DESIGN AND CHARACTERIZATION OF NANOSPRAY WITH SELF-NANOEMULSIFYING DRUG DELIVERY SYSTEM USING SINERGISTIC COMBINATION OF MELASTOMA MALABATHRICUM L. FRACTION AND GENTAMICIN
Keywords:Nanospray, SNEDDS, Melastoma malabathricum, Gentamicin
Objective: This study aimed to design a formula using Design-Expert software to obtain optimal Self-Nanoemulsifying Drug Delivery System (SNEDDS) formulas and to analyze nanospray characteristics of optimal SNEDDS.
Methods: The study began with preparing ethanol extract from Melastoma malabathricum. The extract was then fractionated using ethyl acetate. The formulation design stage began with a solubility test of Melastoma malabathricum fraction and gentamicin (MFG) in various surfactants, co-surfactants and oils. Furthermore, the 14 formula of SNEDDS with various compositions of the selected surfactants, co-surfactants and oils were formulated and evaluated with pH response and emulsification time. Analysis was carried out using Design-Expert software with the simplex lattice design method in order to obtain the optimal formula profile. The pH, emulsification time, particle size, and zeta potential of the nanospray from SNEDDS optimal formulas were physically characterized. Stability of SNEDDS and the nanospray was then tested with freeze-thaw cycling and in vitro diffusion studies with Franz diffusion.
Results: Based on the study, the ratios of optimal formula SNEDDS composition of Tween 80, propylene glycol, and soybean oil were 2.69: 2.64: 1.67 parts. Nanospray with SNEDDS technology had characteristics of pH 5.61±0.16, emulsification time 7.68±0.18, particle size 270.7 nm, and zeta potential-37.20 mV, and it was stable.
Conclusion: Nanospray can be formulated from optimal SNEDDS using Design-Expert software. Nanospray with SNEDDS technology has physical characteristics and is stable. In vitro diffusion studies revealed that the release of Melastoma malabathricum from nanospray was faster than that without preparation.
Sarbadhikary, Basu S, Bhowmik S, Datta BK, Mandal NC. Antimicrobial and antioxidant activity of leaf extracts of two indigenous angiosperm species of tripura. Int J Curr Microbiol Appl Sci 2015;4:643-55.
Alnajar ZA, Abdulla MA, Ali HM, Alshawsh MA, Hadi AH. Acute toxicity evaluation, antibacterial, antioxidant and immunomodulatory effects of Melastoma malabathricum. Molecules 2012;17:3547-59.
Diris AM, Basri F, Metali N, Ahmad H, Taha. Phytochemicals and antimicrobial activities of Melastoma malabathricum and Melastoma beccarianum leaf crude extracts. Res J Phytochem 2017;11:35-41.
Devi AS, Rajkumar J, Modilal MR, Ilayaraja R. Antimicrobial activities of Avicennia marina, Caesalpinia pulcherrima and Melastoma malabathricum against clinical pathogens isolated from UTI. Int J Pharma Bio Sci 2012;3:698-705.
Rajenderan MT. Ethno medicinal uses and antimicrobial properties of Melastoma malabathricum. SEGi Rev 2010;3:34-44.
Date AA, Neha D, Rahul D, Mangal N. Self-nanoemulsifying drug delivery system: formulation insights applications and advances. Nanomedicine 2010;5:1596-616.
Alwadei M, Kazi M, Alanazi FK. Novel oral dosage regimen based on self-nanoemulsifying drug delivery systems for codelivery of phytochemicals-curcumin and thymoquinone. Saudi Pharm J 2019;27:866-76.
Dokania S, Amita KJ. Self-microemulsifying drug delivery system (SMEDDS)–challanges and road ahead. Drug Delivery 2015;22:675-90.
Zhao Y, Changguang W, Albert HL, Ke R, Tao G, Zhirong Z, et al. Self-nanoemulsifying drug delivery system (SNEDDS) for oral delivery of Zedoary essential oil: formulation and bioavability studies. Int J Pharm 2010;383:170-7.
Baloch J, Sohail MF, Sarwar HS, Kiani MH, Khan GM, Jahan S, et al. Self-nanoemulsifying drug delivery system (SNEDDS) for improved oral bioavailability of chlorpromazine: in vitro and in vivo evaluation. Medicina 2019;55:210.
Verma R, Kaushik D. Design and optimization of candesartan loaded self-nanoemulsifying drug delivery system for improving its dissolution rate and pharmacodynamic potential. Drug Delivery 2020;27:756–71.
Alsulays S, Imam S, Hussain H, Alyousef A, Altamimi M, Alsulays B, et al. Flufenamic acid-loaded self-nanoemulsifying drug delivery system for oral delivery: from formulation statistical optimization to preclinical anti-inflammatory assessment. J Oleo Sci 2020;69:1257-71.
Kontogiannidou E, Meikopoulos M, Gika H, Panteris E, Vizirianakis I, Müllertz A, et al. In vitro evaluation of self-nano-emulsifying drug delivery systems (SNEDDS) containing room temperature ionic liquids (RTILs) for the oral delivery of amphotericin b. Pharmaceutics 2020;12:699.
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. IJPPS 2011;1:112–8.
Pratiwi L, Sari R, Apridamayanti P. Self-nanoemulsifying drug delivery system (SNEDDS) with enhanched solubilization of ethanol extract from mangosteen peels (Garcinia mangostana L.,) for treatment of topical gangrene foot: design and optimization. IJDDT 2017;7:314-9.
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.
Tranggono R, Fatma L. Cosmetic science handbook. Jakarta, Indonesia: Gramedia Pustaka Utama; 2007.
Mustika A, Fatimah N, Sari GM. Formulation and characterizations of self-nanoemulsifying drug delivery system of extract Petiveria Alliacea (Singawalang) leaves. Int J Appl Pharm 2019;11:61-5.
Vilas P, Gujarathi N, Bhushan R. Preparation and in vitro evaluation of self-nanoemulsifying drug delivery system (SNEDDS) containing clopidogrel. Int J Pharm Sci Rev Res 2014;25:10-5.
Parmar N, Singla N, Amin S, Kohli K. Study of cosurfactant effect on nanoemulsifying area and development of lercanidipine loaded (SNEDDS) self nanoemulsifying drug delivery system. Colloids Surf B 2011;86:327–38.
Beg S, Jena SS, Patra CN, Rizean M, Swain S, Sruti J, et al. Development of solid self-nanoemulsifying granules (SSNEGs) of ondancentron hydrochloride with enhanced bioavailability potential. Colloids Surf B 2013;101:414-23.
Eid AM, Baie SH, Arafat OM. The effect of surfactant blends on the production of a novel switeria macrophylla oil self-nanoemulsifying system. Int J Pharm Pharm Sci 2012;46:85-95.
Basalious EB, Shawky N, Badr-Eldin SM. SNEDDS containing bioenhancers for improvement of dissolution and oral absorption of lacidipine: development and optimization. Int J Pharm 2010;391:203-11.
Sakloetsakun D, Dunnhaupt S, Barthelmes J, Perera G, Bernkop Schnurch A. Combining two technologies: multifunctional polymers and self-nanoemulsifying drug delivery system (SNEDDS) for oral insulin administration. Int J Biol Macromol 2013;61:363–72.
Shafiq-un-Nabi S, Shakeel F, Talegaonkar S, Ali J, Baboota S, Ahuja A, et al. Formulation development and optimization using nanoemulsion technique: a technical note. Am Assoc Pharm Sci 2007;8:12–7.
Pyka A. Evaluation of the lipophilicity of fat-soluble vitamins. J Planar Chromatography Modern TLC 2009;22:211-5.
Singh AP, Gopal L, Khatik, Mishra V, Khurana N, Sharma N, et al. Formulation development and in vitro antioxidant and antidiabetic evaluation of Erioborya Japonica based self nano emulsifying drug delivery system. Int J Appl Pharm 2019;11:313-9.
Oza N, Sagar S, Khodakiya A. Use of simplex lattice design in development of oral self-nanoemulsifying drug delivery system containing rosuvastatin calcium. Int J Appl Pharm 2020;12:40-7.
Amrutkar C, Salunkhe KS, Chaudhari SR. Review on self nanoemulsifiying drug delivery system. Am J PharmTech Res 2014;4:2249-3387.
Nasr A, Gardouh A, Ghonaim H, Abdelghany E, Ghorab M. Effect of oils, surfactants and cosurfactants on phase behaviour and physicochemical properties of self-nanoemulsifying drug delivery system (SNEDDS) for irbesartan and olmesartan. Int J Appl Pharm 2016;8:13-24.
Pouton CW, Porter CJ. Formulation of lipid-based delivery systems for oral administration: materials, methods and strategies. Adv Drug Delivery Rev 2008;60:625–37.
Constantinides PP, Scalart JP. Formulation and physical characterization of water in oil microemulsion containing long versus medium chain glycerides. Int J Pharm 1997;158:57–68.
Gupta RK, Srinivasan MP, Dharmarajan R. Synthesis of short chain thiol capped gold nanoparticles, their stabilization and immobilization on silicon surface. Colloids Surf A 2011;390:149–56.
Farooq SU, Kumar S, Shahid AA. Formulation development and evaluation of self-nanoemulsifying drug delivery system of vitamin a for better bioavailability syed. Asian J Pharm 2019;13:9-16.
Kassem A, Mohsen AM, Ahmed RS, Essam TM. Self-nanoemulsifying drug delivery sytem (SNEDDS) with enhanced solubilization of nystatin for treatment of oral candidiasis: design, optimization, in vitro and in vivo evaluation. J Mol Liquids 2016;218:219–32.
Xi J, Chang Q, Chan CK, Meng ZY, Wang GN, Sun JB, et al. Formulation development and bioavailability evaluation of a self-nanoemulsified drug delivery system of oleanolic acid. Am Assoc Pharm Sci 2009;10:172–82.
Fahmy UA, Ahmed OA, Hosny KM. Development and evaluation of avanafil selfnanoemulsifying drug delivery system with rapid onset of action and enhanced bioavailability. AAPS J 2015;16:53–8.
Hosny KM, Banjar ZM. The formulation of a nasal nanoemulsion zaleplon in situ gel for the treatment of insomnia. Expert Opinion Drug Delivery 2013;10:1033–41.
Singh SK, Verma PR, Razdan B. Glibenclamide-loaded self-nanoemulsifying drug delivery system: development and characterization. Drug Dev Ind Pharm 2010;36:933–45.
Fernandez P, Andre V, Rieger J, Kuhnle A. Nanoemulsion formation by emulsion phase inversion. Colloids Surf A 2004;251:53-8.
Larsen AT, Akesson P, Jureus A, Saaby L, Abu-Rmaileh R, Abrahamsson B, et al. Bioavailability of cinnarizine in dogs: effect of SNEDDS loading level and correlation with cinnarizine solubilization during in vitro lipolysis. Pharm Res 2013;30:3101–13.
Badran MM, Taha EI, Tayel MM, Al-Suwayeh SA. Ultra-fine self nanoemulsifying drug delivery system for transdermal delivery of meloxicam: dependency on the type of surfactants. J Mol Liquids 2014;190:16–22.
Setiawan SD, Ramadhani CC, Veronika A, Nugroho BH, Syukri Y. Formulation of self nano-emulsifying drug delivery system (SNEDDS) loaded red fruit oil (Pandanus conoideus Lamk.) using biodegradable nutraceutical surfactant. Proceedings of International Conference on Technology and Social Science; 2018.
Dixit AR, Rajput SJ, Patel SG. Preparation and bioavailability assessment of SMEDDS containing valsartan. AAPS J 2010;11:314–21.
Yoo JH, Shanmugam S, Thapa P, Lee ES, Balakrishnan P, Baskaran R, et al. Novel self-nanoemulsifying drug delivery system for enhanced solubility and dissolution of lutein. Arch Pharmacal Res 2010;33:417–26.
Kanwala T, Kawisha M, Maharjana R, Ghaffara I, Alib HS, Imrana M, et al. Design and development of permeation enhancer containingself-nanoemulsifying drug delivery system (SNEDDS) for ceftriaxonesodium improved oral pharmacokinetics. J Mol Liquids 2019;289:1-9.
Patel MJ, Patel N, Patel M. A self-microemulsifying drug delivery system (SNEDDS). Int J Pharm Pharm Sci 2010;4:29–33.
Balakumar K, Raghavan CV, Selvan NT, Prasad RH, Abdu S. Self nanoemulsifying drug delivery system (SNEDDS) of rosuvastatin calcium: design, formulation, bioavailability and pharmacokinetic evaluation. Colloids Surf B 2013;112:337–43.
Shakeel F, Haq N, Alanazi FK, Alsarra IA. Polymeric solid self-nanoemulsifying drug delivery system of glibenclamide using coffee husk as a low cost biosorbent. Powder Technol 2014;256:352–60.
Honary S, Zahir F. Effect of zeta potential on the properties of nano-drug delivery systems-a review (Part 2). Trop J Pharm Res 2013;12:265-73.
Wissing SA, Kayser O, Müller RH. Solid lipid nanoparticles for parenteral drug delivery. Adv Drug Delivery Rev 2014;56:1257–72.
Agrawal M, Agrawal Y, Itankar P, Patil A, Vyas J, Kelkar A. Phytochemical and HPTLC studies of various extracts of Annona squamosa (Annonaceae). Int J PharmTech Res 2012;4:364–8.
Choi KO, Aditya NP, Ko S. Effect of aqueous pH and electrolyte concentration on structure, stability and flow behavior of non-ionic surfactant based solid lipid nanoparticles. Food Chem 2014;147:239–44.
Alkhatib MA, Aly MM, Rahbeni RA, Balamash KS. Antimicrobial activity of biocompatible microemulsions against Aspergillus niger and herpes simplex virus type 2. Jundishapur J Microbiol 2016;9:374-7.
Pouton CW. Lipid formulations for oral administration of drugs: non-emulsifying, self-emulsifying and self-microemulsifying drug delivery systems. Eur J Pharm Sci 2000;11:93–8.
Bandyopadhyay S, Katare OP, Singh B. Optimized self nanoemulsifying systems of ezetimibe with enhanced bioavailability potential using long chain and medium chain triglycerides. Colloids Surf B 2012;100:50-61.
Sinko JP. Martin's physical pharmacy and pharmaceutical sciences. 5th edition: Lippincott Williams and Wilkins. United State of America; 2006. p. 232-3, 378, 409.
Graca M, Bongaerts JH, Stokes JR, Granick S. Friction and adsorption of aqueous polyoxyethylene (Tween) surfactants at hydrophobic surfaces. J Colloid Interface Sci 2007;315:662–70.
Songkro S, Wungsintaweekul J, Chartwaingaam S. Investigation of enhancing activity and skin irritation of Zingiber officinale, Zingiber cassumunar and Curcuma zedoaria. J Drug Delivery Sci Technol 2008;18:169-79.
Villar AM, Naveros BC, Campmany AC, Trenchs MA, Rocabert CB, Bellowa LH. Design and optimization of self-nanoemulsiying drug delivery systems (SNEDDS) for enhanced dissolution of gemfibrozil. Int J Pharm 2012;431:161-75.
Scalia S, Trotta V, Iannuccelli V, Bianchi A. Enhancement of in vivo human skin penetration of resveratrol by chitosan-coated lipid microparticles. Colloids Surf B 2015;135:42–9.
Smejkalova D, Muthny T, Nesporova K, Hermannova M, Achbergerova E, Huerta Angeles G, et al. Hyaluronan polymeric micelles for topical drug delivery. Carbohydr Polym 2017;156:86–96.
Alvi J, Madan D, Kaushik S, Sardana RS, Pandey A Ali. Comparative study of transfersomes, liposomes, and niosomes for topical delivery of 5-fluorouracil to skin cancer cells: preparation characterization, In vitro release, and cytotoxicity analysis. Anticancer Drugs 2011;22:774–82.
Prasanthi DP, Lakshmi. Vesicle-mechanism of transdermal permeation: a review. Asian J Pharm Clin Res 2012;5:18-25.
Rahimpour YH, Hamishehkar. Lactose engineering for better performance in dry powder inhalers. Adv Pharm Bull 2012;2:183–7.
Preethi GB, Shivakumar HN, Ravikumar M, Swet N. Prototype self emulsifying system of etravirine: design, formulation and in vitro evaluation. Int J Appl Pharm 2018;10:13-9.