D-optimal Mixture Experimental Design Research Articles

Optimization of the physical properties of recycled plastic hybrid composites reinforced with rubberwood flour and crab shell flour for underwater use

This research aimed to optimize the composition and physical properties of recycled high-density polyethylene (rHDPE) hybrid composites reinforced with rubberwood flour (RWF) and crab shell flour (CS) for application in water immersion. The effects of composition and deterioration in physical properties after immersion in different water conditions (distilled water and seawater) were investigated. D-optimal mixture experimental design and response surface methodology were applied. The findings showed that all the physical properties deteriorated with an increase in immersion times. The increasing addition of CS increased the density, water absorption, thickness swelling, and surface roughness of the samples before and after being immersed in distilled water and seawater. Further, the results revealed that the optimal composition for application in water immersion included 60.0 wt% rHDPE, 29.5 wt% RWF, 5.6 wt% CS, 3.5 wt% maleic anhydride-grafted polyethylene, 0.5 wt% ultraviolet stabilizers, and 1.0 wt% lubricant with a desirability score value of 95.80 %. The predicted response of density, color measurement, surface roughness, water absorption, and thickness swelling were 0.89 g/cm3, 10.11, 4.59 µm, 10.27 %, and 7.73 %, respectively. Based on the findings in this research, the effective application of naturally sourced additives in composite products, and using the optimized rHDPE, RWF, and CS contents would enable the development of alternative materials for applications in water immersion.

Taste-Masked Flucloxacillin Powder Part 2: Formulation Optimisation Using the Mixture Design Approach and Storage Stability.

Flucloxacillin is prescribed to treat skin infections but its highly bitter taste is poorly tolerated in children. This work describes the application of the D-optimal mixture experimental design to identify the optimal component ratio of flucloxacillin, Eudragit EPO and palmitic acid to prepare flucloxacillin taste-masked microparticles that would be stable to storage and would inhibit flucloxacillin release in the oral cavity while facilitating the total release of the flucloxacillin load in the lower gastrointestinal tract (GIT). The model predicted ratio was found to be very close to the stoichiometric equimolar component ratio, which supported our hypothesis that the ionic interactions among flucloxacillin, Eudragit EPO and palmitic acid underscore the polyelectrolyte complex formation in the flucloxacillin taste-masked microparticles. The excipient-drug interactions showed protective effects on the microparticle storage stability and minimised flucloxacillin release at 2 min in dissolution medium. These interactions had less influence on flucloxacillin release in the dissolution medium at 60 min. Storage temperature and relative humidity significantly affected the chemical stability of the microparticles. At the preferred storage conditions of ambient temperature under reduced RH of 23%, over 90% of the baseline drug load was retained in the microparticles at 12 months of storage.

Development, Optimization and Evaluation of Enriched Custard Powder from Selected Local Food Ingredients

Custard powder is a breakfast cereals meal, primarily, made from corn starch; processed with added flavour and fortified with vitamins and minerals. The aim of this study is to formulate, characterize, and optimize enriched custard powder from bio-fortified cassava, pearl millet, soybeans, Africa locust beans fruit pulp, ginger, egg powder, and milk powder; using a seven-component constrained, D-optimal mixture experimental design, with thirty-eight randomized experimental runs. The formulation design constraints were: bio-fortified cassava (10% - 70%), pearl millet (10% - 70%), soybeans (10% - 60%), Africa locust beans fruit pulp (5% - 30%), ginger (1% - 2%), egg powder (0.5% - 1.5%), and milk powder (0.5% - 1%). The formulated samples were analyzed and evaluated for proximate properties, functional properties, vitamin contents, mineral contents, anti-nutritional contents, and sensory properties; using standard procedures. The result of the numerical optimization gave optimized enriched custard with an overall desirability index of 0.833, based on the set optimization goals and individual quality desirability indices. The optimal formulated enriched custard was obtained from 51.3% bio-fortified cassava, 30.469% pearl millet, 10.0 % soybeans, 5.0% Africa locust beans fruit pulp, 2.0% ginger, 0.5% egg powder, and 0.731 % milk powder. The quality properties of this optimal enriched custard are 6.202 % moisture content, 1.139 % crude fibre, 2.548 % ash content, 20.0 % protein content, 6.668 % lipid, 61.786 % carbohydrate, 0.157 (mL/g) water absorption capacity, 0.121 (mL/g) oil absorption capacity, 19.005 (% vol) foaming capacity, 8.886 (%) foaming stability, 52.474 (deg C) gelation temperature, 5.178 (%) least gelation concentration, 0.758 (g/cubic metre) bulk density, 88.383 (mg/100g) vitamin C, 1.832 (mg/100g) beta carotene, 0.6 (%) tannin, 3.072 (mg/100g) cyanide, 19.032 (%) phytate, 5.313 (mg/100g) oxalate, 16.737 (mg/100g) sodium, 469.150 (mg/100g) potassium, 201.332 (mg/100g) calcium, 167.254 (mg/100g) magnesium, 585.770 (mg/100g) phosphorus, 4.694 (mg/100g) iron, and 6.10 overall acceptability, The result of the study showed that the formulated enriched custard was found to be of higher quality than the traditional custard which are produced from mono-cereals. Improving the nutritional quality of food and tackling nutrient deficiencies, particularly protein energy malnutrition in populations, is possible through the application of numerical optimization technique in the development of new food products.

Optimization of Vat-Polymerization binder formulation for 3D printing ceramic slurry using D-optimal mixture experimental design

The aim of the present study was to optimize a formulation of the vat-polymerization binder of 3D printing ceramic slurry using a D-optimal mixture experimental design. The selected methodology was based on an extreme vertices approach with 13 combinations, selecting three types of resin monomers (TMPTA, NPG2PODA, HDDA) and one type of plasticizer (TXIB) as independent variables, while mechanical properties (including tensile strength and elongation at break), volume shrinkage, viscosity, and curing depth were considered as response variables. The experimental data were analyzed to generate statistical models and response surfaces for analyzing the effects of component fractions on individual responses. Analysis of variance was performed. This method was applied to predict the optimal formulation. Based on the DoE results, the mixture of resins and plasticizer with an optimized composition ratio after curing showed better mechanical properties, lower volume shrinkage, lower viscosity, and an appropriate curing depth. Furthermore, a ceramic slurry containing 55 vol% Al2O3 was prepared to evaluate the printability of the optimized mixture. The relatively dense ceramic parts and smooth surface were successfully manufactured after de-binding and sintering. Our findings demonstrate the efficiency, reliability, and feasibility of the D-optimal mixture experimental design in modeling, predicting, and optimizing the formulation of the TMPTA/NPG2PODA/HDDA/TXIB composite. Overall, this study can be helpful in designing experiments and optimizing the vat-polymerization of 3D printing ceramic slurry.

Loteprednol-Loaded Nanoformulations for Corneal Delivery by Quality-by-Design Concepts: Optimization, Characterization, and Anti-inflammatory Activity.

Loteprednol etabonate (LE) is a topical corticosteroid that uses inflammatory conditions of the eye. It has a low ocular bioavailability and side effects such as corneal disorder, eye discharge, and ocular discomfort. Therefore, it was decided to select the delivery systems, which are solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), and nanoemulsion (NE). Design of experiments (DoE) of SLN, NLC, and NE formulations were formulated by using the quality by design (QbD) approach. Precirol® ATO 5 and oleic acid were used as solid and liquid lipids, respectively, in SLN, NLC, and NE formulations. Physiochemical characterization was performed on the formulations. The optimized formulations' inflammatory effects have been appraised on human corneal epithelial cells employing the ELISA test. Physicochemical characterization studies and inflammatory effects were appraised. The sizes of optimized formulations of SLN, NLC, and NE were 86.19nm, 82.38nm, and 126.35nm, respectively, with minimum polydispersity. The release behavior of the formulations is composed of both diffusion and erosion. ELISA test results proved that the formulations significantly reduced IL-1 and IL-6 levels (p < 0.05). D-optimal mixture experimental design allowed us to develop the most precise formulations of SLN, NLC, and NE. Furthermore, the optimized formulations could be promising candidates for treating an inflammation-based corneal disease of the eye.

Formulation and Hardness Evaluation of Tablets Containing Citrus limon and Hylocereus polyrhizus Powder using D-Optimal Mixture Design

The powder of mixed fruits that are Lemon (Citrus limon) and Red Pitaya (Hylocereus polyrhizus) was used as a nutritional supplement in tablet form for nutraceutical application. D-optimal mixture experimental design (D-Optimal MED) was employed to investigate the influence of different components on the response hardness of the tablet. For tablet formulation, magnesium stearate, A (0.2-1.0% w/w), menthol, B (0.2-1.0% w/w), lemon powder, C (1.0-10.0 w/w), maltodextrin, D (5.0 -10.0) and glucose, E (37.5-53.1%) are the variables while red pitaya powder and preservative are fixed components. The experimental data were used to analyze analysis of variance (ANOVA) and to develop a polynomial regression model for tablet hardness in terms of the five design factors considered in this study. D-Optimal MED predicted the hardness of the tablet at 8.5 kg/cm2. The results showed that the best mixture was the formulation that included 0.66% A, 0.74% B, 6.15% C, 7.61% D and 44.34% E, with the actual hardness of the optimized tablet recorded at 8.581 kg/cm2 (R2 = 0.9925). The study demonstrated the potentiality of mixed fruit tablets as a nutritional supplement with therapeutic properties for general consumers well-being.

Optimization of nutritional and sensory properties of fermented oat-based composite beverage

Oat (Avena sativa) is well-known for its nutritional value and health-promoting properties. There are only a few oat-based value-added products on the market in Ethiopia, and this study attempted to develop a new product that is both nutritionally enhanced and sensory acceptable, therefore, the objective of this study was to optimize the nutritional and sensory properties of a beverage made from oat, lupine (Lupinus albus), stinging nettle (Urtica simensis), and premix. D-optimal mixture experimental design was used to generate 11 runs applying the following constraints: 60–70% toasted oat, 10–25% roasted and soaked de-bittered white lupine, 5–15% boiled stinging nettle leaves, and 10% premix (flour of toasted black cardamom (2.8%), malted wheat (2.8%), pumpkin (2.6%), spiced chili peppers (1.1%), and table salt (0.7%). Statistical model evaluation and optimization were carried out using Minitab 19 software. The nutritional composition of the product was assessed, and results show that increasing the proportion of oat flour in the blend resulted in a significant (p < 0.05) increase in fat, carbohydrate, gross energy, and mineral contents (Fe, Zn). An increase in lupine flour increased crude protein, crude fiber, gross energy, phytate, tannin, oxalate, and antinutrient to mineral molar ratios. In contrast increased in stinging nettle leaf powder increased the ash and beta-carotene contents. Sensory of 11 composite sample beverages and control (90% oat plus 10% premix) were also carried out by 50 untrained panelists. Consequently, eight responses were optimized: protein, fat, Fe, Zn, beta-carotene, taste, appearance, and overall acceptability. The optimal blending ratio obtained was 70% oats, 11.3% lupine, 8.7% stinging nettle flour, and 10.0% premix. The study's findings suggested that the optimal combination of these traditionally processed ingredients in a beverage can be considered a valuable food with the potential to improve diet quality.

Hydrochlorothiazide/Losartan Potassium Tablet Prepared by Direct Compression.

Hydrochlorothiazide (HCTZ)/losartan potassium (LOS-K) was used as a model drug to prepare compound tablets through the investigation of the compression and mechanical properties of mixed powders to determine the formulation and preparation factors, followed by D-optimal mixture experimental design to optimize the final parameters. The type and amount of lactose monohydrate (SuperTab®14SD, 19.53–26.91%), microcrystalline cellulose (MCC PH102, 32.86–43.31%), pre-gelatinized starch (Starch-1500, 10.96–15.91%), and magnesium stearate (0.7%) were determined according to the compressive work, stress relaxation curves, and Py value. Then, the compression mechanism of the mixed powder was investigated by the Kawakita equation, Shapiro equation, and Heckel analysis, and the mixed powder was classified as a Class-II powder. The compaction pressure (150–300 MPa) and tableting speed (1200–2400 Tab/h) were recommended. A D-optimal mixture experimental design was utilized to select the optimal formulation (No 1, 26.027% lactose monohydrate, 32.811% MCC PH102, and 15.462% pregelatinized starch) according to the drug dissolution rate, using Hyzaar® tablets as a control. Following oral administration in beagle dogs, there were no significant differences in bioavailability between the No. 1 tablet and the Hyzaar® tablet in HCTZ, losartan carboxylic acid (E-3174), and LOS-K (F < F0.05). Thus, formulation and preparation factors were determined according to the combination of the compression and mechanical properties of the mixed powder and quality of tablets, which was demonstrated to be a feasible method in direct powder compression.

Optimization of AC/TiO2/CeO2 composite formulation for petroleum refinery wastewater treatment via simultaneous adsorption-photocatalytic process using D-optimal mixture experimental design

This study aims to optimize the formulation of activated carbon/titanium oxide/cerium oxide (AC/TiO2/CeO2) composite for petroleum refinery wastewater (PRW) treatment via simultaneous adsorption and photocatalytic process. D-optimal mixture experimental design was applied to predict the optimal formulation of the composite. The experimental data were assessed to generate empirical models for analyzing the effects of components fraction on individual responses. The fitted models were statistically examined (through the standard error of design), considerably validated (via analysis of variance (ANOVA) and model adequacy indicators), and experimentally verified (by estimating errors, root-mean square error (RMSE), and standard error of prediction (SEP) between the predicted and actual values). Finally, the optimized formulation was accepted to have 36.85% total dissolved solid (TDS) removal, 49.23% chemical oxygen demand (COD) removal, treated PRW with pH = 7.22 and electrical conductivity (EC) = 2937.11 µS/cm, 53.76% phenol removal, and 52.86% NH3-N removal, by applying 53.43%-wt of AC, 21.96%-wt of TiO2, and 24.61%-wt of CeO2 with reasonably high desirability score of 0.8874. Based on the characterization results, it can be concluded that the optimized AC/TiO2/CeO2 composite was successfully synthesized. From the diffuse reflectance spectrometry (DRS), the estimated bandgap energy of the synthesized AC/TiO2/CeO2 composite was successfully reduced through the use of CeO2. Our findings show the efficiency, reliability, and feasibility of the D-optimal mixture experimental design from modeling, predicting, and optimizing the formulation of AC/TiO2/CeO2 composite. Overall, our findings prove that the optimized AC/TiO2/CeO2 composite is a prominent and effective material for PRW treatment.

FORMULATION OPTIMIZATION AND CHARACTERIZATION OF AQUEOUS INJECTION CONTAINING POORLY SOLUBLE DRUG USING MIXED HYDROTROPIC SOLUBILIZATION

Objective: Mefenamic acid (MFA) is an NSAID that exhibits anti-inflammatory analgesic and antipyretic activity. Peak plasma levels are attained in 2-4 h and the elimination half-life approximates 2 h, repetitive administration of tablets for 3-5 times a day is desired. It is supplied only in the form of tablets for oral administration. In acute conditions drug administered parenterally could give rapid relief from severe symptoms like pain. Thus, formulation of injectable formulation of MFA could be better alternative compared to conventional tablet dosage form. The low aqueous solubility of MFA precludes its use in parenteral formulation development.&#x0D; Methods: In this work attempt were made to enhance the aqueous solubility of mefenamic acid using mixed solvency technique. For that different hydrotropic agents such as Urea, Sodium acetate, sodium benzoate, sodium citrate and their blends were evaluated. Optimal concentration of hydrotropic agent in blend was determined using D-optimal mixture experimental design. The optimized bled was used to develop the aqueous injection of mefenamic acid. The developed injection was subjected for various quality control tests and stability of developed formulation was also evaluated.&#x0D; Results: The aqueous solubility in optimized blend of hydrotropic agent batches (U: SA: SB: SC, 4:4:23:9 %w/v) showed 835.71-fold compared to MFA solubility in distilled water. The quality control tests for parenteral formulation and accelerated stability study were found to be within prescribed limits and stable.&#x0D; Conclusion: The inadequate solubility of MFA was overcome, and aqueous injection was successfully developed which can be serve as cost effective treatment in various indications.

Optimization of nutritional and sensory qualities of complementary foods prepared from sorghum, soybean, karkade and premix in Benishangul - Gumuz region, Ethiopia

Consumption of nutritionally deficient complementary foods in developing countries is among the main contributing factors to infants and young children's malnutrition. Therefore, this study was aimed to optimize the nutritional and sensory properties of complementary food made from malted sorghum, blanched soybean, boiled karkade seeds and premix. A D-optimal mixture experimental design with 18 runs was generated by design expert software within in the constrained: 40–60% malted sorghum, 20–30% blanched soybean, 10–20% boiled karkade seeds and 10% premix (5.0% figl leaf powder, 4.5% sugar and 0.5% iodized table salt). Statistical model evaluation and optimization were done using D-optimal mixture design expert software. Sensory evaluation was conducted using 53 untrained panelists on two selected formulations and the control (local formulation). The study shows that with an increasing ratio of blanched soybean and boiled karkade seeds flour in the blend, a significant (p < 0.05) increase in protein, fat, energy and mineral contents, and a decrease in tannin and phytic acid contents of high mineral bioavailability except for oxalate: calcium ratio in the formulations were observed. The optimal blending ratio was 45.0% malted sorghum, 26.0% blanched soybean, and 19.0% boiled karkade seeds flour plus 10.0% premix. The gruel made from the new formula was significantly (p < 0.05) liked in terms of aroma, flavor, mouthfeel and overall acceptability than the control sample. The findings suggested that the optimal mix of these traditionally processed ingredients can potentially alleviate protein-energy malnutrition and micronutrient deficiency to mitigate expensive commercial infant complementary foods sold in the market.

Formulation and optimization of radiation-curable nonisocyanate polyurethane wood coatings by mixture experimental design

Radiation-curable urethane acrylates have been extensively used and successfully implemented in industrial wood coatings thanks to their capability to provide a balance of mechanical and chemical properties. However, isocyanates, one of the main building blocks in the conventional urethane acrylates, pose toxicity and health hazards both in the manufacturing and application, and therefore, are targeted for restricted use and limited occupational exposure in the impending environmental regulations. In this regard, this study presents the development of urethane acrylate oligomers using nonisocyanate approaches and their application in industrial wood coatings. Two acrylic-functional nonisocyanate polyurethane oligomers (NIPU-ACs), NIPU-AC-2 with longer urethane chains and higher flexibility and NIPU-AC-1 with shorter urethane chains, were synthesized as main building blocks of radiation-curable wood coatings. Next, a series of 20 wood coating systems were formulated using a D-optimal mixture experimental design methodology to find the optimized quaternary mixtures composed of the two synthetic NIPU-ACs, and trimethylolpropane triacrylate (TMPTA) and dipropylene glycol diacrylate (DPGDA) as reactive diluents. The results of the study revealed that at a constant 5 wt% of TMPTA, formulations rich in NIPU-AC-2 showed higher impact resistance, scratch resistance, and pull-off adhesion, which was attributed to the flexible structure of this oligomer. On the other hand, coatings including higher contents of NIPU-AC-1, which induces higher crosslink density (XLD) to the system, demonstrated higher Tg and pendulum hardness. Evaluation of the optimal coatings not only validated the predictability of models, but also determined that the coatings have promising stain and abrasion resistance, and good thermal stability. The results show that NIPU-ACs developed in this study have excellent potential as an alternative to conventional urethane acrylates in the development of low-VOC and sustainable industrial wood coatings.

Microemulsion and microemulsion gel formulation for transdermal delivery of rutin: Optimization, in-vitro/ex-vivo evaluation and SPF determination

In this research work, the designation of a new microemulsion formulation for the transdermal application of rutin was investigated. After the construction of pseudo-ternary phase diagrams containing tween 80 as a surfactant, ethylene glycol as co-surfactant and IPM (Isopropyl myristate) as the oil phase, the D-optimal mixture experimental design was used for the optimization process. The independent variables were oil, surfactant/co-surfactant and water weight concentrations and the two response variables were rutin solubility in microemulsions and drug release from microemulsions. After that, physicochemical characterization and stability studies were performed. In the other part the rutin, as an active pharmaceutics agent was loaded in the optimized microemulsion formulation to study kinetic of its release and sun protection factor. To investigate the ex-vivo skin permeation and retention of the drug from the carriers, the optimized formulation and its gel form, were examined on rat skin at similar conditions. The proposed formulation showed different release rate, skin permeation, sun protection factor and particle size, compared to recent works. Obtained results indicated that the microemulsion formulation can be used, especially in gel form, as an effective vehicle for prolong transdermal delivery of rutin desirably in sunscreen formulations.

Modeling the Effect of Composition on Formation of Aerosolized Nanoemulsion System Encapsulating Docetaxel and Curcumin Using D-Optimal Mixture Experimental Design.

The synergistic anticancer effect of docetaxel (DTX) and curcumin (CCM) has emerged as an attractive therapeutic candidate for lung cancer treatment. However, the lack of optimal bioavailability because of high toxicity, low stability, and poor solubility has limited their clinical success. Given this, an aerosolized nanoemulsion system for pulmonary delivery is recommended to mitigate these drawbacks. In this study, DTX- and CCM-loaded nanoemulsions were optimized using the D-optimal mixture experimental design (MED). The effect of nanoemulsion compositions towards two response variables, namely, particle size and aerosol size, was studied. The optimized formulations for both DTX- and CCM-loaded nanoemulsions were determined, and their physicochemical and aerodynamic properties were evaluated as well. The MED models achieved the optimum formulation for DTX- and CCM-loaded nanoemulsions containing a 6.0 wt% mixture of palm kernel oil ester (PKOE) and safflower seed oils (1:1), 2.5 wt% of lecithin, 2.0 wt% mixture of Tween 85 and Span 85 (9:1), and 2.5 wt% of glycerol in the aqueous phase. The actual values of the optimized formulations were in line with the predicted values obtained from the MED, and they exhibited desirable attributes of physicochemical and aerodynamic properties for inhalation therapy. Thus, the optimized formulations have potential use as a drug delivery system for a pulmonary application.

D-optimal mixture design for the optimization of extraction induced by emulsion breaking for multielemental determination in edible vegetable oils by microwave-induced plasma optical emission spectrometry

A sample pretreatment based on an extraction process by emulsion breaking for multi-element determination in edible oils was developed. The determination of eight trace elements (Al, Ba, Cu, Cr, P, Ni, Ti, and Zn) was carried out by microwave-induced plasma optical emission spectrometry (MIP OES) after the extraction procedure. A D-optimal mixture experimental design was used to obtain the best experimental conditions for the extraction induced by emulsion breaking (EIEB). The proportion of HNO3 solution, Triton X-100 solution and sample was evaluated in a multivariate manner. The best recovery efficiency was obtained with 1.0 mL of 30% (v/v) HNO3, 1.0 mL of 30% (w/v) Triton-X 100 and 3.0 mL of the sample. The precisions, established as the relative standard deviation (RSD, %), were better than 2.5% for all analytes. The developed method was applied to the analysis of commercial vegetable oils with low limits of detection and good precision.

OPTIMIZATION OF SELF-NANOEMULSIFYING DRUG DELIVERY SYSTEMS OF LEMONGRASS (CYMBOPOGON CITRATUS) ESSENTIAL OIL

Objective: Focus of this study was to optimize and to characterize the self-Nano emulsifying drug delivery system using lemongrass (Cymbopogon citratus) essential oil.Methods: The optimum formulas were analyzed using a D-Optimal mixture experimental design and performed using a Design Expert® Ver. 7.1.5. Formulation variables which include in the design were: oil component X1 (a mixture of Cymbopogon citratus essential oil and virgin coconut oil/VCO), surfactant X2 (Tween 80), and co-surfactant (PEG 400), while emulsification time in a sec (Y1) and transmittance in percent (Y2) as responses.Results: The optimum formula for SNEDDS in the current study were: Cymbopogon citratus essential oil (7.147%), VCO (7.147%), Tween 80 (71.417%), and PEG 400 (14.290%). From the optimizing formula can be shown that the mean of droplet size, polydispersity-index, zeta potential, and viscosity were: 13.17±0.06 nm, 0.17±0.05,-20.90±1.47 mV, 200±0mPa. s (n=3), respectively. Furthermore, the optimized formula has passed the thermodynamic stability test; meanwhile, transmission electron microscopy displayed spherical shape.Conclusion: The optimized SNEDDS formula was improving solubility of poorly soluble Cymbopogon citratus essential oil.

Development of a kojic monooleate-enriched oil-in-water nanoemulsion as a potential carrier for hyperpigmentation treatment

IntroductionKojic monooleate (KMO) is an ester derived from a fungal metabolite of kojic acid with monounsaturated fatty acid, oleic acid, which contains tyrosinase inhibitor to treat skin disorders such as hyperpigmentation. In this study, KMO was formulated in an oil-in-water nanoemulsion as a carrier for better penetration into the skin.MethodsThe nanoemulsion was prepared by using high and low energy emulsification technique. D-optimal mixture experimental design was generated as a tool for optimizing the composition of nanoemulsions suitable for topical delivery systems. Effects of formulation variables including KMO (2.0%–10.0% w/w), mixture of castor oil (CO):lemon essential oil (LO; 9:1) (1.0%–5.0% w/w), Tween 80 (1.0%–4.0% w/w), xanthan gum (0.5%–1.5% w/w), and deionized water (78.8%–94.8% w/w), on droplet size as a response were determined.ResultsAnalysis of variance showed that the fitness of the quadratic polynomial fits the experimental data with F-value (2,479.87), a low P-value (P<0.0001), and a nonsignificant lack of fit. The optimized formulation of KMO-enriched nanoemulsion with desirable criteria was KMO (10.0% w/w), Tween 80 (3.19% w/w), CO:LO (3.74% w/w), xanthan gum (0.70% w/w), and deionized water (81.68% w/w). This optimum formulation showed good agreement between the actual droplet size (110.01 nm) and the predicted droplet size (111.73 nm) with a residual standard error <2.0%. The optimized formulation with pH values (6.28) showed high conductivity (1,492.00 µScm−1) and remained stable under accelerated stability study during storage at 4°C, 25°C, and 45°C for 90 days, centrifugal force as well as freeze–thaw cycles. Rheology measurement justified that the optimized formulation was more elastic (shear thinning and pseudo-plastic properties) rather than demonstrating viscous characteristics. In vitro cytotoxicity of the optimized KMO formulation and KMO oil showed that IC50 (50% inhibition of cell viability) value was >100 µg/mL.ConclusionThe survival rate of 3T3 cell on KMO formulation (54.76%) was found to be higher compared to KMO oil (53.37%) without any toxicity sign. This proved that the KMO formulation was less toxic and can be applied for cosmeceutical applications.

Development of ternary solid dispersions with hydrophilic polymer and surface adsorbent for improving dissolution rate of carbamazepine

In this study solid dispersions of carbamazepine in the hydrophilic Kollidon® VA64 polymer, adsorbed onto Neusilin® UFL2 adsorption carrier have been employed to improve carbamazepine dissolution rate. In order to evaluate effects of changing in the proportions of all solid dispersion components on carbamazepine dissolution rate, D-optimal mixture experimental design was used in the formulation development. From all prepared solid dispersion formulations, significantly faster carbamazepine dissolution was observed compared to pure drug. Ternary solid dispersions containing carbamazepine, Kollidon® VA64 and Neusilin® UFL2 showed superior dissolution performances over binary ones, containing only carbamazepine and Neusilin® UFL2. Proportion of Kollidon® VA64 showed the most profound effect on the amount of carbamazepine dissolved after 10 and 30 min, whereby these parameters increase upon increasing in Kollidon® VA64 concentrations up to the middle values in the studied range of Kollidon® VA64 concentrations. Physicochemical characterization of the selected samples using differential scanning calorimetry, FT-IR spectroscopy, powder X-ray diffraction and polarizing light microscopy showed polymorphic transition of carbamazepine from more thermodynamically stable monoclinic form (form III) to less thermodynamically stable triclinic form (form I) in the case of ternary, but not of binary solid dispersion formulations. This polymorphic transition can be one of the factors responsible for improving of carbamazepine dissolution rate from studied solid dispersions. Ternary solid dispersions prepared with Kollidon® VA64 hydrophilic polymer and Neusilin® UFL2 adsorption carrier resulted in significantly improvement of carbamazepine dissolution rate, but formation of metastable polymorphic form of carbamazepine requires particular care to be taken in ensuring product long term stability.

Enhancement of physicochemical properties of nanocolloidal carrier loaded with cyclosporine for topical treatment of psoriasis: in vitro diffusion and in vivo hydrating action.

Psoriasis is a chronic autoimmune disease that cannot be cured. It can however be controlled by various forms of treatment, including topical, systemic agents, and phototherapy. Topical treatment is the first-line treatment and favored by most physicians, as this form of therapy has more patient compliance. Introducing a nanoemulsion for transporting cyclosporine as an anti-inflammatory drug to an itchy site of skin disease would enhance the effectiveness of topical treatment for psoriasis. The addition of nutmeg and virgin coconut-oil mixture, with their unique properties, could improve cyclosporine loading and solubility. A high-shear homogenizer was used in formulating a cyclosporine-loaded nanoemulsion. A D-optimal mixture experimental design was used in the optimization of nanoemulsion compositions, in order to understand the relationships behind the effect of independent variables (oil, surfactant, xanthan gum, and water content) on physicochemical response (particle size and polydispersity index) and rheological response (viscosity and k-value). Investigation of these variables suggests two optimized formulations with specific oil (15% and 20%), surfactant (15%), xanthan gum (0.75%), and water content (67.55% and 62.55%), which possessed intended responses and good stability against separation over 3 months’ storage at different temperatures. Optimized nanoemulsions of pH 4.5 were further studied with all types of stability analysis: physical stability, coalescence-rate analysis, Ostwald ripening, and freeze–thaw cycles. In vitro release proved the efficacy of nanosize emulsions in carrying cyclosporine across rat skin and a synthetic membrane that best fit the Korsmeyer–Peppas kinetic model. In vivo skin analysis towards healthy volunteers showed a significant improvement in the stratum corneum in skin hydration.

Transungual Gel of Terbinafine Hydrochloride for the Management of Onychomycosis: Formulation, Optimization, and Evaluation.

The present study was aimed to optimize, develop, and evaluate microemulsion and microemulsion-based gel as a vehicle for transungual drug delivery of terbinafine hydrochloride for the treatment of onychomycosis. D-optimal mixture experimental design was adopted to optimize the composition of microemulsion having amount of oil (X 1), Smix (mixture of surfactant and cosurfactant; X 2), and water (X 3) as the independent variables. The formulations were assessed for permeation (micrograms per square centimeter per hour; Y 1), particle size (nanometer; Y 2), and solubility of the drug in the formulation (milligrams per milliliter; Y 3). The microemulsion containing 3.05% oil, 24.98% Smix, and 71.96% water was selected as the optimized formulation. The microemulsion-based gel showed better penetration (∼5 folds) as well as more retention (∼9 fold) in the animal hoof as compared to the commercial cream. The techniques used to screen penetration enhancers (hydration enhancement factor, ATR-FTIR, SEM, and DSC) revealed the synergistic effect of combination of urea and n-acetyl cysteine in disruption of the structure of hoof and hence, leading to enhanced penetration of drug.