Formulation of Dacarbazine-loaded Cubosomes—Part II: Influence of Process Parameters

Abstract

Abstract. The purpose of this study is to investigate the combined influence of process parameters (independent variables) such as homogenization speed (X 1 ), duration (X 2 ), and temperature (X 3 ) during the preparation of dacarbazine-loaded cubosomes. Box-Behnken design was used to rationalize the influence of these three factors on two responses, namely particle size (Y 1 ) and encapsulation efficiency (Y 2 ). Independent and dependent variables were analyzed with multiple regressions to establish a fullmodel second-order polynomial equation. F value was calculated to confirm the omission of insignificant parameters or interactions of parameters from the analysis to derive a reduced-model polynomial equation to predict the Y 1 and Y 2 of dacarbazine-loaded cubosomes. Pareto charts were also obtained to show the effects of X 1 , X 2 , and X 3 on Y 1 and Y 2 . For Y 1 , there was a model validated for more accurate prediction of response parameter by performing checkpoint analysis. The optimization process and Pareto charts were obtained automatically and they predicted the levels of independent parameters X 1 , X 2 , and X 3 (0.889794, 0.11886, and 0.56201, respectively) and minimized Y 1 . The optimal process parameters (homogenization's speed=~24,000 rpm, duration=5.5 min, and temperature=76°C) led to the production of cubosomes with 85.6 nm in size and 16.7% in encapsulation efficiency. The Box-Behnken design proved to be a useful tool in the preparation and optimization of dacarbazine-loaded cubosomes. For encapsulation efficiency (Y 2 ), further studies are needed to enhance the result and improve the model for such water-soluble drug encapsulation in cubosomes.

Formulation of Dacarbazine-loaded Cubosomes. Part III. Physicochemical Characterization

“…The method of preparation of DTIC-loaded cubosomes was adapted from previous work of Esposito et al (17)(18)(19). Briefly, for each sample, a volume of 15 ml chloroform was used to completely dissolve 500 mg GMO and 75 mg F127.…”

“…Previous studies reported that even lipophilic drugs were rapidly released from cubosomes after ultrafiltration (26). However, sample #2 (F2+) and control #2 (F2−) were prepared using the method resulting from the process parameters study (19). In this case, using 500 mg of GMO, 75 mg of F127, and 10 mg of DTIC, minimal particle size was achieved with approximately 24,000 rpm of homogenization speed, 5.4 min of duration, at 76°C±2°C temperature.…”

Optimization of Formulation Variables Affecting Spray-Dried Oily Core Nanocapsules by Response Surface Methodology

“…23,24 The authors have recently combined the concept of design of experiments with nanoformulation. 25,26 In this study, an easy and effective method of preparing spray-dried NCs without using the classical rotary evaporator was developed. The influence of three different formulation variables was studied using a Box-Behnken design to optimize spray-dried NCs.…”

Comparative Biophysical Properties of Tenofovir-Loaded, Thiolated and Nonthiolated Chitosan Nanoparticles Intended for HIV Prevention

“…The obtained t , which indicates the main effect of the independent variables and interactions on the Y 1 value, is compared with a tabulated critical t-value (the absolute value of t Critical = 2.57) at p < 0.05, which is determined at α = 0.05 for the residual degrees of freedom (df), where df = 5 [39]; both t Critical values are shown in the two vertical lines in Figure 1B. The factors whose length passed the vertical line indicate significance on the response value [40]. The positive sign of the coefficient shows a positive effect on the size of the responses, while the negative signs indicate a negative effect.…”