INTRODUCTION:

Efavirenz¹,²is an inhibitor of reverse transcriptase that is not nucleoside (NNRTI). Following FDA and EMEA approval in 1998 and 1999, respectively, Efavirenz was rapidly adopted as a key stay of highly active antiretroviral therapy (HAART) in industrialized nations for the treatment of HIV-1 infections. There are currently three NNRTIs on the market: Efavirenz, nevirapine, and delavirdine in the US.

The majority of the existing data supports Efavirenz over delavirdine and nevirapine³. Nevirapine may not be as beneficial for certain patients as it is for others due to potentially fatal side effects such as severe hepatotoxicity or rash/Stevens-Johnson syndrome (e.g., patients with higher CD4 cell counts; women > 250; and males > 400 CD4 cells/µl). Because Efavirenz is teratogenic, it should not be used in women who are pregnant or who are highly likely to become pregnant³. For this reason, the majority of African women who are capable of carrying children are prescribed nevirapine rather than Efavirenz. Because it is less expensive, nevirapine is also utilized in Africa. Compared to Efavirenz, it has a little better impact on the blood lipid profile. This may support the use of nevirapine in individuals who already have coronary heart disease risk factors⁴. The low genetic barrier that prevents drug-resistant virus variations from developing is one of the main drawbacks of the current generation of NNRTIs. A substantial degree of drug resistance may result from specific single amino acid mutations in the NNRTI-binding region (K103N, V106M, G190S/A/E, Y181C, Y188L, M230L)⁵. There is a great deal of cross-resistance within the licensed NNRTIs. Novel medications in this class are being developed to combat cross-resistance within classes⁶. The low genetic barrier to resistance may be a general drawback, but it also provides compelling evidence for starting with nucleoside reverse transcriptase inhibitors (NRTIs) when the NRTI backbone is strongest. As one of the recommended first-line antiretroviral regimens, current treatment guidelines for individuals with HIV-1 infection advise using Efavirenz in conjunction with zidovudine or tenofovir disoproxil fumarate, along with lamivudine or emtricitabine^7,8. A general limitation of the low genetic barrier to resistance may be that it supports the idea of commencing with nucleoside reverse transcriptase inhibitors (NRTIs) when the NRTI backbone is strongest. According to current treatment guidelines for HIV-1 infection, Efavirenz should be used in combination with zidovudine or tenofovir disoproxil fumarate, lamivudine, or emtricitabine as one of the recommended first-line antiretroviral regimens⁹.

STRUCTURE AND MECHANISM OF ACTION:

Efavirenz is chemically designated (S)-6-chloro-4-(cyclopropyl ethynyl)-1,4-dihydro-4-(trifluoromethyl)-2H-3,1-benzoxazin-2-individual. Its chemical structure is C14H9CIF3NO2. Efavirenz has a microscopic volume of 315.68 and is almost secretive in water (< 10µg/ml). The structure of Efavirenz is shown in Figure 1. All approved NNRTIs primarily interfere with HIV-1 reverse transcriptase function and have some inhibitory effect on HIV-2 reverse transcriptase and human basic DNA polymerases -α, -β, -γ, and -δ. When they occupy a specific hydrophobic pocket in HIV-1 reverse transcriptase, NNRTIs restrict the process of RNA-dependent DNA polymerization¹⁰.

The antiviral activity of Efavirenz is dependent on intracellular conversion to the active triphosphorylated form. The rate of Efavirenz phosphorylation varies, depending on cell type. It is believed that inhibition of reverse transcriptase interferes with the generation of DNA copies of viral RNA, which, in turn, are necessary for the synthesis of new virions. Intracellular enzymes subsequently eliminate the HIV particle that previously had been uncoated, and left unprotected, during entry into the host cell. Thus, reverse transcriptase inhibitors are virstatin and do not eliminate HIV from the body. Even though human DNA polymerase is less susceptible to the pharmacologic effects of triphosphorylated Efavirenz, this action may nevertheless account for some of the drug's toxicity¹⁰.

Fig 1. Structure of Efavirenz

PHYSICOCHEMICAL PROPERTIES:

Solubility:

Efavirenz is reported to be practically insoluble in water. A water solubility of less than 10g/mL was reported, but the temperature at which the tests were performed was not reported. Rabel et al.¹⁰. reported an intrinsic solubility of 8.3g/mL by calculating the solubility of Efavirenz in the pH range of 18. The solubility tests were performed at different pH values by adding hydrochloric acid or sodium hydroxide solution to deionized water.18 Gao et al.19 reported on the solubility of Efavirenz in biorelevant media, which was higher than in aqueous buffer. Since no solubility data compliant with the Biopharmaceutics Classification System (BCS) are available in the literature, additional solubility studies were performed on the API in accordance with WHO guidelines¹¹.

Stereochemistry and polymorphism:

Efavirenz possesses a chiral carbon atom at position 4. The 4S enantiomer is used in commercially available formulations. A 3mg/mL solution in methanol shows a specific optical rotation of 89100 at 20°C.9 No polymorphs of Efavirenz have been reported in the open literature¹².

pKa:

A pKa for Efavirenz was reported to be 10.1±0.1¹³.

Partition coefficient (log P):

A log P value of 2.07±0.12 was determined using the octanol-water shake flask method, 20 although the temperature at which this value was obtained was not reported. Rowe et al. Reported a higher log P value of 5.4, but no information was given on the experimental conditions¹³.

Available dosage form strengths:

Efavirenz is available as a single agent and as a fixed-dose combination product in the form of capsules, tablets, and oral solutions. IR dosage forms containing a single API are available in 50, 100, 200, and 600mg dosage strengths. The highest recommended dose strength of Efavirenz in the 17th edition of the WHO Model List of Essential Medicine is 600mg tablets and 200mg capsules¹³.

PHARMACOKINETIC PROPERTIES:

There are three different forms of Efavirenz available: 50, 100, or 200mg capsules for oral treatment; 600mg film-coated tablets; and 30mg/ml liquid formulation. In the US, Efavirenz, tenofovir, and emtricitabine, the whole HAART combination, is already accessible as a single pill. To reduce potential neuropsychiatric adverse effects, the suggested Efavirenz dosage is 600mg once a day, given orally, on an empty stomach, and preferably right before bed. Efavirenz can harm the foetus during the first trimester of pregnancy, which is why it is prohibited in pregnancy (category D). There have been reports of neural tube abnormalities in babies delivered to mothers who took Efavirenz during the first trimester. Pregnancy testing is recommended, and women of reproductive potential should get birth control counsellingbefore beginning Efavirenz.Efavirenz has a good oral bioavailability. Five hours after a single oral dose of 100–1600mg given to healthy volunteers, peak Efavirenz plasma concentrations of 1.6–9.1µM are reached. Peak plasma concentrations occur in approximately 3 to 5 hours, and steady-state plasma concentrations are attained in 6 to 10 days. The steady-state Cmax was 12.9±3.7µM (mean±SD), the steady-state Cmin was 5.6±3.2µM, and the AUC was 184±73 µM/h in individuals receiving 600mg of Efavirenz. When food is consumed together with Efavirenz administration, the Cmax and AUC of Efavirenz are higher than when fasting circumstances are met. Efavirenz passes the blood–brain barrier easily; its concentrations in the cerebrospinal fluid range from 0.26 to 1.19% of those in blood plasma. There are contradicting reports about Efavirenz's penetration of the male genital canal. The median Efavirenz level in semen was only 3.4% (range 2.0 – 5.0%) of that in blood plasma, according to Reddy et al¹⁴. Allsemen Efavirenz concentrations, however, were still more than forty times greater than the IC90 for HIV-1 wild-type. These findings suggest that Efavirenz can effectively inhibit HIV-1 in the male genital tract when it reaches high enough concentrations. However, despite excellent quantities in blood plasma, Ghosn et al¹⁵.reported three patients on an Efavirenz-containing regimen having undetectable Efavirenz concentrations in semen. To make a firm determination regarding Efavirenz's penetration into the vaginal tract, more information is required. 99.5–99.75 percent of Efavirenz is linked to human plasma proteins, mostly albumin. The CYP450 system primarily breaks down Efavirenz into hydroxylated metabolites, which are then glucuronidated. The two most significant isoenzymes are CYP2B6 and CYP3A4. Efavirenz's metabolism is an enzymatic process that can be induced by itself¹⁶.

The terminal half-lives of Efavirenz are 40–55hours after repeated doses and 52–76hours after a single dose. Patients with renal impairment do not require a dosage change because less than 1% of Efavirenz is eliminated in the urine. In the initial months following Efavirenz treatment, liver enzyme levels in patients with hepatic impairment or co-infection with hepatitis B (HBV)/hepatitis C virus (HCV) should be closely monitored¹⁷.

METHODS OF SYNTHESIS:

The original synthesis of EFV in 1998 was a seven- step process that resulted in 62% overall yield as seen in given fig. the biggest challenge in EFV’s synthesis was to create the quaternary carbon center in the fourth step.23 the fifth step includes the addition of cyclopropyl acetylene (CA) side chain¹⁸.

Table 1: Medicinal uses of Efavirenz

Disease	Target	Single or combination treatment	Reference
Alzheimer	CYP46A1	Single	^[20]
Colorectal cancer	In vitro approach	Combination	^[21]
Pancreatic Cancer	Activating phosphorylation of the tumour suppressor protein p53	As a single treatment or in combination with radiotherapy	^[22]
Prostate cancer	Prostate-specific antigen (PSA) non-progression rate	Single	^[23]
Lung cancer	In vitro approach (MRC-5 and A549 ling cells)	Single	^[24]
Glioblastoma	CYP46A1/ 24OHC axis, a potential therapeutic target	Single	^[25]
Leukaemia	Induce apoptosis	Single	^[26]
Prion disease	Cellular prion protein (PrP^c)	Single	^[27]
Zika virus	Non-structural protein genes	In combination with rilpivirine and etravirine	^[28]
Dravet syndrome	5-HT on- or off- target	single	^[29]

Table 2: Some marketed formulations of Efavirenz.

Formulation type	Brand name	Company name	Dose	Reference
Tablet	Sustiva	Bristol Myers Squibb Co.	50mg, 100mg, 200mg	^[30]
Tablet	Stocrin	Merck Sharp and Dohme Corp.	50mg, 100mg, 200mg	^[31]
Capsule	Efavir	Cipla Limited	200mg	^[32]
Capsule	Efavir	Cipla Limited	200mg	^[32]
Tablet	Efavir	Cipla Limited	600mg	^[32]
Film Coated tablet	Efavir	Cipla Limited	600mg	^[32]
Tablet	Efcure	Emcure Pharmaceuticals Lim.	-	^[32]
Syrup	EfcureSoln	Emcure Pharmaceuticals Lim.	-	^[32]
Capsule	Estiva	Genix Pharma Lim.	-	^[32]
Tablet	Revenz	Sain Medicaments Pvt Lim.	-	^[32]

Table 3: Patent List of EfavirenzDrug.

Patent Number	Approved	Expiries
US5811423	1998-09-22	2012-08-07
CA2279198	2009-04-14	2018-02-02
CA2101572	2001-08-28	2013-07-29
US5914331	1999-06-22	2018-01-02
US6043230	2000-03-28	2018-01-25
US5814639	1998-09-29	2017-03-29
US6555133	2003-04-29	2019-10-06
US6939964	2005-09-06	2018-07-20
US6639071	2003-10-28	2018-08-14
US6238695	2001-05-29	2019-10-06

PATENT:

In most countries, the compound patent for Efavirenz expired in or around August 2013. There are some instances where it is anticipated to end later due to patent term extensions (for example, for instance, the expiration date in Ukraine is 2018). The compound patent was in effect in Argentina, China, Dominican Republic, Indonesia, Mexico, Pakistan (method patent only), South Africa, Thailand, and Ukraine but is likely to have expired in the majority of these nations, according to the information that is now accessible. Several South African businesses have been granted permits to produce and export Efavirenz to ten of its neighbors. Brazil, Indonesia, and Thailand have all awarded Efavirenz mandatory licenses³³. Some patents and their approved year are mentioned in Table3.

CONCLUSION:

Efavirenz is a popular antiretroviral medication for the treatment of HIV, to sum up. Due to its favorable pharmacokinetic profile, a once-daily dose can improve patient compliance. However, before prescribing Efavirenz, a patient's medical history and current drugs must be considered due to possible drug interactions and contraindications. To maintain the best efficacy and safety in HIV-infected patients, regular monitoring of medication levels and clinical response is required.

CONFLICT OF INTEREST:

The authors have no conflicts of interest regarding this investigation.

REFERENCES:

1. Vrouenraets, S. M. E., Wit, F. W., van Tongeren, J., and Lange, J. M. A. Efavirenz: a review. Expert Opinion on Pharmacotherapy. 2007; 8(6): 851–871. https://doi.org/10.1517/14656566.8.6.851

2. Sustiva, C., and Mg, 100. Reverse Transcriptase Inhibitor (NNRTI). Yahoo.com. Retrieved March 28, 2024

3. Pg, Y., and Sm, H. Treatment for adult HIV infection: 2004 recommendations of the International AIDS Society-USA Panel. JAMA. 2004; 292(2): 251–265.

4. van Leth, F., Phanuphak, P., Stroes, E., Gazzard, B., Cahn, P., Raffi, F., Wood, R., Bloch, M., Katlama, C., Kastelein, J. J. P., Schechter, M., Murphy, R. L., Horban, A., Hall, D. B., Lange, J. M. A., and Reiss, P. Nevirapine and efavirenz elicit different changes in lipid profiles in antiretroviral-therapy-naive patients infected with HIV-1. PLoS Medicine. 2004; 1(1): e19. https://doi.org/10.1371/journal.pmed.0010019

5. Young, S. D., Britcher, S. F., Tran, L. O., Payne, L. S., Lumma, W. C., Lyle, T. A., Huff, J. R., Anderson, P. S., Olsen, D. B., and Carroll, S. S. L-743, 726 (DMP-266): a novel, highly potent nonnucleoside inhibitor of the human immunodeficiency virus type 1 reverse transcriptase. Antimicrobial Agents and Chemotherapy. 1995; 39(12): 2602–2605. https://doi.org/10.1128/aac.39.12.2602

6. Pauwels, R. New non-nucleoside reverse transcriptase inhibitors (NNRTIs) in development for the treatment of HIV infections. Current Opinion in Pharmacology. 2004; 4(5): 437–446. https://doi.org/10.1016/j.coph.2004.07.005

7. Gallant, J. E., DeJesus, E., Arribas, J. R., Pozniak, A. L., Gazzard, B., Campo, R. E., Lu, B., McColl, D., Chuck, S., Enejosa, J., Toole, J. J., and Cheng, A. K. Tenofovir DF, emtricitabine, and efavirenz vs. Zidovudine, lamivudine, and efavirenz for HIV. The New England Journal of Medicine. 2006; 354(3): 251–260. https://doi.org/10.1056/nejmoa051871

8. HIV/AIDS Treatment Guidelines. Hiv.gov. Retrieved March 28, 2024, from https://clinicalinfo.hiv.gov/en/guidelines

9. Mannheimer, S., Friedland, G., Matts, J., Child, C., Chesney, M., and Terry Beirn Community Programs for Clinical Research on AIDS. The consistency of adherence to antiretroviral therapy predicts biologic outcomes for human immunodeficiency virus–infected persons in clinical trials. Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 2002; 34(8): 1115–1121. https://doi.org/10.1086/339074

10. Wu, K., Koethe, J., Hulgan, T., Brown, T., Bares, S. H., Tassiopoulos, K., Lake, J. E., Leonard, M., Samuels, D. C., Erlandson, K., and Haas, D. W. Pharmacogenetics of weight gain following switch from efavirenz- to integrase inhibitor-containing regimens. Pharmacogenetics and Genomics. 2024; 34(2): 25–32. https://doi.org/10.1097/FPC.0000000000000515

11. Plöger, G. F., Abrahamsson, B., Cristofoletti, R., Groot, D. W., Langguth, P., Mehta, M. U., Parr, A., Polli, J. E., Shah, V. P., Tajiri, T., and Dressman, J. B. Biowaiver monographs for immediate release solid oral dosage forms: Proguanil hydrochloride. Journal of Pharmaceutical Sciences. 2018;107(7): 1761–1772. https://doi.org/10.1016/j.xphs.2018.03.009

12. Rabel, S. R., Maurin, M. B., Rowe, S. M., and Hussain, M. Determination of the pKaand pH-solubility behavior of an ionizable cyclic carbamate, (S)-6-chloro-4-(cyclopropylethynyl)-1,4-dihydro-4-(trifluoromethyl)-2H-3,1-benzoxazin-2-one (DMP 266). Pharmaceutical Development and Technology. 1996; 1(1): 91–95. https://doi.org/10.3109/10837459609031422

13. Cristofoletti, R., Nair, A., Abrahamsson, B., Groot, D. W., Kopp, S., Langguth, P., Polli, J. E., Shah, V. P., and Dressman, J. B. Biowaiver monographs for immediate release solid oral dosage forms: Efavirenz. Journal of Pharmaceutical Sciences. 2013; 102(2): 318–329. https://doi.org/10.1002/jps.23380

14. Reddy, Y. S., Gotzkowsky, S. K., Eron, J. J., Kim, J. Y., Fiske, W. D., Fiscus, S. A., Petch, L., Cohen, M. S., and Kashuba, A. D. M. Pharmacokinetic and pharmacodynamic investigation of efavirenz in the semen and blood of human immunodeficiency virus type 1–infected men. The Journal of Infectious Diseases. 2002; 186(9): 1339–1343. https://doi.org/10.1086/344311

15. Ghosn, J., Chaix, M.-L., Peytavin, G., Rey, E., Bresson, J.-L., Goujard, C., Katlama, C., Viard, J.-P., Tréluyer, J.-M., andRouzioux, C. Penetration of enfuvirtide, tenofovir, efavirenz, and protease inhibitors in the genital tract of HIV-1-infected men. AIDS (London, England). 2004; 18(14): 1958–1961. https://doi.org/10.1097/00002030-200409240-00014

16. Adkins, J. C., and Noble, S. (). Efavirenz. Drugs, 56(6), 1055–1064. https://doi.org/10.2165/00003495-199856060-00014

17. Dieterich, D. T., Robinson, P. A., Love, J., and Stern, J. O. Drug-induced liver injury associated with the use of nonnucleoside reverse-transcriptase inhibitors. Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America, 2004; 38(Supplement 2): S80–S89. https://doi.org/10.1086/381450

18. Bautista, E. S. Various synthetic pathways towards Efavirenz and its analogs; The replacement of the side chain. Southeastern University. 2023

19. Frutos, R. P., Wei, X., Patel, N. D., Tampone, T. G., Mulder, J. A., Busacca, C. A., and Senanayake, C. H. One-pot synthesis of 2,5-disubstituted pyrimidines from nitriles. The Journal of Organic Chemistry. 2013; 78(11): 5800–5803. https://doi.org/10.1021/jo400720p

20. Schneider, M., Buzdin, A., Weber, A., Clavien, P.-A., and Borger, P. Combination of antiretroviral drugs zidovudine and efavirenz impairs tumor growths in a mouse model of cancer. Viruses. 2021; 13(12): 2396. https://doi.org/10.3390/v13122396

21. Hecht, M., Erber, S., Harrer, T., Klinker, H., Roth, T., Parsch, H., Fiebig, N., Fietkau, R., and Distel, L. V. Efavirenz has the highest anti-proliferative effect of non-nucleoside reverse transcriptase inhibitors against pancreatic cancer cells. PloS One, 2015; 10(6): e0130277. https://doi.org/10.1371/journal.pone.0130277

22. Schneider, M., Buzdin, A., Weber, A., Clavien, P.-A., and Borger, P. Combination of antiretroviral drugs zidovudine and efavirenz impairs tumor growths in a mouse model of cancer. Viruses, 2021; 13(12): 2396. https://doi.org/10.3390/v13122396

23. Hecht, M., Harrer, T., Korber, V., Sarpong, E., Moser, F., Fiebig, N., Schwegler, M., Sturzl, M., Fietkau, R., and Distel, L.Cytotoxic effect of Efavirenz in BxPC 3 pancreatic cancer cells is based on oxidative stress and is synergistic with ionizing radiation. Oncology Letters. 2017. https://doi.org/10.3892/ol.2017.7523

24. Houede, N., Pulido, M., Mourey, L., Joly, F., Ferrero, J.-M., Bellera, C., Priou, F., Lalet, C., Laroche-Clary, A., Raffin, M. C., Ichas, F., Puech, A., and Piazza, P. V. A phase II trial evaluating the efficacy and safety of efavirenz in metastatic castration-resistant prostate cancer. The Oncologist. 2014; 19(12): 1227–1228. https://doi.org/10.1634/theoncologist.2014-0345

25. Marima, R., Hull, R., Dlamini, Z., and Penny, C. Efavirenz and lopinavir/ritonavir alter cell cycle regulation in lung cancer. Frontiers in Oncology. 2020; 10. https://doi.org/10.3389/fonc.2020.01693

26. Han, M., Wang, S., Yang, N., Wang, X., Zhao, W., Saed, H. S., Daubon, T., Huang, B., Chen, A., Li, G., Miletic, H., Thorsen, F., Bjerkvig, R., Li, X., and Wang, J. Therapeutic implications of altered cholesterol homeostasis mediated by loss of CYP46A1 in human glioblastoma. EMBO Molecular Medicine. 2020; 12(1): https://doi.org/10.15252/emmm.201910924

27. Brüning, A., Jückstock, J., Kost, B., Tsikouras, P., Weissenbacher, T., Mahner, S., and Mylonas, I. Induction of DNA damage and apoptosis in human leukemia cells by efavirenz. Oncology Reports. 2017; 37(1): 617–621. https://doi.org/10.3892/or.2016.5243

28. Ali, T., Hannaoui, S., Nemani, S., Tahir, W., Zemlyankina, I., Cherry, P., Shim, S. Y., Sim, V., Schaetzl, H. M., andGilch, S. Oral administration of repurposed drug targeting Cyp46A1 increases survival times of prion infected mice. Acta Neuropathologica Communications. 2021; 9(1): https://doi.org/10.1186/s40478-021-01162-1

29. Pereira, M., and Vale, N. Evolution of antiretroviral drug rilpivirine and approach to oncology. International Journal of Molecular Sciences. 2023; 24(3): 2890. https://doi.org/10.3390/ijms24032890

30. Sustiva Prescribing Information. Bristol Myers Squibb Company Sustiva Prescribing Information. Bristol Myers Squibb Company

31. Fda.gov. Retrieved March 28, 2024, from https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/091471Orig1s000lbl.pdf

32. Pricing for 18 Efavirenz brands. Medindia. Retrieved March 28, 2024, from https://www.medindia.net/drug-price/efavirenz.html

33. Patents and licences on antiretrovirals - A snapshot. HIV/AIDS Data Hub for the Asia Pacific. Retrieved March 28, 2024, from https://www.aidsdatahub.org/resource/unitaid-patents-licences-antiretrovirals-snapshot

34. Gosavi, S., Joshi, P., Bhogate, V., Gawade, S., Sangelkar, P., andKanekar, S. Comparative study on treatment of rheumatoid arthritis. Asian Journal of Pharmacy and Technology. 2021; 11(1): 5–12. https://doi.org/10.5958/2231-5713.2021.00002.7

35. Maurya, A., Verma, S. C., Gupta, V., and Shankar, M. B. Angelica archangelica L.-A Phytochemical and Pharmacological Review. Asian Journal of Research in Chemistry. 2017; 10(6): 852. https://doi.org/10.5958/0974-4150.2017.00142.0

36. Rajaram, C. U. Review of Captopril Drug Formulation, Mechanism of action, Dosage, Use and Adverse drug reactions. Research Journal of Pharmaceutical Dosage Forms and Technology. 2021; 157–160. https://doi.org/10.52711/0975-4377.2021.00028

37. Jaitak, D., Nacchammai, K., Pavithra, K., Nair, K. G. S., and Kumar, S. S. Polymeric nanoparticles for Anti-cancer treatment-A review of its mechanisms. Research Journal of Pharmacy and Technology. 2021; 14(3): 1747–1754. https://doi.org/10.5958/0974-360x.2021.00311.5

38. Kumar, M. P. S., and Nandhini, T. Mechanism of action of Bone Morphogenic Protein 3 in the maintenance of Tissue Homeostasis. Research Journal of Pharmacy and Technology, 2018; 11(3): 1270. https://doi.org/10.5958/0974-360x.2018.00236.6

39. Kumar, U., Narang, R., Nayak, S. K., Singh, S. K., and Gupta, V. Benzimidazole: Structure activity relationship and mechanism of action as antimicrobial agent. Research Journal of Pharmacy and Technology. 2017; 10(7): 2400. https://doi.org/10.5958/0974-360x.2017.00425.5

40. Maria, J. D., and Aanandhi, M. V. An Overview on Antibiotic use and resistance. Research Journal of Pharmacy and Technology, 2017; 10(8): 2793. https://doi.org/10.5958/0974-360x.2017.00494.2

41. Mukhopadhyay, N., Sampath, V., Pai, S., Babu, U. V., and Lobo, R. Antiarthritic medicinal plants: A review. Research Journal of Pharmacy and Technology. 2019; 12(1): 375. https://doi.org/10.5958/0974-360x.2019.00068.4

42. Nisha, and Rao, P. B. Trigonella foenum-graecum: A Common Indian Spice with Medicinal Properties. Research Journal of Pharmacy and Technology. 2016; 9(2): 173. https://doi.org/10.5958/0974-360x.2016.00031.7

43. Rathod, C. P., andGhante, M. H. Pharmacological importance of Saracaasoca: A review. Research Journal of Pharmacognosy and Phytochemistry. 2021: 131–135. https://doi.org/10.52711/0975-4385.2021.00022

44. Vijayalakshmi, S., Raj, D., Bennet, R., Arun, K., and Arun, A. Value added jam from wine sediments and augments income for the fruit processing industry. Research Journal of Pharmacy and Technology. 2017; 10(11): 3753. https://doi.org/10.5958/0974-360x.2017.00681.3

45. Yadollahpour, A., and Rashidi, S. Electromagnetic fields for the treatment of osteoarthritis: A review of potential clinical applications. Research Journal of Pharmacy and Technology, 2017; 10(2): 641. https://doi.org/10.5958/0974-360x.2017.00122.6

Received on 27.01.2024 Modified on 12.03.2024

Res. J. Pharmacology and Pharmacodynamics.2024;16(3):175-180.

DOI: 10.52711/2321-5836.2024.00030