Oil-in-Water Nanosized Emulsions for Drug Delivery and Targeting. Tamilvanan Shunmugaperumal. Читать онлайн. Newlib. NEWLIB.NET

Автор: Tamilvanan Shunmugaperumal
Издательство: John Wiley & Sons Limited
Серия:
Жанр произведения: Химия
Год издания: 0
isbn: 9781119585251
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variations in particle size without a distinct distribution shape (Müllar 1990; Cegnar et al. 2004). The experimental CPPs involved in the preparation of topical ophthalmic emulsions may influence the performance of CQAs (PDI). All of the studied CPPs (amounts of castor oil, chitosan, and poloxamer) produced a direct relationship with PDI values observed. An increase in CPPs amounts increases the PDI values (Fig. 2.6d–f). Higher is the amount of castor oil, lesser is the oil breakdown frequency during emulsification promoting the formation of larger sized oil droplets and thus the PDI to attain a higher value. Increasing the amounts of these two emulsifying agents (chitosan and poloxamer) either alone (Fig. 2.6d and e) or in combination (Fig. 2.6f) also increased the PDI values. For instance, the PDI value of >0.6 was noted when the interaction between chitosan and castor oil occurred (Fig. 2.6d). But the interaction between poloxamer and castor oil yielded the PDI value of ~0.6 (Fig. 2.6e). However, the combined interaction of two emulsifying agents produced the PDI value of <0.6 (Fig. 2.6f). These effects are possibly due to the progressive increase in the apparent viscosity of the emulsion, which ultimately provides a higher flow resistance in the batch emulsification process (Müllar 1990). In consequence, this condition increased the coalescence rate resulting in a large particle size to form. Moreover, the large particles with inadequate emulsifier film coverage tend to coalesce faster than small particles. This phenomenon contributed to the high PDI value. Figure 2.6g–i demonstrates that by increasing the chitosan or castor oil concentration, the ZP value increases. In contrast, a biphasic manner, i.e., an initial increase followed by decrease in the ZP values, was observed with an increase in poloxamer concentration (Fig. 2.6h and i). It should be added that the present topical ophthalmic emulsions were stabilized by both electrostatic and steric mechanisms due to the chitosan and poloxamer emulsifier combination. Whatever the strong repulsive Coulomb force occurred between the protonated chitosan molecules must be counterbalanced by the week van der Waals attraction forces or the steric hindrance effect of poloxamer. That is why the biphasic attitude was seen for the influence of poloxamer concentration on ZP values (Tamilvanan 2009).

       2.5.1.7. Optimization of Responses for Formulation of CsA‐Loaded Nanosized Emulsion

      To substantiate further the established optimized formula for topical ophthalmic emulsion within the design space, the predictability of chosen face‐centered CCD model is at first corroborated by evaluating the randomly selected six different formulae along with the optimized formula for the actual CQAs values and comparing them with the predicted CQAs values. The diagnostic plot of actual versus predicted CQAs (R1:MPS, R2:PDI, and R3:ZP) values are shown in Fig. 2.7a–f. Interestingly, the actual versus predicted plots for all of the CQAs were shown the r2 value of greater than 0.9 indicating the establishment of the closeness between the values and hence conformed/justified the predictability of chosen model within the design space (Fig. 2.7b, d, and f). The value of randomness of scatter and deviations was found to be within ±4% in residual versus predicted value plot (Fig. 2.7a, c, and e). Furthermore, the chosen model also showed an overall mean percent error value of 0.30 ± 0.13%. In addition, an adequate precision should measure the signal‐to‐noise ratio, and its value of greater than 4 is desirable. As per the selected face‐centered CCD model, the signal‐to‐noise ratio values shown by Design‐Expert® software for MPS, PDI, and ZP were 8.701, 6.415, and 4.6524, respectively. This directly indicates that the adequate precision is produced and therefore this model can be used to navigate the design space to find out the optimized formula for topical ophthalmic emulsion.

Graphs depict derived plots obtained from 3-dimensional-response surface model describing residual versus predicted plot (a, c, e), actual versus predicted plot (b, d, f), and overlay plot (g).

      1 Abele, S., Sjöberg, M., Hamaide, T. et al. (1997), Reactive surfactants in heterophase polymerization. 10. Characterization of the surface activity of new polymerizable surfactants derived from maleic anhydride, Langmuir, 13, 176–181. doi: 10.1021/la960577n

      2 Akkar, A. and Müller, R.H. (2003a), Formulation of intravenous carbamazepine emulsions by SolEmuls® technology, Eur. J. Pharm. Biopharm., 55, 305–312. doi:10.1016/s0939‐6411(03)00028‐6

      3 Akkar, A. and Müller, R.H. (2003b), Intravenous itraconazole emulsions produced by SolEmuls technology, Eur. J. Pharm. Biopharm., 56, 29–36. doi:10.1016/s0939‐6411(03)00063‐8

      4 Aveyard, R., Binks, B.P., and Clint, J.H. (2003), Emulsions stabilized solely by colloidal particles, Adv. Colloid Interf. Sci., 100 (102), 503–546. doi:10.1016/S0001‐8686(02)00069‐6

      5 Badawy, S.I., Narang, A.S., LaMarche, K.R. et al. (2016), Integrated application of quality‐by‐design principles to drug product development: a case study of brivanib alaninate film‐coated tablets, J. Pharm. Sci., 105 (1), 168–181. doi:10.1016/j.xphs.2015.11.023

      6 Benichou, A., Aserin, A., and Garti, N. (2004), Double emulsions stabilized