Chrysin-Loaded Microemulsion: Formulation Design, Evaluation and Antihyperalgesic Activity in Mice

Chrysin is a bioactive flavonoid found in pollens, passion flowers, honey, royal jelly, and propolis, which is commonly used as an ingredient in natural food supplements and is primarily responsible for their pharmacological properties. A transparent chrysin-loaded microemulsion (CS-ME) prepared through a ternary phase diagram was evaluated for use as an antihyperalgesic formulation. It was formulated with 40% Labrasol® (surfactant), 5% isopropyl myristate (oil phase) and 55% water (aqueous phase) and classified as an oil-in-water (O/W) microsized system (74.4 ± 15.8 nm). Its negative Zeta potential (−16.1 ± 1.9 mV) was confirmed by polarized light microscopy and dynamic light scattering analysis. In vitro studies in Franz-type static diffusion cells showed that chrysin release from CS-ME followed zero-order kinetics. Oral administration of CS-ME in mice resulted in a statistically significantly reduction (p < 0.05) in carrageenan-induced mechanical hyperalgesia compared to the control group. Treatment with CS-ME also showed anti-inflammatory activity by significantly decreasing the TNF-α level (p < 0.01) and increasing that of IL-10 (p < 0.05) compared to the control group. These results suggest that the proposed microsystem is a promising vector for the release of chrysin, being able to improve its capacity to modulate inflammatory and nociceptive responses.

Preparation of Blueberry Anthocyanin Nanoemulsion And Its Stability and Skin Safety Evaluation

BACKGROUND: Blueberry anthocyanins have strong antioxidant activity, but their instability and low bioavailability limit their use. Nanoemulsion is a new type of food and drug carrier with stable thermodynamic properties. Therefore, anthocyanins will be encapsulated with nanoemulsion to improve its stability and application value.RESULTS: In this study, the best surfactants, oil phases and cosurfactants for the preparation of blueberry anthocyanin nanoemulsion were screened by pseudo-ternary phase diagram method and the solubility of blueberry anthocyanin nanoemulsion was taken into consideration. Deep purplish red, clear and transparent anthocyanin nanoemulsion was prepared by simple and cheap low-energy emulsification method according to the formula. Normal and high temperature test and high speed centrifugal test proved that the blueberry anthocyanin nanoemulsion had good stability. Guinea pig skin irritation test and sensitization test showed that there was no irritation and sensitization to guinea pig hair removal skin. CONCLUSION: The blueberry anthocyanin nanoemulsion prepared in this study has good stability at room temperature and is safe for guinea pig hair removal skin. It provides a basis for improving the stability and bioavailability of blueberry anthocyanin, and provides a reference for the application of blueberry anthocyanin nanoemulsion in skin beauty and transdermal drug delivery.

Improvement of the Solubilization and Extraction of Curcumin in an Edible Ternary Solvent Mixture

A water-free, ternary solvent mixture consisting of a natural deep eutectic solvent (NADES), ethanol, and triacetin was investigated concerning its ability to dissolve and extract curcumin from Curcuma longa L. To this purpose, 11 NADES based on choline chloride, acetylcholine, and proline were screened using UV–vis measurements. A ternary phase diagram with a particularly promising NADES, based on choline chloride and levulinic acid was recorded and the solubility domains of the monophasic region were examined and correlated with the system’s structuring via light scattering experiments. At the optimum composition, close to the critical point, the solubility of curcumin could be enhanced by a factor of >1.5 with respect to acetone. In extraction experiments, conducted at the points of highest solubility and evaluated via HPLC, a total yield of ~84% curcuminoids per rhizome could be reached. Through multiple extraction cycles, reusing the extraction solvent, an enrichment of curcuminoids could be achieved while altering the solution. When counteracting the solvent change, even higher concentrated extracts can be obtained.

Optimization and Characterization of Self Nano Emulsifying Drug Delivery System loaded with 18- β Glycerrhetinic acid

The purpose of this study was to prepare, optimize and evaluate self nano emulsifying drug delivery system (SNEDDS) containing 18- β glycerrhetinic acid which enhances the dissolution profile or bioavailability of the drug in comparison to pure suspension of 18- β glycerrhetinic acid.18- β glycerrhetinic acid loaded SNEDDS having geranium oil as oil phase, tween 80 as a surfactant, and dimethyl sulfoxide (DMSO) as co-surfactant were prepared using pseudo ternary phase diagram and Box-Behnken experimental design was used to optimize the different formulations. Optimized formulations were characterized for self-emulsifying time, globule size, zeta potential, and drug release. The mean droplet size and PDI of the optimized formulation were found to be in a variation of 93.42 nm and 0.401 respectively. FTIR data showed no physicochemical interaction between excipients and drug. The encapsulation efficiency of optimised 18- β glycerrhetinic acid SNEDDS was found 80.12±1.52% , % transmittance was found 99.34±0.134% and the viscosity of all the formulations was found 0.8872 cp. Three-dimensional response surface plots and two-dimensional contour plots of the responses across the selected factors were constructed that explained the relationship between the independent and dependent variables. Release kinetics was calculated by using KinetDS3.0. It was concluded that prepared formulations were formulated with approximately desired mean droplet size confirmed by Box- Behnken experimental design as well as properly optimized and characterized.

Antioxidant, Antimicrobial and Formulation of Borage (Borago officinalis) Seeds Oil and Leaves Extracts as Microemulsion

Aims: This study aims to investigate antioxidant and antibacterial activities of borage (seeds and leaves) extracts, and to prepare different topical microemulsion formulations using borage oil. Study Design: Borage seeds and leaves were collected from Hebron -Palestine, then the borage leaves and seeds were prepared for extraction and then extracted with Soxhlet using ethanol. The antimicrobial and antioxidant activity of the extracts were studied, and then Ternary Phase Diagram was constructed using the borage extracts (from seeds and leaves). Methodology: The seeds were cultivated upon their ripening season in April of 2016 from the Halhul mountains in Hebron/Palestine. Soxhlet method was used to extract borage seeds and leaves oil by using ethanol 95%. A ternary phase diagram was constructed by determining appropriate nonionic surfactant to assess the ability for microemulsion formulation and durability of each system. Tween 80 was found to be more suitable to solubilize each of borage seeds and leaves extracts compared with Tween 20 due to its prominent hydrophobic properties. The antibacterial activity was evaluated for both borage seeds and leaves extracts using a well diffusion method against Staphyloococcus aureus, Escherichia coli, &Candida albicans. Results: Results showed that the seeds extract has inhibition zone (12 mm) against S. aureus (gram positive bacteria) higher than inhibition zone that leaves extracts exhibited (7.5mm), but no significant effects observed for both extracts against E. coli and C. albicans. In addition, antibacterial activity for microemulsions formulation was measured against S. aureus, E. coli, and C. albicans. Results showed that there is minor activity against S. aureus when compared to PenicillinG and the pure seed oil or leaves extract. In contrast no activity was reported against E. coli and C. albicans. The antioxidant activity was further indicated by the quiet good ability to reduce the FRAP reagent for both extracts with the indication of higher seeds extract activity. This variation is explained by the higher seeds extract content of polyphenol, tocopherol and vitamin C than leaves extract. Conclusion: Borage seeds and leaves were extracted, and the extracts were showed antimicrobial and antioxidant activity and showed that they can be used in microemulsion using ternary phase diagram.

A comprehensive insight on self emulsifying drug delivery systems

Background: The oral route is a highly recommended route for the delivery of a drug. But most lipophilic drugs are difficult to deliver via this route due to their low aqueous solubility. Selfemulsifying drug delivery systems (SEDDS) have emerged as a potential approach of increasing dissolution of a hydrophobic drug due to spontaneous dispersion in micron or nano sized globules in the GI tract under mild agitation. Objective: The main motive of this review article is to describe the mechanisms, advantages, disadvantages, factors affecting, effects of excipients, possible mechanisms of enhancing bioavailability, and evaluation of self-emulsifying drug delivery systems. Result: Self emulsifying systems incorporate the hydrophobic drug inside the oil globules, and a monolayer is formed by surfactants to provide the low interfacial tension, which leads to improvement in the dissolution rate of hydrophobic drugs. The globule size of self-emulsifying systems depends upon the type and ratio of excipients in which they are used. The ternary phase diagram is constructed to find out the range of concentration of excipients used. This review article also presents recent and updated patents on self-emulsifying drug delivery systems. Self-emulsifying systems have the ability to enhance the oral bioavailability and solubility of lipophilic drugs. Conclusion: This technique offers further advantages such as bypassing the first pass metabolism via absorption of drugs through the lymphatic system, easy manufacturing, reducing enzymatic hydrolysis, inter and intra subject variability, and food effects.

Formulation and Evaluation of Solid Self-Nanoemulsifying Drug Delivery System for Enhancing the Solubility and Dissolution Rate of Budesonide

Objective: To enhance solubility and dissolution rate of budesonide through development of solid self-nanoemulsifying drug delivery system (S-SNEDDS). Methods: Liquid self-nanoemulsifying drug delivery systems (L-SNEDDS) were prepared and ternary phase diagram was constructed using Origin pro 8. Liquid self-nanoemulsifying formulation LF2 having 20% oil and 80% of surfactant/co-surfactant was optimized from the three formulations (LF1-LF3) to convert in to solid, through various characterization techniques like self-emulsification, in vitro drug release profile and drug content estimation. The prepared L-SNEDDS converted into S-SNEDDS, SF1-SF6 by adsorption technique using Aerosil 200, Neusilin US2, and Neusilin UFL2 to improve flowability, compressibility and stability. Results: Formulation LF2 exhibited globule size of 82.4 nm, PDI 0.349 and Zeta potential -28.6 mV with drug indicating the stability and homogeneity of particles. The optimized formulation SF4 containing Neusilin UFL2 was characterized by DSC, FTIR, X-Ray diffraction studies and found no incompatibility and no major shifts were noticed. Formulation SF4 released 100 % drug in 20 min against pure drug release of 47 % in 60 min. Regardless of the form (i.e. liquid or solid) similar performance of emulsification efficiency is observed. Conclusion: The results demonstrated that the technique of novel solid self-nanoemulsifying drug delivery system can be employed to enhance the solubility and dissolution rate of poorly water-soluble drug budesonide.

Formulation and Evaluation of Solid Self Nano Emulsifying drug delivery System of Olanzapine to Enhance Aqueous Solubility and Dissolution Rate

Present research work was aimed to enhance aqueous solubility and dissolution rate of olanzapine by solid self nano emulsifying drug delivery system(S-SNEDDS). Olanzapine is a BCS class II drug having 65% oral bioavailability; it is used in the treatment of psychosis, depression and mania conditions. Oils, Surfactants, Co surfactants were selected depending upon the saturated solubility of olanzapine in those components; excipients were screened depending on olanzapine solubility in various oils, surfactants and co surfactants. Surfactant: co surfactant {Smix} ratios i.e., 3:1 and 4:1 were prepared to determine nano emulsion regions and also to formulate liquid self nano emulsifying drug delivery system (L-SNEDDS). Pseudo ternary phase diagram were plotted by using Triplot version 4.1.2 software, nano emulsion region was determined and evaluated. Formulations were designed based on saturated solubility of olanzapine and Pseudo ternary phase diagram using various ratios of oils [Capryol 90], surfactants [Kolliphor EL], co surfactants [Lauroglycol 90] depending on its solubility and nano emulsion formation four formulations were developed which are further selected for characterisation of L-SNEDDS like robustness to dilution, self emulsification, determination of droplet size, PDI, Drug loading efficacy, zeta potential and also Invitro drug release. Among those four formulations, F1 (SB184J 4:6) was optimum because compared to other three formulations F3 gave best results in terms of droplet size (66nm) with PDI (0.24), Invitro drug release, dissolution rate of F1 SNEDDS having (88.201± 0.25%). Invitro drug release of F1 formulation was compared with that of Olanzapine [API] (45.281± 0.52%) the results indicating that there is a increase in solubility and dissolution rate of olanzapine by 2.2 times more compared to pure olanzapine (API). F1 (SB184J 4:6) were converted into S-SNEDDS by adsorption process by addition porous carriers (Aerosil 200). Formulated S-SNEDDS were undergone various evaluation parameters and also reconstitution parameters to determine Droplet size and Invitro drug release of solid F1 (SB184J4:6) formulation. The results of present study demonstrates that olanzapine SNEDDS has an ability and potential to enhance solubility and dissolution rate.

Development of Licorice Flavonoids Loaded Microemulsion for Transdermal Delivery Using CCD-Optimal Experimental Approach: Formulation Development and Characterization

In this research, we sought to surmount the poor dissolvability and transdermal absorption rate of licorice flavonoids (LFs) by fabricating a LFs microemulsion. LFs content was determined using high performance liquid chromatography. Initial studies such as dissolution testing, emulsification testing, and pseudo ternary phase diagram generation were implemented for screening components and optimized adopting the central composite design. While the tested responses were solubility, droplet size and PDI, thirteen trials were performed using two different variables, oil percentage and optimized emulsifier and co-emulsifier ratio. Microemulsions were then characterized for droplet size, PDI, transmission electron microscopy, viscosity, electrical conductivity, pH, entrapment efficiency, drug content and stability. Additionally, skin release profile, percutaneous absorption and retention were investigated adopting Franz diffusion cell. The optimal formulation was found to compose of laureth-9 (emulsifier, 6.72 g), propylene glycol (co-emulsifier, 1.80 g), isopropyl myristate (IPM, oil, 1.48 g), LFs (1.50 g) and at least more than 85% deionized water. The optimized and storage for 3 months of microemulsion was found to clear, light yellow color without phase separation or precipitation indicated the stability of the preparation to long-term placement. The mean droplet size, PDI, entrapment efficiency and drug content were discovered as 12.68 ± 0.12 nm, 0.049 ± 0.005, 97.28 ± 0.13% and 122.67 ± 0.40 mg·g−1, respectively. Furthermore, the optimal formulation sustained release LFs, remarkably deliver more LFs through the skin layer (644.95 ± 6.73 μg cm−2) and significantly retained LFs in the skin layer (9.98 μg cm−2). The study concluded that optimized microemulsion has potential and enhanced the dissolvability and cumulative penetration amount of LFs.