International Journal of Current Research and Review
ISSN: 2231-2196 (Print)ISSN: 0975-5241 (Online)
logo
slider
slider
slider
slider
Bootstrap Slider

Indexed and Abstracted in: Crossref, CAS Abstracts, Publons, Google Scholar, Open J-Gate, ROAD, Indian Citation Index (ICI), ResearchGATE, Ulrich's Periodicals Directory, WorldCat (World's largest network of library content and services)

Search Articles

Track manuscript

Full Html

IJCRR - Vol 13 Issue 07, April, 2021

Pages: 149-155

Date of Publication: 12-Apr-2021


Print Article   Download XML  Download PDF

Formulation and Evaluation of Tocopheryl Polyethylene Glycol (TPGS) Stabilised Nanoemulsion of Curcumin for Topical Application

Author: Jasjeet Kaur Narang, Anmoldeep Kaur, R.S. Narang, Ravika Nanda, Mehak, Karanbir Singh

Category: Healthcare

Abstract:Introduction: Poorly water-soluble curcumin have limited penetration through stratum corneum after its topical administration and therefore advanced formulation is warranted. Objectives: The present study aimed to formulate and evaluate a TPGS stabilised nanoemulsion based topical gel of curcumin. Methods: The nanoemulsion was formulated using Sefsol-218:TPGS (1:1), Tween 60 and Solutol HS 15 as the oil phase, surfactant and cosurfactant respectively based on the results of solubility studies and miscibility studies using aqueous titration method followed by ultrasonication. Results: The formulated nanoemulsion exhibited a pH of 5.86 \? 0.018, percentage transmittance of 99.31\? 0.710, particle size and polydispersity index of 195.3 and 0.153 respectively and in vitro release of 90.1%, which was significantly higher (p≤0.05) as compared to that of drug suspension which exhibited a drug release of 43.9%. The results of in vitro skin permeation studies revealed that optimised nanoemulsion formulation exhibited a permeation of 78.7% which was significantly higher (p≤0.05) than the Curcumin suspension (37.61%) after 8 h study. The flux 143.7 (µg/cm2 /h) and permeability coefficient 9.58×10-2 of optimised nanoemulsion was significantly higher (p≤0.05) as compared to drug suspension which exhibits 65.85 µg/cm2 /h flux and 4.39×10-2 permeability coefficient. From drug retention studies it was observed that a significantly higher (p≤0.05) percentage of Curcumin was retained in the skin after nanoemulsion application (7.46%) in comparison to drug suspension (3.73%). Further, the results of the histopathological evaluation conducted using excised skin of rats confirmed that the curcumin loaded nanoemulsion was safe for topical application. Conclusion: The results of the study established that the formulated curcumin loaded nanoemulsion could be used topically for the treatment of various skin infections.

Keywords: Curcumin, Nanoemulsion, Histopathological emulsion, Topical application

Full Text:

INTRODUCTION

Curcumin, a poorly water-soluble phytoconstituent, is limited superficially to stratum corneum after its topical administration.1 Therefore, it necessitates the formulation of lipophilic carriers that release the drug in a controlled manner. Among the different lipophilic carriers investigated nanoemulsions have gained immense importance for the delivery of drugs. Reports in the literature suggest that nanoemulsions are a promising strategy for the delivery of drugs as they can penetrate through the subcutaneous barrier into the skin.2,3 Nanoemulsions are thermodynamically stable formulations made by using oils, surfactants, cosurfactants and water.4 As compared to the conventional formulations meant for topical administration nanoemulsions facilitate an increased amount of drug entrapment. In the present study, a nanoemulsion of curcumin for topical administration with enhanced skin retention has been formulated and evaluated.

MATERIALS AND METHODS

Chemicals and reagents

Curcumin was purchased from Sigma Aldrich Corporation(St. Louis, USA), Sefsol 218 was obtained as a gift sample from Nikko Chemicals(Tokyo, Japan), Labrasol, Labrafac, Capryol 90 were obtained as gift samples from gattefosse (Saint-Priest, France). Tween 80 was purchased from Central Drug House, New Delhi, India. PEG was purchased from Spectrochem Pvt Ltd Mumbai, India. Water was obtained from the Milli-Q-water purification system (Millipore, MA). All other chemicals and reagents were of analytical grade and procured from Merck (Mumbai, India) and S.D. Fine Chem. (Mumbai, India). The Ethical Clarence has been taken from the Institutional Ethical cum Research board with vide letter no. SGR/2019-51- 20

Formulation Development and Optimization

Solubility Studies

Assessment of solubility of the drug was done to select the most appropriate oil, surfactant and co-surfactant for the nanoemulsion formulation containing curcumin. For determination of the solubility of curcumin the oils (Arachis Oil, Castor oil, Cinnamon oil, Clove oil, Corn oil, Olive oil, TPGS: Sefsol-218 Oil (1:1), Sunflower oil and Tea tree oil ), surfactants (Span 80, Tween 20, tween 60 and tween 80) and cosurfactants (Glycerol, Labrafac, Lauroglycol FCC, PEG 600 and Solutol HS 15) were taken in 5 ml stoppered vials and drug in excess quantities was put in the oils, surfactants and cosurfactants to produce supersaturated solutions and using a vortex mixer kept at 25±1°C in an incubator shaker mixed for 72h for the attainment of equilibrium, after which the samples were centrifuged for 15 min at 3000 rpm. The supernatant was collected after filtration through a 0.45µm membrane filter diluted with methanol if necessary and analysed by UV spectrophotometer at 420 nm. The experiment was done in triplicate. Miscibility studies were also performed to select the cosurfactants. For the conduct of the miscibility study, surfactant and co-surfactant were mixed in the ratio of 1:1 in 5ml vials with the help of a vortex mixer. These vials were then kept at 25±1°C in an incubator shaker for 72h for attaining equilibrium. After 72h the vials were kept overnight to ascertain the miscibility of the surfactants and co surfactants5. To confirm the miscibility, visual observations were done. The transparent or clear mixtures were considered for other studies.

Construction of Pseudoternary phase diagrams for formulation selection

For the formulation of nanoemulsions, an aqueous titration method was used and pseudo ternary phase diagrams were constructed with water, a mixture of surfactant and cosurfactant (Smix) as well as the oil phase. TheSmix was made in different ratios (1:1, 2:1, 3:1, 4:1, 5:1) by increasing the amount of surfactant added. Fourteen combinations of oil :Smix ratios (1:9, 1:8, 1:7, 1:6, 1:5, 1:4, 1:3.5, 1:3, 3:7, 1:2, 4:6, 7:3, 8:2, 9:1) were made. The aqueous phase was used for carrying out slow titration for all ratios of oil &Smix. The titrations were continued till a clear, transparent low viscosity nanoemulsion was obtained. The formulated nanoemulsions were kept undisturbed for 24 h to attain equilibrium and to eliminate metastable formulations.6 From the phase diagrams constructed, different combinations of placebo formulations were selected based on the presence of the minimum quantity of oil that could solubilise the drug dose and the minimum Smix quantity. For drug-containing nanoemulsions, the same procedure was followed except for the incorporation of the drug.  

Thermodynamic stability studies                                         

These stability studies are a very integral part of nanoemulsion formulation development as they help in choosing the nanoemulsions which are stable and also help in eliminating the metastable and unstable formulations. The following thermodynamic studies were done for the drug-loaded nanoemulsions.7

Centrifugation study

In the centrifugation study, nanoemulsions were centrifuged at 25°C and 3000 rpm for 30 mins after which the presence of any physical instability, creaming or cracking them was Ssesses visually. 

Heating cooling cycle

            After passing the centrifugation study, the nanoemulsions were assessed for stability by performing the heating-cooling cycle. The temperature variation effect on nanoemulsion stability was checked by keeping the formulations between refrigerator temperature 4°C and 40°C for six cycles, with storage of not less than 48 hrs at each temperature.

Freeze-thaw cycle

            Further stability was assessed by freeze-thaw cycle in which the nanoemulsions were kept at -21°C and +25°C with storage for not less than 48 hrs at each temperature.

Characterization of Nanoemulsion

The optimized telmisartan loaded oral nanoemulsions were assessed for : 

Viscosity measurement

The nanoemulsion viscosity was evaluated by Brookfield Viscometer (Model DV-1 Prime) using spindle # 61 at 37± 0.5°C at 60 rpm. A two minutes wait time was used. The experiment was done in triplicate and the standard deviation ascertained.

pH

The pH of the nanoemulsions was checked using a digital pH meter. The experiment was done in triplicate and the standard deviation ascertained.

Percentage transmittance

For the percentage transmittance, a hundred times dilution was done for one ml of the formulation using the blank as distilled water and analyzed at 650nm by UV visible spectrophotometer (UV-1800, Shimadzu Corporation, Kyoto, Japan Shimadzu). The observations were taken in triplicate and the standard deviation was calculated.8

Refractive index

Refractive indices of the nanoemulsions were evaluated using Abbe’s refractometer. The observations were taken in triplicate and the standard deviation was calculated.

In vitro drug release and determination of release rate orders

Franz diffusion cell, with treated dialysis membrane mounted between the donor and receptor compartment, was used for the study.35 ml of acetate buffer pH 5.5:PEG 600 (6:4) was used as the release media which was maintained at 37±1°C with continuous stirring at 75 rpm. Drug loaded nanoemulsion (1 ml) was placed over the dialysis membrane in the donor compartment. Samples (3ml) were taken at 0.5,1, 1.5,2,2.5 3,3.5, 4, 5, 6, 7 and 8 hrs and analyzed by using UV spectrophotometer (Shimadzu, 1800, Japan)9. The experiments were done in triplicate.

To establish the kinetics of drug release of the formulation, data of in vitro drug release studies was plotted in different kinetic models: zero-order, First order, Higuchi model and Korsmeyer–Peppas model. The model which had the value of correlation coefficient near to 1 was confirmed to be the best fit model.10

In vitro skin permeation study and drug retention study of optimized nanoemulsion using excised rat skin

Excised rat skin was used for the study after cleaning. The skin was held between the compartments of the Franz diffusion cell. Phosphate buffer pH 7.4 with methanol (6:4)(35ml), kept at 37 ± 1 °C with stirring at 75 rpm was used as the media. The nanoemulsion(1ml) was placed over the skin in the donor compartment. Samples (5 ml) were taken at time intervals of 1,1.5, 2,2.5, 3,3.5, 4, 5, 6, 7 and 8 hrs and analyzed at 428 nm using a UV spectrophotometer (Shimadzu, 1800, Japan). A graph was plotted between the cumulative amount of nanoemulsion permeated through the Wistar rat skin (Q, µg/cm2) as a function of time (hrs). From the slope and intercept of the straight line, drug flux (Jss, µg/cm2/h) was calculated. After dividing the flux with initial drug concentration (Co)  permeability coefficient (kp) was obtained.

       Further, the formulation remaining on the skin was removed and the skin after the cleaning was weighed, cut into small pieces followed by sonication with methanol for 15 mins for extracting curcumin. The solution so obtained was centrifuged, filtered and the drug content (µg/cm2) was evaluated by using a UV spectrophotometer.

Histopathological Study

       To ascertain whether the curcumin loaded nanoemulsion was suitable for topical application histopathological study was performed. Freshly excised abdominal rat skin was taken and after washing with phosphate-buffered saline pH 7.4 mounted in a franz diffusion cell with the epidermis facing the upper side. 1ml of the nanoemulsion was placed over the skin in the donor compartment. The receptor compartment was filled with Phosphate buffer pH 7.4 with methanol (6:4) and left for 24 hours under constant magnetic stirring. After 24 hours, the rat skins were removed; blot dried and sent for histopathological evaluation using eosin and haematoxylin staining. The results were compared with those obtained for normal rat skin without the application of the formulation.

Droplet size and zeta potential

Malvern Zetasizer (Malvern, Worcestershire, UK) was used to determine the average particle size (z-average) and polydispersity index (PDI) of the developed nanoemulsion, after dilution and filtration using a 0.22µm membrane filter. The observations were taken in triplicate for each nanoemulsion evaluated.

RESULTS

Formulation Development and Optimization

Solubility Studies

The solubility of curcumin was evaluated in different oils and the results are given in Figure 1. Among the different oils evaluated, curcumin exhibited maximum solubility (8.01±0.026 mg/ml) in a combination of TPGS: Sefsol-218 Oil (1:1) and the combination was therefore chosen as the oily phase for the formulation of nanoemulsion.

The solubility of curcumin in various surfactants was evaluated as per the given procedure. Curcumin exhibited the highest solubility in Tween 60.
Based on the results of miscibility and solubility studies, Sefsol-18:TPGS (1:1), Tween 60 and Solutol HS 15were selected as oil, surfactant and cosurfactant respectively.

Construction of Pseudoternary phase diagrams for formulation selection

Placebo nanoemulsions were formulated using the chosen oil, surfactant and cosurfactants. Pseudo ternary phase diagrams were constructed for each Smix ratio prepared to identify the nanoemulsion region.

When Smix 1:0 was used (Figure 4), a reduced nanoemulsion area was observed with macroemulsions comprising most of the region in the constructed pseudo ternary phase diagrams. As the cosurfactant amount was increased from 0 to 1 (Smix 1:1), the nanoemulsion region was observed to increase. An increase in the surfactant concentration from 1:1 to 4:1in Smix increased the nanoemulsion area. The maximum nanoemulsion area was obtained with Smix 4:1.

Thermodynamic stability studies

The placebo formulations selected from pseudo ternary phase diagrams were subjected to thermodynamic studies. In those placebo nanoemulsions which remained stable, the drug was added and then the drug-loaded formulations prepared were again subjected to thermodynamic stability studies. The formulations which exhibited turbidity and phase separation were discarded as they failed the tests for physical stability. Table 1 gives the compositions of stable drug-loaded nanoemulsion formulations which were taken up for further evaluation studies.

Characterization of nanoemulsion formulations

Viscosity

The nanoemulsions exhibited viscosity in the range 17cp to 20cp.

pH

The nanoemulsions had a pH between 5 to 6, which was similar to the skinpH.

Percentage Transmittance

The percentage transmittances of all the developed formulations were found to be near 100% which confirmed the clarity and transparency of the optimized formulation.8

Refractive index

The refractive index of nanoemulsions was close to that of sefsol-218:TPGS (1:1). Since no significant difference (p<0.05) was observed in the refractive index value of placebo as well as drug-loaded nanoemulsions, the absence of any interaction between excipient and drug was confirmed.

In vitro drug release and determination of release rate orders

Thestudy was performed for comparing the curcumin release from stable formulations (A1, R8 and H1) with that of drug suspension. The results are given in Figure  1.

In vitro release of formulation A1 showed maximum release (90.10%) which was significantly higher (p< 0.05) than the formulations R8 (82.9%), H1(61.60 %) and curcumin suspension (43.90%) after 8h of study. 

Based on the observations of viscosity, refractive index, pH, percentage transmittance, and in vitro release studies, nanoemulsion A1 was chosen as an optimized formulation and further assessed for various parameters. Kinetic analysis of the in vitro data of optimized nanoemulsion (A1) done revealed that the correlation coefficient (R2) for the Higuchi model was near to unity. It was confirmed that the release of curcumin from nanoemulsion obeyed the Higuchi model.

In vitro skin permeation and drug retention study using excised rat skin

The results of the permeation studies revealed that nanoemulsion A1 exhibited an in-vitro permeation of 78.7% which was significantly higher (p<0.05) in comparison to that of the suspension of the drug which exhibited a permeation of 37.61%. The results are given in figure 2.

The results of flux (Jss), as well as permeability coefficient (kp) of formulation (A1) and suspension of drug, are given in Table 2.

The drug retention (mg) and % drug retained in the skin were determined and the results are given in Figures 3 and 4.

Histopathological Study

      The histopathological evaluation of the curcumin loaded nanoemulsion treated skin samples showed normal skin histology with the well-defined epidermis, dermis, subcutaneous tissue; similar to that of untreated skin samples. The epidermis revealed a normal stratified squamous keratinized epithelium, with no significant and remarkable evidence of necrosis or destructive changes. Thus the results of histopathological evaluation confirmed that the curcumin loaded nanoemulsion was safe as no changes were observed in the skin after application of the formulation as compared to the control skin (Figure 5).

Droplet size and zeta potential

The average particle size and polydispersity index of all the formulations was in the nano range with formulation A1 exhibiting a particle size of195.3and polydispersity index of 0.153 respectively. Zeta potential for formulation A1 was -17.51± 0.121 which was between -30mV to +30mVand confirmed the stability of the nanoemulsion.

DISCUSSION

For the selection of oil for the formulation of nanoemulsion, the most important factor to be taken into consideration is the drug solubility in the selected oil. For the drug to be and remain in a solubilised form in the nanoemulsion, the oil solubility of the drug is a very important consideration (Bali et al., 2010). Among the different oils evaluated, curcumin exhibited maximum solubility (8.01±0.026 mg/ml) in a combination of TPGS: Sefsol-218 Oil (1:1) and the combination was therefore chosen as the oil phase for the formulation of nanoemulsion.9,10

Surfactants and cosurfactants have a very important role to play in the formulation of nanoemulsions. They are reported to decrease the free energy required for the formulation of emulsion and thereby improve the thermodynamic stability of the nanoemulsion.11 They also form a flexible lipophilic film around the globules and thereby prevent their coalescence. Among the different cosurfactants evaluated curcumin exhibited maximum solubility in Tween 60 and was therefore chosen for further studies.

Cosurfactants are also a very important component of the nanoemulsion formulation. Although they are beneficial when used at a proper concentration, using them at high concentrations makes the system unstable with increased globule size.12 Among the different cosurfactants evaluated curcumin exhibited maximum solubility in Solutol HS 15 and was therefore chosen for further studies. Based on the results of miscibility and solubility studies, Sefsol-18:TPGS (1:1), Tween 60 and Solutol HS 15were chosen for the nanoemulsion formulation.

            For each Smix ratio, Pseudoternary phase diagrams were prepared to identify the nanoemulsion region. When Smix 1:0 was used (Figure 4), a reduced nanoemulsion area was observed with macroemulsions comprising most of the region in the constructed pseudo ternary phase diagrams. The observations suggested the inability of the surfactant alone to solubilise the oil, because of which the interfacial tension did not decrease to low levels sufficiently which in turn led to the production of a non-homogeneous solution.15,16 As the cosurfactant amount was enhanced from 0 to 1 (Smix 1:1), an enhancement in the nanoemulsion region was seen, which could be attributed to the higher and better penetration of the oil phase in the hydrophilic portion of the surfactant monomers which in turn caused a reduction in the interfacial tension which in turn enhanced the fluidity of the interface with an increase in the system entropy. An increase in the surfactant concentration from 1:1 to 4:1 in Smix increased the nanoemulsion area. The maximum nanoemulsion area was obtained with Smix 4:1. This was attributed to increased solubilisation of oil, decreased interfacial tension which resulted in increased fluidity and formulation of a flexible film around the oil globules of the dispersed phase and enhanced entropy of the formulated system.12,13

The drug-loaded formulations prepared were subjected to thermodynamic stability studies. The formulations which exhibited turbidity and phase separation were discarded as they failed the tests for physical stability. Two reasons namely Ostwald ripening and temperature quenching occurring due to segregation of oily phase as well as distribution of small size droplets supported by alteration in curvature free energy were attributed for instability in the system.14The nanoemulsions that passed the studies were chosen for further studies.

The viscosities of various formulations were optimum. The viscosity, if optimum of nanoemulsion meant for topical administration, aids in its easy application on the skin. Undesirable effects which can cause skin irritancy can result in case the pH of the topical formulation is not similar to that of the skin. All three nanoemulsion formulations had a  pH between 5-6. The percentage transmittance values of various nanoemulsions were found to be close to 100%. Higher percentage transmittance indicated a more clear and transparent nanoemulsion.

            The formulations exhibited a refractive index close to that of sefsol -218:TPGS (1:1). The absence of any interaction between excipient and drug was confirmed due to the absence of any significant difference between the placebo and drug-loaded nanoemulsions. In vitro release of formulation A1 showed maximum release (90.10%) which was significantly higher (p< 0.05) than the formulations R8 (82.9%), H1(61.60 %) and curcumin suspension (43.90%) after 8h of study.  The enhanced drug release from the nanoemulsion in comparison to the curcumin suspension could be attributed to the nanosize of the developed formulation, which in turn resulted in increased release of the drug from the nanoemulsion.14,15

            From the results of in vitro skin permeation studies, maximum permeation of Curcumin (78.7%) was detected for the formulation A1 which was significantly higher (p≤0.05) than the Curcumin suspension (37.61%) after 8 h study. The flux 143.7 (µg/cm2/h) and permeability coefficient 9.58×10-2 of A1 nanoemulsion were significantly higher (p≤0.05) as compared to drug suspension which exhibited 65.85 µg/cm2/h flux and 4.39×10-2 permeability coefficient. The reason could be attributed to the nanosize of the formulation.16

From the above results, a significantly higher (p≤0.05) amount of Curcumin was localized into the skin after application of nanoemulsion formulation (7.46) in comparison to drug suspension (3.73). The higher retention of the nanoemulsion formulation (A1)  in the skin could be attributed to the greater extraction efficiency of skin lipids.15,16 The results of the study confirmed that the formulation was safe for topical application, which could be attributed to the use of excipients that were in GRAS (Generally regarded as Safe ) category.

Droplet size analysis is a critical factor influencing the stability and absorption of nanoemulsion. The smaller the droplet size, the larger the interfacial surface which leads to greater absorption. The average particle size and polydispersity index of all the formulations was in the nano range with formulation A1 exhibiting a particle size of195.3 and polydispersity index of 0.153 respectively.17,18 Since the stability of nanoemulsions is directly related to the surface charge, 16 determination of zeta potential is a very important characterization parameter for nanoemulsions. Instability in nanoemulsions occurs when the electrostatic repulsive forces decrease. Zeta potential for formulation A1 was -17.51± 0.121 indicating that the nanoemulsion was stable.

CONCLUSION

The curcumin-loaded nanoemulsion was successfully formulated with satisfactory pH, viscosity, refractive index, in-vitro drug release and in-vitro permeation. The formulation has the potential for topical application for the treatment of various skin diseases.

Conflict of interest: None

The Ethical Clarence has been taken from the Institutional Ethical cum Research board with vide letter no. SGR/2019-51- 20.

References:

  1. Ahmad N, Ahmad R, Al-Qudaihi A, Alaseel SE, Fita IZ, Mohammed Saifuddin Khali MS and Pottoo FH.Preparation of a novel curcumin nanoemulsion by ultrasonication and its comparative effects in wound healing and the treatment of inflammation. RSC Adv 2019;9:20192-20206.

  2. Teichmann A, Heuschkel S, Jacobi U, Presse G, Neubert RH, Sterry W, et al. Comparison of stratum corneum penetration and localization of a lipophilic model drug applied in an o/w microemulsion and an amphiphilic cream. Eur J Pharm Biopharm 2007;67(3):699–706.

  3. Ahmad N, Alam MA, Ahmad FJ, Sarafroz M, Ansari K, Sharma S, Amir M.Ultrasonication techniques used for the preparation of novel eugenol–nanoemulsion in the treatment of wounds healings and anti-inflammatory. J Drug Del Sci Technol 2018;46:461–473.

  4. Anwer MK, Jamil S, Ibnouf EO, Shakeel F. Enhanced antibacterial effects of clove essential oil by nanoemulsion. J Oleo Sci 2014;63:347–354.

  5. Bali V, Ali M, Ali, J. Study of surfactant combinations and development of a novel nanoemulsion for minimising variations in bioavailability of ezetimibe. Colloids Surf B Biointerfaces 2010;76:410-420.

  6. Sharma S, Sahni JK, Ali J. Effect of high-pressure homogenization on formulation of TPGS loaded nanoemulsion of rutin – Pharmacodynamic and antioxidant studies. J Drug Del Sci Technol 2014;22(4):1-11.

  7. Mishra RK, Soni GC, Mishra RP. Nanoemulsion: A review article. World J Pharm Sci 2014;3(9):258-274.

  8. Wani RR, Patil MP, Chaudhari CA, Dhurjad PK, Shirsagar SJ. Microemulsion based gel: A novel approach in the delivery of hydrophobic drugs. Int J Pharm Res Scholars 2015;4(2):397-410.

  9. Kharwade RS, Mahajan NM. Formulation and Evaluation of Nanostructured Lipid Carriers Based Anti-Inflammatory Gel for Topical Drug Delivery System. Asian J Pharm Clin Res 2019;12(4):286–291.

  10. Bhagat KA, Bhura MRG, Shah SK. Formulation and evaluation of topical nanoemulgel of adapalene.World J Pharm Sci 2015;3(4):1013-1024.

  11. Dhawan B, Aggarwal G, Harikumar SL. Enhanced transdermal permeability of piroxicam through novel nanoemulgel formulation. Int J Pharm Invest 2015;4(2):65-76.

  12. Groves MJ, Mustafa RMA, Carless JE.  Phase studies of mixed phosphate surfactants, n-hexane and water. J Pharm Pharmacol 1974;26:616–623.

  13. Zhang QZ, Jiang XG, Jiang WM, Lu W, Su LN, Shi ZQ. Preparation of nimodipine-loaded microemulsion for intranasal delivery and evaluation on the targeting efficiency to the brain. Int J Pharm 2004;275:85-96.

  14. Baboota S, Alazki A, Kohli K, Ali J, Dixit N, Shakeel F. Development and evaluation of a microemulsion formulation for transdermal delivery of terbinafine. J Pharm Sci Technol 2007;61:276-285.

  15. Mate A, Ade P, Kharwade R, Pise S, More S. Formulation and evaluation of polyherbal gel for the management of acne. 2021;13(4):116-119.

  16. Wennerstrom H, Olsson U. Microemulsion as model systems. CR Chim 2009;12:4–17.

  17. Hussain A, Samad A, Singh SK, Ahsan MN, Faruk A, Ahmed FJ. Enhanced stability and permeation potential of nanoemulsion containing sefsol-218 oil for topical delivery of amphoterecin-B. Drug Dev Indust Pharm 2015;41(5):780-790.

  18. Ahmad J, Kohli K, Mir SR, Amin S. Formulation of Self –Nanoemulsifying Drug Delivery System for Telmisartan with improved dissolution and oral bioavailability. J Disper Sci Technol 2011;32:958-968.

Announcements

Dr. Pramod Kumar Manjhi joined Editor-in-Chief since July 2021 onwards

COPE guidelines for Reviewers

SCOPUS indexing: 2014, 2019 to 2021


Awards, Research and Publication incentive Schemes by IJCRR

Best Article Award: 

One article from every issue is selected for the ‘Best Article Award’. Authors of selected ‘Best Article’ are rewarded with a certificate. IJCRR Editorial Board members select one ‘Best Article’ from the published issue based on originality, novelty, social usefulness of the work. The corresponding author of selected ‘Best Article Award’ is communicated and information of award is displayed on IJCRR’s website. Drop a mail to editor@ijcrr.com for more details.

Women Researcher Award:

This award is instituted to encourage women researchers to publish her work in IJCRR. Women researcher, who intends to publish her research work in IJCRR as the first author is eligible to apply for this award. Editorial Board members decide on the selection of women researchers based on the originality, novelty, and social contribution of the research work. The corresponding author of the selected manuscript is communicated and information is displayed on IJCRR’s website. Under this award selected women, the author is eligible for publication incentives. Drop a mail to editor@ijcrr.com for more details.

Emerging Researcher Award:

‘Emerging Researcher Award’ is instituted to encourage student researchers to publish their work in IJCRR. Student researchers, who intend to publish their research or review work in IJCRR as the first author are eligible to apply for this award. Editorial Board members decide on the selection of student researchers for the said award based on originality, novelty, and social applicability of the research work. Under this award selected student researcher is eligible for publication incentives. Drop a mail to editor@ijcrr.com for more details.


Best Article Award

A Study by Humaira Tahir et al. entitled "Comparison of First Analgesic Demand after Major Surgeries of Obstetrics and Gynecology between Pre-Emptive Versus Intra-Operative Groups by Using Intravenous Paracetamol: A Cross-Sectional Study" is awarded Best Article for Vol 14 issue 14
A Study by Monica K. entitled "Risk Predictors for Lymphoma Development in Sjogren Syndrome - A Systematic Review" is awarded Best Article for Vol 14 issue 13
A Study by Mokhtar M Sh et al. entitled "Prevalence of Hospital Mortality of Critically Ill Elderly Patients" is awarded Best Article for Vol 14 issue 12
A Study by Vidya S. Bhat et al. entitled "Effect of an Indigenous Cleanser on the Microbial Biofilm on Acrylic Denture Base - A Pilot Study" is awarded Best Article for Vol 14 issue 11
A Study by Pandya S. et al. entitled "Acute and 28-Day Repeated Dose Subacute Toxicological Evaluation of Coroprotect Tablet in Rodents" is awarded Best Article for Vol 14 issue 10
A Study by Muhammad Zaki et al. entitled "Effect of Hemoglobin Level on the Severity of Acute Bronchiolitis in Children: A Case-Control Study" is awarded Best Article for Vol 14 issue 09
A Study by Vinita S & Ayushi S entitled "Role of Colour Doppler and Transvaginal Sonography for diagnosis of endometrial pathology in women presenting with Abnormal Uterine Bleeding" is awarded Best Article for Vol 14 issue 08
A Study by Prabhu A et al. entitled "Awareness of Common Eye Conditions among the ASHA (Accredited Social Health Activist) Workers in the Rural Communities of Udupi District- A Pilot Study" is awarded Best Article for Vol 14 issue 07
A Study by Divya MP et al. entitled "Non-Echoplanar Diffusion-Weighted Imaging and 3D Fiesta Magnetic Resonance Imaging Sequences with High Resolution Computed Tomography Temporal Bone in Assessment and Predicting the Outcome of Chronic Suppurative Otitis Media with Cholesteatoma" is awarded Best Article for Vol 14 issue 06
A Study by Zahoor Illahi Soomro et al. entitled "Functional Outcomes of Fracture Distal Radius after Fixation with Two Different Plates: A Retrospective Comparative Study" is awarded Best Article for Vol 14 issue 05
A Study by Ajai KG & Athira KN entitled "Patients’ Gratification Towards Service Delivery Among Government Hospitals with Particular Orientation Towards Primary Health Centres" is awarded Best Article for Vol 14 issue 04
A Study by Mbungu Mulaila AP et al. entitled "Ovarian Pregnancy in Kindu City, D.R. Congo - A Case Report" is awarded Best Article for Vol 14 issue 03
A Study by Maryam MJ et al. entitled "Evaluation Serum Chemerin and Visfatin Levels with Rheumatoid Arthritis: Possible Diagnostic Biomarkers" is awarded Best Article for Vol 14 issue 02
A Study by Shanthan KR et al. entitled "Comparison of Ultrasound Guided Versus Nerve Stimulator Guided Technique of Supraclavicular Brachial Plexus Block in Patients Undergoing Upper Limb Surgeries" is awarded Best Article for Vol 14 issue 01
A Study by Amol Sanap et al. entitled "The Outcome of Coxofemoral Bypass Using Cemented Bipolar Hemiarthroplasty in the Treatment of Unstable Intertrochanteric Fracture of Femur in a Rural Setup" is awarded Best Article Award of Vol 13 issue 24
A Study by Manoj KP et al. entitled "A Randomized Comparative Clinical Trial to Know the Efficacy of Ultrasound-Guided Transversus Abdominis Plane Block Against Multimodal Analgesia for Postoperative Analgesia Following Caesarean Section" is awarded Best Article Award of Vol 13 issue 23
A Study by Karimova II et al. entitled "Changes in the Activity of Intestinal Carbohydrases in Alloxan-Induced Diabetic Rats and Their Correction with Prenalon" is awarded Best Article of Vol 13 issue 22
A Study by Ashish B Roge et al. entitled "Development, Validation of RP-HPLC Method and GC MS Analysis of Desloratadine HCL and It’s Degradation Products" is awarded Best Article of Vol 13 issue 21
A Study by Isha Gaurav et al. entitled "Association of ABO Blood Group with Oral Cancer and Precancer – A Case-control Study" is awarded Best Article for Vol 13 issue 20
A Study by Amr Y. Zakaria et al. entitled "Single Nucleotide Polymorphisms of ATP-Binding Cassette Gene(ABCC3 rs4793665) affect High Dose Methotrexate-Induced Nephrotoxicity in Children with Osteosarcoma" is awarded Best Article for Vol 13 issue 19
A Study by Kholis Ernawati et al. entitled "The Utilization of Mobile-Based Information Technology in the Management of Dengue Fever in the Community Year 2019-2020: Systematic Review" is awarded Best Article for Vol 13 issue 18
A Study by Bhat Asifa et al. entitled "Efficacy of Modified Carbapenem Inactivation Method for Carbapenemase Detection and Comparative Evaluation with Polymerase Chain Reaction for the Identification of Carbapenemase Producing Klebsiella pneumonia Isolates" is awarded Best Article for Vol 13 issue 17
A Study by Gupta R. et al. entitled "A Clinical Study of Paediatric Tracheostomy: Our Experience in a Tertiary Care Hospital in North India" is awarded Best Article for Vol 13 issue 16
A Study by Chandran Anand et al. entitled "A Prospective Study on Assessment of Quality of Life of Patients Receiving Sorafenib for Hepatocellular Carcinoma" is awarded Best article for Vol 13 issue 15
A Study by Rosa PS et al. entitled "Emotional State Due to the Covid – 19 Pandemic in People Residing in a Vulnerable Area in North Lima" is awarded Best Article for Vol 13 issue 14
A Study by Suvarna Sunder J et al. entitled "Endodontic Revascularization of Necrotic Permanent Anterior Tooth with Platelet Rich Fibrin, Platelet Rich Plasma, and Blood Clot - A Comparative Study" is awarded Best Article for Vol 13 issue 13
A Study by Mona Isam Eldin Osman et al. entitled "Psychological Impact and Risk Factors of Sexual Abuse on Sudanese Children in Khartoum State" is awarded Best Article for Vol 13 issue 12
A Study by Khaw Ming Sheng & Sathiapriya Ramiah entitled "Web Based Suicide Prevention Application for Patients Suffering from Depression" is awarded Best Article for Vol 13 issue 11
A Study by Purushottam S. G. et al. entitled "Development of Fenofibrate Solid Dispersions for the Plausible Aqueous Solubility Augmentation of this BCS Class-II Drug" is awarded Best article for Vol 13 issue 10
A Study by Kumar S. et al. entitled "A Study on Clinical Spectrum, Laboratory Profile, Complications and Outcome of Pediatric Scrub Typhus Patients Admitted to an Intensive Care Unit from a Tertiary Care Hospital from Eastern India" is awarded Best Article for Vol 13 issue 09
A Study by Mardhiah Kamaruddin et al. entitled "The Pattern of Creatinine Clearance in Gestational and Chronic Hypertension Women from the Third Trimester to 12 Weeks Postpartum" is awarded Best Article for Vol 13 issue 08
A Study by Sarmila G. B. et al. entitled "Study to Compare the Efficacy of Orally Administered Melatonin and Clonidine for Attenuation of Hemodynamic Response During Laryngoscopy and Endotracheal Intubation in Gastrointestinal Surgeries" is awarded Best Article for Vol 13 issue 07
A Study by M. Muthu Uma Maheswari et al. entitled "A Study on C-reactive Protein and Liver Function Tests in Laboratory RT-PCR Positive Covid-19 Patients in a Tertiary Care Centre – A Retrospective Study" is awarded Best Article of Vol 13 issue 06 Special issue Modern approaches for diagnosis of COVID-19 and current status of awareness
A Study by Gainneos PD et al. entitled "A Comparative Evaluation of the Levels of Salivary IgA in HIV Affected Children and the Children of the General Population within the Age Group of 9 – 12 Years – A Cross-Sectional Study" is awarded Best Article of Vol 13 issue 05 Special issue on Recent Advances in Dentistry for better Oral Health
A Study by Alkhansa Mahmoud et al. entitled "mRNA Expression of Somatostatin Receptors (1-5) in MCF7 and MDA-MB231 Breast Cancer Cells" is awarded Best Article of Vol 13 issue 06
A Study by Chen YY and Ghazali SRB entitled "Lifetime Trauma, posttraumatic stress disorder Symptoms and Early Adolescence Risk Factors for Poor Physical Health Outcome Among Malaysian Adolescents" is awarded Best Article of Vol 13 issue 04 Special issue on Current Updates in Plant Biology to Medicine to Healthcare Awareness in Malaysia
A Study by Kumari PM et al. entitled "Study to Evaluate the Adverse Drug Reactions in a Tertiary Care Teaching Hospital in Tamilnadu - A Cross-Sectional Study" is awarded Best Article for Vol 13 issue 05
A Study by Anu et al. entitled "Effectiveness of Cytological Scoring Systems for Evaluation of Breast Lesion Cytology with its Histopathological Correlation" is awarded Best Article of Vol 13 issue 04
A Study by Sharipov R. Kh. et al. entitled "Interaction of Correction of Lipid Peroxidation Disorders with Oxibral" is awarded Best Article of Vol 13 issue 03
A Study by Tarek Elwakil et al. entitled "Led Light Photobiomodulation Effect on Wound Healing Combined with Phenytoin in Mice Model" is awarded Best Article of Vol 13 issue 02
A Study by Mohita Ray et al. entitled "Accuracy of Intra-Operative Frozen Section Consultation of Gastrointestinal Biopsy Samples in Correlation with the Final Histopathological Diagnosis" is awarded Best Article for Vol 13 issue 01
A Study by Badritdinova MN et al. entitled "Peculiarities of a Pain in Patients with Ischemic Heart Disease in the Presence of Individual Combines of the Metabolic Syndrome" is awarded Best Article for Vol 12 issue 24
A Study by Sindhu Priya E S et al. entitled "Neuroprotective activity of Pyrazolone Derivatives Against Paraquat-induced Oxidative Stress and Locomotor Impairment in Drosophila melanogaster" is awarded Best Article for Vol 12 issue 23
A Study by Habiba Suhail et al. entitled "Effect of Majoon Murmakki in Dysmenorrhoea (Usre Tams): A Standard Controlled Clinical Study" is awarded Best Article for Vol 12 issue 22
A Study by Ghaffar UB et al. entitled "Correlation between Height and Foot Length in Saudi Population in Majmaah, Saudi Arabia" is awarded Best Article for Vol 12 issue 21
A Study by Siti Sarah Binti Maidin entitled "Sleep Well: Mobile Application to Address Sleeping Problems" is awarded Best Article for Vol 12 issue 20
A Study by Avijit Singh"Comparison of Post Operative Clinical Outcomes Between “Made in India” TTK Chitra Mechanical Heart Valve Versus St Jude Mechanical Heart Valve in Valve Replacement Surgery" is awarded Best Article for Vol 12 issue 19
A Study by Sonali Banerjee and Mary Mathews N. entitled "Exploring Quality of Life and Perceived Experiences Among Couples Undergoing Fertility Treatment in Western India: A Mixed Methodology" is awarded Best Article for Vol 12 issue 18
A Study by Jabbar Desai et al. entitled "Prevalence of Obstructive Airway Disease in Patients with Ischemic Heart Disease and Hypertension" is awarded Best Article for Vol 12 issue 17
A Study by Juna Byun et al. entitled "Study on Difference in Coronavirus-19 Related Anxiety between Face-to-face and Non-face-to-face Classes among University Students in South Korea" is awarded Best Article for Vol 12 issue 16
A Study by Sudha Ramachandra & Vinay Chavan entitled "Enhanced-Hybrid-Age Layered Population Structure (E-Hybrid-ALPS): A Genetic Algorithm with Adaptive Crossover for Molecular Docking Studies of Drug Discovery Process" is awarded Best article for Vol 12 issue 15
A Study by Varsha M. Shindhe et al. entitled "A Study on Effect of Smokeless Tobacco on Pulmonary Function Tests in Class IV Workers of USM-KLE (Universiti Sains Malaysia-Karnataka Lingayat Education Society) International Medical Programme, Belagavi" is awarded Best article of Vol 12 issue 14, July 2020
A study by Amruta Choudhary et al. entitled "Family Planning Knowledge, Attitude and Practice Among Women of Reproductive Age from Rural Area of Central India" is awarded Best Article for special issue "Modern Therapeutics Applications"
A study by Raunak Das entitled "Study of Cardiovascular Dysfunctions in Interstitial Lung Diseas epatients by Correlating the Levels of Serum NT PRO BNP and Microalbuminuria (Biomarkers of Cardiovascular Dysfunction) with Echocardiographic, Bronchoscopic and HighResolution Computed Tomography Findings of These ILD Patients" is awarded Best Article of Vol 12 issue 13 
A Study by Kannamani Ramasamy et al. entitled "COVID-19 Situation at Chennai City – Forecasting for the Better Pandemic Management" is awarded best article for  Vol 12 issue 12
A Study by Muhammet Lutfi SELCUK and Fatma entitled "Distinction of Gray and White Matter for Some Histological Staining Methods in New Zealand Rabbit's Brain" is awarded best article for  Vol 12 issue 11
A Study by Anamul Haq et al. entitled "Etiology of Abnormal Uterine Bleeding in Adolescents – Emphasis Upon Polycystic Ovarian Syndrome" is awarded best article for  Vol 12 issue 10
A Study by entitled "Estimation of Reference Interval of Serum Progesterone During Three Trimesters of Normal Pregnancy in a Tertiary Care Hospital of Kolkata" is awarded best article for  Vol 12 issue 09
A Study by Ilona Gracie De Souza & Pavan Kumar G. entitled "Effect of Releasing Myofascial Chain in Patients with Patellofemoral Pain Syndrome - A Randomized Clinical Trial" is awarded best article for  Vol 12 issue 08
A Study by Virendra Atam et. al. entitled "Clinical Profile and Short - Term Mortality Predictors in Acute Stroke with Emphasis on Stress Hyperglycemia and THRIVE Score : An Observational Study" is awarded best article for  Vol 12 issue 07
A Study by K. Krupashree et. al. entitled "Protective Effects of Picrorhizakurroa Against Fumonisin B1 Induced Hepatotoxicity in Mice" is awarded best article for issue Vol 10 issue 20
A study by Mithun K.P. et al "Larvicidal Activity of Crude Solanum Nigrum Leaf and Berries Extract Against Dengue Vector-Aedesaegypti" is awarded Best Article for Vol 10 issue 14 of IJCRR
A study by Asha Menon "Women in Child Care and Early Education: Truly Nontraditional Work" is awarded Best Article for Vol 10 issue 13
A study by Deep J. M. "Prevalence of Molar-Incisor Hypomineralization in 7-13 Years Old Children of Biratnagar, Nepal: A Cross Sectional Study" is awarded Best Article for Vol 10 issue 11 of IJCRR
A review by Chitra et al to analyse relation between Obesity and Type 2 diabetes is awarded 'Best Article' for Vol 10 issue 10 by IJCRR. 
A study by Karanpreet et al "Pregnancy Induced Hypertension: A Study on Its Multisystem Involvement" is given Best Paper Award for Vol 10 issue 09

List of Awardees

A Study by Ese Anibor et al. "Evaluation of Temporomandibular Joint Disorders Among Delta State University Students in Abraka, Nigeria" from Vol 13 issue 16 received Emerging Researcher Award


A Study by Alkhansa Mahmoud et al. entitled "mRNA Expression of Somatostatin Receptors (1-5) in MCF7 and MDA-MB231 Breast Cancer Cells" from Vol 13 issue 06 received Emerging Researcher Award


RSS feed

Indexed and Abstracted in


Antiplagiarism Policy: IJCRR strongly condemn and discourage practice of plagiarism. All received manuscripts have to pass through "Plagiarism Detection Software" test before Toto Macau forwarding for peer review. We consider "Plagiarism is a crime"

IJCRR Code of Conduct: To achieve a high standard of publication, we adopt Good Publishing Practices (updated in 2022) which are inspired by guidelines provided by Committee on Publication Ethics (COPE), Open Access Scholarly Publishers Association (OASPA) and International Committee of Medical Journal Editors (ICMJE)

Disclaimer: International Journal of Current Research and Review (IJCRR) provides platform for researchers to publish and discuss their original research and review work. IJCRR can not be held responsible for views, opinions and written statements of researchers published in this journal.



ABOUT US

International Journal of Current Research and Review (IJCRR) provides platform for researchers to publish and discuss their original research and review work. IJCRR can not be held responsible for views, opinions and written statements of researchers published in this journal

Contact

148, IMSR Building, Ayurvedic Layout,
        Near NIT Complex, Sakkardara,
        Nagpur-24, Maharashtra State, India

editor@ijcrr.com

editor.ijcrr@gmail.com


Copyright © 2022 IJCRR. Specialized online journals by ubijournal .Website by Ubitech solutions


Fatal error: Uncaught Error: Function name must be a string in /home/u845032518/domains/ijcrr.com/public_html/footer-bottom.php:487 Stack trace: #0 /home/u845032518/domains/ijcrr.com/public_html/article_html.php(51): include() #1 {main} thrown in /home/u845032518/domains/ijcrr.com/public_html/footer-bottom.php on line 487