Pharmacodynamics of diclofenac from novel Eudragit entrapped microspheres

Figures & data

Figure 1. DSC thermogram of unloaded matrix (DF-0) contain (RS/RL 1:1 without drug).

Figure 2. DSC thermogram of pure DS.

Figure 3. DSC thermogram of microsphere (DF-1) contains RS/RL (1:1 plus 50 mg of DS).

Figure 4. DSC thermogram of microsphere (DF-2) contains RS/RL (1:2 plus 50 mg of DS).

Figure 5. DSC thermogram of microsphere (DF-3) contains RS/RL (2:1 plus 50 mg of DS).

Figure 6. DSC thermograms (overlayed) of the various formulations.

Table 1. Thermal properties of DS microspheres.

Formulation code	DF-1	DF-2	DF-3	RS	RL
Thermal properties
Melting peak (°C) (1)	62.9	62.2	62.7	60.2	61.1
Melting peak (°C) (2)	78.5	–	204.6	81.8	85.0
Enthalpy (Mw/mg) (1)	−4.319	−3.328	−2.342	−6.052	−7.205
Enthalpy (Mw/mg) (2)	−2.978	–	−2.879	−4.834	−7.431

DF-1, RS/RL (1:1) + 50 mg of DS; DF-2, RS/RL (1:2) + 50 mg of DS;DF-3, RS/RL (2:1) + 50 mg of DS, RS, Eudragit RS-100; RL, Eudragitr RL-100.

Table 2. Physical characteristics and micromeritics profiles of the microspheres.

Batch	% EE	MPS (µm)	% YD	BD (g/cm^3)	TD (g/cm^3)	CI (%)	AR (^o)
DF-0	–	398 ± 0.61	89.10 ± 0.21	0.65 ± 0.10	0.63 ± 0.22	19.11 ± 0.12	24.63 ± 0.41
DF-1	86.61 ± 0.11	437 ± 0.01	94.13 ± 0.32	0.68 ± 0.31	0.65 ± 0.14	11.40 ± 4.39	19.01 ± 0.12
DF-2	88.14 ± 0.16	456 ± 0.11	97.40 ± 0.15	0.63 ± 0.21	0.64 ± 0.21	9.01.45 ± 4.11	15.11 ± 0.13
DF-3	85.50 ± 0.21	479 ± 0.21	98.27 ± 0.13	0.66 ± 0.14	0.67 ± 0.11	14.45 ± 4.39	20.11 ± 0.10

% EE, Percentage encapsulation efficiency; MPS, mean particle size; % YD, percentage yield of microsphere; TD, tapped density; BD, bulk density; CI, Carr's index; AR, Angle of repose; DF-0, RS/RL (1:1) without drug; DF-1, RS/RL (1:1) + 50 mg of DS; DF-2, RS/RL (1:2) + 50 mg of DS; DF-3, RS/RL (2:1) + 50 mg of DS.

Figure 7. (DF0-DF3) Photomicrographs of representative batches of microspheres containing different ratios of RS:RL 100 and 50 mg of DS: DF-1, DF-2 and DF-3 contain 1:1, 1:2 and 2:1 of polymer ratio, respectively.

Figure 8. In vitro release of DS from Eudragit RS/Eudragit RL microspheres in pH 1.2 buffer solution: DF-1 = (◊) RS/RL (1:1) + 50 mg of DS, DF-2 = (×)RS/RL (1:2) + 50 mg of DS and DF-3 = (▴) RS/RL (2:1) + 50 mg of DS. Each data point represents the mean ± SEM from n = 3.

Figure 9. In vitro release of DS from Eudragit RS/Eudragit RL microspheres in pH 7.4 buffer solution: DF-1 = (◊) RS/RL (1:1) + 50 mg of DS, DF-2 = (×) RS/RL (1:2) + 50 mg of DS and DF-3 = (▴) RS/RL (2:1) + 50 mg of DS. Each data point represents the mean ± SEM from n = 3.

Table 3. Kinetics of release of diclofenac from microspheres in phosphate buffer (7.4).

Batch code	Zero-order (r^2)	First-order square root (r^2)	Higuchi (r^2)	Korsmeyer (r^2)	Hixon–Crowel (r^2)
DF-1	0.966	0.882	0.973	0.818	0.975
DF-2	0.971	0.767	0.978	0.867	0.978
DF-3	0.930	0.894	0.954	0.918	0.997

DF-1, RS/RL (1:1) + 50 mg of DS; DF-2, RS/RL (1:2) + 50 mg of DS; DF-3, RS/RL (2:1) + 50 mg of DS.

Figure 10. Anti-inflammatory profiles of the formulations: DF-1 = (▪) RS/RL (1:1) + 50 mg of DS, DF-2 = (□) RS/RL (1:2) + 50 mg of DS, DF-3 = (Δ) RS/RL (2:1) + 50 mg of DS, DF-0 = (×) RS/RL (1:1) no drug, NS = (*) normal saline and MKT-S = (0) market sample. Each data point represents the mean ± SEM from n = 3.