Preparation and In vitro/Ex vivo Evaluation of Nanoemulsion-Based in Situ Gel for Intranasal Delivery of Lasmiditan

Authors

DOI:

https://doi.org/10.31351/vol33iss3pp128-141

Keywords:

Nanoemulsion, Ex-vivo permeation study, Lasmiditan, intranasal, and in situ gel.

Abstract

Lasmiditan (LAS) was formulated as a nanoemulsion based in situ gel (NEIG)with the aim of improving its oral bioavailability via application intranasally. The solubility of LAS in oils, emulsifiers, and co-emulsifiers was determined to identify nanoemulsion (NE)components. Phase diagrams were constructed to identify the area of nanoemulsification. LAS NE was formulated using the spontaneous nanoemulsification method.

Four NEs (F19, F24, F31, and F34) containing 7-15 % oleic acid (OA) as an oily phase, 40-55% labrasol (LR), and transcutol (TC) as emulsifier mixture at (1:1), (2:1), (3:1), and (1:2) ratio with 30-53 % (w/w) aqueous phase, having suitable optical transparency of 95–98%, globule size of 104-140 nm and polydispersity of 0.253–0.382 were selected for ex vivo permeation study.

F31 with the highest flux value (2.32 ± 0.01 mg/cm2.min) relative to the other NEs. It achieves an enhancement ratio of 3.3 as compared to LAS aqueous suspension (8% LAS) also it achieves a significantly higher value of permeability coefficient. F31 was selected for the incorporation of different percentages of pH-sensitive in situ gelling polymer (Carbopol 934) to prepare NEIGs 4,5 and 6. The gel strength, pH, gelation time, and viscosity were predicted for the prepared NEIGs. In vitro release and ex vivo, nasal permeation were determined for NEIG5, which exerts comparable release and permeation values as F31 with more residence time in order to overcome the normal nasal physiological clearance.

 

References

Beauchene JK, Levien TL. Lasmiditan: Acute Migraine Treatment Without Vasoconstriction. A Review. J Pharm Technol. 2021; 37(5): 244–53.

Mecklenburg Jasper, et al. The potential of lasmiditan in migraine. Ther. Adv. Neurol. Disord. 2020; 13:1-11.

REYVOW (Lasmiditan) Tablets, Eli Lilly and Company. Available online: https://www.accessdata.fda.gov/ drugs at fda-docs/label/2019/211280s000lbl.pdf (accessed on 30 June 2020).

Ramirez AL, Beltran ER, Haanes KA, Chan KY, Garrelds IM, Johnson KW, et al. Lasmiditan inhibits calcitonin gene-related peptide release in the rodent trigeminovascular system. Pain. 2020; 161(5): 1092–99.

Fiedler DS. Pharmacokinetics, pharmacodynamics, and drug–drug interactions of new anti-migraine drugs—Lasmiditan, gepants, and calcitonin-gene-related peptide (CGRP) receptor monoclonal antibodies. Pharmaceutics.2020;12(12), 1180.

Korani S, Bahrami S, Korani M, Banach M, Johnston TP, Sahebkar A. Parenteral systems for statin delivery. Lipids Health Dis.2019;18:193.

Sabri LA, Hussein AA. Oral liquid self-nanoemulsion of nebivolol: formulation and in-vitro characterization for dissolution rate enhancement. IJDDT. 2021;11(3):1083-91.

Elshafeey AH, Kamel AO, Fathallah MM. Utility of nanosize nanoemulsion for transdermal delivery of tolterodine tartrate: ex-vivo permeation and in-vivo pharmacokinetic studies. Pharm Res. 2009; 226:2446-53.

Huang C, Wang C, Zhang W, Yang T, Xia M, Lei X, et al. Preparation, in vitro and in vivo evaluation of nanoemulsion in-situ gel for transnasal delivery of traditional chinese medicine volatile oil from ligusticum sinense oliv. cv. chaxiong. Molecules.2022;27(21): 7644.

Abdulla N A, Balata G F, El-Ghamry H A, Gomaa E. Intranasal delivery of Clozapine using nanoemulsion-based in-situ gels: an approach for bioavailability enhancement. Saudi Pharm J. 2021;29(12):1466-1485.‏

Fadhel AY, Rajab NA. Tizanidine intranasal nanoemulsion in-situ gel: formulation and in-vivo brain study. J. Pharm. Negat.2022;13(2): 582-591.‏

Barbara V, et al. Recent advances in the development of in situ gelling drug delivery systems for non-parenteral administration routes. Pharmaceutics, 2020; 12(9): 859.‏

Chakrabarty S, Nath B. Oral in-situ gel for periodontitis: A review. World j. Pharm res.2018;7(11):262-76.

Hosny KM, Banjar ZM. The formulation of a nasal nanoemulsion zaleplon in situ gel for the treatment of insomnia. Expert opinion on drug delivery. 2013;10(8):1033-41.

Khames A. Formulation and characterization of eplerenone nanoemulsion liquid solids, an oral delivery system with higher release rate and improved bioavailability. Pharmaceutics. 2019;11(1):18.

Kumar R, Puppala K, Lakshmi V. Optimization and solubilization study of nanoemulsion budesonide and constructing pseudo ternary phase diagram. Asian J Pharm Clin Res.2019; 12 (1): 551-53.

Almajidi YQ, Mahdi ZH, Maraie NK. Preparation and in vitro evaluation of montelukast sodium oral nanoemulsion. Int J App Pharm. 2018; 10 (5): 49-53.

Suminar MM, Jufri M. Physical stability and antioxidant activity assay of a nanoemulsion gel formulation containing tocotrienol. Int J App Pharm.2017;9(1):140-3.

Patel HC, Parmar G, Seth AK, Patel JD, Patel SR. Formulation and evaluation of o/w nanoemulsion of ketoconazole. PSM. 2013;4(4):338-51.

Moghimipour E, Salimi A, Yousefvand T. Preparation and evaluation of celecoxib nanoemulsion for ocular drug delivery. Asian J. Pharm. 2017; 11 (3):543-50.

Mohamadi SS, Abdolalizadehb J, Herisa SZ. Ultrasonic/sonochemical synthesis and evaluation of nanostructured oil in water emulsions for topical delivery of protein drugs. Ultraso-Sonochem.2019; 55:86–95.

Patel G, Shelat P, Lalwani A. Statistical modeling, Optimization and characterization of solid self-nano emulsifying drug delivery system of lopinavir using design of experiment. Drug Deliv. 2016; 23(8):3027- 42.

Mundada VP, Sawant KS. Enhanced oral bioavailability and anticoagulant activity of dabigatran etexilate by self-micro emulsifying drug delivery system: Systematic Development, in vitro, ex vivo and in vivo evaluation. J Nanomed Nanotechnol. 2018; 9(1):1-13.

Alshahrani SM. Anti-inflammatory studies of ostrich oil-based nanoemulsion. J Oleo Sci.2019; 208(3):203–8.

Pratiwi L, Fudholi A, Martien R, Pramono S. Design and Optimization of self-nano emulsifying drug delivery systems (SNEDDS) of ethyl acetate fraction from mangosteen peel (Garcinia mangostana, L.). Inter J of PharmTech Res. 2016;9(6): 380-87

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(03): 431- 4.

Edresi S, Baie S. Formulation and stability of whitening VCO-in-water nano-cream.Int. j. of pharmaceutics. 2009;373(48):174-8.

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(5):1-13.

Bayanati M, Khosroshahi AG, Alvandi M, Mahboobian MM. Fabrication of a thermosensitive in situ gel nanoemulsion for nose to brain delivery of temozolomide. J. Nanomater. 2021: 1-11.‏

Ahmad N, Ahmad R, Buheazaha TM, AlHomoud HS, Al-Nasif HA, Sarafroz MD. A comparative ex vivo permeation evaluation of a novel 5-Fluorocuracilnanoemulsion-gel by topically applied in the different excised rat, goat, and cow skin. Saudi J Biol Sci. 2020;7: 1024–40.

Abdulla NA, Balata GF, El-Ghamry HA, Gomaa E. Intranasal delivery of Clozapine using nanoemulsion-based in-situ gels: An approach for bioavailability enhancement. Saudi Pharm J. 2021;29(12):1466-85.

Ameen D, Michniak-Kohna B. Transdermal delivery of dimethyl fumarate for Alzheimer's disease: Effect of penetration enhancers. Inter of Pharm. 2017; 529, 465–73.

Bhalerao H, Koteshwara KB, Chandran S. Design, Optimization and evaluation of in situ gelling nanoemulsion formulations of brinzolamide. Drug Deliv. Transl. Res. 2020;10: 529-47.

Kolsure PK, Rajkapoor B. Development of zolmitriptan gel for nasal administration. Asian J Pharm Clin Res. 2012; 5:88-94.

Alkufi HK, Kassab HJ. Formulation and evaluation of sustained release sumatriptan mucoadhesive intranasal in-situ gel. Iraqi J Pharm Sci. 2019;28(2):95-104.

Rajaa A D, Nawal AR. Formulation and investigation of lacidipine as nanoemulsions. Iraqi J Pharm Sci. 2020;29(1):41-45.

Da Costa S, Basri M, Shamsudin N, Basri H. Stability of Positively Charged Nanoemulsion Formulation Containing Steroidal Drug for Effective Transdermal Application. J. Chem. 2014:1-9.

Kaur G, Singh P, Sharma S. Physical, morphological, and storage studies of cinnamon-based nanoemulsions developed with Tween 80 and soy lecithin: A comparative study. J. Food Meas. Charact. 2021;15: 2386–98.

Morsi N, Ibrahim M, Refai H. Nanoemulsion-based electrolyte triggered in situ gel for ocular delivery of acetazolamide. Eur. J Pharm Sci. 2017;104: 302-14.‏

Misra SK, Pathak K. Nose-to-Brain Targeting via Nanoemulsion: Significance and Evidence. J. Colloid Interface Sci. 2023; 7(1):23.

Kawakami K, Yoshikawa T, Moroto Y, et al. Microemulsion formulation for enhanced absorption of poorly soluble drugs I. Prescription design. J Control Release 2002; 81:65-74.

Hanifah M, Jufri M. Formulation and stability testing of nanoemulsion lotion containing Centella asiatica extract. J Young Pharm. 2018;10(4):404–8.

An Y, Yan X, Li B, Li Y. Microencapsulation of capsanthin by self-emulsifying nanoemulsions and stability evaluation. Eur. Food Res. Technol. 2014; 239:1077–85.

Sarheed O, Dibi M, Ramesh K. 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):1223.

Sadoon NA, Ghareeb MM. Formulation and Characterization of Isradipine as Oral Nanoemulsion. Iraqi J Pharm Sci. 2020;29(1):143-15.

Hadi AS, Ghareeb MM. Rizatriptan benzoate nanoemulsion for intranasal drug delivery: preparation and characterization. IJDDT.2022;2 (2) :546-52.

Drais HK, Hussein AA. Formulation and characterization of carvedilol nanoemulsion oral liquid dosage form. Int J Pharm Pharm Sci. 2015;7(12):209-16.

Al-sakini SJ, Maraie NK. Optimization and in vitro evaluation of the release of class II drug from its nanocubosomal dispersion. Int J Appl Pharm. 2019;11(2):86–90.

Hamed SB, Alhammid SNA. Formulation and Characterization of Felodipine as an Oral Nanoemulsion. Iraqi J Pharm Sci. 2021;30(1):209–217.

Pandya D, Rana B, Solanki N. Oral bioavailability enhancement of bromocryptine mesylate by self-micro emulsifying drug delivery system (smedds). int j pharm pharm sci.2016; 8(6):76-81.

Baboota S, Shakeel F, Ahuja A, Ali J, Shafiq S. Design, development and evaluation of novel nanoemulsion formulations for the transdermal potential of celecoxib. Acta Pharmaceutica. 2007; 57(3): 315-32.‏

Mahajan HS, Mahajan MS, Nerkar PP, Agrawal A. Nanoemulsion-based intranasal drug delivery system of saquinavir mesylate for brain targeting. Drug Deliv. 2014;21(2):148–54.

Patel MR, Patel MH, Patel RB. Preparation and in vitro/ex vivo evaluation of nanoemulsion for transnasal delivery of paliperidone. Appl Nanosci. 2016;6(8):1095–104.

54.Sulaiman HT, Jabir SA, Al-kinani KK. Investigating the effect of different grades and concentrations of pH-sensitive polymer on preparation and characterization of lidocaine hydrochloride as in situ gel buccal spray. Asian J Pharm Clin Res.2018; 11(11):1-7.

Patil S, Kadam A, Bandgar S, Patil SH. formulation and evaluation of an in-situ gel for ocular drug delivery of anti-conjunctival drug. Cellulose Chem. Technol. 2015;49 (1): 35-40.

Nief RA, Tamer MA, Abd Alhammid SHN. Mucoadhesive oral in situ gel of itraconazole using pH-sensitive polymers: Preparation, and in vitro characterization, release, and rheology study. Drug Invent. Today. 2019; 11(6):1450-55.

Jaber SH& Rajab NA. Lasmiditan nanoemulsion based in situ gel intranasal dosage form: formulation, characterization and in vivo study. Farmacia.2023; 71(6):1241-53.

58.Changediya VV, Jani R, Kakde P. A Review on Nanoemulsions: A Recent Drug Delivery Tool. J Drug Deliv. Ther. 2019; 9(5):185-91.

59. Prajapati BG, Patel AG, Paliwal H. Fabrication of nanoemulsion-based in situ gel using moxifloxacin hydrochloride as a model drug for the treatment of conjunctivitis. Food Hydrocoll.2021;1:7.

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Published

2024-09-15

How to Cite

1.
Saba Abdulhadi Jaber, Nawal Ayash Rajab. Preparation and In vitro/Ex vivo Evaluation of Nanoemulsion-Based in Situ Gel for Intranasal Delivery of Lasmiditan. IJPS [Internet]. 2024 Sep. 15 [cited 2024 Oct. 9];33(3):128-41. Available from: https://bijps.uobaghdad.edu.iq/index.php/bijps/article/view/2734