AAPS PharmSciTech

, 20:56 | Cite as

Taste Evaluation by Electronic Tongue and Bioavailability Enhancement of Efavirenz

  • Monica R. P. RaoEmail author
  • Kirti Bhutada
  • Pauroosh Kaushal
Research Article


Self-nanoemulsifying drug delivery systems (SNEDDS) are isotropic and thermodynamically stable mixtures of oil, surfactant, co-surfactant, and drug which emulsify spontaneously on contact with aqueous phase under mild agitation. Efavirenz used for treatment of acquired immune deficiency syndrome, is poorly water soluble and bitter tasting drug resulting in “burning mouth syndrome (BMS).” The objective of this study was to improve solubility and oral bioavailability by formulating liquid-SNEDDS and to mask bitter taste and minimize BMS. Capmul PG8 NF, Cremophor RH40, and Transcutol HP were selected as oil, surfactant, and co-surfactant. Ternary phase diagrams were constructed to evaluate the nanoemulsification region. A 32 factorial design was employed to optimize L-SNEDDS with droplet size and drug release as responses. Optimized batch was subjected to evaluation of taste by human panel method and electronic tongue, cloud point determination, phase separation, in vivo and stability studies. The optimized batch exhibited droplet size of 21.53 nm, polydispersibility index 0.155, and in vitro drug release of 92.26% in 60 min. The in vivo studies revealed 4.5 times enhancement in oral bioavailability. Taste evaluation indicated reduced the intensity and shortened duration of BMS. The formulation was stable at 40°C ± 75% RH after 3 months. Comparison between standard bitter drug and efavirenz in SNEDDS formulation using e-tongue by principal component analysis revealed significant differences in discrimination index, computed by multivariate data analysis. This study demonstrated that L-SNEDDS may be an alternative approach to improve solubility and oral bioavailability and for masking the bitterness of efavirenz.


burning mouth syndrome efavirenz electronic tongue oral bioavailability SNEDDS 



The authors would like to thank Dr. Ashwini Madgulkar Principal, AISSMS College of Pharmacy, Pune, Maharashtra, India, and also to Dr. R. P Mudhalwadkar, IEEE-Member, Department of Instrumentation & Control, College of Engineering, Pune, India, for helping to carry out the research work.


  1. 1.
    Kulkarni LV, Metkari VB, Bamane GS, Jadhav PA, Raut GS. Recent trends on achieving taste masking of bitter drug. J Cur Pharma Res. 2014;4(3):1246–57.Google Scholar
  2. 2.
    Schlatter AF, Deathe AR, Vreeman R. The need for pediatric formulations to treat children with HIV. AIDS Res Treat. 2016:1–8.Google Scholar
  3. 3.
    Sosnik A, Augustine R. Challenges in oral drug delivery of antiretrovirals and the innovative strategies to overcome them. Adv Drug Deliv Rev. 2016:1–14.Google Scholar
  4. 4.
    Mody DS. Pediatric ibuprofen composition. U.S. Pat. No. 4,788,220 to Am Home Prod Corp. 1998.Google Scholar
  5. 5.
    Roy G. Taste masking in oral pharmaceuticals. Pharm Technol. 1994;18:84–99.Google Scholar
  6. 6.
    Hasan NM, Al-aram MS, Al-wadie MS, Althobaiti FA, Al-Malki MJ. Flavoured self microemulsifying lipid formulations for masking the organoleptic taste of pharmaceutical actives. J App Pharm Sci. 2015;5(11):127–34.CrossRefGoogle Scholar
  7. 7.
    Gao R. Taste masking of oral quinolone liquid preparations using ion exchange resins. PCT Int. Appl. Wo 01/05431 to Schering Plough Ltd. 2001.Google Scholar
  8. 8.
    Agarwal R, Mital R. Studies of ion exchange resin complex of chloroquine phosphate. Drug Dev Ind Pharm. 2000;26:773–6.CrossRefGoogle Scholar
  9. 9.
    Bhalekar MR, Madgulkar AR, Padalkar RR, Sathe AH. Formulation and evaluation of taste masked suspension of oseltamivir phosphate. World J Pharm Pharm Sci. 2015;4(10):382–93.Google Scholar
  10. 10.
    Katsurgi Y, Kashiwayanagi M. Specific inhibitor for bitter taste inhibition of taste nerve responses and human taste sensation to bitter stimuli. Brain Res Protocol. 1997;1:292–8.CrossRefGoogle Scholar
  11. 11.
    Takagi S, Toka K. Detection of suppression of bitterness by sweet substance using a multichannel taste sensor. J Pharm Sci. 1987:552–5.Google Scholar
  12. 12.
    Ibuprofen. Eur. Pat. Appl. EP 05,60,207 to Aziende chemiche Riunite Angelini Francesco (ACRAF) S.P.A. 1993.Google Scholar
  13. 13.
    Choi DH, Kim NA, Nam TS, Lee S, Jeong SH. Evaluation of taste-masking effects of pharmaceutical sweeteners with an electronic tongue system. Drug Dev Ind Pharm. 2013:1–10.Google Scholar
  14. 14.
    Sarkar S, Ghosh D, Bhattacharyya N, Bandyopadhyay R, Mandal AK. Basic and mixed taste analysis using voltammetric electronic tongue. Int J Comput Appl. 2011:27–33.Google Scholar
  15. 15.
    Podrażka M, Bączyńska E, Kundys M, Jeleń PS, Nery EW. Electronic tongue—a tool for all tastes? Biosensors. 2017;8(3):1–24.Google Scholar
  16. 16. (access date: 25/09/2018).
  17. 17.
    Cristofolettti R, Nair A, Abrahamsson B, Groot DW, Kopp S, Langguth P, et al. Biowaiver monographs for immediate release solid Oral dosage forms: efavirenz. J Pharm Sci. 2013;102(2):318–29.CrossRefGoogle Scholar
  18. 18.
  19. 19.
    Savitha C, Shantaraj S. Etiology, diagnosis and management of burning mouth syndrome: an update. J Adv Oral Res. 2012;3(3):7–14.CrossRefGoogle Scholar
  20. 20.
    Borres-Blasco J, Belda A, Rosique-Robles JD, Elvira Casterá MD, Abad FJ. Burning mouth syndrome due to efavirenz therapy. Ann Pharmacother. 2006;40(7–8):1471–2.CrossRefGoogle Scholar
  21. 21.
    Chiappetta DA, Hocht C, Sosnik A. A highly concentrated and taste-improved aqueous formulation of efavirenz for a more appropriate pediatric management of the anti-HIV therapy. Curr HIV Res. 2010;8:223–31.CrossRefGoogle Scholar
  22. 22.
    Mistry RB, Sheth SN. A review: self emulsifying drug delivery system. Int J Pharm Pharm Sci. 2011;3(2):23–8.Google Scholar
  23. 23.
    Savale SK. A review—self nanoemulsifying drug delivery system (SNEDDS). Int J Res Pharma Nano Sci. 2015;4(6):385–97.Google Scholar
  24. 24.
    Amrutkar C, Salunkhe K, Chaudhari S. Study on self nano emulsifying drug delivery system of poorly water soluble drug rosuvastatin calcium. World J Pharma Res. 2014;3(4):2137–51.Google Scholar
  25. 25.
    Anandakumar K, Abirami G, Murugan S, Ashok B. RP-HPLC method for simultaneous estimation of lamivudine, tenofovir disoproxil fumarate and efavirenz in tablet formulation. J Anal Chem. 2013;68(9):815–21.CrossRefGoogle Scholar
  26. 26.
    Panner SR, Kulkarni PK, Dixit M. Preparation and evaluation of self-nanoemulsifying formulation of EFV. Ind J Pharm Edu Res. 2013;47(1):47–54.Google Scholar
  27. 27.
    Priya K, Bhikshapathi DVRN. Development and in vivo evaluation of lovastatin by self-nanoemulsifying drug delivery system. Int J Pharm Sci Drug Res. 2018;10(3):165–72.Google Scholar
  28. 28.
    Kamble R, Mehta PP, Kumar A. Efavirenz self-nano-emulsifying drug delivery system: in vitro and in vivo evaluation. AAPS PharmSciTech. 2016;17(5):1240–7.CrossRefGoogle Scholar
  29. 29.
    Patel G, Shelat P, Lalwani A. Statistical modeling, optimization and characterization of solid self-nanoemulsifying drug delivery system of lopinavir using design of experiment. Drug Deliv. 2016:1–16.Google Scholar
  30. 30.
    Ghori VL, Patel DM, Omri A. Formulation and optimization of self nano emulsifying drug delivery system of lercanidipine hydrochloride using response surface methodology. Int J Pharm Res Bio Sci. 2017;6(4):162–76.Google Scholar
  31. 31.
    Honório TDS, Pinto EC, Rocha HVA, Esteves V, Santos TCD, Castro HCR, et al. In vitro–in vivo correlation of efavirenz tablets using GastroPlus®. AAPS PharmSciTech. 2013;14(3):1244–54.CrossRefGoogle Scholar
  32. 32.
    The United States Pharmacopoeia and National Formulary. 34th ed. Rockville, MD: USP Convention Inc.; 2011.Google Scholar
  33. 33.
    Rachid O, Simons FER, Rawas-Qalaji M, Simons KJ. An electronic tongue: evaluation of the masking efficacy of sweetening and/or flavoring agents on the bitter taste of epinephrine. AAPS PharmSciTech. 2010;11(2):550–7.CrossRefGoogle Scholar
  34. 34.
    Kshirsagar S, Mudhalwadkar R. Development of electronic tongue for sorghum quality detection. Int J Res Engg Tech. 2015;4(4):401–5.CrossRefGoogle Scholar
  35. 35.
    Latha RS, Lakshmi PK. Electronic tongue: an analytical gustatory tool. J Adv Pharm Technol Res. 2012;3(1):3–8.PubMedPubMedCentralGoogle Scholar
  36. 36.
    Podrazka M, Nska EB, Kundys M, Jelen PS, Nery EW. Electronic tongue—a tool for all tastes? Biosensors. 2018;8(3):1–24.Google Scholar
  37. 37.
    Mulay MS, Bankar V, Upasani SV. Preparation and evaluation of taste masking complex of ciprofloxacin hydrochloride by using inclusion complexation approach. World J Pharma Res. 2014;3(5):1035–45.Google Scholar
  38. 38.
    Gupta AK, Mishra DK, Mahajan SC. Preparation and in-vitro evaluation of self emulsifying drug delivery system of antihypertensive drug valsartan. Int J Pharm Life Sci. 2011;2(3):633–9.Google Scholar
  39. 39.
    Senapati PC, Sahoo SK, Sahu AN. Mixed surfactant based (SNEDDS) self-nanoemulsifying drug delivery system presenting efavirenz for enhancement of oral bioavailability. Biomed Pharmacother. 2016;80:42–51.CrossRefGoogle Scholar
  40. 40.
    Miryala V, Kurakula M. Self-nano emulsifying drug delivery system (SNEDDS) for oral delivery of atorvastatin—formulation and bioavailability studies. J Drug Del Ther. 2013;3(3):131–42.Google Scholar
  41. 41.
    Meena AK, Sharma K, Kandaswamy M, Rajagopal S, Mullangi R. Formulation development of an albendazole self-emulsifying drug delivery system (SEDDS) with enhanced systemic exposure. Acta Pharma. 2012;62:563–80.CrossRefGoogle Scholar
  42. 42.
    Patel J, Kevin G, Patel A, Raval M, Sheth N. Design and development of a self-nanoemulsifying drug delivery system for telmisartan for oral drug delivery. Int J Pharm Investig. 2011;1(2):112–8.CrossRefGoogle Scholar
  43. 43.
    Ramachandran G, Hemanth Kumar AK, Swaminathan S, Venkatesan P, Kumaraswami V, Greenblatt DJ. Simple and rapid liquid chromatography method for determination of efavirenz in plasma. J Chromatogr B. 2006;835:131–5.CrossRefGoogle Scholar
  44. 44.
    Panner SR, Kulkarni PK. Preparation and statistical optimization of self nanoemulsifying tablets of efavirenz using 23 factorial designs. Int J Drug Del. 2014;6:50–7.Google Scholar
  45. 45.
    Gurram AK, Deshpande PB, Kar SS, Nayak UY, Udupa N, Reddy MS. Role of components in the formation of self-microemulsifying drug delivery systems. Indian J Pharm Sci. 2015;77(3):249–57.CrossRefGoogle Scholar
  46. 46.
    Rajinikanth PS, Suyu Y, Garg S. Development and in-vitro characterization of self-nanoemulsifying drug delivery systems of valsartan. World Acad Sci Eng Technol. 2012;6:12–28.Google Scholar
  47. 47.
    Rajpoot BS. Method development and validation of RP-HPLC method in the detection of efavirenz in bulk drug and tablet formulation. Int Res J Pharm. 2012;3(7):297–300.Google Scholar
  48. 48.
    Matsaridou I, Barmpalexis P, Salis A, Nikolakakis I. The influence of surfactant HLB and oil/surfactant ratio on the formation and properties of self-emulsifying pellets and microemulsion reconstitution. AAPS PharmSciTech. 2012;13(4):1319–30.CrossRefGoogle Scholar
  49. 49.
    Prathyusha CH, Murthy TEGK. Compatibility studies of donepezil with different excipients by using HPLC and FTIR. J Adv Pharm Edu Res. 2013;3(3):273–8.Google Scholar
  50. 50.
    Dash RN, Habibuddin M, Humaira T, Ramesh D. Design, optimization and evaluation of glipizide solid self-nanoemulsifying drug delivery for enhanced solubility and dissolution. Saudi Pharm J. 2015:1–12.Google Scholar
  51. 51.
    Shah A, Thool P, Sorathiya K, Prajapati H, Dalrymple D, Serajuddin ATM. Effect of different polysorbates on development of self-microemulsifying drug delivery systems using medium chain lipids. Drug Dev Ind Pharm. 2017:1–31.Google Scholar
  52. 52.
    Ujilestari T, Martien R, Ariyadi B, Dono ND, Zuprizal. Self-nanoemulsifying drug delivery system (SNEDDS) of Amomum compactum essential oil: design, formulation, and characterization. J Appl Pharm Sci. 2018;8(6):14–21.CrossRefGoogle Scholar
  53. 53.
    Sisinthy SP, Rao NK, Sarah CL. Design, optimization and in vitro characterization of self nano emulsifying drug delivery system of olmesartan medoxomil. Int J Pharm Pharm Sci. 2017;9(1):94–101.CrossRefGoogle Scholar
  54. 54.
    Panikumar AD, Venkat Y, Sunitha G, Sathesh PR, Subrahmanyam CVS. Development of biorelevant and discriminating method for dissolution of efavirenz and its formulations. Asian J Pharm Clin Res. 2012;5(3):220–3.Google Scholar
  55. 55.
    Tripathi CB, Beg S, Kaur R, Shukla G, Bandopadhyay S, Singh B. Systematic development of optimized SNEDDS of artemether with improved biopharmaceutical and antimalarial potential. Drug Deliv. 2016;23(9):1–35.CrossRefGoogle Scholar
  56. 56.
    Kaushal P, Mudhalwadkar RP, Mhatre GR. An automatic electronic tongue system for classification of Indian wine. Int Conf Sensing Tech (ICST). 2017:1–4.Google Scholar
  57. 57.
    Zang X, Zhang Y, Meng Q, Li N, Ren L. Evaluation of beef by electronic tongue system TS-5000Z: flavor assessment, recognition and chemical compositions according to its correlation with flavor. PLoS One. 2015;10(9):1–7.Google Scholar
  58. 58.
    Choi DH, Kim NA, Nam TS, Lee S, Jeong SH. Evaluation of taste-masking effects of pharmaceutical sweeteners with an electronic tongue system. Drug Dev Ind Pharm. 2014 Mar;40(3):308–17.CrossRefGoogle Scholar
  59. 59.
    Rao MRP, Bhingole RC. Nanosponge-based pediatric-controlled release dry suspension of gabapentin for reconstitution. Drug Dev Ind Pharm. 2015;41(12):2029–36.CrossRefGoogle Scholar
  60. 60.
    Saharan VA, Dev K, Kharb V, Singh A, Jadhav H, Purohit S. Bitterness score and its correlation to drug concentration: an approach for estimating bitterness suppression in a marketed product of ofloxacin. J Anal Chem Lett. 2014;4(4):232–9.CrossRefGoogle Scholar
  61. 61.
    Dasankoppa FS, Komal S, Sholapur HN, Nanjundaswamy N, Sajjanar VM. Design, optimization and evaluation of chewable tablets of clarithromycin using ion exchange resins. Indian J Pharm Sci. 2016;78(6):818–26.Google Scholar
  62. 62.
    Reddy MS, Reddy NS, Reddy SM. Solubility enhancement of poorly water soluble drug efavirenz by solid self emulsifying drug delivery systems. Int J Pharm Res Rev. 2014;3(4):20–8.Google Scholar
  63. 63.
    Patil PP, Kate V, Payghan S. Potential investigation of Peceol for formulation of ezetimibe self nano emulsifying drug delivery systems. Asian J Biomed Pharm Sci. 2016;6(54):21–32.Google Scholar
  64. 64.
    Dash RN, Habibuddin M, Humaira T, Ramesh D. Design, optimization and evaluation of glipizide solid self nanoemulsifying drug delivery for enhanced solubility and dissolution. Saudi Pharma J. 2015;23(5):528–40.CrossRefGoogle Scholar
  65. 65.
    Puri R, Mahajan M, Sahajpal NS, Singh H, Singh H, Jain SK. Self-nanoemulsifying drug delivery system of docosahexanoic acid: development, in vitro, in vivo characterization. Drug Dev Ind Pharm. 2015:1–10.Google Scholar
  66. 66.
    Viana ODS, Medeiros FPM, Grangeiro-Júnior S, Albuquerque MM, Soares MFLR, Soares-Sobrinho JL, et al. Development and validation of a HPLC analytical assay method for efavirenz tablets: a medicine for HIV infections. Braz J Pharm Sci. 2011;47(1):97–102.Google Scholar
  67. 67.
    Pathak CN. Preparation and in vitro evaluation of self-nanoemulsifying drug delivery system (SNEDDS) containing clopidogrel. Int J Pharm Sci Rev Res. 2014;25(1):10–5.Google Scholar
  68. 68.
    Reddy LHV, Murthy RSR. Lymphatic transport of orally administered drugs. Indian J Exp Biol. 2002;40:1097–09.PubMedGoogle Scholar
  69. 69.
    Kalepu S, Manthina M, Padavala V. Oral lipid-based drug delivery systems—an overview. Acta Pharm Sin B. 2013;3(6):361–72.CrossRefGoogle Scholar
  70. 70.
    Sobhani H, Tarighi P, Ostad SN, Shafaati A, Nafissi-Varcheh N, Aboofazeli R. Rapamycin-Loaded, Capryol™ 90 and oleic acid mediated nanoemulsions: formulation development, characterization and toxicity assessment. Iran J Pharm Res. 2018;17(3):830–50.PubMedPubMedCentralGoogle Scholar
  71. 71.
    Yen CC, Chen YC, Wu MT, Wang CC, Wu YT. Nanoemulsion as a strategy for improving the oral bioavailability and anti-inflammatory activity of andrographolide. Int J Nanomedicine. 2018;13:669–80.CrossRefGoogle Scholar
  72. 72.
    Puri R, Mahajan M, Sahajpal NS, Singh H, Singh H, Jain SK. Self-nanoemulsifying drug delivery system of docosahexanoic acid: development, in vitro, in vivo characterization. Drug Dev Ind Pharm. 2016;42(7):1032–41.CrossRefGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  • Monica R. P. Rao
    • 1
    Email author
  • Kirti Bhutada
    • 1
  • Pauroosh Kaushal
    • 2
  1. 1.Department of PharmaceuticsAISSMS College of PharmacyPuneIndia
  2. 2.Department of Instrumentation and ControlCollege of EngineeringPuneIndia

Personalised recommendations