Response Surface Plots Research Articles

Development and Ex vivo evaluation of Rasagiline Mesylate mucoadhesive microemulsion for intranasal delivery using Box-Behnken design

Rasagiline mesylate (RM), an irreversible, selective inhibitor of MAO-B enzyme, is used in the treatment of Parkinson’s disease as oral tablets. It has low oral bioavailability (36%) due to hepatic first pass metabolism. Oral route of administration is associated with nausea and vomiting. Hence present research work was aimed to develop intranasal RM- loaded mucoadhesive microemulsions for brain targeting via olfactory pathway. The microemulsions were developed using Box Behnken design and evaluated for globule size, PDI, Zeta potential, pH, viscosity and ex vivo permeation on excised porcine nasal mucosa. Based on drug solubility, Capmul MCM, Tween 20 and Transcutol P were selected as oil, surfactant and cosurfactant respectively. Microemulsions were prepared by water titration method. Pseudoternary phase diagrams were constructed and the levels of surfactants, oil were selected. The influence of independent variables such as oil, Smix and water on responses size, zeta potential and flux were studied with the help of polynomial equations, contour plots and 3D response surface plots generated by design expert software. Optimized microemulsion formulation (ME18) was composed of oil (Capmul MCM), Smix (Tween 20: Transcutol P; 1:1), water and drug in the ratio 5:42:65:5.The globule size, zeta potential and flux of the optimized microemulsion was 150 nm, -29.6 mV and 291.7 μg/cm2/h respectively. Mucoadhesive agent (Chitosan) was added at 0.5% concentration to optimized microemulsion formulation (MME18). The size, zeta potential and flux of the MME18 was 176.4 nm, 12.1 mV and 323.1 μg/cm2/h respectively. The flux of ME18 and MME 18 was significantly higher than drug solution. The enhancement ratio of MME 18 was 4.2 times to that of drug solution, indicating potential advantage of microemulsion formulation.

Design of experiment for optimization of nitrophenol reduction by green synthesized silver nanocatalyst

Phenol derived molecules are considered as critical pollutants in the environment and need to be decontaminated to safeguard our mother Earth. This may sometimes be achieved by degradation using nanomaterials. Plant mediated biosynthesis of nanoparticles is truly encouraging for environmental safety as well as easy availability of precursor materials.The present report demonstrates the catalytic reduction of 4-nitrophenol using silver nanoparticle, synthesized from rhizome of Cyperus Rotundus. It is characterized by UV–vis and FTIR spectra, DLS, SEM-EDS, AFM, FESEM and TEM. The size of the particle is estimated to be in the range of 10–40 nm. Degradation pathway using NaBH4 and silver nanoparticle catalyst is followed under visible light. The influence of variables such as time, dose of NaBH4, 4-nitrophenol (4-NP) and silver nanoparticle was investigated following response surface methodology. A mathematical model is built up to correlate the interactive influences of the significant variables and the reduction. The mutual interactions of these variables are mapped in the design space by response surface and contour plots. The process follows a pseudo first-order kinetic model and the activation energy was evaluated to be 53.3 kJ mol−1. The conversion of 4-NP–4-AP was confirmed from NMR studies.

Formulation development of methylprednisolone dispersible tablets using quality by design approach

The objective of this study was to enhance the solubility of Methylprednisolone by choosing micronized form of drug and to enhance patient compliance by formulating it as dispersible tablets using quality by design (QbD) approach. Dispersible tablets of Methylprednisolone were developed by 23 factorial design. In this study independent variables were concentrations of MCC 102, CCS and Magnesium stearate and dependent variables were disintegration time, hardness and dissolution. The resulting data was fitted into Design Expert Software (Trial Version) and analyzed statistically using analysis of variance (ANOVA). The response surface plots were generated to determine the influence of concentration of MCC 102, CCS and magnesium stearate on responses. The tablets were prepared by direct compression method by choosing micronized form of drug and formulations were evaluated for the standard of dispersible tablets. Results showed that no significant drug-polymer interactions in FTIR studies. According to QbD suggestion the formulation O1 (Desirability- 0.73) with MCC-38mg, CCS-3.5mg and magnesium stearate-2.5mg was formulated and evaluated. The disintegration time was found to be 69 seconds, hardness was found to be 64N and in vitro dissolution with in 30minutes. Optimized O1 formulation was within the limits of standards of dispersible tablets with increased water solubility and better patient compliance. Stability study on optimized O1 formulation showed that there is no significant changes during study period. Thus, O1 formulation was found to be stable. The study indicates that formulation of Methylprednisolone dispersible tablets by using QbD approach is a promising formulation development method.
 Keywords: Dispersible tablets, Methylprednisolone, Direct compression, Quality by Design and ANOVA.

Optimization of process parameters of direct metal laser sintering process using fuzzy-based desirability function approach

CL50WS material has been mainly used in tooling industries for making die, tool insert, mould or casting die. As the manufacturing of the CL50WS material parts from the DMLS machine differs from the conventional machining process, it is very essential to understand of DMLS behaviour and determine the proper optimal process parameter. Hence, the present study highlights the application of Box–Behnken method (BBD) of response surface methodology with fuzzy-based desirability function approach in order to optimize the multiple process parameters of direct metal laser sintering. The study also focused to investigate the effects of process parameters, viz. the laser power, scanning speed, layer thickness and hatch spacing, on the performance characteristics such as surface roughness, hardness and impact strength for the fabricated specimen using response surface plot. Fuzzy inference system has been applied in order to aggregate the aforementioned performance characteristics into a single objective response, i.e. multi-performance characteristic index. The optimum values of process parameters such as laser power 130 W, scan speed 550 mm/sec, layer thickness 0.03 mm and hatch spacing of 0.010 mm have been observed in the present study.

Evaluation of the Spray Drying Conditions of Blueberry Juice-Maltodextrin on the Yield, Content, and Retention of Quercetin 3-d-Galactoside.

The influence of the processing conditions during the spray drying of mixtures of blueberry juice (BJ) and maltodextrin (MX) was determined quantitatively by the analysis of variance (ANOVA), and qualitatively by the surface response plots (SRP). The effect of two independent variables (inlet temperature, and MX concentration), and one categorical variable (type of MX), was determined on the yield (Y), content (Q), and retention (R) of the antioxidant quercetin 3-d-galactoside. From the ANOVA results, the concentration was the main variable affecting Y and Q, while temperature had a negligible effect, and the low molecular weight MXs exhibited a better response. The physicochemical characterization showed that the powder appearance and microstructure remained unaffected, but size and morphology of the particles varied with the processing conditions. This study established the optimal processing conditions for the spray drying of BJ-MX, and the application limits of the MXs based on the molecular weight distribution.

Optimization of mesoporous alumina sol‐gel synthesis by Taguchi and response surface methodology

AbstractTaguchi method (TM) and response surface methodology (RSM) have been employed to optimize three parameters, including the amounts of P123, the amounts of nitric acid and calcination temperature, in order to define an optimal setting for sol‐gel synthesis of high surface area mesoporous alumina powder (MA). Herein, the comparison of the both statistical approaches has been examined and discussed considering the nitrogen adsorption as the response variable because this important character for mesoporous materials is exceedingly sensitive to the synthesis parameters. The BET surface area (SBET) and pore volume of MA under Taguchi optimal condition were 323.5 m2 g−1 and 0.551 cm3 g−1, respectively, by conducting confirmation test. Furthermore, the confirmation test showed high SBET of MA (363.4 m2 g−1), which was in a good agreement with calculated SBET result (431.25 m2 g−1) by a quadratic model under RSM optimal condition. Moreover, 3D response surface plots and 2D contour plots of desirability have been discussed to visualize the influence of input factors on response variable. It is also concluded that RSM shows more appropriate (12.33% higher SBET than TM) and efficient optimal condition with determining a quadratic function as the relationship between SBET and synthesis parameters.

Method for the determination of polonium-210 in tea samples using response surface methodology (RSM)

The method based on solvent parameters (mass, cycle of acidification, and autodeposition time), combined with response surface methodology (RSM) modeling and optimization, has been developed for maximizing 210Po activity in tea samples, as observed by an alpha spectrometer. RSM based on 3-factor and 5-level composite center design was used to obtain the optimal combination of solvent conditions. As solvent parameters for 210Po activity, different masses (0.5, 0.75, 1, 1.5, and 2 g), different cycles of acidification (2, 3, 4, 5, and 6 times), and different autodeposition times (2, 3, 4, 5, and 6 h) were studied. The 3D response surface plot and the contour plot derived from the mathematical models were used to determine the optimal conditions. According to the obtained results, the experimental value of 210Po activity was in good agreement (R2 = 0.96) with the value predicted by the model. We found a favorable effect of mass on the 210Po activity (p < 0.05).

Formulation and characterization of acyclovir based topical microemulsions by QBD approach

Objective: The proposed study is focussed at developing acyclovir microemulsions for topical drug delivery systems. QbD was applied for better understanding of the process and to generate design space, using quality target product profile, critical quality attributes, and risk assessment. The aim of the experiment is to prepare a safe, efficacious, stable and patient compliant microemulsion dosage form of Acyclovir. Materials and methods: Pre-formulation studies were carried out which helped in developing a suitable dosage form. UV, FTIR and DSC studies were done for pre-formulation and post-formulation evaluations. QbD was applied to generate design space, using QTPP, CQA, and risk assessment. Microemulsions of acyclovir were developed by using 32 factorial designs. Pseudo terneary phase diagrams were constructed to screen various surfactants and co-surfactants for the preparation of microemulsions. Two independent variables Oil Concentration (X1) and Smix Concentration (X2) at three levels low, medium and high were selected and response surface plots were generated. The microemulsions were prepared by plotting pseudo terneary phase diagrams. Various characterizations that were carried out include % transmittance, Viscosity and % drug release. Statistical analyses of batches and surface response studies were done to understand the effect of various independent variables on the dependent variables. Results and Discussions: The λmax was confirmed at 251 nm by UV spectroscopy. The melting point was determined experimentally to be 2460C which confirms the drug to be Acyclovir. FTIR and DSC studies confirmed that the drug is Acyclovir. Conclusion: The study indicates that microemulsions of Acyclovir by QbD approach were successfully developed.&#x0D; Keywords: Microemulsion, Acyclovir, DoE, QbD

Quality by Design based formulation and evaluation of acyclovir microsponges

Objective: The proposed study is focussed at developing acyclovir microsponges for oral drug delivery systems. QbD was applied for better understanding of the process and to generate design space, using quality target product profile, critical quality attributes, and risk assessment. The aim of the experiment is to prepare a safe, efficacious, stable and patient compliant microsponge dosage form of Acyclovir. Materials and methods: Pre-formulation studies were carried out which helped in developing a suitable dosage form. UV, FTIR, DSC, and SEM studies were done for pre-formulation and post-formulation evaluations. QbD was applied to generate design space, using QTPP, CQA, and risk assessment. Microsponges of acyclovir were developed by 23 factorial designs. Three variables Drug: Polymer ratio (X1), Concentration of surfactant (X2) and Stirring speed (RPM) (X3) at two levels low and high were selected and response surface plots were generated. The microsponges were prepared by Quassi-emulsion solvent diffusion method. Various characterizations that were carried out include entrapment efficiency, percentage yield, particle size determination, in-vitro drug release studies and kinetic modelling of drug release. Statistical analyses of batches and surface response studies were done to understand the effect of various independent variables on the dependent variables. Results and Discussions: The λmax was confirmed at 251 nm by UV spectroscopy. The melting point was determined experimentally to be 2460C which confirms the drug to be Acyclovir. FTIR and DSC studies confirmed that the drug is Acyclovir. Eight trials were taken as per the by 23 factorial designs. Conclusion: The study indicates that microsponges of Acyclovir by QbD approach were successfully developed.&#x0D; Keywords: Microsponge, Acyclovir, DoE, QbD

Sustainable treatment of municipal landfill leachate by combined association of air stripping, Fenton oxidation, and enhanced coagulation.

The present world has been facing the problem of municipal solid waste disposal with the generation of highly complex and toxic landfill leachate. Thus, in this research work, treatability of landfill leachate had been investigated by the combined approach of air stripping, Fenton oxidation, and enhanced coagulation to comply with discharge standard. At the initial stage of treatment, air stripping of raw leachate was implemented which removes around 51.50% of COD, 74.60% of BOD5, and 97.60% of NH3-N within 36h of optimum retention time. Following air stripping, Fenton oxidation was applied with an optimum molar ratio of 1.9 of H2O2/Fe+2 which register a maximal removal of 67.70% of COD, 92.30% of BOD5, and 14.90% of Hg. Finally, enhanced coagulation (EC) with in situ formed Mn-Fe hydr(oxides) was employed and optimized by central composite design (CCD) of response surface methodology (RSM). Response surface plots denote an optimum condition of 0.13M ratio of Mn/Fe, 22.67mM of coagulant dose, and 7.78 of pH which corresponds to a maximum removal of 55.98% of COD and 77.68% of Hg. FTIR analysis of the precipitates of EC explained that the hydroxyl groups are primarily involved in the process of Hg removal. Moreover, EDAX spectrum also assured the removal of Hg by its existence with Mn-Fe complexes. Thus, the present line of treatment record an overall removal of 90.80% of COD, 98.0% of BOD5, 97.60% of NH3-N, and 82.68% of Hg which proves to be effective for the removal of leachate pollutants.

Integration of RSM with Grey based Taguchi Method for optimization of pulsed TIG welding process parameters

Abstract This research paper focused on process parameters optimization of Tungsten Inert Gas (TIG). Taguchi method is very effective and efficient to solve the process parameter optimization problem to the find optimum processing parameter, but it is found that the traditional Taguchi method is not sufficient to solve the problem with multi response problem to get optimum results and to meet the global challenges of the manufacturer as it is impractical to obtain more than one optimal processing parameter through Taguchi. In order to survive in the global market it is necessary to used advanced and modified optimization techniques. To intensify the efficiency of Taguchi method, it is absolutely necessary to integrate it with the other optimization approach. However, it is important to integrated Taguchi method with Grey Retion Analysis (GRA) to solve multi response optimizaton promblem futher Taguchi method is integrated with Response Surface Methodology (RSM) to determine optimum value of each parameters. Using orthogonal array L9 experiments were performed. Experimental data are used to obtain signal to noise ratio by using Minitab18 and then response surface plot is developed to obtain optimum level for every input parameter. Further, the process is integrated with RSM to developed mathematical model by using design expert 11 statistical software through full-factorial central composite design (CCD). RSM is a useful statistical tool for process optimization to obtain the required quality of weld. The Surface plot obtained from Design Expert Software 11 represent that the actual value of response i.e. depth of penetration (DOP) and width of penetration (WOP) versus the predicted value of response are close to each other. The higher value of DOP and WOP represents higher strength; analysis of variance (ANOVA) gives the highest value of F-ratio of welding speed in DOP and WOP, this result obtained from RSM showed that welding speed is the most influencing parameter which affects response characteristics.

Parametric optimization of non-traditional machining processes using Taguchi method and super ranking concept

In order to achieve higher dimensional accuracy along with better surface quality, the conventional machining processes have now-a-days being replaced by non-traditional machining (NTM) processes, because of their ability to generate intricate shape geometries on various advanced engineering materials. In order to exploit their fullest machining potential, it is often recommended to operate those NTM processes at their optimal parametric settings. Several optimization tools and techniques are now available which can be effectively applied to obtain the optimal parametric conditions of those processes. In this paper, Taguchi method and super ranking concept are integrated together to present an efficient optimization technique for simultaneous optimization of three NTM processes, i.e. electro-discharge machining process, wire electro-discharge machining process and electro-chemical discharge drilling process. The derived results are validated with the help of developed regression equations, which show that the proposed approach outperforms the other popular multi-response optimization techniques. Analysis of variance is also performed to identify the most influencing control parameters for the considered NTM processes. The developed response surface plots further help the process engineers in identifying the effects of various NTM process parameters on the calculated sum of squared rank values.

Response surface methodology analysis towards biodegradability and antimicrobial activity of biopolymer film containing turmeric oil against Aspergillus niger

The antimicrobial activity and biodegradability of the biopolymer film (as a coating for kraft paper) was analysed using response-surface methodology. The results of the study showed that both the coating thickness and the turmeric oil volume significantly affected these responses. From the response-surface plot, the highest value for the inhibition zone of Aspergillus niger and the lowest weight loss during the biodegradation study were due to the slow release of antimicrobial agents. This indicates that the released of antimicrobial agents occurred during the correct stipulated period of time required to inhibit the microorganisms' growth. Therefore, the results suggested that applying a biopolymer film containing turmeric oil as a kraft-paper coating can improve the paper's packaging functionality by prolonging the shelf life of foods. In addition, all the samples degraded in typical soil conditions, showing that this coating can be disposed of in landfills after use.

Optimization of used cooking oil methyl ester production using response surface methodology

ABSTRACTMonoalkyl ester of vegetable oil, animal fat, and used cooking oil (UCO) is termed as biodiesel. Biodiesel obtained from UCO is gaining importance as an alternate fuel for usage in diesel engines since its fuel properties are compatible with that of diesel fuel. The percentage of free fatty acid (FFA) in the oil determines the production process of biodiesel. In this work, the FFA value of one-time and multi-time UCO was determined using titration method as 2.20% and 3.20%, respectively. The raw UCO is converted into biodiesel by means of acid esterification or alkali transesterification. It involves the addition of methanol with raw oil in the presence of catalysts such as H2SO4 or NaOH. In the current study, one-time UCO has been selected for which alkali-based transesterification was found to be the most suitable methodology to extract the biodiesel. The transesterification process is governed by reaction parameters such as methanol–oil ratio, reaction temperature, reaction time, and catalyst loading. The optimization of the above parameters was carried out by means of response surface methodology using Box–Behnken design. The response surface plot and contour plot have been plotted among various parameters that influence the biodiesel production. An optimized UCOmethyl ester yield of 92.43% is achieved at 1:8 molar ratio, 0.6 wt% catalyst loading, 80 min reaction time, and 55°C reaction temperature. Based on these parameters, the experimental yield was found to be 91.75% which has been found in accordance with the optimized yield, and this proves that response surface methodology is an effective approach in increasing the yield.

Design-of-experiment approach for the development and validation of a high-performance thin-layer chromatography method for the simultaneous estimation of berberine chloride and galangin inTinospora cordifoliaM. andAlpinia galangaL. and their herbal formulations

In the present study, a design-of-experiment (DoE) approach Was used to determine optimized mobile-phase compositions for the development of a high-performance thin-layer chromatography (HPTLC) method for the simultaneous estimation of berberine chloride (BER-H) and galangin (GAL) in Tinospora cordifolia M. and Alpinia galanga L., respectively, and their formulations. A Box—Behnken design (BBD) was used to optimize the compositional parameters and evaluate the main effect, interaction effects and quadratic effects of the mobile-phase compositions on the retardation factor (RF) of both drugs. HPTLC separation was performed on aluminum plates pre-coated with silica gel 60 F254 as the stationary phase, using toluene—ethyl acetate—formic acid (3:6:1, v/v) as the mobile phase at a wavelength of 267 nm. A sharp and well-resolved peak was obtained for BER-H and GAL at RF values of 0.17 ± 0.01 and 0.82 ± 0.01, respectively. The calibration curve was in the range of 200–1200 ng per band for both BER-H and GAL, with r2 = 0.984 and r2 = 0.980, respectively. Statistical insight was achieved with analysis of variance (ANOVA). The method was validated for linearity, accuracy, precision, limit of detection, limit of quantification, robustness, and specificity. To provide a better visualization of the statistically significant factors derived from the statistical analysis, the perturbation plot and response surface plot for the effect of independent variables on the RF of BER-H and GAL were evaluated. The developed HPTLC method was found to be simple, accurate, precise, sensitive, and specific for the simultaneous quantification of berberine chloride and galangin in Tinospora cordifolia M. and Alpinia galanga L., respectively, and their formulations.

Development and evaluation of metronidazole loaded carbopol 934P mucoadhesive microcapsules for sustained drug release at the gastric mucosa

ABSTRACT Metronidazole [1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole) is a broad spectrum antimicrobial agent used for the eradication of Helicobacter pylori. Due to the short biological half-life (6 to 8 h) and bitter taste which may lead to non-compliance issue; the purpose of this study was to develop and evaluate metronidazole loaded carbopol 934P mucoadhesive microcapsules for sustained drug release at the gastric mucosa. Metronidazole mucoadhesive microcapsule was formulated by ion gelation technique using 32 factorial designs. A 32 full factorial design was used to derive a statistical equation, ANOVA analysis, contour plots and 3D response surface plots. FT-IR spectroscopy result showed interaction between the drug and polymers combined. The optimized formulation exhibited a high drug entrapment efficiency of 87.74±0.01%, particle size of 845.40±0.02 (μm), percentage yield of 97.80±0.02%, swelling index of 102.33±0.03%, % mucoadhesion after 8 h was 64.00±0.01% and the drug release 52.30±0.01%. The microcapsules adhered more strongly to the gastric mucous layer and could be retained in the gastric mucosa for an extended period of time consequently increasing bioavailability, improving patient’s compliance and reducing dosing frequency; which is more effectively used for sustained drug release to the gastric mucosa in the treatment of upper GIT infection.

Grain-like bismuth-rich bismuth/bismuth oxychlorides intra-heterojunction: Efficacious solar-light-driven photodegradation of fluoroquinolone antibiotics and 2-level factorial approach

Abstract The grain-like BiOCl (60%)–Bi24O31Cl10 (40%) intra-heterojunction nanophotocatalyst was fabricated by a facile one-pot combustion route using sorbitol fuel. It was characterized by the utilization of XRD, FESEM, PSD, BET–BJH and DRS, which proved its successful synthesis. The solar-light-driven photocatalytic activity of BiOCl (60%)–Bi24O31Cl10 (40%) was appraised through the destruction of fluoroquinolone antibiotics (FQAs) such as ciprofloxacin, ofloxacin and levofloxacin as persistent and resisting emerging pollutants in an aqueous solution. Consequences obtained were implied to its prominent performance. To investigate the individual and interplay influences of the input operating parameters (catalyst loading, initial pollutant concentration, initial pH and reaction time), the modelling of the photocatalytic destruction of ofloxacin as the response was done by 2-level full factorial experimental design approach. A semi-empirical fourth-order regression model with R2= 0.9878 was expressed to relate between the response and independent variables. Results obtained of the mentioned approach demonstrated the high adequacy of the model. The influence of individual parameters and their interactions on the photocatalytic degradation efficiency of ofloxacin was possessed by the main effect graphs, contour and response surface plots. This study not only illustrates a hopeful application of the grain-like BiOCl–Bi24O31Cl10 in the solar-light-driven photo-destruction of resistant pollutants such as FQAs but also shows the favourable direction to gain the high-performance.

Synthesis of Co3O4 nanoparticles and their performance towards methyl orange dye removal: Characterisation, adsorption and response surface methodology

This research article describes the synthesis of cobalt-oxide nanoparticles by simple precipitation technique and their environmental application. The prepared Co3O4 nanoparticles were characterised by field emission scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, transmission electron microscopy, selected area diffraction, and energy-dispersive X-ray spectroscopy, along with elemental mapping analysis. The characterisation images revealed that as-synthesised nanomaterial had a hexagonal sheet-like morphology with average particle size 10–20 nm and was crystalline in nature. The nano-adsorbent displayed its efficiency in methyl orange adsorption from aqueous solution. Several adsorption factors such as pH, initial concentration, time, and temperature were examined, and isotherm, kinetic, and thermodynamic data were observed. The adsorption rate was fast and followed a pseudo–second-order kinetic model. The adsorption isotherm could be suited with both Langmuir and Freundlich isotherms. The adsorption process turned out to be spontaneous and exothermic. The effects of the various factors for methyl orange removal were analysed using the Box–Behnken design. A second-order quadratic model was used to project the response. Analysis of variance analysed the significance of the factors and their interactions. Three-dimensional response surface plots were used to determine the interactive effects of the independent factors on methyl orange adsorption capacity. The successful regeneration of Co3O4 nanoparticles suggested their usefulness in wastewater treatment and various other industrial settings. The reusability and efficient adsorptive capacity of nano-adsorbent for environmental management represent the importance of this work.

Optimization of the Electrophoretic Deposition Parameters for Biocomposite Hydroxyapatite/Chitosan/Collagen/h-BN Coatings on Ti6Al4V Biomedical Implants

Ti6Al4V alloy biomedical implant materials were coated with a biocomposite hydroxyapatite/chitosan/collagen/h-BN layer using electrophoretic deposition at room temperature. Response surface methodology (RSM) and central composite design (CCD) were employed for modeling and optimizing the electrophoretic deposition parameters of chitosan concentration, deposition potential, and agitation speed. The mutual effects of these parameters on the responses (deposition yield and Ecorr) have been analyzed and displayed by response surface plots. Predicted and experimental values agreed well with each other. The average absolute errors between experimental and predicted values were calculated as 2.0 and 2.2 pct for response-1 (deposition yield) and response-2 (Ecorr), respectively. A 5-level-3-factor experimental design has been utilized to optimize electrophoretic deposition parameters. According to deposition yield and Ecorr models, optimized values were for chitosan concentration: 2.57 and 2.59 g/L, for deposition potential: 16.09 and 16.25 V, and for agitation speed: 247 and 229 rpm, respectively. The findings of this research suggest that statistical design methodologies (i.e., RSM and CCD) may effectively be employed for the modeling and optimizing of multi-electrophoretic deposition parameters. These results are encouraging and may be practiced for functionalization of Ti6Al4V biomedical implant devices to provide better in vivo biocompatibility performance.

Optimization of a novel in situ gel for sustained ocular drug delivery using Box-Behnken design: In vitro, ex vivo, in vivo and human studies

The aim of the present research work was to formulate, optimize and evaluate the in-situ gel for the ophthalmic drug delivery using the combination of gellan gum and carbopol 934P. The Box-Behnken design was applied to optimize the concentration of gellan gum (X1), carbopol 934P (X2) and benzododecenium bromide (X3) to achieve the maximum viscosity [at physiological condition; 35 °C, pH 7.4, and simulated tear fluid (STF)], mucoadhesive strength, permeability coefficient and sustained release of the drug from the gel with constraint on the viscosity under the non-physiological condition (25 °C, pH 5). Response surface plots were drawn, the statistical validity of the polynomials was established, and optimized formulation was selected by the feasibility and grid search. The design proposed the optimized batch by selecting the independent variables as gellan gum (0.55% w/v), carbopol 934P (0.35% w/v) and benzododecenium bromide (0.013% w/v) to achieve the maximum viscosity (3363 cps) at physiological condition, mucoadhesive strength (22.35 dyn/cm2), t90% (1200 min), permeability coefficient (1.36 × 10−5 sq.cm/sec), with minimum viscosity (131 cps) under the non-physiological condition. The combination of gellan gum and carbopol 934P improved the gelation (synergistic effect) characteristics of the in situ gel. The optimized in situ gel was clear, isotonic, pH 4.7 and showed pseudoplastic flow, high in vitro gelling capacity, low contact angle, acceptable hardness (51018 gm), compressibility (64617 gm) and adhesiveness (74 gm) values for the ocular application. The ex vivo study showed the significant protection of the mast cell from the degranulation. The ocular irritation and histopathology studies in the rabbit eyes confirmed the safety of in situ gel for human use. The in vivo drug release studies showed the presence of drug in the rabbit tear fluid up to 3 h in comparison to just 1 h with the eye drop solution. The contact time of the in situ gel in the human eye was 15.0 ± 2.5 min, which was >2 folds higher than the marketed gel (6.0 ± 3.2 min), which could reduce the dosing frequency and total dose of drug. The Box-Behnken design facilitated the optimization of in situ gel for sustained ophthalmic drug delivery.