Preparation and evaluation of topical nanoformulations for treatment of melasma / by Shymaa Hatem Abd El-Azeem Saleh ; Supervisors : Prof. Dr. Seham Abd El-Khalek ElKheshen Professor of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Prof.Dr. Amany Osama Kamel Professor of Pharmaceutics & Industrial Pharmacy and Dean of Faculty of Pharmacy, Ain shams University, Assoc. Prof. Dr. Maha Nasr Sayed Associate Professor of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain shams University, Dr. Reham Samir Atia Lecturer of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain shams University, Dr. Nada Mohamed El Hoffy Lecturer of Pharmaceutics and Pharmaceutical technology, Faculty of Pharmacy, Future University in Egypt.

Supervisors : Prof. Dr. Seham Abd El-Khalek ElKheshen Professor of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Prof.Dr. Amany Osama Kamel Professor of Pharmaceutics & Industrial Pharmacy and Dean of Faculty of Pharmacy, Ain shams University, Assoc. Prof. Dr. Maha Nasr Sayed Associate Professor of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain shams University, Dr. Reham Samir Atia Lecturer of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain shams University, Dr. Nada Mohamed El Hoffy Lecturer of Pharmaceutics and Pharmaceutical technology, Faculty of Pharmacy, Future University in Egypt.

Thesis (Ph.D.)--Ain shams University, Faculty of pharmacy, pharmaceutical & industrial pharmacy Department, 2022.

Includes bibliographical references (pages 364- 442).

Effect of formulation factors on the EE% of the obtained CSNPs
The EE% is one of the most important physicochemical characteristics of nanocarriers. High encapsulation efficiency ensures more bioavailability and high concentration of targeted drug, which helps in the reduction of the required dose for therapy and thereby decreases the dose-related systemic side effects (Rangasamy et al., 2008). As shown in Table 19, the percent EE% of α-arbutin in CSNPs varied from 63.65% to 88.45%.
ANOVA results revealed the significance for the proposed model (P<0.0001). The model showed high values of R^2 (0.9210), adjusted R^2 (0.8469), and moderate predicted R^2 (0.6839), with high adequate-precision value (8.742). Similarly, the Box-Cox Plot for power transformations (Fig. 11) showed that the current lambda lied within the 95% confidence interval suggesting no recommended transformation.
Assessment of main effects and interactions by the experimental design study showed that the EE% of the prepared α-arbutin-CSNPs was only affected by the chitosan concentration (XA). The estimated contribution of each term in the model showed the great influence of the term X_A (concentration of chitosan) when compared to the other three factors, as reported in Table 20. Similarly, the interaction factors did not play an important role as previously observed in the P.S and PDI analysis models. The linear regression model as obtained from the full factorial study is represented by Eq.15:
Y = 76.23–10.15X_A + 0.24X_B + 0.50X_C–1.06X_D- 0.76X_A X_B+ 0.71X_A X_C- 0.33X_A X_D-0.68X_B X_C+0.19X_B X_D – 2.04X_C X_D+0.44X_A X_B X_C - 0.29X_A X_B X_D+0.14X_A X_C X_D+0.46X_B X_C X_D+ 0.44X_A X_B X_C X_D. (Eq.15)

The effect of the concentration of chitosan (XA) on the EE% of α-arbutin within CSNPs was confirmed by its statistical significant effect (P < 0.0001) as shown in Table 21 compared to the other four independent variables, in which by increasing the chitosan concentration from 0.15 to 0.30 % w/v, the EE% of the prepared CSNPs decreased significantly (P<0.05). This might be caused by the dramatic increase in viscosity and gel formation with increased chitosan concentration, which hindered the encapsulation of α-arbutin, thereby decreasing the encapsulation efficiency as previously discussed in the preliminary section. This is in accordance with the findings of Gulati et al., 2013 who studied the formulation of sumatriptan succinate into CSNPs, as well as Shah et al., 2009 who investigated the incorporation of venlafaxine hydrochloride into the CSNPs.


Three-dimensional surface plots are shown in Figures 12(a-d) to determine the influence of the independent factors on the EE% of α-arbutin-loaded CSNPs and clarify the relationship between factors X_A and X_B at both high and low levels of factors X_C and X_D.

Text in English, Abstract in English and Arabic