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1. Visual Assessment
SMEDDS form fine oil in water emulsions with gentle agitation upon their introduction into aqueous media. Since the free energy required to form an emulsion is very low, the formation is thermodynamically spontaneous.
Surfactants in the system form a layer around the emulsion droplets and hence reduce the interfacial energy as well as providing a mechanical barrier to coalescence. The visual test is a measure of an apparent spontaneity of emulsion formation.
A series of SMEDDS were prepared and their self micro-emulsifying properties were observed visually Visual observations indicated that at higher levels of surfactant, the spontaneity of the self micro emulsification process was increased. This may be due to excess penetration of water into the bulk oil causing massive interfacial disruptions and ejection of droplets into the bulk aqueous phase.
When a co-surfactant is added to the system, it lowers the interfacial tension, fluidizes the hydrocarbon region of the interfacial film, and decreases the bending stress of the interface. It was reported that when a self micro-emulsified system is diluted by the aqueous phase, various mesomorphic phases are absorbed between the formulation and the water. A delay in the progress of emulsion formation may be due to the time required for the transformation from one liquid crystalline structure to another during the first stages of the disruption process.
On the other hand, addition of co-surfactant increase the interfacial fluidity by penetrating into the surfactant film creates void space among surfactant molecules and facilitates the progress of emulsion formation. The inclusion of a greater proportion of surfactant resulted in clearer emulsion and lower emulsion sizes; the emulsification properties appear to be highly dependent on composition, with higher HLB oil and surfactant systems in combination with high co-surfactant content resulting in smaller droplets.
The surfactant may have the effect of enhancing the solubility of the drug and smaller emulsion droplet possibly due to reverse micelle formation.

2. Phase Separation
The results of the phase separation study of SMEDDS formulation were showed that the phase separation did not occur in most of the Formulations but occurs in few of the Formulations.

3. Emulsion Droplet Size
The globule size and zeta potential was determined using Malvern Zetasizer. The average globule size was taken into consideration. The average diameters of vesicles were in nano size range. Droplet size distribution is one of the most important characteristics of emulsion for stability and in vivo absorption. Poly dispersity index (PDI) below 0.3 indicates good uniformity in the droplet size distribution after dilution with water. In this study the poly dispersity index below 0.3 was seen in few formulations. The zeta potential of the liquid systems is of considerable importance from the stability point of view. In this study the zeta potential was less then –30, indicating good stability.

4. Pseudoternary Phase Diagram
Pseudo ternary phase diagram was constructed to identify the self micro-emulsifying regions and to establish the optimum concentration of Oil, Surfactant and Co-surfactant. It was reported that the mechanism of self micro emulsification involves erosion of a fine cloud of small droplets from the surface of large droplets, rather than progressive reduction in droplet size.
Micro-emulsion preparation requires adjusting the HLB value of the formulation by including a co-surfactant, which makes the polar solvent less hydrophilic. The results indicate that the area of the micro-emulsion region increased in the system containing co-surfactant.
Efficiency of emulsification was good when the surfactant concentration was more than 40%. It was observed that increasing the concentration of co surfactant within the self micro-emulsifying region increased the spontaneity of the self-emulsification process.
When co-surfactant is added to the system it further lowered the interfacial tension between the oil and water interface and also influences the interfacial film curvature, which thereby readily deforms around oil droplets. It can also be seen that formulation with combined use of two surfactants appeared to have the largest region of microemulsion among the formulations.
14.2% oil can be incorporated in the pre concentrate and be diluted into micro-emulsion. This is significant in the pre concentrate formulation development, as more oil in the composition help to solubilize poorly water-soluble drug in the pre concentrate; this is an important observation, suggesting that the combined use of surfactants is significantly more effective in generating micro-emulsions.

5. HLB Determination
The HLB value of SMEDDS formulation can be determined by following formula.
HLB blend of mixtures = (A×PA/100) + (B×PB/100) + (C×PC/100)
A, B, C → HLB value of Oil, Surfactant and Co-Surfactant respectively.
PA, PB, PC → Percentage of Oil, Surfactant and Co-Surfactant respectively.

6. Assessment of Self Emulsification Efficiency
The assessment of the efficiency of self-emulsification was adopted to evaluate the formulation in pH 4.5 Acetate Buffer. The emulsification characteristics were observed when the formulations were dispersed in the pH 4.5 Acetate Buffer.
The visual grading and emulsions formed on dispersion are shown in few formulations. The SMEDDS formulation formed micro-emulsions which were visually graded A; whereas SMEDDS formulation formed emulsions which are turbid and less clear and were graded B, SMEDDS formulation formed milky emulsion and were graded C and SMEDDS formulation remained as unemulsified oily liquid and were graded E.

7. Drug Content
Drug content was estimated for the optimized Pimozide SMEDDS formulation by HPLC method, and is within the limit of not less than 95% and not more than 105%.

8. In- Vitro dissolution study in comparison with ORAP® 2 mg tablet by TEVA Pharmaceuticals USA
In-Vitro drug release study was performed using USP-I (Basket) apparatus, 100 RPM, 900 mL of pH 4.5 Acetate buffer. The percentage release of Pimozide from Formulation was found to be more than 99% at the end of 45 minutes and 100% micelles were formed. These formulations showed clear transparent solution, broad micro-emulsion region, more percentage release of drug and less rate of emulsification (min). The dissolution profile of marketed product ORAP® (Pimozide) Tablets, 2 mg showed only 42.9% of drug release. As per the USFDA’s Dissolution data base, dissolution profile for pimozide needs to be generated in 0.01N HCl medium. Pimozide is less soluble in pH 4.5 Acetate buffer and is a perfect discriminative dissolution medium to check on the dissolution enhancement. The dissolution results of Pimozide SMEDDS in comparison with marketed product ORAP® suggests that changing the concentration of oil, surfactant and co-surfactant in SMEDDS improved the solubility through in situ micro emulsion resulting in more release of drug in the discriminative dissolution medium.
Prepared Pimozide loaded SMEDDS showed excellent self emulsification efficiency and released more than 90% of the drug in 45 minutes whereas ORAP® showed about 45% drug release.
The mean globule size of optimized Pimozide SMEDDS was 29.39 nm. The positive outcome of this research is Pimozide SMEDDS improved the solubility of drug which is evident from the drug release in discriminative dissolution medium (pH 4.5 Acetate Buffer). Hence we can expect a better in vivo bioavailability.
Based on the bioavailability results, the daily dose of the drug can be reduced and patient compliance can be improved through once daily dosing for effective anti psychosis in treating Schizophrenia and Chronic psychosis.