Author(s):
Neelam Patel, Sunita Chaudhary, Ankit Chaudhary
Email(s):
patel.neelam86@gmail.com , sunitaankitchaudhary@gmail.com , ankitbchaudhary@gmail.com
DOI:
10.52711/0974-360X.2023.00471 
Address:
Neelam Patel1*, Sunita Chaudhary2, Ankit Chaudhary3
1Department of Pharmaceutics, SAL Institute of Pharmacy, Gujarat Technological University, Ahmedabad, Gujarat - 380060, India.
2Sunita Chaudhary, Department of Pharmaceutics, Arihant School of Pharmacy and Bio- Research Institute, Gujarat Technological University, Ahmedabad, Gujarat - 382421, India.
3Ankit Chaudhary, Department of Pharmaceutical Analysis, Saraswati Institute of Pharmaceutical Science, Gujarat Technological University, Gandhinagar, Gujarat - 382355, India.
*Corresponding Author
Published In:
Volume - 16,
Issue - 6,
Year - 2023
ABSTRACT:
Apremilast is a selective phosphodiesterase 4 inhibitor administered orally in the treatment of moderate-to-severe plaque psoriasis and active psoriatic arthritis. It is classified as class IV drug as per BCS classification so it indicates low solubility and lower permeability through the skin. Therefore the objective of the research is to improve permeability of Apremilast through the skin and improve solubility by using oil and surfactant by formulating Nanoemulsion. Nanoemulsion was prepared by selecting Captex 355, Cremophore RH 40, Labrafil and Propylene glycol as the oil, surfactant,co-surfactant and co-solvent respectively after solubility study. Pseudo-ternary phase diagrams were constructed to find out the optimum ratio of oil: Smix (surfactant: co-Surfactant). Simple lattice design was applied to the optimization of the prepared nanoemulsion. The nanoemulsion was evaluated for Physical parameter, pH, Droplet size, zeta potential, in-vitro diffusion study etc. Results of Droplet size measurements, zeta potential and % drug diffusion indicated A5 batch optimized batch than other formulation of the nanoemulsion. So, optimized formulation further tested for Skin irritation study and stability study.The Apremilast loaded stable Nanoemulsion system was prepared and various process variables were evaluated. Batch A5 was selected as an optimized batch containing 10 % Captex 355, 40 % Smix (Cremophore RH 40 and Labrafil) and 50% water. Optimized batch was found to be stable after three month at ambient condition of temperature and humidity, giving reproducible results when evaluated.
Cite this article:
Neelam Patel, Sunita Chaudhary, Ankit Chaudhary. Formulation Development and Evaluation of Apremilast Nanoemulsion. Research Journal of Pharmacy and Technology 2023; 16(6):2859-6. doi: 10.52711/0974-360X.2023.00471
Cite(Electronic):
Neelam Patel, Sunita Chaudhary, Ankit Chaudhary. Formulation Development and Evaluation of Apremilast Nanoemulsion. Research Journal of Pharmacy and Technology 2023; 16(6):2859-6. doi: 10.52711/0974-360X.2023.00471 Available on: https://www.rjptonline.org/AbstractView.aspx?PID=2023-16-6-49
REFERENCES:
1. Pradhan M, Singh D, Singh MR. Novel colloidal carriers for psoriasis: current issues, mechanistic insight and novel delivery approaches. J. Controlled Release. 2013; 170(3): 380–395. DOI: 10.1016/j.jconrel.2013.05.020.
2. Puig L, Julià A, Marsal S. The pathogenesis and genetics of psoriasis. Acta Dermosifiliogr. 2014; 105(6): 535–545. DOI: 10.1016/j.ad.2012.11.006.
3. Kaltwasser JO, Nash P, Gladman D, Rosen CF, Behrens F, Jones P et al. Efficacy and safety of leflunomide in the treatment of psoriatic arthritis and psoriasis. Arthritis Rheum. 2004; 50 (6) :1939–1950. DOI: 10.1002/art.20253.
4. RahamatUnissa, P. Mahesh Kumar, Gella Sunil. Psoriasis: A Comprehensive Review. Asian J. Res. Pharm. Sci. 2019; 9(1):29-38.
5. Afra TP, Razmi TM, Dogra S. Apremilast in psoriasis and beyond: Big hopes on a small molecule. Indian Dermatol. Online J. 2019; 10(1):1–12.DOI: 10.4103/idoj.IDOJ.437.18.
6. Butler T, Maravent S, Boisselle J, Valdes J, Fellner C. A review of 2014 cancer drug approvals, with a look at 2015 and beyond. P T. 2014; 40(3) 191–205.
7. Ighani A, Georgakopoulos JR, Zhou LL, Walsh S, Shear N, Yeung J . Efficacy and safety of apremilastmonotherapy for moderate to severe psoriasis: Retrospective study. J Cutan Med Surg. 2018; 22(3): 290-6. DOI: 10.1177/1203475418755982.
8. Abdulrahim H, Thistleton S, Adebajo AO, Shaw T, Edwards C, Wells A. Apremilast: A PDE4 inhibitor for the treatment of psoriatic arthritis. Expert Opin. Pharmacother. 2015; 16 (7): 1099–1108. DOI: 10.1517/14656566.2015.1034107.
9. Edwards CJ, Blanco FJ, Crowley J, Birbara CA, Jaworski J, Aelion J et.al. Apremilast, an oral phosphodiesterase 4 inhibitor, in patients with psoriatic arthritis and current skin involvement: a phase III, randomised, controlled trial (PALACE 3) Ann Rheum Dis,2016;75(6):1065-73. DOI: 10.1136/annrheumdis-2015-207963.
10. Afra TP, Razmi TM, Dogra S. Apremilast in Psoriasis and Beyond: Big Hopes on a Small Molecule. Indian Dermatol Online J. 2019; 10(1):1–12. doi: 10.4103/idoj.IDOJ_437_18.
11. Nastiti C, Ponto T, Abd E, Grice J, Benson H, Roberts M . Topical Nano and Microemulsions for Skin Delivery. Pharmaceutics. 2017; 9(4):37. DOI: 10.3390/pharmaceutics9040037.
12. Mrunali RP, Rashmin BP, Jolly RP , Bharat GP. Novel microemulsion-based gel formulation of tazarotene for therapy of acne. Pharm Dev Technol. 2016; 21(8):921-932. Doi: 10.3109/10837450.2015.1081610
13. Vikram V.B.K. Mishra, S. B. Bhanja, B. B Panigrahi. Development and Evaluation of Nanoemulsion gel for transdermal delivery of Valdecoxib, Research J. Pharm. and Tech. 2019; 12(2):600-610.
14. Mu, H, Holm R, Müllertz A. Lipid-based formulations for oral administration of poorly water-soluble drugs. Int. J. Pharm. 2013;453:215–224. DOI: 10.1016/j.ijpharm.2013.03.054.
15. Munch S,Wohlrub J, Neubert RH. Dermal and transdermal delivery of pharmaceutically relevant macromolecules. European journal of Pharmaceutics and Biopharmaceutics. 2017; 119:235-242. Doi.org/10.1016/j.ejpb.2017.06.019
16. Rahul P. Jadhav, Vikranti W. Koli, Amruta B. Kamble, Dr. Mangesh A. Bhutkar. A Review on Nanoemulsion. Asian J. Res. Pharm. Sci. 2020; 10(2):103-108.
17. Kulkarni P, Deshpande A. Analytical Methods for Determination of Apremilast from Bulk, Dosage Form and Biological Fluids: A Critical Review, Critical Reviews in Analytical Chemistry. 2021; 51(3): 258-267, DOI: 10.1080/10408347.2020.1718481
18. Singh G,Pai RS. Trans-resveratrol self-nano-emulsifying drug delivery system (SNEDDS) with enhanced bioavailability potential: optimization, pharmacokinetics and in situ single pass intestinal perfusion (SPIP) studies. Drug Delivery. 2015; 22(4): 522–530.DOI: 10.3109/10717544.2014.885616.
19. Pund, S., Thankur, R., More, U., Joshi, A. Lipid based nanoemulsifying resveratrol for improved physicochemical characteristics, in vitro cytotoxicity and in vivo antiangiogenic efficacy. Colloids Surf. B Bio Interfaces. 2014; 120: 110–117. DOI: 10.1016/j.colsurfb.2014.05.016.
20. Amra K, Momin M. Formulation evaluation of ketoconazole microemulsion‐loaded hydrogel with nigella oil as a penetration enhancer. J CosmetDermatol. 2019; 1–9. DOI :10.1111/jocd.12945.
21. Espitia PJP. Fuenmayor CA. Otoni CG. Nanoemulsions: Synthesis, Characterization, and Application in Bio-Based Active Food Packaging.Compr. Rev. Food Sci. Food Saf. 2019; 18: 264–285.Doi :10.1111/1541-4337.12405.
22. Samadhan K. Deore, Rajendra K Surawase, Avish Maru. Formulation and Evaluation of O/W Nanoemulsion of Ketoconazole. Res. J. Pharma. Dosage Forms and Tech. 2019; 11(4):269-274.
23. Nishant Oza, Swati Sagar, Akruti Khodakiya. Use Of Simplex Lattice Design In Development of Oral Self-Nanoemulsifying Drug Delivery System Containing Rosuvastatin Calcium. International Journal of Applied Pharmaceutics. 2020; 12 (3):40-47.
24. Tandel H, Raval K, Nayani A, Upadhay M. Preparation and evaluation of cilnidipinemicroemulsion. J Pharm Bioallied Sci. 2012; 4(1):114–S115.DOI: 10.4103/0975-7406.94162
25. Date AA, Nagarsenker MS. Design and Evaluation of Microemulsion for improved Parenteral delivery of Propofol. AAPS PharmSciTech. 2008; 9(1): 138-145. DOI: 10.1208/s12249-007-9023-7.
26. R.B. Saudagar, ShraddhaVaishnav. Pharmaceutical Nano emulsion as a Rational Carrier for Drug Delivery. Research J. Pharm. and Tech. 9(3): Mar., 2016; Page 298-304.
27. Barot BS, Parejiya PB, Patel HK, Gohel MC , Shelat PK.Microemulsion-based gel of terbinafine for the treatment of onychomycosis: Optimization of formulation using D-optimal design. AAPS Pharm Sci Tech. 2012; 13(1): 184–192. DOI: 10.1208/s12249-011-9742-7
28. VaibhavChangediya, RupalbenJani, PradipKakde. Development and Evaluation of Mefenamic acid Nanoemulsion. Research J. Pharm. and Tech. 2021; 14(2):1003-1007.
29. Choudhury H, Gorain B, Pandey M, Chatterjee LA,Sengupta P, Das A et al.Recent Update on Nanoemulgel as Topical Drug Delivery System. J Pharm Sci. 2017; 106(7): 1736-1751. DOI: 10.1016/j.xphs.2017.03.042.
30. Wasim Khan, Vaseem Ahmad Ansari, Zeashan Hussain3, Noor Fatima Siddique. Nanoemulsion: A Droplet Nanocarrier System for Enhancing Bioavailability of Poorly Water Soluble Drugs. Research J. Pharm. and Tech. 2018; 11(11): 5191-5196.
31. Butani D, Yewale C, Misra A. Amphotericin B topical microemulsion: Formulation, characterization and evaluation. Colloids Surf B Biointerfaces. 2014; 116: 351–358. DOI: 10.1016/j.colsurfb.2014.01.014
32. Pople PV, Singh KK. Development and evaluation of topical formulation containing solid lipid nanoparticles of vitamin A. AAPS Pharm Sci Tech. 2006; 7: 91.
33. Vishali Mathialagan, Abimanyu Sugumaran, Damodharan Narayanaswamy. Nanoemulsion: Importance in Pharmaceutical Nanotechnology. Research J. Pharm. and Tech. 2020; 13(4):2005-2010.
34. Asif Eqbal, Vaseem Ahamad Ansari, Abdul Hafeez, Farogh Ahsan, Mohd Imran, SaquibTanweer. Recent Applications of Nanoemulsion Based Drug Delivery System: A Review. Research Journal of Pharmacy and Technology. 2021; 14(5):2852-8.
35. M. Nagajyothi, K. Pramod, E.N. Bijin, Jomon N. Baby, J. Valsalakumari. Accelerated Stability Studies of Atorvastatin Loaded Nanoemulsion Gel. Asian J. Pharm. Tech. 2015; 5(3):188-191.
36. Kanchan R. Pagar, A. B. Darekar. Nanoemulsion: A new concept of Delivery System. Asian J. Res. Pharm. Sci. 2019; 9(1):39-46.
37. R. G. Maskare, N. H. Indurwade, R. A. Deshmukh, P. V. Kuthe, P. M. Londhe, M. T. Deshmukh. Nanoemulsions: Increasing Possibilities in Oral Drug Delivery. Asian J. Pharm. Tech. 2021; 11(1):53-58.