Bioactivity, Analytical Techniques and Formulative approaches for Embelin

 

Elizabeth N. Xavier1, Jashna K. Kani2

1Assistant Professor, Department of Pharmaceutics, Nirmala College of Pharmacy,

Muvattupuzha, Ernakulam (Dist), Kerala, 686661.

2Student, M Pharm Pharmaceutics, Nirmala College of Pharmacy,

Muvattupuzha, Ernakulam (Dist), Kerala, 686661.

*Corresponding Author E-mail: jashna92@gmail.com

 

ABSTRACT:

Embelia ribes or black pepper contains many bioactive constituents of pharmaceutical importance. It contains alkaloids, tannins, fixed oils, and traces of volatile oils and benzoquinone derivative Embelin. Embelin (2,5- dihydroxy 3-undecyl, 1, 4-benzoquinone), a benzoquinone derivative has reported to have anticancer, anti-inflammatory, antimicrobial, anti-diabetic, wound healing, antioxidant, analgesic, antitumor and anthelmintic activities. Due to poor aqueous solubility, bioavailability its therapeutic potential is not fully utilized. This review summarises recent literature on biological, analytical and formulative aspects of EMB. Proposed mechanisms for various bioactivities of EMB are brought under limelight. UV double beam spectrophotometry, thin layer chromatography, high performance liquid chromatography (HPLC) and HPTLC techniques for EMB quantification are discussed. Types of dosage forms and its potential for controlled and targeted delivery of EMB are also discussed. This review will open the ways for development of an optimum formulation of EMB for its reported biological activities.

 

KEYWORDS: Embelin (EMB), bioavailability, solubility, formulations, controlled and targeted drug delivery.

 

 


INTRODUCTION:

The use of natural products gained significant popularity globally over the past few decades due to their potential health benefits. Natural products are often perceived as less toxic compared to synthetically derived products[1]. Embelia ribes Burm. f, as an important medicinal plant, has been used extensively in many Ayurvedic medicines for the treatment of various diseases over a long period of time.[2,3] It belongs to the family Myrsinaceae. It is medicinal woody climber commonly known as vidang or black pepper. This species is seen to be vulnerable in the Western Ghats of Tamil Nadu and Karnataka states of India and at a lower risk in Kerala state of peninsular India. E. ribes grows in semi-evergreen and deciduous forests at an altitude of 1,500 m, throughout India.[4]

EMB has been reported to possess many pharmacological effects including antifertility[5], analgesic, anti-inflammatory[6], antioxidant, anti-diabetic [7,8], hepato-protective[9], anticonvulsant[10], anxiolytic[11], and antimicrobial activity[12]. The main parts of plants used include fruits (berries), roots and leaf, to cure various diseases. It has also found a valuable role in different diseases like Huntington disease, myocardial infarction, acute respiratory distress syndrome and ulcerative colitis.

 

Chemistry:

Chemical composition of Embelia ribes consist of embelin (2.3%), quercitol (1.0%), an alkaloid christembine; tannin; vilangin (methylene-bis-2-5-dihydroxy-4-undecyl 3-6-benzoquinone) from ripe fruit berries and fatty ingredients (5.2%), including resinoid, fixed oil and traces of volatile oil[13]. Phytochemical investigation resulted in three new compounds namely embelinol, embelia ribyl ester and embeliol. Along with high carbohydrates the seeds of E.ribes showed the presence of Cr, K, Ca, Cu, Zn and Mn[15].

Constituents of Embelia ribes

 

Fig 1: Embelin

 

Fig 2: Embeliol

CH2(CH2)23CH2OCO(CH2)5CH=CHCH(OH)(CH2)9CH3

 

EMB (C17H26O4, molecular weight: 294.29g/mol; orange-yellow solid of melting point 142.5°C) is virtually insoluble in water (log P 4.34) but soluble in polar organic solvents such as DMSO and diethylether [14]. SAR studies revealed that anticancer activity of EMB analogues is dependent on polarity of the side chain[16]. EMB forms binary complexes with biologically important metal ions such as (Co (II), Ni(II), Cu(II) and Zn(II)[17].

 

Bioactivity:

EMB has an ability to affect multiple biological targets and exhibit activity against various diseases, like cancer, diabetes, neurological and autoimmune diseases. It has antimicrobial and wound healing activity. Through several mechanism like apoptosis, anti-proliferation, pro-inflammatory cytokines/mediators and cell-cycle arrest, EMB modulate several biological targets. EMB modulates tumor growth via autophagy, caspase pathways[18].

 

Anti-Cancer:

Proposed mechanisms of the potential anticancer activities of EMB are through apoptosis, anti- proliferation, anti-metastasis and anti- angiogenesis.[19]. EMB blocks prostate cancer cell migration and invasion. EMB induces mitochondrial-dependent apoptosis[20]. EMB enhances therapeutic efficacy by radiation therapy in human prostate cancer PC-3 both in vitro and in vivo. EMB combined with X-ray radiation, has shown to increase the tumor growth inhibition and apoptosis, which is accompanied by the EMB-induced cell cycle arrest in S-phase[21]. In another study EMB causes apoptosis in a dose-and time-dependent manner. The mitochondria and lysosomes are main targets of EMB-induced cell death response. It leads to loss of mitochondrial membrane potential[22].

 

 

Wound healing:

Phytoconstituent with wound healing activity showed more effect in diabetic patients when encapsulated as nanoparticles[23]. Study shows that the epithelialization of the incision wound was faster with a high rate of wound contraction. The tensile strength of incision wound, weight of granulation collagen content also increased.[24]

 

Anti-inflammatory:

EMB showed suppressed edema and mucosal damage, inhibited abnormal secretion, and m-RNA expression of inflammatory cytokines such as TN-α and IL-6. EMB showed maximum anti-inflammatory effect at colon rectal regions due to the down regulation of production and expression of inflammatory mediators[6].

 

Anti-Diabetic:

Meta-analysis data supports that EMB shows significant anti-diabetic activity by considering restoration of insulin, lipid profile, heamodynamic parameters, serum and oxidative stress markers[25]. Significant reduction in the serum blood glucose level and improvement in the body mass was observed in EMB treated, alloxan induced diabetic rats.[7,8].

 

Anti-microbial:

EMB showed bactericidal activity against Gram positive organisms, whereas against Gram negative organisms it showed bacteriostatic activity[26]. EMB at sub inhibitory concentrations possesses synergy with oxacillin and tetracycline against antibiotic resistant strains of S.aureus. EMB act as tetracycline efflux inhibitor in bacterial cell and hence antimicrobial resistance to tetracycline would be bypassed[27]. The highest antibacterial activity was recorded by methanolic extract against P. aerugenosa and the lowest activity was seen in ethyl acetate extract against E. coli and P. aeruginosa.

 

In antifungal activity, the highest activity was seen in methanolic extract against A. Niger and the lowest activity was reported by acetone extract against A. flavus. Acetone extract showed lowest antifungal activity. This may be due to the unavailability of fungicidal content of plant extract[28].

 

Central nervous system:

EMB can be used in CNS disorders like depression, anxiety, tumor, convulsions etc. It act through chloride channel by increasing the conductance. Antiepileptic activity is linked to its ability to decrease conductance of sodium ion channel. Antianxiety was mediated through the benzodiazepine receptor mediated GABA site. EMB has use in cerebral ischemia and it was through restoration of antioxidant enzyme and decrease in lipid peroxides. EMB induce decrease in the inflammation of neurons is by inhibition of NF-Kb pathway[29].

 

Analytical method:

Some of the common analytical methods used to determine the strength, purity and for the standardization of phytoconstituents are UV spectrophotometric methods [30], HPTLC, HPLC and RP-HPLC[31]. The first and most commonly used analytical technique of embelin is HPLC. Using various solvents LOD and LOQ values are determined. Solvents like methanol, tri-fluro acetic acid and water shows a very high sensitive LOD and LOQ values for EMB. The TLC method using chloroform as solvent system has been reported. HPTLC with chloroform, ethyl acetate and acetic acid as solvent system and LC-MS as detector is also been reported. UV double beam spectrophotometric method is also developed with methanol as solvent and max absorption at 289 nm with a linear range of 10-90µg/ml.

 

Recent literature on analytical methods for EMB are summarised in table 1.


 

Table 1: quantitative analytical method of EMB

Analytical method

Research objective/title

Matrix and sample preparation method

Results

Reference

TLC

Estimation of EMB by UV spectrophotometer in Embelia ribes

Air dried grinded sample(powder) extracted using chloroform

Rf value observed at above as 0.65, the calibration curve was found to be linear b/w 5-20 µg

[32]

HPLC

Development and validation of a liq chromatographic method for determination of EMB from crude extract of E. ribes

Methanol and chloroform as solvent crude EMB extract using soxhlet and maceration

Of integrated peak area and concentration of EMB was found to be linear over a range of 6.25-200 µg/ml. The LOD is 1.5and LOQ (µg/ml) levels is 4.5. The recovery of EMB was 98.6%.

[33]

RP- HPLC

Development and validation of RP-HPLC method

Embelin powder in vidangi churna in reverse phase C18 eluted with acetonitrile and water as solvent

Calibration curve showed good linear correlation coefficient(r˛>0.995)

[34]

HPLC

To obtain the extraction parameters of EMB and to quantify the EMB content in different parts

Extracts of E.ribes using solvents like acetone, methanol, chloroform, ethyl acetate, diethyl ether, hexane through sonication

The extraction of EMB through RSM extraction time 27.50 min temp 45°C and drug: solvent ratio 8:1 and maximum EMB content was found ethyl acetate 23.74%

[35]

HPLC

Estimation of EMB by photo diode array dectector method

The EMB was separated by using isocratic mode consisting of 0.1 % trifluoroacetic acid in water and methanol (in proportion of 88:12) at a flow rate of 1.0 mL/min

EMB content in various solvent extract a mean content of 0.44-33% w/w, EMB was found to be linear over the range of 5.0-75.0 µg/mL and the relative standard deviation is 0.61-0.96 %. The limit of detection was 20 ng on column and the limit of quantitation was 50 ng on column

[36]

HPTLC

Determination of EMB from methanolic extract of leaves, fruits and stem

Dried powder, using the solvent system of chloroform: ethyl acetate: acetic acid (5:4:1 v/v/v).

Rf=0.58, confirmation was done by LC-MS analysis in which EMB was observed at 295.1904 m/z ratio and retention time (RT) was 11.546 minute

[37]

RP-HPLC DAD

Quantitative estimation of EMB by DAD detection

Dried powder, homogenized at 200rpm separately with hexane, ethyl acetate, chloroform and methanol (2 Ą 250mL) for 20min at room temperature

hexane with high extractability, linearity (15–250 mg/mL), LOD (3.97 mg/mL), LOQ (13.2 mg/mL), recovery (99.4–103.8%) and precision (1.43– 2.87%)

[38]

UV spectrophotometry

Development of double wavelength UV spectrophotometry

Dried powder dissolved in methanol using UV double beam spectroscopic method

maximum absorption at 289 nm, linear over the range of 10-90µg/ml with correlation coefficient 0.9991, The % relative standard deviation (RSD) value < 2 indicate that the method was precise. The Limit of detection (LOD) and Limit of quantification (LOQ) of EMB were found 3.96 µg/mL and 12 µg/mL respectively

[39]

 

 

Table 2: embelin formulations and their in vitro or outcomes

Embelin activity

Formulation

In-vivo/in-vitro

Results

Reference

Ulcerative colitis

Enteric coated microspheres with polymer eudragit S 100

Both, 30 wistar rats were used

Time dependent and pH-dependent sustained release with drug delivery specified to colon

[47]

Microfibre containing EMB

Solubilizing embelin in a biodegradable and biocompatible polymer matrix of poly(e-caprolactone) (PCL

in vitro

Crystallinity of EMB is decreased, in situ bioavailability of EMB proved topical drug delivery

[48]

Diabetes

Self solid nano emulsified DDS using polymers Capmul® MCM, NEUSILIN® UFL2, PEG 400

Both, wistar rats

Percentage cumilative release was increased from 34.29±1.20% to 90.63±3.67%

[49]

Ulcerative colitis

Lipid nano spheres with soya bean oil and virgin coconut oil

Both, 42 male wistar rats

The mechanism of drug release were non-fickian, in vivo studies revealed that it is suitable for ulcerative colitis

[50]

Enhancement of dissolution

liquisolid system using solutol hs -15 and synperonic PE/L6

in vitro

Significant enhancement of drug release from the formulation

[51]

ulcerative colitis

guar gum micro particles

Both, wistar rats

The drug release is site-specific and sustained, with less side effect

[52]

Skin cancer

Transferosome with span 80 and tween 80, carbopol 934 and propylene glycol

in vitro

Higher entrapment efficiency and can be used for transdermal preparations

[53]

Enhancement of solubility

Phospholipids

in vitro

EMB content increased up to 92% and solubility increased from 2.3-39µg/ml

[54]

diabetes

Oral niosomes

Both, wistar rats

EMB show higher antioxidant activity and also useful for diabetes in wistar rats

[55]

Ulcerative colitis

Eudragit coated microspheres

In vitro

pH dependent and delayed release for targeting drugs specifically to inflamed local site of colon

[56]

Topical delivery

Emulgel with tween and propylene glycol

in vitro

Emulgel formulation having potent antioxidant activity and EMB is well incorporated in the formulation

[57]

Improvement of solubility and dissolution property

Nano suspension with pluronic F68 as stabilizer and zirconium beads as milling agent

in vitro

Significant improvement of dissolution property after several in vitro studies like X ray and DSC

[58]

Dissolution enhancement

EMB compressed tablets

in vitro

Solubility tested in different dissolution medium and find out pH 7.4 as good dissolution medium

[59]

Brain targeting

Nano lipid carriers with cetyl-palmitate and octayl- dodecanol as excipients

Both, wistar rats

Sustained release pattern from drug formulation, high drug concentration reaches brain compared to plain drug

[60]

Improve solubility and micrometric property

spherical microcrystals with hydrophilic polymer PVP K30

in vitro

Improves the dissolution rate and flow property without changes in the crystalline structure of EMB

[61]

To improve oral bio availability

Self emulsiyfing with ethyl oleate, tween 80 and span 20

in vitro

EMB SEDDS shows highest cumulative drug release as compared to conventional dosage form with uniform drug release

[62]

Solubility enhancement

Solid dispersion with carriers like PVP,PVPK30, PEG 4000 , PEG 6000

in vitro

Using phosphate buffer of pH 7.4 shows improved solubility and dissolution rate within 2 hours

[63]

Dissolution enhancement for porous based S-SNEDDS

Self nano emulsifying system with caproyl 90 as oil phase

in vitro

Enhancement of dissolution without any changes in the physiochemical characteristics after 6 months of accelerated stability studies

[64]

 


Dosage forms:

 Improvement of bioavailability and aqueous solubility can be achieved by formulating into phospholipid complexes[40], SEDDS[41], SNEDDS[42], nanoparticles[43], solid dispersion techniques[44], liquisolid technique[45] and microemulsions. Site specific drug delivery of phytoconstituents through nanoparticles and microparticles. Based on the reported bioactivity of EMB, immediate release, topical release, controlled and targeted drug delivery approaches has been developed. Most of the reported literature aims at improving aqueous solubility or poor solubility issues[46] of EMB. EMB emulgel was prepared using carbomer as the gelling agent and evaluated for its antioxidant potential. Release of EMB from microparticulate system of eudragit showed pH dependent and sustained drug release. Most of them were for targeted drug delivery for ulcerative colitis. Nanolipid carriers of EMB for targeting to colon and brain has been reported. Solubility enhancement was also observed with SEDD, microcrystals, SNEDDS and with phospholipids. Formulation approaches for EMB are summarised in table 2

 

CONCLUSION:

EMB is a promising molecule and major physiochemical property limiting its use is low aqueous solubility. Mechanisms of anticancer and neurological activities of EMB are well exploited and provide potential targets for the treatment of cancer and neurological disorders. Mechanism of anti-inflammatory, wound healing and antimicrobial activities are yet to be unveiled. Formulation approaches are limited and their efficacy has to be confirmed by in vivo studies or clinical trials. Reports on successful brain and colon targeting and drug delivery of EMB need further scale up. Although various analytical techniques are reported, a model solvent system for chromatographic techniques is yet to develop.

 

REFERENCES:

1.      Kunnumakkara AB, Sailo BL, Banik K, Harsha C, Prasad S, Gupta SC, Bharti AC, Aggarwal BB. Chronic diseases, inflammation, and spices: how are they linked?. Journal of translational medicine. 2018 Dec;16(1):14.

2.      Li Z, Chen SJ, Yu XA, Li J, Gao XM, He J, Chang YX. Pharmacokinetic And Bioavailability Studies Of Embelin After Intravenous And Oral Administration To Rats. Evidence-Based Complementary And Alternative Medicine. 2019;2019.

3.      Kocak C, Kocak FE, Akcilar R, Isiklar OO, Kocak H, Bayat Z, Simsek H, Taser F, Altuntas I. Molecular and biochemical evidence on the protective effects of embelin and carnosic acid in isoproterenol-induced acute myocardial injury in rats. Life sciences. 2016 Feb 15;147:15-23.

4.      Asadulla S, Ramandang R. Pharmacognosy of Embelia ribes Burm f. Int J Res Pharm Chem. 2011;1(4):1236-51.

5.      Agrawal S, Chauhan S, Mathur R. Antifertility effects of embelin in male rats. Andrologia. 1986 Mar 4;18(2):125-31.

6.      Kumar K, Dhamotharan R, Kulkarni NM, Honnegowda S, Murugesan S. Embelin ameliorates dextran sodium sulfate-induced colitis in mice. International immunopharmacology. 2011 Jun 1;11(6):724-31.

7.      Mahendran S, Badami S, Maithili V. Evaluation of antidiabetic effect of embelin from Embelia ribes in alloxan induced diabetes in rats. Biomedicine & Preventive Nutrition. 2011 Jan 1;1(1):25-31.

8.      Durg S, Veerapur VP, Neelima S, Dhadde SB. Antidiabetic activity of Embelia ribes, embelin and its derivatives: A systematic review and meta-analysis. Biomedicine & Pharmacotherapy. 2017 Feb 1;86:195-204.

9.      Sahu BD, Anubolu H, Koneru M, Kumar JM, Kuncha M, Rachamalla SS, Sistla R. Cardioprotective effect of embelin on isoproterenol-induced myocardial injury in rats: possible involvement of mitochondrial dysfunction and apoptosis. Life sciences. 2014 Jun 27;107(1-2):59-67.

10.   Mahendran S, Thippeswamy BS, Veerapur VP, Badami S. Anticonvulsant activity of embelin isolated from Embelia ribes. Phytomedicine. 2011 Jan 15;18(2-3):186-8.

11.   Afzal M, Gupta G, Kazmi I, Rahman M, Upadhyay G, Ahmad K, Imam F, Pravez M, Anwar F. Evaluation of anxiolytic activity of embelin isolated from Embelia ribes. Biomedicine & Aging Pathology. 2012 Apr 1;2(2):45-7.

12.   Feresin GE, Tapia A, Sortino M, Zacchino S, de Arias AR, Inchausti A, Yaluff G, Rodriguez J, Theoduloz C, Schmeda-Hirschmann G. Bioactive alkyl phenols and embelin from Oxalis erythrorhiza. Journal of ethnopharmacology. 2003 Oct 1;88(2-3):241-7.

13.   Lal B, Mishra N. Importance of Embelia ribes: An update. International Journal of Pharmaceutical Sciences and Research. 2013 Oct 1;4(10):3823.

14.   Shuveksh PS, Ahmed K, Padhye S, Schobert R, Biersack B. Chemical and biological aspects of the natural 1, 4-benzoquinone embelin and its (semi-) synthetic derivatives. Current medicinal chemistry. 2017 Jun 1;24(18):1998-2009.

15.   Souravi K, Rajasekharan Pe. Ethnopharmacological Uses Of Embelia Ribes Burm. F. A Review. Iosr Journal Of Pharmacy And Biological Sciences. 2014;9(3):23-30.

16.   Poojari R. Embelin–a drug of antiquity: shifting the paradigm towards modern medicine. Expert opinion on investigational drugs. 2014 Mar 1;23(3):427-44.

17.   Rani VU, Jyothi G, Rao GN, Sailaja BB. Chemical speciation of binary complexes of embelin with some biologically important metal ions. Acta Chimica Slovenica. 2010 Dec 1;57(4).

18.   Ko JH, Lee SG, Yang WM, Um JY, Sethi G, Mishra S, Shanmugam MK, Ahn KS. The application of embelin for cancer prevention and therapy. Molecules. 2018 Mar;23(3):621.

19.   Nikolovska-Coleska Z, Xu L, Hu Z, Tomita Y, Li P, Roller PP, Wang R, Fang X, Guo R, Zhang M, Lippman ME. Discovery of embelin as a cell-permeable, small-molecular weight inhibitor of XIAP through structure-based computational screening of a traditional herbal medicine three-dimensional structure database. Journal of medicinal chemistry. 2004 May 6;47(10):2430-40.

20.   Park N, Baek HS, Chun YJ. Embelin-induced apoptosis of human prostate cancer cells is mediated through modulation of Akt and β-Catenin signaling. PloS one. 2015;10(8).

21.   Dai Y, DeSano J, Qu Y, Tang W, Meng Y, Lawrence TS, Xu L. Natural IAP inhibitor Embelin enhances therapeutic efficacy of ionizing radiation in prostate cancer. American journal of cancer research. 2011;1(2):128.

22.   Nigam N, Grover A, Goyal S, Katiyar SP, Bhargava P, Wang PC, Sundar D, Kaul SC, Wadhwa R. Targeting mortalin by embelin causes activation of tumor suppressor p53 and deactivation of metastatic signaling in human breast cancer cells. PLoS One. 2015;10(9).

23.   Rezkita F, Wibawa KG, Nugraha AP. Curcumin loaded Chitosan Nanoparticle for Accelerating the Post Extraction Wound Healing in Diabetes Mellitus Patient: A Review. Research Journal of Pharmacy and Technology. 2020 Feb 15;13(2):1039-42

24.   Swamy HK, Krishna V, Shankarmurthy K, Rahiman BA, Mankani KL, Mahadevan KM, Harish BG, Naika HR. Wound healing activity of embelin isolated from the ethanol extract of leaves of Embelia ribes Burm. Journal of ethnopharmacology. 2007 Feb 12;109(3):529-34.

25.   Bhandari U, Jain N, Pillai KK. Further studies on antioxidant potential and protection of pancreatic β-cells by Embelia ribes in Experimental diabetes. Journal of Diabetes Research. 2007;2007.

26.   Radhakrishnan N, Gnanamani A, Mandal AB. A potential antibacterial agent Embelin, a natural benzoquinone extracted from Embelia ribes. Biology and medicine. 2011;3(2):1-7.

27.   Rondevaldova J, Leuner O, Teka A, Lulekal E, Havlik J, Van Damme P, Kokoska L. In vitro antistaphylococcal effects of Embelia schimperi extracts and their component embelin with oxacillin and tetracycline. Evidence-Based Complementary and Alternative Medicine. 2015;2015.

28.   Thyloor R. Phytochemical analysis of Embelia ribes seeds for antimicrobial activities. Journal of Medicinal Plants. 2018;6(4):41-3.

29.   Kundap UP, Bhuvanendran S, Kumari Y, Othman I, Shaikh M. Plant derived phytocompound, embelin in CNS disorders: a systematic review. Frontiers in pharmacology. 2017 Feb 27;8:76.

30.   Prathyusha P, Sundararajan R. UV spectrophotometric method for determination of Bilastine in bulk and pharmaceutical formulation. Research Journal of Pharmacy and Technology. 2020 Feb 15;13(2):933-8.

31.   Thoddi P, Gautam GK, BH CN. Stability indicating validated RP-HPLC method for Simultaneous estimation of Elbasvir and Grazopravir in Bulk and Pharmaceutical Dosage form. Research Journal of Pharmacy and Technology. 2020 Feb 15;13(2):950-5.

32.   Chauhan SK, Singh BP, Agarwal S. A TLC identification and spectrophotometric estimation of embelin in Embelia ribes. Ancient science of life. 1999 Jul;19(1-2):46.

33.   Rastogi S, Bhatia AK, Kushwaha A, Pandey MK, Sharma A, Prakash J, Singh GN. Development and validation of a liquid chromatography method for determination of embelin in crude extract of Embelia ribes. Asian Journal of Biomedical and Pharmaceutical Sciences. 2014 Sep 1;4(36):9.

34.   Patel RK, Patel VR, Patel MG. Development and validation of a RP-HPLC method for the simultaneous determination of Embelin, Rottlerin and Ellagic acid in Vidangadi churna. Journal of pharmaceutical analysis. 2012 Oct 1;2(5):366-71.

35.   Alam MS, Damanhouri ZA, Ahmad A, Abidin L, Amir M, Aqil M, Khan SA, Mujeeb M. Development of response surface methodology for optimization of extraction parameters and quantitative estimation of embelin from Embelia ribes Burm by high performance liquid chromatography. Pharmacognosy magazine. 2015 May;11(Suppl 1):S166.

36.   Shelar R, Maurya C, Tekale P, Katkar K, Naik V, Suthar A, Chauhan VS. Embelin-An HPLC method for quantitative estimation in Embelia ribes Burm. F. Int J Pharm Clin Res. 2009;1:146-9.

37.   Swami D, Fulzele D, Malpathak N. Identification and Quantification of Embelin by Validated HPTLC Method and Confirmation by LC-MS from Mangrove Plant Aegiceras corniculatum L. Journal of Chemical and Pharmaceutical Research. 2017;9(1):168-73.

38.   Madhavan SN, Arimboor R, Arumughan C. RP‐HPLC‐DAD method for the estimation of embelin as marker in Embelia ribes and its polyherbal formulations. Biomedical chromatography. 2011 May;25(5):600-5.

39.   Prasad SB, Bist M, Verma SP. Development and validation of the UV-spectrophotometric method for determination of embelin. Int J Pharm Quality Assurance. 2016 Aug 22;7(3):51-4.

40.   Singh AK, Singh A. Phyto-Phospholipid Complexes: A Potential Novel Carrier System for Improving Bioavailability of Phytoconstituents. Research Journal of Pharmacy and Technology. 2020 Feb 15;13(2):1059-66.

41.   Mohanrao BM, Sundar PS, Nagsen S. Oral bioavailability enhancement of a poor water soluble drug by cosurfactant free self-emulsifying drug delivery system (SEDDS). Research Journal of Pharmacy and Technology. 2011;4(10):1557-62

42.   Akiladevi D, Prakash H, Gb B, Madumitha N. Nano-novel approach: Self Nano Emulsifying Drug Delivery System (SNEDDS)-Review Article. Research Journal of Pharmacy and Technology. 2020 Feb 15;13(2):983-90.

43.   Prabhakar C, Krishna KB. A Review on Polymeric Nanoparticles. Research Journal of Pharmacy and Technology. 2011;4(4):496-8

44.   Pradeep NS. A Review: Increasing Solubility of Poorly Soluble Drugs, by Solid Dispersion Technique. Research Journal of Pharmacy and Technology. 2011;4(12):1933-40.

45.   Asija R, Patel P, Asija S. The Liquisolid Technique for Enhancement of Drug Dissolution. Research Journal of Pharmacy and Technology. 2012;5(10):1270-4.

46.   Vyas A, Gidwani B. Technologies to counter poor solubility issues: A review. Research Journal of Pharmacy and Technology. 2013;6(11):1258-70.

47.   Nidhi, Dadwal A, Hallan SS, Sharma S, Mishra N. Development of enteric-coated microspheres of embelin for their beneficial pharmacological potential in ulcerative colitis. Artificial cells, nanomedicine, and biotechnology. 2017 Aug 18;45(6):1092-100.

48.   Tornello PR, Feresin GE, Tapia A, Veiga IG, Moraes ÂM, Abraham GA, Cuadrado TR. Dispersion and release of embelin from electrospun, biodegradable, polymeric membranes. Polymer journal. 2012 Nov;44(11):1105-11.

49.   Rashid M, Wani TU, Mishra N, Sofi HS, Ashraf R, Sheikh FA. Development and characterization of drug-loaded self-solid nano-emulsified drug delivery system for treatment of diabetes. Material Science Research India. 2018 Apr 20;15(1):01-11.

50.   Badamaranahalli SS, Kopparam M, Bhagawati ST, Durg S. Embelin lipid nanospheres for enhanced treatment of ulcerative colitis–Preparation, characterization and in vivo evaluation. European journal of pharmaceutical sciences. 2015 Aug 30;76:73-82.

51.   Parmar K, Patel J, Sheth N. Formulation and development of embelin liquisolid systems using quality by design approach. Journal of Pharmaceutical Investigation. 2016 Oct 1;46(6):547-56.

52.   Sharma A, Kaur N, Sharma S, Sharma A, Rathore MS, Ajay K, Mishra N. Embelin-loaded guar gum microparticles for the management of ulcerative colitis. Journal of microencapsulation. 2018 Feb 17;35(2):181-91.

53.   Jain S, Jain N. PUB040 Formulation and Evaluation of Embelin Loaded Transfersome for Effective Treatment of Skin Cancer. Journal of Thoracic Oncology. 2017 Nov 1;12(11):S2378.

54.   Pathan RA, Bhandari U. Preparation & characterization of embelin–phospholipid complex as effective drug delivery tool. Journal of Inclusion Phenomena and Macrocyclic Chemistry. 2011 Feb 1;69(1-2):139-47.

55.   Alam MS, Ahad A, Abidin L, Aqil M, Mir SR, Mujeeb M. Embelin-loaded oral niosomes ameliorate streptozotocin-induced diabetes in Wistar rats. Biomedicine & Pharmacotherapy. 2018 Jan 1;97:1514-20.

56.   Nidhi NM. Eudragit Coated Microspheres of Embelin for Treatment of Ulcerative Colitis. Ann Pharmacol Pharm. 2017; 2 (14).;1076.

57.   Sekar M. Formulation and evaluation of embelin emulgel for topical delivery. International Journal of Green Pharmacy (IJGP). 2019 Mar 9;13(01).

58.   Parmar K, Patel J, Sheth N. Self nano-emulsifying drug delivery system for Embelin: Design, characterization and in-vitro studies. asian journal of pharmaceutical sciences. 2015 Oct 1;10(5):396-404.

59.   Patel R, Pundarikakshudu K, Momin M, Patel M. Studies On Formulation And Studies On Formulation And In Vitro Dissolution Of Dissolution Of Embelin T Embelin Tablets. Indian Journal Of Pharmaceutical Sciences. 2006 Mar:228.

60.   Sharma N, Bhandari S, Deshmukh R, Yadav AK, Mishra N. Development and characterization of embelin-loaded nanolipid carriers for brain targeting. Artificial cells, nanomedicine, and biotechnology. 2017 Apr 3;45(3):409-13.

61.   Gadhave MV, Banerjee SK. Preparation and Characterization of Spherical Crystals of Embelin to Improve the Solubility and Micromeritic Properties. Int. J. Pharm. Clin. Res. 2014;6:363-9.

62.   Neeraj, Mittal V, Nanda A. Development And In Vitro Evaluation Of Self Emulsifying Formulation For Embelin. International Journal Of Pharmaceutical Sciences And Research. 2018 Feb 1;9(2):633-41.

63.   Shrotriya SN, Chidrawar KR, Nagras MA, Mulgund SV. Solubility Enhancement Studies Of Embelin By Solid Dispersion Technique. Inventi Rapid: Pharm Tech. 2012 Jan 7.

64.   Parmar K, Patel J, Sheth N. Self nano-emulsifying drug delivery system for Embelin: Design, characterization and in-vitro studies. asian journal of pharmaceutical sciences. 2015 Oct 1;10(5):396-404.

 

 

 

 

 

Received on 31.03.2020           Modified on 19.05.2020

Accepted on 01.07.2020         © RJPT All right reserved

Research J. Pharm. and Tech. 2021; 14(1):487-492.

DOI: 10.5958/0974-360X.2021.00089.5