OPTIMIZATION OF SODIUM BICARBONATE-CITRIC ACID CONCENTRATION IN APHRODISIAC EFFERVESCENT GRANULE DOSAGE FORM OF A COMBINATION OF JAVANESE CHILI EXTRACT AND RED GINGER EXTRACT AND EVALUATION OF ITS PHYSICAL PROPERTIES

RIZA MAULANA; ARIFAH SRI WAHYUNI; MUHAMMAD DAI

doi:10.22159/ijap.2025v17i4.53539

Authors

RIZA MAULANA Faculty of Pharmacy, Universitas Muhammadiyah Surakarta, Jl. A. Yani No 1, Pabelan, Surakarta, Indonesia https://orcid.org/0009-0000-9491-3262
ARIFAH SRI WAHYUNI Faculty of Pharmacy, Universitas Muhammadiyah Surakarta, Jl. A. Yani No 1, Pabelan, Surakarta, Indonesia https://orcid.org/0000-0002-0088-7727
MUHAMMAD DAI Faculty of Pharmacy, Universitas Muhammadiyah Surakarta, Jl. A. Yani No 1, Pabelan, Surakarta, Indonesia https://orcid.org/0000-0003-3083-7875

DOI:

https://doi.org/10.22159/ijap.2025v17i4.53539

Keywords:

Aphrodisiacs, Blueberry, Effervescent, Javanese chili, Red ginger

Abstract

Objective: Javanese chili and red ginger have been recognized as natural ingredients that are potential to act as aphrodisiac agents. The flavonoids and alkaloids in these two natural ingredients can help to increase testosterone hormone. The value of novelty in this study is to combine the two active ingredients into one effervescent granule dosage form that, to be best of our knowledge, has not been done in previous similar studies. This study aims to optimize the concentration of citric acid and sodium bicarbonate in the effervescent granule dosage form of a combination of Javanese chili extract and red ginger extract to obtain an acceptable physical properties.

Methods: The research started from the extraction process of Javanese chili and red ginger until obtaining the dry extract, to the formula optimization stage and evaluation of physical properties, including organoleptical evaluation, granule flow speed, pH, and dispersion time of effervescent granules. The optimization process was carried out through the D-Optimal method with the help of Design Expert version 13 software.

Results: The results from the extraction of Javanese chili and the extraction of red ginger obtained 2.23% and 18.85%, respectively. The optimization results obtained the optimum formula of sodium bicarbonate: citric acid concentration ratio at 1225.08 and 280.92 mg, respectively. Furthermore, the results of statistical analysis using one sample t-test with SPSS software showed granule flowability at 13.78±0.94 g/sec (p value= 0.280; p>0.05), pH 6.02±0.09 (p value= 0.016; p<0.05), and dispersion time at 76.99±8.37 sec (p value= 0.245; p>0.05).

Conclusion: These results showed that granule flowability and dispersion time parameters were not significantly different between the predicted and verified values; however, for pH it was significantly different although the pH obtained still met the pH requirements of effervescent dosage form.

References

Liu Q, Zhang Y, Wang J, Li S, Cheng Y, Guo J. Erectile dysfunction and depression: a systematic review and meta-analysis. J Sex Med. 2018;15(8):1073-82. doi: 10.1016/j.jsxm.2018.05.016, PMID 29960891.

Wati W, Rahman EY, Rosida L, Sutapa H, Panghiyangani R. Literature review: relationship between age severity of benign prostate hyperplasia (BPH) and incidence of erectile dysfunction. Homeostasis. 2021 Apr 30;4(1):237–44.

Goldstein I, Goren A, Li VW, Tang WY, Hassan TA. Epidemiology update of erectile dysfunction in eight countries with high burden. Sex Med Rev. 2020;8(1):48-58. doi: 10.1016/j.sxmr.2019.06.008.

Wahyuni AS, Wahyuningtyas N, Arifiyanti. Aphrodisiac activity of essential oil from Syzygium aromaticum (L.) Merr. and perry. Pharmacon J Farm Indones. 2010;11(2):43-6.

Sri Wahyuni A, Maulana R, Maryati M, Da’i M. Exploration of indonesian herbal plants as aphrodisiac agents and testing their activity in animal testing. Res J Pharm Technol. 2024;17(8):3969-75. doi: 10.52711/0974-360X.2024.00616.

Salleh M, Ahmad F. Phytopharmacological investigations of Piper retrofractum Vahl. a review. Agric Conspec Sci. 2020;85(3):193-202.

Sharma M, Arya D, Bhagour K, Gupta RS. Natural aphrodisiac and fertility enhancement measures in males: a review. Curr Med Res Pract. 2017;7(2):51-8. doi: 10.1016/j.cmrp.2017.02.007.

Rachmawati L, Ismaya AP. Correlation between testosterone hormone libido and sperm quality in bligon kejobong and peranakan etawah goats. Bul Peternak. 2014;38(1):8-15.

Muslichah S. Aphrodisiac potential of active ingredients of java chili fruit (Piper retrofactrum Vahl.) in male wistar rats. J Agrotek. 2011;5(2):11-20.

Himayani R. The relationship of giving Javanese chili extract Piper retrofractum to the number of spermatozoa of adult male mice. J Kedokt Kesehat Univ Lampung. 2012;2(1):73-6.

Listiana O, Nurhidayati LG, Fia NS. Test of aphrodisiac activity of effervescent tablet preparations of combination extracts of bitter melon (Momordica charantia L.) and garlic (Allium sativum L.) in male white mice (Mus musculus L.). USADHA J Integr Obat Tradis. 2023;2(3):30-6.

Oktadiana I. Preformulation and evaluation of capsule preparations from red ginger (Zingiber officinale) as antidisminorhea. MEDFARM J Farm Kesehat. 2022;11(1):93-100. doi: 10.48191/medfarm.v11i1.99.

Jadhav S, Gangurde A. A bird eye view on effervescent drug delivery system. Int J Drug Deliv Technol. 2023;13(3):1046-58. doi: 10.25258/ijddt.13.3.45.

Vanhere KG, Derle DV, Khatale SB, Nangude SL. A comprehensive review on effervescent tablets. J Drug Delivery Ther. 2023;13(7):141-50. doi: 10.22270/jddt.v13i7.6120.

Yulianti DA, Sutoyo S. Formulation of effervescent tablets of katuk leaf extract (Sauropus androgynous L. Merr.) with variation of acid and base concentration. J Farm Sains Terap. 2021;8:34-40. doi: 10.36858/ipj.v2i1.44

Septianingrum NM, Hapsari WS, Amin MK. Formulation and test of effervescent powder preparation of okra extract (Abelmoschus esculentus) as nutridrink in patients with diabetes. Media Farm. 2019;16(1):11-20.

Rani KC, Parfati N, Muarofah D, Sacharia SN. Effervescent granule formulation of herba meniran (Phyllanthus niruri L.) with variations of suspending agent xanthan gum Cmc-Na, and combination of Cmc-Na-Microcrystalline cellulose Rc-591. J Sains Farm Klin. 2021;7(1):39-51.

Dani DH, Naqvi SB, Akram M, Khaliq SA, Nasiri MI. Design formulation optimization and stability studies of paracetamol effervescent tablets. Pak J Pharm Sci. 2023;36(1):247-54. doi: 10.36721/PJPS.2023.36.1.SP.247-254.1.

Diyya AS, Thomas NV. Formulation and evaluation of metronidazole effervescent granules. Int J Pharm Sci Res. 2018;9(6):2525-9. doi: 10.52711/2231-5691.2024.00055.

Sholikhah AM, Amal S, Susilowati F. Effervescent tablet formulation of kersen leaf (Muntingia calabura L.) with variation of effervescent mix concentration. Pharmasipha. 2018;2(2):37-42. doi: 10.21111/pharmasipha.v2i2.2779.

Azahra AS, Prabowo A, Yasmin AA. Development and evaluation of effervescent powder formulations combining red ginger extract and honey. IJHMS. 2024;2(2):41-5. doi: 10.46336/ijhms.v2i2.101.

Ministry of Health of Indonesia Republic. Indonesian pharmacopoeia. VI. Jakarta; 2020.

Kailaku SI, Sumangat J. Hernani. Formulation of antioxidant rich effervescent granule from gambir leaf extract. J Pascapanen. 2012;9(1):27-34.

Syaputri FN, Saila SZ, Tugon TD, R AP, Lestari D. Formulation and test of physical characteristics of effervescent granule preparations of ethanol extract of red betel leaf (Piper crocatum Ruiz) as antidiabetics. J Ilmu Kefarmasian. 2023;4(1):191-8.

Putri N, Slamet N, Wicita P, Imran A. Effervescent granule from combination of telang flower (Clitoria ternatea) and kalamansi orange (Citrus microcarpa) as alternative health drink. J Exp Clin Pharm. 2021;1(1):16-23.

Gopalan S, Gozali D. Article review: formulation and evaluation of effervescent granule and tablet preparations by wet granulation method. Farmaka. 2018;16(1).

Ministry of Health of Indonesia Republic. Indonesian Herbal Pharmacopoeia. II. Jakarta; 2017.

Dhondale MR, Thakor P, Nambiar AG, Singh M, Agrawal AK, Shastri NR. Co-crystallization approach to enhance the stability of moisture sensitive drugs. Pharmaceutics. 2023;15(1):189. doi: 10.3390/pharmaceutics15010189, PMID 36678819.

Jutkus RA, Li N, Taylor LS, Mauer LJ. Effect of temperature and initial moisture content on the chemical stability and color change of various forms of vitamin C. Int J Food Prop. 2015;18(4):862-79. doi: 10.1080/10942912.2013.805770.

Nadendla RR, Kanna S, Satyanarayana J. Design and evaluation of rivaroxaban effervescent granules. Indian Drugs. 2024 Mar 1;61(3):61-4. doi: 10.53879/id.61.03.14149.

Debiasi BW, Rodrigues PG, Torres MP, Bonacorsi C, Andrighetti CR, Ribeiro EB. Comparison between maceration and ultrasound assisted extraction of white bracts with flowers of Bougainvillea spectabilis willd. Sci Elec Arch. 2021;14(2):47. doi: 10.36560/14220211297.

Oprescu EE, Enascuta CE, Radu E, Ciltea Udrescu M, Lavric V. Does the ultrasonic field improve the extraction productivity compared to classical methods maceration and reflux distillation? Chem Eng Process Process Intensif. 2022 Sep 1;179:109082. doi: 10.1016/j.cep.2022.109082.

Atnip AA, Sigurdson GT, Bomser J, Giusti MM. Time concentration and pH-dependent transport and uptake of anthocyanins in a human gastric epithelial (NCI-N87) cell line. Int J Mol Sci. 2017;18(2):446. doi: 10.3390/ijms18020446, PMID 28218720.

Quina FH, Bastos EL. Chemistry inspired by the colors of fruits flowers and wine. An Acad Bras Cienc. 2018;90(1 Suppl 1):681-95. doi: 10.1590/0001-3765201820170492, PMID 29742202.

Bhatt U, Garishma SV. Therapeutic protective and industrial significances of anthocyanins: a review. Avicenna J Med Biochem. 2022;11(2):x-x. doi: 10.34172/ajmb.2338.

Olas B, Bialecki J, Urbanska K, Brys M. The effects of natural and synthetic blue dyes on human health: a review of current knowledge and therapeutic perspectives. Adv Nutr. 2021 Nov 1;12(6):2301-11. doi: 10.1093/advances/nmab081, PMID 34245145.

Duan Y, Tarafdar A, Chaurasia D, Singh A, Bhargava PC, Yang J. Blueberry fruit valorization and valuable constituents: a review. Int J Food Microbiol. 2022;381:109890. doi: 10.1016/j.ijfoodmicro.2022.109890, PMID 36095867.

Panjaitan EN, Saragih A, Purba D. Gel formulation of red ginger rhizome extract (Zingiber officinale Roscoe) gel formulation of red ginger (Zingiber officinale roscoe) extract. J Pharm Pharmacol. 2012;1(1):9-20.

Rullyansyah S, Muzakky F, Samlan K, Hanistya R, Maulidiyanti ET. Phytochemical screening and evaluation of red ginger extracts on aphrodisiac activity. Gac Med Caracas. 2022;130 Supll 1:S143-8. doi: 10.47307/GMC.2022.130.s1.26.

Erjon SY, Lely N, Sari E. Effects of Javanese chili extract (Piper retrofractum Vahl) on libido enhancement of male white mice. Fitofarmaka J Ilm Farm. 2020;10(2):133-9. doi: 10.33751/jf.v10i2.2176.

Alipoor M, Maier SE, Gu IY, Mehnert A, Kahl F. Optimal experiment design for monoexponential model fitting: application to apparent diffusion coefficient imaging. BioMed Res Int. 2015;2015:138060. doi: 10.1155/2015/138060, PMID 26839880.

Adi Dako O, Kumadoh D, Egbi G, Okyem S, Addo PY, Nyarko A. Strategies for formulation of effervescent granules of an herbal product for the management of typhoid fever. Heliyon. 2021 Oct 9;7(10)::e08147:1–8. doi: 10.1016/j.heliyon.2021.e08147.

Al Mousawy J, Al Hussainy Z, Alaayedi M. Formulation and evaluation of effervescent granules of ibuprofen. Int J App Pharm. 2019;11(6):66-9. doi: 10.22159/ijap.2019v11i6.34912.

Vasiljevic I, Turkovic E, Aleksic I, Parojcic J. Mathematical approaches for powders and multiparticulate units processability characterization in pharmaceutical development. Arh Farm. 2022;72(6):637-60. doi: 10.5937/arhfarm72-40961.

Nikam V, Bhosale A. Design development and physicochemical evaluation of effervescent tablets of antihistamine drug. Int J Drug Deliv Technol. 2023;13(4):1520-6. doi: 10.25258/ijddt.13.4.61.

Parajuli Baral K. Formulation and evaluation of quality parameters of effervescent granules from the potent antioxidant between two variants of the adaptogenic herb Ocimum tenuiflorum L. Sci World J. 2023 Apr 25;2023:1-8. doi: 10.1155/2023/2050846.

Forestry D, Abdurrahman, Ramadhan H. Effervescent tablet formulation ethanol extracts 70% kelakai root (Stenochlaena palutris (Burm. F.) Bedd.) with variation concentration of gas generating agent. Int J Appl Pharm. 2022;14( 2):10-6. doi: 10.22159/ijap.2022.v14s2.44740.

Zhou M, Wang Y, Wu F, Shen L, Lin X, Feng Y. Development on porous particles of pueraria lobatae radix for improving its compactibility and dissolution. RSC Adv. 2018;8(43):24250-60. doi: 10.1039/c8ra04125c, PMID 35539169.

Jamei R, Babaloo F. Tandfonline; 2017. International journal of food properties stability of blueberry (cornus mas-yulyush) anthocyanin pigment under ph and co-pigment treatments. Available from: https://www.com/action/journalinformationjournalcode=ljfp20. [Last accessed on 23 Feb 2025].

Verma D, Sharma N, Malhotra U. Structural chemistry and stability of anthocyanins. Pharma Innovation. 2023;12(7):1366-73. doi: 10.22271/tpi.2023.v12.i7p.21416.

Aulifa DL, Wibowo DP, Safitri N, Budiman A. Formulation of effervescent granules from red ginger (Zingiberis officinale roscoe var. rubrum) extract and its antioxidant activity. Int J Appl Pharm. 2022;14(1):112-5. doi: 10.22159/ijap.2022v14i1.43377.

Arote R, Malpure P, Talele G, Chaudhary J, Chaudhary R, Dhamane P. A review on Moringa olifera effervescent tablet. Asian J Pharm Res Dev. 2024;12(6):168-71. doi: 10.22270/ajprd.v12i6.1489.

Oza N, Sagar S, Khodakiya A, Sahu A. A statistical approach to development of taste masked effervescent tablets of sildenafil citrate containing kyron T134. Int J App Pharm. 2020;12(4):135-43. doi: 10.22159/ijap.2020v12i4.37624.

Pramono YB, Nurwantoro N. Evaluasi kadar gula kadar air kadar asam dan pH pada pembuatan tablet effervescent buah nangka. J Teknol Pang. 2019;3(1):36-41. doi: 10.14710/jtp.2019.20519.

Meisner M, Duda P, Szulc Musiol B, Sarecka Hujar B. Characteristics of commercial effervescent tablets using selected pharmacopeial and novel analytical methods. Appl Sci. 2023;13(5):3171. doi: 10.3390/app13053171.

Kholidah S, Yuliet KA. Formulation of ginger effervescent tablets (Zingiber officinale roscoe) with variation of acid and base source concentration. Online J Nat Sci. 2014;3:216-29.

Dubray C, Maincent P, Milon JY. From the pharmaceutical to the clinical: the case for effervescent paracetamol in pain management a narrative review. Curr Med Res Opin. 2021;37(6):1039-48. doi: 10.1080/03007995.2021.1902297, PMID 33819115.

Jaipal A, Pandey MM, Charde SY, Sadhu N, Srinivas A, Prasad RG. Controlled release effervescent buccal discs of buspirone hydrochloride: in vitro and in vivo evaluation studies. Drug Deliv. 2016;23(2):452-8. doi: 10.3109/10717544.2014.917388, PMID 24892624.

Taymouri S, Mostafavi A, Javanmardi M. Formulation and optimization of effervescent tablet containing bismuth sub-citrate. J Reports Pharm Sci. 2019 Jul 1;8(2):236–44.

Iwansyah AC, Fauzi H, Cahyadi W, Hariadi H, Indriati A, Wardhani R. Development physiochemical and sensory evaluation of a new effervescent tablet formulation based on Moringa oleifera leaves extract. Int J Food Eng. 2023;19(3-4):133-41. doi: 10.1515/ijfe-2022-0170.

Laili N, Komala M, Maulida H, Suprapto. Optimization of sago amylum concentration (Metroxylon rumphii) as co-processed in theophylline tablets. Pharmacon J Farm Indones. 2017;14(2):72-80.

Ramadhani RA, Riyadi DH, Triwibowo B, Kusumaningtyas RD. Review pemanfaatan design expert untuk optimasi komposisi campuran minyak nabati sebagai bahan baku sintesis biodiesel. J Tek Kim Ling. 2017;1(1):11-6. doi: 10.33795/jtkl.v1i1.5.

Asyhari HF, Cabral KB, Wikantyasning ER. Optimization of soursop (Annona muricata L.) leaf extract in nanoemulgel and antiacnes activity test against propionibacterium acnes staphylococcus aureus staphylococcus epidermidis bacteria. Pharmacon. 2023;20(2):216-25. doi: 10.23917/pharmacon.v20i2.23308.

Peter EL, Sesaazi CD. D-optimal mixture design optimized solid formulation containing fruits extracts of Momordica charantia and Abelmoschus esculentus. PLOS One. 2022;17(6):e0270547. doi: 10.1371/journal.pone.0270547, PMID 35749521.

Hazra A, Gogtay N. Biostatistics series module 1: basics of biostatistics. Indian J Dermatol. 2016;61(1):10-20. doi: 10.4103/0019-5154.173988, PMID 26955089.

Rahmana AY, Nurwaini S. Optimization of ethanol extract preparation gel formula from the combination of lime peel and neem leaves: optimum physical properties and antibacterial activity. 2024;21(1):9–18. doi: 10.23917/pharmacon.v21i0.23586.

Suksaeree J, Monton C. Applying design of experiments on the mechanical properties of mefenamic acid loaded transdermal films. Trends Sci. 2023;20(10):6-13. doi: 10.48048/tis.2023.7065.

Ghasemian E, Motaghian P, Vatanara A. D-optimal design for preparation and optimization of fast dissolving bosentan nanosuspension. Adv Pharm Bull. 2016;6(2):211-8. doi: 10.15171/apb.2016.029, PMID 27478783.

Zheng X, Wu F, Hong Y, Shen L, Lin X, Feng Y. Improvements in sticking hygroscopicity and compactibility of effervescent systems by fluid bed coating. RSC Adv. 2019;9(54):31594-608. doi: 10.1039/c9ra05884b, PMID 35527953.

Jang EH, Park YS, Kim MS, Choi DH. Model based scale up methodologies for pharmaceutical granulation. Pharmaceutics. 2020;12(5):453. doi: 10.3390/pharmaceutics12050453, PMID 32423051.

Brunetti P, LO Faro AF, Tini A, Busardo FP, Carlier J. Pharmacology of herbal sexual enhancers: a review of psychiatric and neurological adverse effects. Pharmaceuticals (Basel). 2020;13(10):309. doi: 10.3390/ph13100309, PMID 33066617.