INTRODUCTION:

Oral route is most convenient route for non- invasive administration; mostly 40% of drugs are lipophilic in nature having poor aqueous solubility^1-4, oral bioavailability and dissolution rate. There are various methods to enhance solubility and dissolution rate they are co solvency, reduction of particle size, salt formation, hydrotrophy etc.., a novel approach has been introduced to enhance solubility and dissolution rate i.e., self emulsifying drug delivery system, which can be classified as nano emulsifying drug delivery system and micro emulsifying drug delivery system. Self emulsifying drug delivery system [SNEDDS] is a novel approach to enhance aqueous solubility and dissolution rate. Self-Nano emulsifying drug delivery systems are thermodynamically stable^5-7, isotropic mixtures of oil, surfactant and co-surfactant along active pharmaceutical ingredient [API], it will spontaneously emulsified when it comes in contact with GI fluids so therefore it forms oil in water type of Nano emulsion. It can be defined as are mixtures of oils⁸, surfactants and co surfactants, ideally isotropic, sometimes including co solvents, which emulsify under conditions of gentle agitation⁹, similar to those which would be encountered in the gastro-intestinal tract.

SNEDDS can form oil in water emulsion spontaneously in GIT; SNEDDS are more stable and effective when compared to normal emulsions. SNEDDS ranges about 300nm to 5μm^10-13, depending upon droplet size SNEDDS are divided into SMEDDS (self micro emulsifying drug delivery system) with a droplet size of 250nm to 300nm^14-19 and SNEDDS (self nano emulsifying drug delivery system) with a droplet of > 100nm or 100 to 200nm. Oral route is convenient route of administration and widely used route, it is cost effective but 40% of drugs in market are lipophilic and these dosage forms will depends upon various factors like solubility, permeability, dissolution rate and oral bioavailability ^20-25.

The study involves formulation and evaluation of solid self-Nano emulsifying drug delivery system (S-SNEDDS) to enhance aqueous solubility and dissolution rate. Excipients were selected depends upon the drug compatibility oils, surfactants and co surfactants^26-27 were selected to formulate Liquid SNEDDS these formulated liquid self nano emulsifying drug delivery system converted into solid by the help of porous carriers, Melted binder or with the help of drying process. Conversion process of liquid to solid involves various techniques they are spray drying; freeze drying and fluid bed coating technique, extrusion, melting granulation technique²⁸.

Liquid SNEDDS has high ability to improve dissolution and solubility of drug but it also has a disadvantage like incompatibility²⁹, decreased drug loading, shorter shelf life, Easy of manufacturing and ability to deliver peptides that are prone to enzymatic hydrolysis. The drug Olanzapine is an anti psychotic drug used for treatment of depression, mania and psychosis which belongs to BCS class II which has poor aqueous solubility and dissolution rate with logP value 4 ³⁰.

MATERIALS AND METHODS:

MATERIALS:

Olanzapine was obtained as gift sample from Hetero labs pvt. Ltd. (Hyderabad, India). Capryol 90, Labrafac Lipophile WL 1349, Labrafac PG, Maisine CC, Lauroglycol 90, Transcutol HP were donated by Gattefosse (Mumbai, India), Kolliphor EL, Kolliphor RH 40 were donated by BASF, Captex 200, Capmul MCM were donated by Abitec corporation, Tween 40 were donated by sigma life sciences, Acetonitrile, Hydrochloric acid were donated by Research lab fine chemicals and Aerosil were donated by Research chemical pvt ltd.

METHOD:

1. Solubility studies:

Solubility studies of Olanzapine was determined in various oils, surfactants and co surfactants, Excess amount of drug added to 500mg of excipients contained in a glass vial. Mixture was then cyclomixed for 2 minutes using cyclomixer (Remi equipment pvt ltd) to enhance drug solubility and also to simplify solubilisation. Mixtures were Sonicated for 5-10 min using Sonicator (PCI analytics pvt ltd) to dissolve drug completely. Resultant mixtures were kept for equilibrium at room temperature in a mechanical rotary shaker (Remi equipment pvt ltd) at a speed of 100rpm for 72 hours. After 72 hours mixtures were centrifuged at 3000rpm for 15-20 minutes, these will separates dissolved drug as supernatant phase and undissolved drug as sediment phase take 0.1 ml of supernatant by utilising micropipette, supernatant were diluted with acetonitrile which is used as a co solvent the concentrations of Olanzapine in each excipient was determined spectrophotometrically at λ_max 270nm.

2. Construction of pseudo ternary phase diagram:

Pseudo ternary phase diagram was constructed to determine nano emulsifying regions and also to select suitable concentrations of oils, surfactants, co surfactants. Pseudo ternary phase diagram was constructed by water titration method. Surfactants and co surfactants (_Smix) ratios were prepared (3:1, 4:1) by mixing accurately weighed amount of surfactant with co surfactant. Oil were mixed in different weight ratios of 9:1 to 1:9 {9:1, 8:2, 7:3, 6:4, 5:5, 4:6, 3:7, 2:8, 1:9} into the glass vials. Each mixture was titrated by water until mixture turned into blue colour emulsion or milky white or coarse emulsion or gel phases. Different phases were plotted on a phase diagram using Triplot version 4.1.2 software. Components used for construction of phase diagram are oil {Capryol 90}, surfactant {Kolliphor EL} and co surfactant {Lauroglycol 90} and Millipore water. The samples which were clear and transparent are considered as nano emulsion.

3. Formulation of liquid self nano emulsifying drug delivery system:

Nano emulsion regions were determined by phase diagrams, once nano emulsion region identified. SNEDDS formulations were prepared with addition of varying ratios of selected S_mix{surfactant: co surfactant} and Oil. In all the formulations drug (Olanzapine) was kept constant (2.5 mg). Weighed amount of drug is dissolved or solubilised in oil phase then cyclomixed for 2 minutes using cyclomixer, Surfactant and co surfactant ratios were prepared and mixed into drug oil mixture and vortexed. The prepared formulations were kept at room temperature for further investigation and evaluation.

4. Evaluation liquid self nano emulsifying drug delivery system:

4.1 Dispersibility test:

It was evaluated using USP dissolution apparatus II i.e., Paddle, Self emulsification efficacy was determined by addition of 0.1ml of formulated Olanzapine L-SNEDDS into 200ml of distilled water with gentle agitation using a magnetic stirrer, Formation of nano emulsion was visually observed and performance of nano emulsion was evaluated using following grading system in table no 01.

Table No: 01 Grading system for nano emulsion

Grade A	Rapidly forming clear blue emulsion with less than 1min
Grade B	Rapidly forming slight blue emulsion within 1 to 2 mins
Grade C	Fine milky white emulsion formed within 2 mins
Grade D	Dull greyish white emulsion formed more than 2 mins
Grade E	Large oil globules formed which indicates minimum emulsion formation

4.2 Self emulsification test:

0.1ml of Olanzapine L-SNEDDS were added into 200ml of distilled water under mild or gentle agitation using a magnetic stirrer at a speed of 100rpm temperature maintained at 37⁰c ± 1⁰c. Self emulsification was visually assessed by changing the appearance of the formulation and self emulsification time will be noted, if it forms clear blue emulsion which indicates formulated Olanzapine L-SNEDDS was good or if it forms less clear or turbid emulsion appearance which indicates bad emulsion.

4.3. Robustness to Dilution:

Robustness to dilution of Olanzapine L-SNEDDS was done by diluting the 0.1ml of formulation to 1000 times with distilled water, 0.1N HCL and phosphate buffer p^H 6.8 temperature maintained at 37±1⁰c to simulate body temperature and gastric mobility. Diluted mixtures were stored for 24 hrs at room temperature then visually observed for any signs of instability like phase separation, creaming, turbidity etc.

4.4 Percentage transmittance:

Olanzapine L-SNEDDS (0.1ml) were diluted to 10ml of distilled water, 0.1N HCL and phosphate buffer p^H 6.8 and observed for percentage transmittance in UV visible spectroscopy at λ_maxscreened with Olanzapine.

4.5 FTIR studies:

FTIR spectrum of pure drug and excipients were obtained by FTIR spectrophotometer. Drug excipient compatibility studies were determined by using Fourier transform infra- red spectroscopy; these studies will give a clear data about the selection of excipients and its compatibility. FTIR spectra were obtained by Scanning from 400 to 4000 cm^-1 range and resolution was 1 cm^-1. Olanzapine and excipients were analysed by FTIR spectroscopy with data acquisition system OPUS, software used is Bruker alpha.

4.6Thermodynamic stability studies:

Thermodynamic stability studies were performed to determine temperature and centrifugation efficacy. The formulation were added to Millipore water at 1:20 ratio and centrifuged at 3500 rpm for 15 to 30 min and observed for changes like phase separation cracking or creaming and precipitation, Formulations are subjected to freeze thaw cycle by diluting formulations at 1:20ratio with Millipore water at a temperature -20 to +25⁰cstored for 48 hrs.

4.7 Drug loading efficacy:

Drug content in formulation was determined by taking 0.1ml of formulated Olanzapine L-SNEDDS and diluted to 10ml of acetonitrile analysed by UV visible spectroscopy. Drug loading efficacy was calculated by equation:

Drug load = Amount of drug in known amount of formulation / Initial drug load*100

4.8 Determination of droplet size, PDI and Zeta potential:

Olanzapine L-SNEDDS were 100 times diluted with water in a test tube or volumetric flask, globule size, PDI and zeta potential were determined after 1 hour by dynamic light scattering spectroscopy using Zetasizer nano ZS 90 version 7.1 {Malvern instruments}.

4.9 Invitro drug release:

Invitro drug release of Olanzapine L-SNEDDS was performed by USP type II dissolution apparatus {DS 8000 Lab India}. 2.5mg of Olanzapine L-SNEDDS was filled into capsules; capsules were placed into 900ml of 0.1N HCL at 37 ± 1⁰c temperature with a speed of 50rpm. Aliquots were withdrawn at 5, 10, 15, 20, 45, 60, 90, 120 minutes respectively time interval with a volume of 5ml and buffer (0.1N HCL) were replaced to maintain sink conditions. Withdrawn samples were analysed in UV visible spectroscopy, from the standard graph of 0.1N HCL with a wavelength of 258nm.

5. Formulation of Olanzapine Solid- SNEDDS:

Evaluation tests were done on 4 different formulations (SB183J3:7, SB183J1:9, SB184J4:6 and SB184J3:7) of Olanzapine SNEDDS, SB184J4:6 has shown good solubility, good self nano emulsifying property and showed less particle size and PDI value, those formulation were selected for formulation of Olanzapine S-SNEDDS. Aerosil placed in china dish and formulated SB184J4:6 were added drop by drop into the adsorbent at 1:2 ratios, filled into capsules and then used for further investigations.

6. Evaluation of Olanzapine S-SNEDDS:

6.1 Flow Characterisation of Olanzapine S-SNEDDS:

A. Angle of repose: Maximum angle possible between horizontal plane and surface of pile of powder, it is denoted asθ. Powder blend were poured into funnel onto the graph and measure height of pile and radius.

Tanθ = h/r

θ = Tan^-h/r

Where,

θ = Angle of repose

h= Height of pile

r= Radius

B. Bulk density and Tapped density:

Weight of powder measured and poured into measuring cylinder and volume of powder blend were noted, denoted as D_b. Bulk density was calculated by an equation:

D_b= Mass of powder / Volume of powder

100 Tapping were given to powder blend in a measuring cylinder and note the tapped volume; Denoted as Dt and tapped density was calculated by an equation:

D_t= Mass of powder / Tapped volume of powder

C. Carr’s Compressibility index:

It determines flow of powder and indicates powder compressibility; Carr’s compressibility index was denoted as I and given with an equation:

I = Tapped density – Bulk density / Tapped density* 100

D. Hausner’s ratio:

Defined as ratio of tapped density to that of bulk density, it is given with an equation:

H_r= Tapped density / Bulk density

6.2 Reconstitution properties of Olanzapine S-SNEDDS:

a. Robustness:

Solid formulation were dissolved at 1:1000 ratios in water, 0.1N HCL and phosphate buffer and gently agitated by using magnetic stirrer. Clear emulsion indicates Good and less clear or dull emulsion indicates Bad emulsion appearance.

b. Dispersibility test:

100mg of Olanzapine S-SNEDDS were dissolved in 200ml of water and gently agitated using magnetic stirrer and test was evaluated by USP II dissolution apparatus. Emulsion performance was assessed by grading system.

c. Self emulsification test:

100mg of formulation dissolved in 200ml of distilled water, 0.1N HCL and phosphate buffer which is gently agitated using magnetic stirrer and emulsification time was noted.

d. Droplet size, Zeta potential and PDI:

1mg of formulation dissolved in 100ml of water and cyclomixed for 1 min and filtered then observed for PDI, Zeta potential and droplet size with the help of Zetasizer nano ZS 90 (Malvern instruments) and

e. Invitro drug release:

Invitro drug release can be assessed by USP II dissolution apparatus 2.5 mg of solid formulation filled in capsules and poured into 900ml of 0.1N HCL and aliquots (5ml) were withdrawn at 5, 10, 15, 20, 45, 60, 90, 120 min time interval respectively and buffer should be replaced to maintain sink conditions.

f. Accelerated stability studies:

Accelerated stability studies of Olanzapine S-SNEDDS were carried out according to ICH guidelines formulation were stored at 40-45⁰c and 70-75% RH for 1 month and later evaluated for robustness, zeta potential, PDI and particle size.

RESULT AND DISCUSSION:

1. Solubility studies:

Solubility of Olanzapine is determined in various oils, surfactants and co surfactants by UV spectrophotometric method. Olanzapine has been shown maximum solubility in oil Capryol 90 (40.02 ±0.5 mg/ml), Surfactant Kolliphor EL (35.54 ± 0.35 mg/ml) and co surfactant Lauroglycol 90 (45.23 ± 0.5). Results were shown in figure no 01 to 03.

Figure No: 01 Comparison of solubility of Olanzapine in various oils

Figure No: 02 Comparison of Olanzapine in various surfactants

Figure No: 03 Comparison of Olanzapine in various co surfactants

2. Pseudo ternary phase diagram:

From pseudo ternary phase diagram, it was found that systems containing Capryol 90 as oil phase, Kolliphor EL as surfactant and Lauroglycol 90 as co surfactant showed good nano emulsifying property. S_mix (SB18J4:1, SB18J3:1) ratios were prepared with oil ratios from 9:1 to 1:9 i.e., 9:1, 8:2, 7:3, 6:4, 5:5, 4:6, 3:7, 2:8, 1:9.S_mix (3:1) formulations of 9:1 to 4:6, 2:8 showed milky white emulsions (MWE), were as 3:7 showed clear blue colour emulsions (CBE) and 1:9 showed bluish white emulsions (BWE), S_mix (4:1) formulation of 9:1 to 5:5, 2:8and 1:9 showed milky white emulsion (MWE), were as 4:6 showed clear blue colour emulsions (CBE) and 3:7 showed bluish white emulsion (BWE) showed in figure no 04,05 and ternary phase diagrams were shown in figure no 06,07.

Figure No: 04 Physical appearance of SB18J3:1

Figure No: 05 Physical appearance of SB18J4:1

Figure No: 06 Pseudo ternary phase diagram of SB18J3:1

Figure No: 07 Pseudo ternary phase diagram of SB18J4:1

3. Selection of formulation:

Four different formulations were prepared using various oils, surfactants and co surfactants, given below table no 02

Table No: 02 Selection of formulation

Formulation	Oil: S_mix	Sur: Cosur	Oil	Surfactant	Cosurfactant
SB18J	3:7	3:1	Capryol 90	Kolliphor EL	Lauroglycol 90
SB18J	1:9	3:1	Capryol 90	Kolliphor EL	Lauroglycol 90
SB18J	4:6	4:1	Capryol 90	Kolliphor EL	Lauroglycol 90
SB18J	3:7	4:1	Capryol 90	Kolliphor EL	Lauroglycol 90

4. Formulation of Olanzapine Liquid SNEDDS:

S_mix (Kolliphor EL: Lauroglycol 90) ratios were prepared, Olanzapine were added into oil (Capryol 90) and mixture were cyclomixed for 2 min, Olanzapine L-SNEDDS were shown in figure no 08.

Figure No: 08 Formulation of Olanzapine L-SNEDDS

5. Evaluation of Olanzapine L-SNEDDS:

a. Self emulsification time:

Olanzapine L-SNEDDS was dispersed completely and quickly when subjected to aqueous dilution under mild agitation results were shown in table no 03. It was clear that the formulations were self emulsified within 29 ± 1.25 to 34 ± 1.35 seconds and indicates good nano emulsion formation.

Table No: 03 Self emulsification time of Olanzapine L-SNEDDS

Formulation	Self emulsification time (sec)	Remarks
SB183J3:7	29 ± 1.25	Good
SB183J1:9	34 ± 1.35	Good
SB184J4:6	25 ± 1.10	Good
SB184J3:7	31 ± 1.55	Good

b. Dispersibility test:

Visual observation of Olan

zapine liquid self nano emulsifying drug delivery system showed that all formulation are grade A, Rapidly emulsion forming within less than 1minute with clear appearance. Formulations were assessed by grading system results were shown in table no 04.

Table No: 04 Dispersibility test values of Olanzapine L-SNEDDS in grading system

Formulation	Observation	Grade
SB183J3:7	Rapidly emulsion formed within < 1min with clear transparent appearance	A
SB183J1:9	Rapidly emulsion formed within < 1min With clear transparent appearance	A
SB184J4:6	Rapidly emulsion formed within < 1min With clear transparent appearance	A
SB184J3:7	Rapidly emulsion formed within < 1min With clear transparent appearance	A

C. Robustness to dilution:

Olanzapine L-SNEDDS were diluted with distilled water, 0.1N HCL and phosphate buffer in the ratio 1:1000 times and observed for phase separation and precipitation. Formulations were found to be clear and transparent without any phase separation after 24 hrs results shown in table no 05.

Table No: 05 Robustness to dilution values of Olanzapine L-SNEDDS

Formulation	Water	0.1NHCL	Phosphate buffer
SB183J3:7	Passed	Passed	Passed
SB183J1:9	Passed	Passed	Passed
SB184J4:6	Passed	Passed	Passed
SB184J3:7	Passed	Passed	Passed

d. Percentage Transmittance:

All formulations showing more than 90% of transmittance indicating that the four formulations are clear emulsions results were shown in table no 06.

Table No: 06 Percentage Transmittance values of Olanzapine L-SNEDDS

Formulation	Distilled water (%)	0.1N HCL (%)	Phosphate buffer (%)
SB183J3:7	91.25 ± 0.35	98.37 ± 0.23	92.86 ± 0.45
SB183J1:9	97.5 ± 0.29	98.26 ± 0.59	96.75 ± 0.58
SB184J4:6	98. 43 ± 0.58	98.73 ± 0.18	98.59 ± 0.38
SB184J3:7	94.61 ± 0.51	95.49 ± 0.76	94.64 ± 0.64

e. Thermodynamic stability studies:

No phase separation or precipitation is observed for formulations SB183J3:7, SB183J1:9, SB184J4:6 and SB184J3:7 which indicate that the formulations are stable formulations under temperature results were shown in table no 07.

Table No: 07 Thermodynamic stability studies of Olanzapine L-SNEDDS

Formulation	Freeze Thaw cycle (2 cycles NLT 48 hrs)	Centrifugation (3500rpm for 30min)
SB183J3:7	Passed	Passed
SB183J1:9	Passed	Passed
SB184J4:6	Passed	Passed
SB184J3:7	Passed	Passed

g. Drug loading efficiency:

h. The drug loading efficiency of all SNEDDS formulations showing uniform dispersion of drug in the formulation, drug loading efficiency was found to be 98.587±0.67 to 95.619 ± 0.54 results were shown in table no 08. Results showing that formulations SB184J4:6 and SB183J3:7 showing highest drug content, those formulations posses high solubilisation capacity to solubilise 25mg dose of Olanzapine due to high surfactant and co surfactant content.

Table No: 08 Drug loading efficiency values of Olanzapine L-SNEDDS

Formulation	Drug loading efficiency (%)
SB183J3:7	98.349 ± 0.49
SB183J1:9	95.619 ± 0.54
SB184J4:6	98.587 ± 0.67
SB184J3:7	97.296 ± 0.55

g. Determination of Globule size and Zeta potential: Results were shown in table no 09 and figure no 09 to 16.

6. Conversion of Olanzapine L-SNEDDS into S-SNEDDS:

Olanzapine liquid self nano emulsifying drug delivery system optimized formulation was converted into solid by adsorption method with the help of porous carriers (Aerosil 200) in the ratio of 1:2. Formulated Olanzapine S-SNEDDS was shown in figure no 23.

Figure No: 23 Olanzapine S-SNEDDS (SB184J4:6)

7. Evaluation of Olanzapine S-SNEDDS:

7.1Flow Characterisation of Olanzapine S-SNEDDS: Formulation Olanzapine S-SNEDDS were evaluated for its flow properties, which can be done by angle of repose, Bulk and tapped density, Carr’s compressibility index and Hausner’s ratio results were shown in table no 11. Results of angle of repose shows that formulated Olanzapine S-SNEDDS having flow character Good and Bulk density, Tapped density, Carr’s compressibility index and Hausner’s ratio shows flow property Passable.

Table no: 11 Flow character values of Olanzapine S-SNEDDS

Formulation

D_b (g/ml)

D_t

(g/ml)

(%)

H_r

SB184J4:6

0.3 ± 0.01

0.4 ± 0.02

25 ± 0.1

1.3 ± 0.05

31.8 ± 0.15⁰

7.2 Reconstitution properties:

7.2.1 Robustness to dilution:

Formulated Olanzapine S-SNEDDS were dissolved in the ratio of 1:1000 with Distilled water, 0.1N HCL and Phosphate buffer kept for 48 hrs and results showed that no phase separation or precipitation results were shown in table no 12.

Table No: 12 Robustness to dilution values of Olanzapine S-SNEDDS

Formulation	Distilled water	0.1NHCL	Phosphate buffer
SB184J4:6	Passed	Passed	Passed

7.2.2 Dispersibility test:

Formulation visually assessed by grading system, Visual observation of Olanzapine S-SNEDDS showed clear emulsion formation within less than 1 min results shown in table no 13.

Table No: 13 Dispersibility values of Olanzapine S-SNEDDS

Formulation

Grade

Property

SB184J4:6

Rapidly emulsion formation

Within <1min

7.2.3 Self emulsification test:

Performed by dissolving Olanzapine S-SNEDDS in distilled water, 0.1N HCL and Phosphate buffer, it was clear that formulation were self emulsified results were shown in table no 14.

Table No: 14 Self emulsification values of Olanzapine S-SNEDDS

Formulation	Self emulsification time (Sec)
SB184J4:6	26 ± 1.05

7.2.4 Droplet size Determination:

Olanzapine S-SNEDDS were dissolved in water and observed in Malvern Zetasizer for its droplet size, PDI and Zeta potential results were shown in table no 15 and figure no 24,25.

Table No: 15 Droplet size, PDI and Zeta potential values of Olanzapine S-SNEDDS

Formulation

Droplet size

(d.nm)

PDI

Zeta potential

SB184J4:6

147.1

0.407

-45.6

Figure No: 24 Droplet size of Olanzapine S-SNEDDS (SB184J4:6)

Figure No: 25 Zeta potential of Olanzapine S-SNEDDS (SB184J4:6)

7.2.5 Invitro drug release:

Formulated Olanzapine S-SNEDDS were assessed for its drug release using dissolution apparatus; results were shown table no 16 and figure no 26.

Figure No: 26 Comparison of dissolution studies of pure drug with Olanzapine S-SNEDDS (SB184J4:6) AND Olanzapine liquid SNEDDS

Table No: 16 Dissolution studies of Olanzapine S-SNEDDS

Time (min)	% drug release of pure drug (Olanzapine)	% drug release of SB184J4:6 Solid SNEDDS formulation
5	2.2614 ± 0.36	9.2497± 0.13
10	6.7953 ± 0.43	14.3284 ± 0.64
15	15.8421 ± 0.26	20.8467 ± 0.63
20	22.6426 ± 0.64	25.2547 ± 0.55
45	31.6918 ± 0.39	31.7894 ± 0.59
60	36.2228 ± 0.46	44.5973 ± 0.67
90	38.4956 ± 0.29	54.9871 ± 0.55
120	45.2835 ± 0.56	90.2658 ± 0.69

7.2.6 Accelerated Stability studies:

Formulated Olanzapine S-SNEDDS were stored at 40-45⁰c temperature and 70-75 % RH for about 1 month and drug release was compared with day 1 results, results were shown in table no 17 and figure no 27.

Table No: 17 Comparison table of Olanzapine S-SNEDDS day 1 with 1 month

Time (min)	% drug release of SB184J4:6 S-SNEDDS month 1	% drug release of SB184J4:6 Solid SNEDDS formulation day 1
5	7.5974± 0.36	9.2497± 0.13
10	13.2547± 0.43	14.3284 ± 0.64
15	20.5987± 0.26	20.8467 ± 0.63
20	26.9587± 0.64	25.2547 ± 0.55
45	31.7254± 0.39	31.7894 ± 0.59
60	44.5373± 0.46	44.5973 ± 0.67
90	59.1387± 0.29	54.9871 ± 0.55
120	90.2358± 0.56	90.2658 ± 0.69

Figure No: 27 Accelerated stability studies of Olanzapine S-SNEDDS

SUMMARY AND CONCLUSION:

Olanzapine is poorly soluble drug which has been selected for SNEDDS study to enhance its solubility and dissolution rate. A series of pseudo ternary phase diagram was constructed by using water titration method with the help of Capryol 90 as oil, Kolliphor EL as surfactant and Lauroglycol 90 as co surfactant at a Smix ratio of 3:1 and 4:1 which gave clear nano emulsion, bluish white emulsion and white emulsion.

Four different formulations were formulated in that F₃ formulation was selected as optimised formulation because of its less particle size (66nm), drug release (88.201±0.25%) and it also shown a good nano emulsion formation. Optimised formulation was further converted into solid and evaluation was performed to solid formulation which has given better results: Invitro drug release (90.2658 ± 0.69%) and particle size (147.1nm), Zeta potential (-45.6mv) and also accelerated stability studies was performed and compared with day 1 formulation, day 1 drug release (90.2658 ± 0.69%) and drug release compared after 1 month (90.2358± 0.56%). Optimized formulation drug release compared with pure drug (45.281± 0.52%).

So finally SB184J4:6 shows better results when compared to other formulations related to drug release and enhanced solubility and dissolution rate. Hence, Olanzapine S-SNEDDS has capability for enhancement of solubility and dissolution rate.

CONFLICTS OF INTEREST:

No conflicts of interest

ACKNOWLEDGEMENTS:

I would like say my sincere thanks to Centre for pharmaceutical sciences, IST, JNTUH for supporting and providing excellent laboratory facilities to carry out this work. I would like to thank Gattefosse, Mumbai for providing gift samples of vehicles. Gift sample Olanzapine was obtained from Hetero laboratories was duly acknowledged.

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Received on 26.07.2021 Modified on 29.08.2021

Asian J. Pharm. Res. 2021; 11(4):227-238.

DOI: 10.52711/2231-5691.2021.00040

Formulation	Globule size (d.nm)	PDI	Zeta potential
SB183J3:7	108.7	0.400	-39.7
SB183J1:9	151.4	0.330	-41.7
SB184J4:6	66.13	0.274	-34.6
SB184J3:7	104.8	0.476	-34.5

Time (min)	% drug release of Pure drug (Olanzapine)	% drug release of SB183J3:7	% drug release of SB183J1:9	% drug release of SB184J4:6	% drug release of SB184J3:7
5	2.2613 ± 0.36	9.0567± 0.49	4.5057 ± 0.39	11.3273 ± 0.56	6.7918 ± 0.52
10	6.7953 ± 0.43	15.8453 ± 0.73	11.3249 ± 0.82	15.8491 ± 0.53	13.5873 ± 0.49
15	15.8421 ± 0.26	18.1128 ± 0.53	20.3729 ± 0.46	20.3789 ± 0.49	22.6483 ± 0.58
20	22.6426 ± 0.64	33.9629 ± 0.28	27.1694 ± 0.39	24.9083 ± 0.57	31.6971 ± 0.79
45	31.6918 ± 0.39	38.4938 ± 0.38	36.2293 ± 0.66	29.4394 ± 0.86	38.4942 ± 0.58
60	36.2228 ± 0.46	43.0186 ± 0.57	38.4973 ± 0.75	40.7389 ± 0.57	40.7519 ± 0.84
90	38.4956 ± 0.29	65.6183 ± 0.42	61.1359 ± 0.83	54.3381 ± 0.67	63.3977 ± 0.43
120	45.2835± 0.56	81.5431 ± 0.61	76.9835 ± 0.58	88.2036 ± 0.79	79.2359 ± 0.55