Preparation and Evaluation of Pimecrolimus Nanoemulsion for Topical Delivery
DOI:
https://doi.org/10.31351/vol34iss3pp131-141Keywords:
nanoemulsion, pimecrolimus , benzyl alcohol , tween80, RP-HPLC.Abstract
One of the innovative approaches to delivering drugs via topical route is nanoemulation (NE), which is easy to manufacture, stable over the long term, and has a potent solubilization property. Pimecrolimus is a low water soluble drug used to treat psoriasis, eczema, atopic dermatitis and vitiligo. This work describes the high-energy ultrasonication technique used to prepare pimecrolimus nanoemulsion. A pseudo-ternary phase diagram was created in order to determine the ideal ratios of oil-surfactant/co-surfactant mixture for the creation of nanoemulsions. Based on pimecrolimus's solubility in various oils, surfactants, and co-surfactants, Tween 80 was chosen as a surfactant, ethanol as a co-surfactant, and benzyl alcohol as an oil phase .The work involved creating twelve NE formulas for optimization, and evaluated for thier droplet size, visual transparency, entrapment efficiency, zeta potential, physical stability, and in vitro release. Droplet size is 45.1 nm, entrapment efficiency is 92.59%, PDI is 0.402, Zeta potential is -0.8 mV, were displayed by the ideal NE formula, which released 76.3% in 5h and 96.6% of pimecrolimus in 24h compared with the commercial cream which released 26.2% in 5h and 42.5% of the drug in 24h. This suggests that the prepared formula has promising potential as an effective nanocarrier to enhance drug solubility and permeability and, consequently, its therapeutic effectiveness topically through the skin. These results demonstrated the formula's promising potential as an effective nanocarrier to improve drug solubility and permeability and, consequently, its therapeutic effectiveness topically through the skin.
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References
Verma V, Easwari TS. A novel approach of leflunomide nanoemulgel for topical drug delivery system. Int J Pharm Investig. 2022;12(2):199–204.
Tadros T, Izquierdo P, Esquena J, Solans C. Formation and stability of nano-emulsions. Adv Colloid Interface Sci. 2004;108–109:303–18.
Mustafa IF, Hussein MZ. Synthesis and technology of nanoemulsion-based pesticide formulation. Nanomaterials. 2020;10(8):1–26.
Pagar KR, Darekar AB. Nanoemulsion: A new concept of delivery system. Asian J Res Pharm Sci. 2019;9(1):39.
Sambyal K, Singh RV. Bioprocess and genetic engineering aspects of ascomycin production: a review. J Genet Eng Biotechnol. 2020;18(1).
NEHA SHARMA AND MUKESH KUMAR GUPTA. Forced degradation studies of pimecrolimus as per ICH guidelines. J Pharm Negat Results. 2022;13(9):5344–57.
Lade S, Rajendra Prasad Y. A new validated stability indicating RP-HPLC method for estimation of pimecrolimus in bulk and topical formulations. Int J Adv Pharm Biotechnol. 2015;1(1):33–44.
Ghareeb MM, Mohammed MS. Topical nanoemulsion-based gel of isoconazole. Al Mustansiriyah J Pharm Sci. 2023;23(4).
Maraie NK, Almajidi YQ. Application of nanoemulsion technology for preparation and evaluation of intranasal mucoadhesive Nano- In-situ Gel for Ondansetron HCl. J Glob Pharma Technol. 2018;10(3):431–42.
Alaayedi MH, Maraie NK. Lomustine’s nanoemulsion as nose-to-brain drug delivery system for CNS tumor treatment. Saudi Pharm J. 2023;31(8):101692.
Nirmala MJ, Durai L, Gopakumar V, Nagarajan R. Preparation of celery essential oil-based nanoemulsion by ultrasonication and evaluation of its potential anticancer and antibacterial activity. Int J Nanomedicine. 2020; 15:7651–66.
Fadhel AY, Rajab NA. Tizanidine nano emulsion: formulation and in-vitro characterization. J Pharm Negat Results. 2022;13(3):572–81
Azizkhani M, Jafari Kiasari F, Tooryan F, Shahavi MH, Partovi R. Preparation and evaluation of food-grade nanoemulsion of tarragon (Artemisia dracunculus L.) essential oil: antioxidant and antibacterial properties. J Food Sci Technol. 2021;58(4):1341–8.
Tarik Alhamdany A, Saeed AMH, Alaayedi M. Nanoemulsion and solid nanoemulsion for improving oral delivery of a breast cancer drug: formulation, evaluation, and a comparison study. Saudi Pharm J. 2021;29(11):1278–88.
Jamal Ali Ashoor1 MMG. Preparation and in vitro evaluation of methotrexate mucoadhesive nanogel proposed for cervical cancer therapy. Kerbala J Pharm Pharm Sci. 2022;
Yuliani S, Noveriza R. Effect of carrier oil and co-solvent on the formation of clove oil nanoemulsion by phase inversion technique. IOP Conf Ser Earth Environ Sci. 2019;309(1).
Huang S, Huang Z, Fu Z, Shi Y, Dai Q, Tang S, et al. A novel drug delivery carrier comprised of nimodipine drug solution and a nanoemulsion: Preparation, characterization, in vitro, and in vivo studies. Int J Nanomedicine. 2020; 15:1161–72.
LIANG CX, QI DL, ZHANG LN, LU P, LIU ZD. Preparation and evaluation of a water-in-oil nanoemulsion drug delivery system loaded with salidroside. Chin J Nat Med. 2021;19(3):231–40.
Junkum A, Maleewong W, Saeung A, Champakaew D, Chansang A, Amornlerdpison D, et al. Ligusticum sinense nanoemulsion gel as potential repellent against aedes aegypti, anopheles minimus, and culex quinquefasciatus (Diptera: Culicidae). Insects. 2021;12(7).
Yuliani S, Noveriza R. Effect of carrier oil and co-solvent on the formation of clove oil nanoemulsion by phase inversion technique. IOP Conf Ser Earth Environ Sci. 2019;309(1).
Jan Y, Al-Keridis LA, Malik M, Haq A, Ahmad S, Kaur J, et al. Preparation, modelling, characterization and release profile of vitamin D3 nanoemulsion. Lwt. 2022;169(May):113980.
Shafiq S, Shakeel F, Talegaonkar S, Ahmad FJ, Khar RK, Ali M. Development and bioavailability assessment of ramipril nanoemulsion formulation. Eur J Pharm Biopharm. 2007;66(2):227–43.
Kim BS, Won M, Lee KM, Kim CS. In vitro permeation studies of nanoemulsions containing ketoprofen as a model drug. Drug Deliv. 2008;15(7):465–9.
Sholihat SI, Indahyanti E, Lestari MLAD, Ningsih Z. Preparation of curcumin nanoemulsion in soybean oil-tween 80 system by wet ball milling method. IOP Conf Ser Mater Sci Eng. 2020;833(1).
Shunmugaperumal T, Ramachandran SS, Raj B, Thenrajan RS. Manufacturing techniques and excipients used during the formulation of oil-in-water type nanosized emulsions for medical applications. J Excipients Food Chem. 2010;1(1):11–29.
Tayel SA, El-Nabarawi MA, Tadros MI, Abd-Elsalam WH. Promising ion-sensitive in situ ocular nanoemulsion gels of terbinafine hydrochloride: Design, in vitro characterization and in vivo estimation of the ocular irritation and drug pharmacokinetics in the aqueous humor of rabbits. Int J Pharm. 2013;443(1–2):293–305.
Çinar K. a Review on nanoemulsions: preparation methods and stability. Trak Univ J Eng Sci 2017;18(1):73–83.
Asadinezhad S, Khodaiyan F, Salami M, Hosseini H, Ghanbarzadeh B. Effect of different parameters on orange oil nanoemulsion particle size: combination of low energy and high energy methods. J Food Meas Charact. 2019;13(4):2501–9.
Ali MS, Alam MS, Alam N, Siddiqui MR. Preparation, characterization and stability study of dutasteride loaded nanoemulsion for treatment of benign prostatic hypertrophy. Iran J Pharm Res. 2014;13(4):1125–40.
Sarheed O, Dibi M, Ramesh KVRNS. Studies on the effect of oil and surfactant on the formation of alginate-based O/W lidocaine nanocarriers using nanoemulsion template. Pharmaceutics. 2020;12(12):1–21.
Gupta A, Eral HB, Hatton TA, Doyle PS. Nanoemulsions: Formation, properties and applications. Soft Matter. 2016;12(11):2826–41.
Gaikwad SG, Pandit AB. Ultrasound emulsification: Effect of ultrasonic and physicochemical properties on dispersed phase volume and droplet size. Ultrason Sonochem. 2008;15(4):554–63.
A. OA, Hernández-Becerra JA, Cavazos-Garduño A, Vernon-Carter EJ, GarcÍa HS. Preparation and characterization of curcumin nanoemulsions obtained by thin-film hydration emulsification and ultrasonication methods. Rev Mex Ing Quim. 2016;15(1):79–90.
Patel K, Sarma V, Vavia P. Design and evaluation of lumefantrine - oleic acid self-nanoemulsifying ionic complex for enhanced dissolution. DARU, J Pharm Sci. 2013;21(1).
Mittal S, Ali J, Baboota S. Enhanced anti-psoriatic activity of tacrolimus loaded nanoemulsion gel via omega 3 - Fatty acid (EPA and DHA) rich oils-fish oil and linseed oil. J Drug Deliv Sci Technol 2021;63 :102458.
McClements DJ. Colloidal basis of emulsion color. Curr Opin Colloid Interface Sci. 2002;7(5–6):451–5.
Gul U, Khan MI, Madni A, Sohail MF, Rehman M, Rasul A, et al. Olive oil and clove oil-based nanoemulsion for topical delivery of terbinafine hydrochloride: in vitro and ex vivo evaluation. Drug Deliv. 2022;29(1):600–12
Beg S, Jena SS, Patra CN, Rizwan M, Swain S, Sruti J, et al. Development of solid self-nanoemulsifying granules (SSNEGs) of ondansetron hydrochloride with enhanced bioavailability potential. Colloids Surfaces B Biointerfaces. 2013; 101:414–23.
Chiesa M, Garg J, Kang YT, Chen G. Thermal conductivity and viscosity of water-in-oil nanoemulsions. Colloids Surfaces a Physicochem Eng Asp. 2008;326(1–2):67–72.
Chen K Di, Lin YF, Tu CH. Densities, viscosities, refractive indexes, and surface tensions for mixtures of ethanol, benzyl acetate, and benzyl alcohol. J Chem Eng Data. 2012;57(4):1118–27.
Agubata CO, Nzekwe IT, Obitte NC, Ugwu CE, Attama AA, Onunkwo GC. Effect of Oil, Surfactant and Co-Surfactant Concentrations on the Phase Behavior, Physicochemical Properties and Drug Release from Self-Emulsifying Drug Delivery Systems. J Drug Discovery Dev Deliv. 2014;1(1):7.
Sun J, Wang F, Sui Y, She Z, Zhai W, Wang C, et al. Effect of particle size on solubility, dissolution rate, and oral bioavailability: Evaluation using coenzyme Q10 as naked nanocrystals. Int J Nanomedicine. 2012; 7:5733–44.
Majeed H, Antoniou J, Hategekimana J, Sharif HR, Haider J, Liu F, et al. Influence of carrier oil type, particle size on invitro lipid digestion and eugenol release in emulsion and nanoemulsions. Food Hydrocoll. 2016; 52:415–22.
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