[Composite excipients for preparing concentrated water pills of personalized traditional Chinese medicine prescriptions by extruding-rounding method].

This study aims to optimize the composite excipients suitable for the preparation of concentrated water pills of personalized traditional Chinese medicine prescriptions by the extruding-rounding method and investigate the roles of each excipient in the preparation process. The fiber materials and powder materials were taken as the standard materials suitable as excipients in the preparation of personalized concentrated water pills without excipient. Water absorption properties and torque rheology were used as indicators for selecting the materials of composite excipients. The ratio of composite excipients was optimized by D-optimal mixture design. Moreover, to demonstrate the universal applicability of the optimal composite excipients, this study selected three traditional Chinese medicine prescriptions with low, medium, and high extraction rates to verify the optimal ratio. Finally, the effects of each selected excipient on the molding of personalized concentrated water pills were investigated with the four parameters of the pill molding quality as indicators. The optimized composite excipients were dextrin∶microcrystalline cellulose(MCC)∶low-substituted hydroxypropyl cellulose(L-HPC) at a ratio of 1∶2∶4. The composite excipients were used for the preparation of personalized concentrated water pills with stable process, good quality, and a wide range of application. Dextrin acted as a diluent and accelerated the speed of extruding. MCC mainly served as an adhesive, increasing the cohesion and viscosity of the pills. L-HPC as a water absorbent and disintegrating agent can absorb and hold the water of the concentrate and has a strong disintegration effect.

A cochleate formulation optimized by D-optimal mixture design enhances oral bioavailability of Revaprazan.

A cochleate formulation was developed to enhance the oral bioavailability of revaprazan (RVP). Dimyristoyl phosphatidylcholine (DMPC) liposome containing dicetyl phosphate (DCP) successfully formed a cochleate after treatment with CaCl2, whereas that containing sodium deoxycholate did not. Cochleate was optimised using a D-optimal mixture design with three independent variables-DMPC (X1, 70.58 mol%), cholesterol (X2, 22.54 mol%), and DCP (X3, 6.88 mol%)-and three response variables: encapsulation efficiency (Y1, 76.92%), released amount of free fatty acid at 2 h (Y2, 39.82%), and released amount of RVP at 6 h (Y3, 73.72%). The desirability function was 0.616, showing an excellent agreement between the predicted and experimental values. The cylindrical morphology of the optimised cochleate was visualised, and laurdan spectroscopy confirmed the dehydrated membrane interface, showing an increased generalised polarisation value (approximately 0.5) over small unilamellar vesicle of RVP (RVP-SUV; approximately 0.1). The optimised cochleate showed greater resistance to pancreatic enzyme than RVP-SUV. RVP was released in a controlled manner, achieving approximately 94% release in 12 h. Following oral administration in rats, the optimised cochleate improved the relative bioavailability of RVP by approximately 274%, 255%, and 172% compared to RVP suspension, a physical mixture of RVP and the cochleate, and RVP-SUV, respectively. Thus, the optimised cochleate formulation might be a good candidate for the practical development of RVP.

D-optimal mixture design inspired modified release tablet formulation of lamotrigine for the treatment of seizures: An in-depth characterization.

OBJECTIVE: Lamotrigine (LTG) an anticonvulsant drug with a dissociation constant (pKa: 5.7), suffers from enhanced blood plasma spike after each dose, when administered as fast release tablet. Being BCS class-II candidate and pH dependent solubility, development of release-controlled tablets of LTG is a major challenge. This investigation aims at designing the release-controlled tablet (RCT) formulation of LTG using a solid dispersion (SD) technique via addressing its solubility and release problems. MATERIAL AND METHODS: RCT of LTG was fabricated using SD blend of Eudragit RL and Eudragit RS and PVP K-30 with different polymer blend ratio (1:5 and 1:7). The optimization of RCT of LTG was performed using D-optimal mixture design with three independent variables, three response variables, and one constraint. The dissolution rate was determined and data were then fitted to different mathematical models. Scanning electron microscopy (SEM) and X-ray diffraction (XRD) studies and tableting parameters were analyzed. RESULT: In vitro studies of predicted optimized batches (POBs) have shown that drug release over a period of 12hours was 88.05±3.4% in media I, 86.10±3.7% in media II and 85.84±4.2% in media III. An in vitro kinetic model equating R2-value for all the tested models indicated that the first order and Higuchi release kinetics model were the most appropriate. CONCLUSION: Based on the optimized formulation consisting of SD of LTG with Eudragit RL, Eudragit RS and PVP K-30, the release rate was consistently similar throughout the GI tract, regardless of the pH of the environment.

Design, optimization, and evaluation for a long-time-released transdermal microneedle delivery system containing estradiol.

Transdermal drug delivery systems (TDDS) have drawbacks such as poor absorption, low blood concentration, and delayed effects. Dissolving microneedle has sharp tips and short length, which overcome patients' pain and improve transdermal efficiency but has low mechanical strength and drug loading capacity. This study thereby proposes a microemulsion-encapsulated and long-time-released transdermal microneedle (MN) delivery system with estradiol (Es) as the model drug. The microemulsion (ME) was optimized by utilizing the pseudo-ternary phase diagram and D-optimal mixture design. The estradiol microemulsion-encapsulated microneedle (Es-ME-MN) was optimized by Box-Behnken design and prepared by freeze-thaw method. The Es-ME-MN obtained was characterized and evaluated through a large variety of studies. Es-ME-MN had sufficient mechanical strength to pierce skin and was safe enough, the length of which was 600 µm, and the Es content was 177.12 ± 0.72 µg/patch without drug-excipient chemical interaction. In vitro permeation study showed that Es-ME-MN has a higher transdermal efficiency and lower retention capacity than commercial estradiol patch and conventional MN. Es plasma concentration began to increase at 3 h and remained at 12.98-23.52 ng/mL until 72 h by pharmacokinetic experiments in the Es-ME-MN group. Es-ME-MN rapidly achieves effective blood concentrations through needle puncture and microemulsion delivery and maintains blood concentrations through the baseplate long-time release. Microemulsion-encapsulated, organic solvent-free, and long-time-released transdermal microneedle will make progress and provide a new idea for transdermal delivery of lipophilic drugs.

Recovery and utilization of waste filtrate from industrial biological fermentation: Development and metabolite profile of the Bacillus cereus liquid bio-fertilizer.

Most fermentation waste filtrates can be used as raw materials for producing bio-fertilizers to reduce wastewater emissions and environmental pollution, but their bio-fertilizer utilization depends on the nutrients contained and their metabolized by functional microorganism. To achieve bio-fertilizer utilization of Acremonium terricola fermented waste filtrate, this study systematically explored the functional microbial species for making good use of waste liquid, optimized material process parameters for bio-fertilizer production based on D-optimal mixture design method, and analyzed the composition of the waste filtrate and its metabolism by functional microorganisms using a non-targeted LC-MS metagenomics technique. The results showed that Bacillus cereus was the functional microbial candidate for producing bio-fertilizer because of its more efficiently utilize the waste filtrate than other Bacillus sp. The optimal material process parameters of the liquid bio-fertilizer were the inoculum dose of 5% (v:v, %), 80% of waste filtrate, 0.25% of N, 3.5% of P2O5, 3.25% of K2O of mass percentage. Under these conditions, the colony forming unit (CFU) of Bacillus cereus could reach (1.59 ± 0.01) × 108 CFU/mL, which met the bio-fertilizer standard requirements of the People's Republic of China (NY/T798). Furthermore, the potential functions of bio-fertilizer were studied based on comparison of raw materials and production components: on the one hand, waste filtrate contained abundant of nitrogen and carbon sources, and bioactive substances secreted by Acremonium terricola, such as ß-alanyl-L-lysine, anserine, UMP, L-lactic acid and etc., which could meet the nutrient requirements of the growth of Bacillus cereus; On the other hand, some compounds of waste filtrate with the potential to benefit the plant growth and defense, such as betaine aldehyde, (2E,6E)-farnesol, homogentisic acid and etc., were significantly up regulated by Bacillus cereus utilization of the filtrate. To sum up, this work highlighted that the waste filtrate could be efficiently developed into liquid bio-fertilizer by Bacillus cereus.

Application of D-Optimal Mixture Design in the Development of Nanocarrier-Based Darifenacin Hydrobromide Gel.

BACKGROUND: Darifenacin hydrobromide, a BCS Class II drug, is poorly bioavailable due to extensive first-pass metabolism. The present study is an attempt to investigate an alternative route of drug delivery by developing a nanometric microemulsion-based transdermal gel for the management of an overactive bladder. METHODS: Oil, surfactant, and cosurfactant were selected based on the solubility of the drug, and surfactant: cosurfactant in surfactant mixture (Smix) was selected at a 1:1 ratio as inferred from the pseudo ternary phase diagram. The D-optimal mixture design was used to optimize the o/w microemulsion wherein the globule size and zeta potential were selected as dependable variables. The prepared microemulsions were also characterized for various physico-chemical properties like transmittance, conductivity, and TEM. The optimized microemulsion was gelled using Carbopol 934 P and assessed for drug release in vitro and ex vivo, viscosity, spreadability, pH, etc. RESULTS: Drug excipient compatibility studies showed that the drug was compatible with formulation components. The optimized microemulsion showed a globule size of less than 50 nm and a high zeta potential of -20.56 mV. The ME gel could sustain the drug release for 8 hours as reflected in in vitro and ex vivo skin permeation and retention studies. The accelerated stability study showed no significant change in applied storage conditions. CONCLUSION: An effective, stable, non-invasive microemulsion gel containing darifenacin hydrobromide was developed. The achieved merits could translate into increased bioavailability and dose reduction. Further confirmatory in vivo studies on this novel formulation, which is a cost-effective & industrially scalable option, can improve the pharmacoeconomics of overactive bladder management.

Rapid detection of sesame oil multiple adulteration using a portable Raman spectrometer.

Multiple adulteration is a commonly used fraud of illegal traders to mask the traditional adulteration detection methods. In this study, rapid detection of multiple adulteration of sesame oil was proposed using a portable Raman spectrometer. Two strategies including simplex theory of mixtures and D-optimal mixture design were used to conduct variable selection and model evaluation, respectively. Based on simplex theory of mixtures, the important variables were selected by orthogonal partial least squares discriminant analysis of preprocessed Raman spectra of sesame oils and four adulterant oils. Moreover, multiple adulteration identification model was built by one-class partial least squares and validated by representative adulterated samples prepared by D-Optimal mixture design. The validation results show that 40 sesame oils adulterated with four types of adulterant oils can be correctly identified, indicating Raman spectroscopy is an effective tool for the detection of multiple adulteration of sesame oil, especially for on-site applications.

Augmented Oral Bioavailability and Prokinetic Activity of Levosulpiride Delivered in Nanostructured Lipid Carriers.

The present study is aimed to develop and optimize levosulpiride-loaded nanostructured lipid carriers (LSP-NLCs) for improving oral bioavailability and prokinetic activity of LSP. LSP-NLCs were optimized with D-optimal mixture design using solid lipid, liquid lipid and surfactant concentrations as independent variables. The prepared LSP-NLCs were evaluated for physicochemical properties and solid-state characterization. The in vivo oral pharmacokinetics and prokinetic activity of LSP-NLCs were evaluated in rats. LSP-NLCs formulation was optimized at Precirol® ATO 5/Labrasol (80.55/19.45%, w/w) and Tween 80/Span 80 concentration of 5% (w/w) as a surfactant mixture. LSP-NLCs showed a spherical shape with a particle size of 152 nm, a polydispersity index of 0.230 and an entrapment efficiency of 88%. The DSC and PXRD analysis revealed conversion of crystalline LSP to amorphous state after loading into the lipid matrix. LSP-NLCs displayed a 3.42- and 4.38-flods increase in AUC and Cmax after oral administration compared to LSP dispersion. In addition, LSP-NLCs showed enhanced gastric emptying (61.4%), intestinal transit (63.0%), and fecal count (68.8) compared to LSP dispersion (39.7%, 38.0% and 51.0, respectively). Taken together, these results show improved oral bioavailability and prokinetic activity of LSP-NLCs and presents a promising strategy to improve therapeutic activity of LSP for efficient treatment of gastric diseases.

Enhanced oral absorption of insulin: hydrophobic ion pairing and a self-microemulsifying drug delivery system using a D-optimal mixture design.

The lipophilicity of a peptide drug can be considerably increased by hydrophobic ion pairing with amphiphilic counterions for successful incorporation into lipid-based formulations. Herein, to enhance the oral absorption of insulin (INS), a self-microemulsifying drug delivery system (SMEDDS) formulation was developed. Prior to optimization, INS was complexed with sodium n-octadecyl sulfate (SOS) to increase the loading into the SMEDDS. The INS-SOS complex was characterized via scanning electron microscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, and its dissociation behavior. The SMEDDS was optimized using a D-optimal mixture design with three independent variables including Capmul MCM (X1, 9.31%), Labrasol (X2, 49.77%), and Tetraglycol (X3, 40.92%) and three response variables including droplet size (Y1, 115.2 nm), INS stability (Y2, 46.75%), and INS leakage (Y3, 17.67%). The desirability function was 0.766, indicating excellent agreement between the predicted and experimental values. The stability of INS-SOS against gastrointestinal enzymes was noticeably improved in the SMEDDS, and the majority of INS remained in oil droplets during release. Following oral administration in diabetic rats, the optimized SMEDDS resulted in pharmacological availabilities of 3.23% (50 IU/kg) and 2.13% (100 IU/kg). Thus, the optimized SMEDDS is a good candidate for the practical development of oral delivery of peptide drugs such as INS.

Development and optimization of cactus pear fruit jelly supplemented with Moringa oleifera leaf extract.

Cactus pear fruit and Moringa (Moringa oleifera Lam) are nutritionally abundant food sources. This study was conducted to evaluate the potential of cactus pear fruit for jelly development with the supplementation of M. oleifera leaves extract as means of postharvest loss, food insecurity and malnutrition reduction. D-optimal mixture design in Minitab Version 16 Statistical Software was used to generate ten experimental runs (formulations for jelly development) using 60-80% cactus fruit juice (CFJ), 0-20% M. oleifera extract (MOE), and 20-40% table sugar (TS). The developed jellies were analyzed for proximate composition, mineral content (Fe, Ca and Zn) and sensory evaluation. Nutritional and sensorial optimization was carried through a graphical approach using a D-optimal mixture design. The results indicated a significant difference in protein, fat, fibre, ash, carbohydrate, energy, iron, calcium, zinc, appearance, aroma, and taste amongst the formulated jellies (p < 0.05). In contrast, the significant difference was not observed in mouth feel and overall acceptability amongst the jellies. The overall optimum nutritional and sensorial attributes of the jelly were found in a range of CFJ (70-73%), MOE (3-14%) and TS (20-26%). However, developing jelly with the formulation of CFJ (68 %), MOE (12%) and TS (20%) was predicted to give the highest nutritional value and sensory acceptability score. The optimized result indicated the jelly would contain 3.97% protein, 0.92% fat, 1.09% fiber, 1.19% ash, 62.95% carbohydrate, 275.97 kcal/100 â€‹g energy, 98.45 mg/100 â€‹g calcium, 0.25 mg/100 â€‹g zinc, 7.43 mg/100 â€‹g iron and overall sensory acceptability score of 4.38 in five-point hedonic scale.

Fabrication of Dragee Containing Spirulina platensis Microalgae to Enrich Corn Snack and Evaluate Its Sensorial, Physicochemical and Nutritional Properties.

In this work, the possibility of enriching snacks with Spirulina palatensis (SP) powder as a dragee was studied. In dragee formulation, the effects of various levels of SP, sunflower oil, NaCl and sour whey powder on sensory, physicochemical and nutritional properties were investigated. The dragee formulation was optimized and the characteristics of the optimal sample were compared with the control sample (containing dragee without SP). The results showed that adding SP increased the flavonoids, total anthocyanin content, vitamins, protein, minerals, essential and non-essential amino acids and fatty acids, including ω3 and ω6, while decreasing the energy intake. Based on the results, the optimal dragee sample was formulated and prepared with a desirability of 0.955. The correlation coefficient indicated that the effective optimization process and the performance of the model were carried out properly. The addition of SP had a significant impact on all color parameters considered by the panelists, and the enriched sample was given a very good taste score (75.10 ± 2.923) and an outstanding overall acceptance rate (91.20 ± 1.549) by the panelists. Although morphological data from scanning electron microscopy showed the distribution of non-uniform SP particles relative to the addition of SP in the extruded product formulation, the preservation of more nutritional properties and the good acceptance of sensory evaluators indicated the success of the application in dragee formulation. Therefore, instead of being utilized in an extruder, we discovered that SP may be used as a dragee for snack fortification.

Optimized self-microemulsifying drug delivery system improves the oral bioavailability and brain delivery of coenzyme Q10.

Our study aimed to develop a self-microemulsifying drug delivery system for the poorly aqueous-soluble drug Coenzyme Q10, to improve the dissolution and the oral bioavailability. Excipients were selected based on their Coenzyme Q10 solubility, and their concentrations were set for the optimization of the microemulsion by using a D-optimal mixture design to achieve a minimum droplet size and a maximum solubility of Coenzyme Q10 within 15 min. The optimized formulation was composed of an oil (omega-3; 38.55%), a co-surfactant (Lauroglycol® 90; 31.42%), and a surfactant (Gelucire® 44/14; 30%) and exhibited a mean droplet size of 237.6 ± 5.8 nm and a drug solubilization (at 15 min) of 16 ± 2.48%. The drug dissolution of the optimized formulation conducted over 8 h in phosphate buffer medium (pH 6.8) was significantly higher when compared to that of the Coenzyme Q10 suspension. A pharmacokinetic study in rats revealed a 4.5-fold and a 4.1-fold increase in the area under curve and the peak plasma concentration values generated by the optimized formulation respectively, as compared to the Coenzyme Q10 suspension. A Coenzyme Q10 brain distribution study revealed a higher Coenzyme Q10 distribution in the brains of rats treated with the optimized formulation than the Coenzyme Q10 suspension. Coenzyme Q10-loaded self microemulsifying drug delivery system was successfully formulated and optimized by a response surface methodology based on a D-optimal mixture design and could be used as a delivery vehicle for the enhancement of the oral bioavailability and brain distribution of poorly soluble drugs such as Coenzyme Q10.

[Optimization of preparation technology for Acanthopanax senticosus total saponins microemulsion by D-optimal mixture design and intestinal absorption characteristics].

Following the preparation of Acanthopanax senticosus total saponins microemulsion, the formulation and preparation technology were optimized and the quality was evaluated. The absorption characteristics of A. senticosus total saponins microemulsion by the self-microemulsifying drug delivery system(SMEDDS) were investigated in the unidirectional intestinal perfusion model in vivo. The oil phase, mass ratio(K_m), number of revolutions, and drug concentration were subjected to single-factor investigation with the area of pseudo-ternary phase diagram as the index. The process was optimized by D-optimal mixture design with the particle size as the index, and then the appearance, morphology, and particle size were investigated. The mass concentrations of eleutherosides B and E in the microemulsion were determined. The results showed that the optimum formulation of A. senticosus total saponins microemulsion was determined as follows: 20.8% of water phase, 31.2% of isopropyl palmitate, and 48.0% of soybean phospholipid and absolute ethanol(K_m=1∶1). As revealed by the observation under a transmission electron microscope, the microemulsion exhibited homogeneous dispersion and was a spherical emulsion droplet in the water-in-oil type. At room temperature, the pH value was 5.19, the refractive index 1.416 5, the average particle size(26.47±0.04)nm, and the polydispersity index(PDI) 0.118±0.03. The content of the eleutherosides B and E was 0.038 9 and 0.166 4 mg·mL~(-1), respectively. The preliminary stability study showed that the solution was clear and transparent within 30 d, without stratification or content change, indicating good stability. The absorption of microemulsion in each intestinal segment was significantly improved as compared with that of the A. senticosus total saponins, with the best absorption effect detected in the ileum, which has laid a foundation for further development and utilization of A. senticosus.

Optimization of formulation and physicochemical, nutritional and sensory evaluation of vegan chickpea-based salad dressings.

The formulation of a vegan salad dressing supplemented with chickpea flour (VC-SD) was optimized by D-optimal mixture design, evaluating the effect of chickpea flour, water and oil on the textural properties of the product. The linear models showed the best fitting and predictive ability, as highlighted by high R2 adj and Q2. The Cox-effects of the textural parameters were significant for water and chickpea flour contents, but not for oil. Sensory evaluation indicated that all the VC-SD were characterized by the predominance of pungent/acid odor notes, whereas sourness was the most perceived fundamental taste, together with a sensation of a grainy texture in mouth due to flour particles. Overall, the product can be consumed by vegans and vegetarians because produced without animal-derived ingredients, and is in synergy with the healthful characteristics of Mediterranean diet, in which pulses and extra-virgin olive oil play beneficial roles. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-021-05288-x.

Preparation, evaluation, and pharmacokinetics in beagle dogs of a taste-masked flunixin meglumine orally disintegrating tablet prepared using hot-melt extrusion technology and D-optimal mixture design.

Flunixin meglumine (FM) is a nonsteroidal anti-inflammatory drug limited by irritation of the respiratory tract and mucosa in veterinary tissue. This study aimed to develop a taste-masked FM solid dispersion (SD) by hot-melt extrusion (HME) and formulate an orally disintegrating tablet (ODT) with selected excipients by direct compression. Eudragit® E PO was chosen as the matrix, and HME parameters were optimized: extrusion temperature, 135℃; screw speed, 100 rpm; and drug loading, 20%. Characterization techniques proved that FM was rendered amorphous in the HME extrudate. In vitro dissolution studies showed that FM SD released significantly slower than the corresponding physical mixture in artificial saliva. Excipients were selected based on compression formability, disintegration, and solubility. A D-optimal mixture design was used to optimize the composition: 25% FM SD, 18.75% microcrystalline cellulose, 52.5% mannitol, 3.75% low-substituted hydroxypropyl cellulose, and 1% magnesium stearate. Taste-masked FM ODT had a tensile strength of 0.7 ± 0.01 MPa and a disintegration time of 17.6 ± 0.1 s. E-tongue and E-nose analysis showed that FM ODT had a better taste-masked effect than commercial granules. Finally, a pharmacokinetic study proved that the main pharmacokinetic parameters of FM ODT were not significantly different from those of commercial granules, which indicated that these formulations had similar pharmacokinetic behaviours in beagles.

Self-emulsifying Drug Delivery System for Improved Dissolution and Oral Absorption of Quetiapine Fumarate: Investigation of Drug Release Mechanism and In-vitro Intestinal Permeability.

In this study, we focused on quetiapine fumarate (QTF), a class II BCS drug. QTF is an atypical antipsychotic used in the treatment of schizophrenia and bipolar disorders. Our objective was to develop a new QTF-loaded self-emulsifying drug delivery system (SEDDS) to improve the dissolution and absorption of the drug. An experimental design approach was used to develop and optimize QTF-loaded SEDDS. The optimized formulation was characterized for droplets size, zeta potential, PDI, and stability. It was then evaluated using an in-vitro combined test for dissolution and Everted gut sac technique. Mathematical modeling and Transmission electron microscopy (TEM) were used to elucidate the mechanism of release. The optimal formulation was type IIIB SEDDS, constituted of 9.1% of oleic acid, 51.6% of Tween®20, and 39.3% of Transcutol® P. It showed a droplets size of 144.8 ± 4.9nm with an acceptable PDI and zeta potential. For in-vitro evaluation tests, we noticed an enhancement of the dissolution rate of the optimal QTF-loaded SEDDS compared to the free drug (98.82 ± 1.24% for SEDDS after 30 min compared to 85.65 ± 2.5% for the pure drug). The release of QTF fitted with the Hopfenberg model indicating the drug was released by water diffusion and erosion mechanism. This result was confirmed by TEM images which showed a smaller droplet size after release. We also found an amelioration of the permeability of QTF of 1.69-fold from SEDDS compared to the free drug. Hence, the SEDDS formulation represented a new way to improve the dissolution and absorption of QTF.

Optimization of maize-millet based soy fortified composite flour for preparation of RTE extruded products using D-optimal mixture design.

Formulation of composite flour comprising of maize (MF), finger millet (FM), defatted soy (DS) and elephant foot yam (YP) was carried out for the preparation of extruded product. The proportion of three major ingredients was varied as maize: 40-55%, finger millet: 20-30%, defatted soy: 10-25% and that of YP was kept constant as 10%. In all 16 experiments were conducted by D-optimal mixture design keeping the upper and lower values of ingredients in the range given above. Extruded products were developed by using twin screw extruder (BTPL lab model) at barrel temperature 100 °C, screw speed 300 rpm and feed moisture content 15% (wb). Physical and functional properties like expansion ratio (ER), bulk density (BD), hardness, water absorption index (WAI) and water solubility index (WSI) of extruded products were analyzed. Composite flour was optimized on the basis of physical and functional properties of extruded products. The values of ER, BD, hardness, WAI and WSI of extruded products were in the range of 2.42-3.30, 0.14-0.26 g cm-3, 11.15-18.67 N, 5.57-6.87 g g-1 and 14.42-19.95%, respectively. Variations in proportion of ingredients in the composite blend significantly affected ER, BD, hardness, WAI and WSI of the product. The regression models for ER, BD, hardness, WAI and WSI were developed to explain the effect of ingredients on the response variables. A blend of ingredients in the ratio of 40:30:20:10 (MF:FM:DS:YP) was found to be optimum with a desirability function of 0.82 which resulted extrudate attributes of ER 3.29, BD 0.14 g cm-3, hardness 11.94 N, WAI 6.13 g g-1 and WSI 17.07%.

Design and characterization of propolis extract loaded self-nano emulsifying drug delivery system as immunostimulant.

This current study aims to optimize, characterize, and observe the stability of the self-nano emulsifying drug delivery system (SNEDDS) of propolis extract (PE) for improving the immune response. Optimization of the selected composition of SNEDDS was conducted using a D-optimal mixture design. SNEDDS was prepared by loading 150 mg/mL of PE in oil, surfactant, and cosurfactant phases. The thermodynamic stability test was carried out with phase separation parameters followed by the robustness to dilution and accelerated stability test. The immunostimulant activity was examined in vitro and in vivo by determining the phagocytic activity, cell proliferation, production of nitrite oxide levels of RAW 264.7 cells, phagocytic activity of macrophages, and the number of leukocytes, neutrophils, and lymphocytes. The formula optimization showed that the formula containing Capryol-90, Cremophor RH40, and PEG 400 at a ratio of 30: 34: 36 was optimum. The verification response of the optimum formula with drug loading showed that the transmittance, droplet size, and zeta potential were 96.90 ± 0.00%, 28.7 ± 1.20 nm, and -56.5 ± 2.05 mV, respectively. The thermodynamic stability test and robustness to dilution did not find any separation phase. The accelerated stability test results were classified as stable. The in vitro and in vivo immunostimulant activity test showed that PE-loaded SNEDDS exhibited a higher immunostimulant effect than PE. In conclusion, the optimum and stable composition of PE loaded SNEDDS was found with a simple and accurate method using the D-Optimal mixture design and demonstrated an immunostimulant activity.

Design, optimization and evaluation of a microemulsion-based hydrogel with high malleability for enhanced transdermal delivery of levamisole.

The objective of the present study was to prepare and evaluate a microemulsion-based hydrogel with high malleability as a transdermal delivery carrier for levamisole (LMS). A pseudo-ternary phase diagram and D-optimal mixture design were utilized to screen and optimize the microemulsion, and the formulation comprised 7.5% MaisineTM35-1, 33% Smix and 59.5% water. The microemulsion was physically stable with an average size of 19.3 ± 0.1 nm and zeta potential of -3.84 ± 0.05 mV. Moreover, a highly malleable alginate-boronic acid (alginate-BA) gel was prepared and could come into close contact with highly curved skin. The optimized microemulsion was loaded into alginate-BA gel and subjected to ex vivo and in vivo investigation. The microemulsion-based gel had desirable characterization, good stability and negligible skin irritation. The results of ex vivo permeation study showed that LMS achieved a significantly higher cumulative amount from the LMS-loaded microemulsion-based gel than that from the LMS-gel. The pharmacokinetic study showed a twofold increase in relative bioavailability compared to the commercial liniment. These results provide insight into the capability of the developed malleable microemulsion-based gel to enhance the transdermal permeation and bioavailability of LMS.

Improved Pharmacodynamic Potential of Rosuvastatin by Self-Nanoemulsifying Drug Delivery System: An in vitro and in vivo Evaluation.

PURPOSE: The purpose of this proposed research was to investigate a nano-formulation developed using self-nanoemulsifying drug delivery system (SNEDDS) to improve the pharmacodynamic potential of rosuvastatin by assisting its transportation through lymphatic circulation. METHODS: The utilized lipids, surfactants, and co-surfactants for SNEDDS were selected on the basis of solubility studies. The SNEDDS formulation was optimized by implementing a D-optimal mixture design, wherein the effect of concentration of Capmul MCM EP (X1), Tween 20 (X2) and Transcutol P (X3) as independent variables was studied on droplet size (Y1), % cumulative drug release (Y2) and self-emulsification time (Y3) as dependent variables. The optimized formulation was evaluated via in vitro parameters and in vivo pharmacodynamic potential in Wistar rats. RESULTS: The D-optimal mixture design and subsequent ANOVA application resulted in the assortment of the optimized SNEDDS formulation that exhibited a droplet size of nano range (14.91nm), in vitro drug release of >90% within 30 minutes, and self-emulsification time of 16 seconds. The in vivo pharmacodynamic study carried out using Wistar rats confirmed the better antihyperlipidemic potential of developed formulation in normalizing the lipidic level of serum in contrast to pure drug and marketed tablets. CONCLUSION: This research reports the application of D-optimal mixture design for successful and systematic development of rosuvastatin-loaded SNEDDS with distinctly enhanced in vitro and in vivo performance in comparison to marketed formulation. Eventually, improved anti-hyperlipidemic efficacy was envisaged which might be attributed to increased drug solubility and absorption. Overall, this study shows the utility of SNEDDS for improving the dissolution rate and bioavailability of poor aqueous-soluble drugs. The present SNEDDS formulation could be a promising approach and alternative to conventional dosage form.