Polysorbate cloud point

Fig. 5 Contour diagrams of (A) turbidity and (B) cloud point as function of % propylene glycol and sucrose invert medium (slice taken at constant value of 4.3% polysorbate 80). (From Ref. f)...

Fig. 9 Superposition of contour plots for turbidity <3 ppm and cloud point <70° to determine an optimum region ( slice at 4.3% polysorbate 80). Compare with Fig. 5. (From Ref l)...

No. X. 2 Polysorbate 80 (%) Propylene glycol (%) Sucrose invert medium (mL) Turbidity (ppm) Cloud point (°C)... 

Senderak et al. (5) studied the effects of polysorbate 80 concentration, propylene glycol, and invert sugar on the turbidity and cloud point of a formulation of a slightly soluble drug, using a central composite design. Both the design and the determination of the model are described in some detail in chapter 5. 

Figure 6.3 shows perturbation plots for the two responses. Figure 6.3a suggests that to lower the turbidity, the polysorbate concentration (ilfi) should be increased, whereas an intermediate concentration of propylene glycol (Xj) should be used. Sucrose (X,) has very little effect on turbidity. On the other hand, in figure 6.3b, sucrose appears to be the only factor affecting the cloud point to any important extent. 

The objective was to reduce the turbidity as far as possible, and to obtain a solution with a cloud point less than 70°C, at a level of invert sucrose that is as high as possible (in spite of its deleterious effect on the cloud point). Figure 6.4 shows slices taken in the propylene glycol, sucrose plane (Xj, X3) at different levels of polysorbate X, (coded levels x, = - /4, 0, Vi, 1). Examination of the response surfaces indicates an optimum compromise formulation at 60 mL sucrose medium, 4.3% polysorbate 80 and 23% polyethylene glycol. 

It is useful to plot the residuals, or the studentized residuals, against the values of the coded variables X, in turn. These should be evenly distributed, with no obvious dependence on the factor. Figure 7.1 gives the example of the response of cloud point, in the case of the formulation of an oral solution (3) already discussed in chapters 3, 5, and 6. The studentized residuals are plotted in turn against the polysorbate 80 concentration (X,), the propylene glycol concentration (Xj), and the invert sucrose medium (X,). 

Figure 7.1 Dependence of the residual of the cloud-point on (a) polysorbate 80, (b) propylene glycol, and (c) sucrose invert medium concentrations... 

Sulphamerazine suspensions are in a deflocculated state when prepared with polysorbate 40 [33] (2 %). On standing, the sedimentation volume is around 0.15 and the system is impossible to redisperse after two weeks. Addition of high concentrations of propylene glycol (i.e. greater than 50 %) flocculates the system and renders the suspension dispersible. Propylene glycol dehydrates the surfactant molecules (the cloud point is lowered) hence reducing its stabilizing properties. 

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