Figure 1.
Solubility of OLZ in (a) solid lipids; (b) surfactants [values expressed as mean ± SD (n=3)].
Table 1.
Effect of SL on particle size, PDI and EE.
| Batch No. | SL (0.5%w/v) | OLZ (mg) | Surfactant (0.2%w/v) | VD (mL) | ST (min) | Particle size (nm) | PdI | EE (%) |
|---|---|---|---|---|---|---|---|---|
| F1 | PRE | 10 | KELP | 10 | 10 | 253.7 | 0.076 | 49 |
| F2 | GMS | 10 | KELP | 10 | 10 | 527.0 | 0.709 | 54 |
| F3 | CMPR | 10 | KELP | 10 | 10 | 630.0 | 1.000 | 47 |
| F4 | PRE + GMS | 10 | KELP | 10 | 10 | 328.2 | 0.312 | 50 |
| F5 | PRE+CMPR | 10 | KELP | 10 | 10 | 164.0 | 0.482 | 40 |
| F6 | GMS+CMPR | 10 | KELP | 10 | 10 | 719.3 | 0.203 | 45 |
[i] Values expressed as mean of triplicates. Explanatory notes: SL-Solid lipid, OLZ-Olanzapine, VD-Volume of dispersion medium, ST-Sonication time, PdI-Polydispersity index, EE-Entrapment efficiency, PRE-Precirol ATO 5, GMS-Glyceryl monostearate, CMPR-Compritol ATO 888, KELP-Kolliphor ELP.
Table 2.
Effect of LC on particle size, PDI and EE.
| Batch No. | SL: PRE (%w/v) | OLZ (mg) | Surfactant (0.2%w/v) | VD (mL) | ST (min) | Particle size (nm) | PdI | EE(%) |
|---|---|---|---|---|---|---|---|---|
| F7 | 0.45 | 10 | KELP | 10 | 10 | 247.1 | 0.325 | 26 |
| F1 | 0.50 | 10 | KELP | 10 | 10 | 253.7 | 0.076 | 49 |
| F8 | 0.55 | 10 | KELP | 10 | 10 | 267.3 | 0.494 | 52 |
[i] Values expressed as mean of triplicates. Explanatory notes: SL-Solid lipid, OLZ-Olanzapine, VD-Volume of dispersion medium, ST-Sonication time, PdI-Polydispersity index, EE-Entrapment efficiency, PRE-Precirol ATO 5, KELP-Kolliphor ELP.
Table 3.
Effect of DC on particle size, PDI and EE.
| Batch No. | SL (0.5%w/v) | OLZ (mg) | Surfactant (0.2%w/v) | VD (mL) | ST (min) | Particle size (nm) | PdI | EE(%) |
|---|---|---|---|---|---|---|---|---|
| F1 | PRE | 10 | KELP | 10 | 10 | 253.7 | 0.076 | 49 |
| F9 | PRE | 12.5 | KELP | 10 | 10 | 299.0 | 0.217 | 53 |
[i] Values expressed as mean of triplicates. Explanatory notes: SL-Solid lipid, OLZ-Olanzapine, VD-Volume of dispersion medium, ST-Sonication time, PdI-Polydispersity index, EE-Entrapment efficiency, PRE-Precirol ATO 5, KELP-Kolliphor ELP.
Table 4.
Effect of surfactant on particle size, PDI and EE.
| Batch No. | SL (0.5%w/v) | OLZ (mg) | Surfactant (0.2%w/v) | VD (mL) | ST (min) | Particle size (nm) | PdI | EE(%) |
|---|---|---|---|---|---|---|---|---|
| F1 | PRE | 10 | KELP | 10 | 10 | 253.7 | 0.076 | 49 |
| F10 | PRE | 10 | KRH40 | 10 | 10 | 298.0 | 0.416 | 26 |
| F11 | PRE | 10 | T80 | 10 | 10 | 647.1 | 0.303 | 58 |
| F12 | PRE | 10 | KELP+T80 | 10 | 10 | 288.5 | 0.413 | 61 |
[i] Values expressed as mean of triplicates. Explanatory notes: SL-Solid lipid, OLZ-Olanzapine, VD-Volume of dispersion medium, ST-Sonication time, PdI-Polydispersity index, EE-Entrapment efficiency, PRE-Precirol ATO 5, KELP-Kolliphor ELP, KRH40-Kolliphor RH 40, T80-Tween 80.
Table 5.
Effect of surfactant ratio on particle size, PDI and EE.
| Batch No. | SL (0.5%w/v) | OLZ (mg) | Surfactant: KELP+T80 (0.2%w/v) | VD (mL) | ST (min) | Particle size (nm) | PdI | EE(%) |
|---|---|---|---|---|---|---|---|---|
| F12 | PRE | 10 | 50:50 | 10 | 10 | 288.5 | 0.413 | 61 |
| F13 | PRE | 10 | 60:40 | 10 | 10 | 266.9 | 0.596 | 59 |
| F14 | PRE | 10 | 70:30 | 10 | 10 | 256.3 | 0.563 | 59 |
| F15 | PRE | 10 | 80:20 | 10 | 10 | 241.6 | 0.283 | 51 |
[i] Values expressed as mean of triplicates. Explanatory notes: SL-Solid lipid, OLZ-Olanzapine, VD-Volume of dispersion medium, ST-Sonication time, PdI-Polydispersity index, EE-Entrapment efficiency, PRE-Precirol ATO 5, KELP-Kolliphor ELP, T80-Tween 80.
Table 6.
Effect of SC on particle size, PDI and EE.
| Batch No. | SL (0.5%w/v) | OLZ (mg) | Surfactant: KELP+T80 (70:30) | VD (mL) | ST (min) | Particle size (nm) | PdI | EE(%) |
|---|---|---|---|---|---|---|---|---|
| F16 | PRE | 10 | 0.15 | 10 | 10 | 309.7 | 1.000 | 63 |
| F14 | PRE | 10 | 0.20 | 10 | 10 | 256.3 | 0.563 | 59 |
| F17 | PRE | 10 | 0.25 | 10 | 10 | 215.8 | 0.026 | 48 |
[i] Values expressed as mean of triplicates. Explanatory notes: SL-Solid lipid, OLZ-Olanzapine, VD-Volume of dispersion medium, ST-Sonication time, PdI-Polydispersity index, EE-Entrapment efficiency, PRE-Precirol ATO 5, KELP-Kolliphor ELP, T80-Tween 80.
Table 7.
Effect of ST on particle size, PDI and EE.
| Batch No. | SL (0.5%w/v) | OLZ (mg) | Surfactant (0.2%w/v) 70:30 | VD (mL) | ST (min) | Particle size (nm) | PdI | EE(%) |
|---|---|---|---|---|---|---|---|---|
| F18 | PRE | 10 | KELP+T80 | 10 | 5 | 303.3 | 0.629 | 54 |
| F14 | PRE | 10 | KELP+T80 | 10 | 10 | 256.3 | 0.563 | 59 |
| F19 | PRE | 10 | KELP+T80 | 10 | 15 | 238.0 | 0.274 | 67 |
[i] Values expressed as mean of triplicates. Explanatory notes: SL-Solid lipid, OLZ-Olanzapine, VD-Volume of dispersion medium, ST-Sonication time, PdI-Polydispersity index, EE-Entrapment efficiency, PRE-Precirol ATO 5, KELP-Kolliphor ELP, T80-Tween 80.
Table 8.
Effect of STM on particle size, PDI and EE.
| Batch No. | SL (0.5%w/v) | OLZ (mg) | Surfactant (0.2%w/v) 70:30 | VD (mL) | ST (min) | STM | Particle size (nm) | PdI | EE(%) |
|---|---|---|---|---|---|---|---|---|---|
| F20 | PRE | 10 | KELP+T80 | 10 | 10 | 2-8 | 285.8 | 0.425 | 38 |
| F19 | PRE | 10 | KELP+T80 | 10 | 10 | RT | 238.0 | 0.274 | 67 |
[i] Values expressed as mean of triplicates. Explanatory notes: SL-Solid lipid, OLZ-Olanzapine, VD-Volume of dispersion medium, ST-Sonication time, STM-Sonication temperature, PdI-Polydispersity index, EE-Entrapment efficiency, PRE-Precirol ATO 5, KELP-Kolliphor ELP, T80-Tween 80.
Table 9.
Effect of VD on particle size, PDI and EE.
| Batch No. | SL (0.5%w/v) | OLZ (mg) | Surfactants (0.2%w/v) 70:30 | VD (mL) | ST (min) | Particle size (nm) | PdI | EE(%) |
|---|---|---|---|---|---|---|---|---|
| F21 | PRE | 10 | KELP+T80 | 5 | 10 | 222.2 | 0.031 | 31 |
| F19 | PRE | 10 | KELP+T80 | 10 | 10 | 238.0 | 0.274 | 67 |
[i] Values expressed as mean of triplicates. Explanatory notes: SL-Solid lipid, OLZ-Olanzapine, VD-Volume of dispersion medium, ST-Sonication time, PdI-Polydispersity index, EE-Entrapment efficiency, PRE-Precirol ATO 5, KELP-Kolliphor ELP, T80-Tween 80.
Figure 2.
Percentage desorption of SLNs from DANs prepared with different adsorbents [Values expressed as mean ± SD (N=3)].
Table 10.
Screening of adsorbents.
| Adsorbent | Mannitol | Lactose | KCL | NUS2 | NUS2 + Mannitol | NUS2 + Lactose | NUS2 + ACL |
|---|---|---|---|---|---|---|---|
| Particle size (nm) | 401.2 | 308.4 | 382.9 | 364.8 | 361.9 | 463.3 | 302.4 |
| PdI | 0.400 | 0.298 | 0.455 | 0.410 | 0.599 | 0.852 | 0.494 |
| HR | Poor | Fair | Passable | Passable | Good | Good | Good |
| CI | Poor | Fair | Fair | Fair | Good | Good | Good |
| Angle of repose | Excellent | Excellent | good | Excellent | Excellent | Excellent | Excellent |
| Remarks | Fungal growth | Particles in the range of 5000 nm also present | Rat Holing | - | Fungal growth | Particles in the range of 5000 nm also present | - |
[i] Values expressed as mean of triplicates. Explanatory notes: KCL-Kollidon CL SF, NUS2-Neusilin US2, ACL-Avicel CL 611, PdI-Polydispersity index, HR-Hausners ratio, CI-Compressibility index.
Figure 3.
In-vitro drug release study of OLZ Suspension, SLNs, DANs in (a) 0.1N HCL; (b) PBS pH 6.8; (c) PBS pH 7.4; and (d) three stage multimedia [Values expressed as mean ± SD (N=3)].
Table 11.
Linearity and diffusion exponent from kinetic plots for different mediums used for in-vitro drug release study for OLZ SLNs DANs
| Media | Model | ||||
|---|---|---|---|---|---|
| Zero order (R2) | First order (R2) | Higuchi (R2) | Korsemeyer–Peppas | ||
| R2 | Diffusion exponent (n) | ||||
| 0.1 N HCL | 0.487 | 0.585 | 0.689 | 0.986 | 0.415 |
| PBS pH 6.8 | 0.866 | 0.940 | 0.970 | 0.984 | 0.434 |
| PBS pH 7.4 | 0.870 | 0.959 | 0.971 | 0.985 | 0.481 |
| Three stage multimedia | 0.416 | 0.640 | 0.961 | 0.837 | 0.264 |
Figure 4.
In-vitro drug release of OLZ SLNs DANs in PBS pH 7.4: (a) Zero order; (b) First order; (c) Higuchi and (d) Korsemeyer–Peppas model.
Figure 5.
(a) DSC thermogram of OLZ and OLZ SLNs; (b) XRD spectra of the OLZ, PRE, SLNs, adsorbents and DANs. Scanning electron microscopy (SEM)
Figure 6.
SEM of (a) OLZ SLNs; (b) adsorbents; (c) and (d) DANs of OLZ SLNs.
Figure 7.
Ex-vivo intestinal permeability of OLZ suspension and SLNs [through treated and untreated jejunum] [values expressed as mean ± SD (N=3)].