<p>Optimization of Processing Parameters of Nanoemulsion Containing Aripiprazole Using Response Surface Methodology</p>

Abstract

Background: Aripiprazole, which is a quinolinone derivative, has been widely used to treat schizophrenia, major depressive disorder, and bipolar disorder. Purpose: A Central Composite Rotatable Design (CCRD) of Response Surface Methodology (RSM) was used purposely to optimize process parameters conditions for formulating nanoemulsion containing aripiprazole using high emulsification methods. Methods: This design is used to investigate the influences of four independent variables (overhead stirring time (A), shear rate (B), shear time (C), and the cycle of high-pressure homogenizer (D)) on the response variable namely, a droplet size (Y) of nanoemulsion containing aripiprazole. Results: The optimum conditions suggested by the predicted model were: 120 min of overhead stirring time, 15 min of high shear homogenizer time, 4400 rpm of high shear homogenizer rate and 11 cycles of high-pressure homogenizer, giving a desirable droplet size of nanoemulsion containing aripiprazole of 64.52 nm for experimental value and 62.59 nm for predicted value. The analysis of variance (ANOVA) showed the quadratic polynomial fitted the experimental values with F-value (9.53), a low p-value (0.0003) and a nonsignificant lack of-fit. It proved that the models were adequate to predict the relevance response. The optimized formulation with a viscosity value of 3.72 mPa.s and pH value of 7.4 showed good osmolality value (297 mOsm/kg) and remained stable for three months in three different temperatures (4°C, 25°C, and 45°C). Conclusion: This proven that response surface methodology is an efficient tool to produce desirable droplet size of nanoemulsion containing aripiprazole for parenteral delivery application.

Optimisation of Epoxide Ring-Opening Reaction for the Synthesis of Bio-Polyol from Palm Oil Derivative Using Response Surface Methodology

“…The quadratic polynomial model is illustrated in Table 2 . The p -value (<0.0001) indicated that the developed model was significant and adequate to demonstrate the actual interaction between the significant variables and the response (hydroxyl value) [ 36 ]. The lack of fit ( F -value = 4.18) showed insignificant data, which was comparative to the pure error of the experiments, which indicated that the quadratic model data were convenient to depict the whole experimental data.…”

Antipsychotic Potential and Safety Profile of TPGS-Based Mucoadhesive Aripiprazole Nanoemulsion: Development and Optimization for Nose-To-Brain Delivery

“…21 Several approaches have been made by different researchers to improve the delivery of ARP. Some of the recent approaches involve the development of mixed micellar delivery to improve solubility and oral bioavailability of ARP, 22 the development strategy of ARP NE using response surface software, 23 and the nose-to-brain delivery approach of ARP using the poly(caprolactone) nanoparticle platform. 17 Emerging researches provoke this novel research towards an extensive study on planning to develop a safe and effective TPGS based mucoadhesive NE of ARP (ARP-MNE) using Box-Behnken statistical design to target the brain via intranasal administration.…”

Antipsychotics-Loaded Nanometric Emulsions for Brain Delivery

“…Aripiprazole was approved by the FDA in 2002, and is an atypical third-generation antipsychotic that, opposed to most other antipsychotic drugs, acts as a partial agonist for dopamine D2 receptors and agonist of serotonin 5-HT1A receptors, being reported to be effective against both positive and negative symptoms of schizophrenia [ 36 , 54 ]. Howver, although it has been considered to be comparatively safer than other similar therapeutics, there have been reports of serious systemic side effects (hypotension, hyperglycemia, neuroleptic malignant syndrome, QT interval prolongation), and it has a very low water solubility (predictably 0.00777 mg/mL), which makes it challenging to formulate at high strength [ 35 , 36 , 37 , 54 ]. In order to tackle these issues, Samiun et al and Masoumi et al [ 35 , 36 ] formulated aripiprazole into an O/W nanoemulsion, for intravenous administration.…”

“…Howver, although it has been considered to be comparatively safer than other similar therapeutics, there have been reports of serious systemic side effects (hypotension, hyperglycemia, neuroleptic malignant syndrome, QT interval prolongation), and it has a very low water solubility (predictably 0.00777 mg/mL), which makes it challenging to formulate at high strength [ 35 , 36 , 37 , 54 ]. In order to tackle these issues, Samiun et al and Masoumi et al [ 35 , 36 ] formulated aripiprazole into an O/W nanoemulsion, for intravenous administration. The nanoemulsion was prepared using high energy emulsification methods, and contained palm kernel oil esters, soybean lecithin (Lipoid S75), Tween ® 80 (polysorbate 80-polyoxyethylene 20 sorbitan monooleate), glycerol and water (specific quantities in Table 8 ).…”