Polyglucoside emulsifiers have been very beneficial for blending natural oils with water for formulation of emollient creams that can serve as effective topical applicants. In the present study, the formulation process for neem (Azadirachta indica A. Juss) oil emollient cream was optimized by phase inversion method in terms of reduced particle size with respect to ultrasonication conditions like duty cycle, time, cavitation intensity and amplitude. Its diluted variant and the one dispersed with titanium dioxide nanoparticles were also synthesized and comparisons of mean particle size, zeta potential and electrophoretic mobility were made with three popular commercial cosmetic creams. Rheological studies showed similar results with respect to relevant parameters like hysteresis loop areas, yield stress, consistency and pseudoplasticity indices. All creams showed non-Newtonian thixotropic behaviour and shear thinning feature that contribute to good flow characteristics and favourable spreading ability. The sun protection factor, determined for the titanium dioxide-loaded cream was found to be better than a popular commercial cream. It was also found to be harmless to representative skin flora as determined by disc diffusion method. Cell toxicity studies on 3T3 cell lines carried out for the oil and emulsifier showed the cells to be viable in the presence of these components. It is thus inferred that this neem emollient base cream can be safely used as a cosmetic topical applicant for skin protection.