Oil-in-Water Nanosized Emulsions for Drug Delivery and Targeting. Tamilvanan Shunmugaperumal

Linear term A 7.61 0.0202 1.09 0.3219 0.0013 0.9714 B 1.14 0.3111 0.5629 0.4704 0.9391 0.3554 C 3.32 0.0986 9.47 0.0117 4.11 0.0702 Interaction term AB 0.2709 0.6141 0.0928 0.7668 2.11 0.1769 AC 4.36 0.0633 3.46 0.0924 0.3590 0.5624 BC 0.1542 0.7028 2.01 0.1872 1.83 0.2054 Quadratic term A ² 0.1161 0.7403 0.0911 0.7689 0.0981 0.7605 B ² 6.89 0.0254 0.0157 0.9027 0.3624 0.5606 C ² 4.08 0.0711 5.99 0.0344 2.69 0.1317

      Note: A/a: Castor oil, B/b: Chitosan, C/c: Poloxamer.

      The coefficient significance of the quadratic polynomial models was evaluated by using Analysis of Variance (ANOVA). For any of the terms in the models, a large F‐value and a small p‐value indicated more significant effect on the respective response variables (Joglekar 1987). Table 2.8 shows the effect of independent variables on the variation of the physicochemical properties of topical ophthalmic emulsions. The variable that exhibited the largest and significant (p < 0.05) effect on the MPS of the emulsion for the linear term was castor oil amount. The other two variables (amounts of chitosan and poloxamer) showed insignificant effects. All the interaction terms showed insignificant effect on MPS. The quadratic terms of chitosan amount exhibited significant effect on MPS while other two terms showed insignificant effect.

      The independent variables that most affect the ZP value of the emulsions for the linear term were poloxamer amount followed by the linear term of chitosan amount and castor oil amount but none of the linear terms has any significant effect. All the three interaction and quadratic effects have insignificant effect (p > 0.05) on the ZP value of the emulsions.

      For the PDI, the linear and quadratic terms of poloxamer amount have the significant effect while all other linear, interaction, and quadratic terms have insignificant effect. Thus, it was indicated that in evaluating the response variation of PDI, it was important to consider the poloxamer amount.

       2.5.1.6. Response Surface Plot Analysis

The 3D response surface graphs for the selected CQAs (R₁:MPS, R₂:PDI, and R₃:ZP) of topical ophthalmic emulsions are shown in Fig. 2.6. To represent the 3D graphs for R₁ (MPS), there are three different plots designated as Fig. 2.6a–c. In a similar way, the 3D graphs for R₂ (PDI) and R₃ (ZP) are also represented, respectively, as Fig. 2.6d–f and Fig. 2.6g–i. From Fig. 2.6a and b, the MPS value increases with an increase in the amount of castor oil. Two possible explanations might be provided with this observation. The oil droplet disruption process during homogenization and probe sonication of coarse emulsion gets somewhat cumbersome due to the progressive increment of castor oil amount because of the resistance in oil flow and thus the diminution/restriction in the oil droplet breakup rate. The MPS value increase due to the increase of castor oil amount might also be attributed to the increased rates of oil droplets—droplets collision frequency especially at lower castor oil amount, which ultimately leads to the higher probability of coalescence of the smaller droplets and thus the bigger droplet formation at the expense of smaller droplets.

Figure 2.6. Response surface plots showing the interaction effects of castor oil and chitosan (a, d, g), castor oil and poloxamer (b, e, h), and chitosan and poloxamer (c, f, i) on response, mean particle size (R₁), polydispersity index (R₂), and zeta potential (R₃), respectively.

The presence of two different emulsifying agents (chitosan and poloxamer) either alone or in combination influenced the MPS in a biphasic manner. An initial increment until to reach a sharp break‐point followed by a progressive decrement in the MPS value was noticed when these two emulsifying agents interacted (Fig. 2.6c) as well as even in the occurrence of interaction between chitosan and castor oil (Fig. 2.6a) or poloxamer and castor oil (Fig. 2.6b). The initial particle size increment might be due to an inadequate amount of emulsifying agent(s) to form a mono‐ or multilayer film onto the dispersed oil droplets of the emulsion during emulsification (Jumaa and Müller 1998). Due to the attainment of the critical interfacial tension reduction at the vicinity of oil and water by the sufficient amount of emulsifying agent(s) resulted in the diminution of Laplace pressure, p, and thus the stress required for droplet deformation is reduced (Tang et al. 2012).

      The PDI value is ranged from 0 to 1 wherein PDI < 0.1 indicates a nearly homogenous monodisperse formulation. The PDI value between 0.1 and 0.2 specifies a particle population with relatively