of SLM-4, PS and MKT-S after oral administration to Albino rats (mean ± SD, n = 3).

Samples	AUC (µgh/ml)	Cmax (µg/ml)	Tmax (h)	T½ (h)
SLM-4	1456.30 ± 1.21	2.70 ± 0.23	2.0	10.23 ± 0.11
PS	412.10 ± 1.13	3.4 ± 0.11	0.5	4.12 ± 1.16
MKT-S	724.23 ± 1.10	1.90 ± 1.20	2.0	5.06 ± 0.20

SLM-4 = batch 4 of the diclofenac sodium-loaded SLMs; PS = pure sample of drug and MKT-S = market sample of diclofenac sodium.