Author(s):
Milon K. Ghosh, Md. Rafiqul I. Khan, Satyajit R. Rony, Biswajit Mukherjee, Mohammad K. M. Uddin, Sayera Banu, Ranjan K. Barman
Email(s):
rkb1976@ru.ac.bd
DOI:
10.52711/0974-360X.2025.00289
Address:
Milon K. Ghosh1,2, Md. Rafiqul I. Khan1, Satyajit R. Rony3, Biswajit Mukherjee4, Mohammad K. M. Uddin5, Sayera Banu5, Ranjan K. Barman1*
1Department of Pharmacy, University of Rajshahi, Rajshahi 6205, Bangladesh.
2Department of Pharmacy, Islamic University, Kushtia 7003, Bangladesh.
3Pharmaceutical Sciences Research Division, BCSIR Laboratories, Dhaka 1205, Bangladesh.
4Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India.
5Infectious Diseases Division, icddr,b, 68, Shaheed Tajuddin Ahmed Sarani, Dhaka 1212, Bangladesh.
*Corresponding Author
Published In:
Volume - 18,
Issue - 5,
Year - 2025
ABSTRACT:
The aim of present investigation was to develop self-nanoemulsifying drug delivery system of rifampicin (RIF) using vegetable oils for improved drug release and tuberculostatic activity (TSA). A number of lipid-based formulations were developed using vegetable oils, polysorbate 80, and ethanol at different weight ratio. The formulations were optimized based on visual assessment, in vitro dissolution study, electro-physical characterization and transmission electron microscopic analysis. The optimized formulation was subjected to in vitro TSA study against two clinically RIF-sensitive strains of M. tuberculosis (Mtb) followed by accelerated stability evaluation. Visual observation ascertained the self-emulsification efficiency of all the emulsions (NEs) in terms of clarity, homogeneity, and phase separation. Dissolution study of RIF-loaded NEs revealed that complete (100%) drug release was obtained by RIF-NE7 within 45 min, whereas pure drug liberated maximum 59.6%. This enhanced drug release was attributed to self-nanoemulsification accomplished through its globule size (GS), poly dispersity index (PDI) and zeta potential (ZP) by 230.2 nm, 0.768 and -79.2 mV, respectively. The in vitro TSA study revealed that the dissolution samples of RIF-NE7 at 30 and 45 min were capable to inhibit the growth of Mtb strains, while pure RIF showed no inhibition till 120 min. Finally, the accelerated stability study indicated no significant variation of RIF-NE7 in aspect to its drug release pattern, GS and ZP. Observation of this study conferred that the newer lipid-based formulation would be a promising alternative to conventional rifampicin therapy to combat tuberculosis.
Cite this article:
Milon K. Ghosh, Md. Rafiqul I. Khan, Satyajit R. Rony, Biswajit Mukherjee, Mohammad K. M. Uddin, Sayera Banu, Ranjan K. Barman. Design, Optimization and In vitro Assessment of Rifampicin Loaded Self-Nanoemulsifying Drug Delivery System. Research Journal of Pharmacy and Technology. 2025;18(5):2023-1. doi: 10.52711/0974-360X.2025.00289
Cite(Electronic):
Milon K. Ghosh, Md. Rafiqul I. Khan, Satyajit R. Rony, Biswajit Mukherjee, Mohammad K. M. Uddin, Sayera Banu, Ranjan K. Barman. Design, Optimization and In vitro Assessment of Rifampicin Loaded Self-Nanoemulsifying Drug Delivery System. Research Journal of Pharmacy and Technology. 2025;18(5):2023-1. doi: 10.52711/0974-360X.2025.00289 Available on: https://rjptonline.org/AbstractView.aspx?PID=2025-18-5-12
REFERENCES:
1. Bhutani U. Basu T. Majumdar S. Oral Drug Delivery: Conventional to Long Acting New-Age Designs. Eur J Pharm Biopharm. 2021; 162: 23-42. doi.org/ 10.1016/j.ejpb.2021.02.008
2. Krishnaiah YSR. Pharmaceutical Technologies for Enhancing Oral Bioavailability of Poorly Soluble Drugs. J Bioequiv Availab. 2010; 2: 028-036.
3. Viswanathan P. Muralidaran Y. Ragavan G. Challenges in oral drug delivery: a nano-based strategy to overcome. Nanostructures Oral Med. 2017; 173-201. doi.org/10.1016/B978-0-323-47720-8.00008-0
4. Kaur G. Grewal J. Jyoti K. Jain UK. Chandra R. Madan J. Oral controlled and sustained drug delivery systems: Concepts, advances, preclinical, and clinical status. Drug Target. and Stimuli Sensitive Drug Deliv. Syst. 2018; 567-626. doi.org/10.1016/B978-0-12-813689-8.00015-X
5. Buddhadev SS. Garala KC. Self-Nano Emulsifying Drug Delivery System: A Potential Solution to the Challenges of Oral Delivery of Poorly Water-Soluble Drugs. Research J. Pharm. and Tech. 2023; 16(10):4943-1. doi.org/10.52711/0974-360X.2023.00801
6. Sachan NK. Bhattacharya A. Pushkar S. Mishra A. Biopharmaceutical classification system: A strategic tool for oral drug delivery technology. Asian J. Pharm. 2009; 3:76-81. doi.org/10.22377/ajp. v3i2.245
7. Argade PS. Magar DD. Saudagar RB. Solid Dispersion: Solubility Enhancement Technique for poorly water-soluble Drugs. J. Adv. Pharm. Edu. & Res. 2013; 3: 427-439.
8. Hussain A. Shakeel F. Singh SK. Alsarra IA. Faruk A. Alanazi FK et al. Solidified SNEDDS for the oral delivery of rifampicin: Evaluation, proof of concept, in vivo kinetics, and in silico GastroPlusTM simulation. Int. J. Pharm. 2019; 566: 203-217. doi.org/ 10.1016/j.ijpharm.2019.05.061
9. Mohyeldin SM. Mehanna MM. Elgindy NA. The relevancy of controlled nanocrystallization on rifampicin characteristics and cytotoxicity. Int J Nanomedicine. 2016; 11: 2209-2222. doi.org/10.2147/IJN.S94089
10. Khadka P. Sinha S. Tucker IG. Dummer J. Hill PC. Katare R et al. Pharmacokinetics of rifampicin after repeated intra-tracheal administration of amorphous and crystalline powder formulations to Sprague Dawley rats. Eur J Pharm Biopharm. 2021; 162:1-11. doi.org/ 10.1016/j.ejpb.2021.02.011
11. Kumar A. Ghosh MK. Bithy MMA. Khan MRI. Huq MM. Wahed MII et al. Development and Evaluation of Stable Paracetamol Loaded Solid Dispersion with Enhanced Analgesic and Hepatoprotective Property. Pharmacology & Pharmacy. 2023; 14: 123-143. doi.org/ 10.4236/pp.2023.144010
12. Sarfaraz M. Hiremath D. Chowdary KPR. Formulation and Characterization of Rifampicin Microcapsules. Indian J Pharm Sci. 2010; 72: 101-105. doi.org/10.4103/0250-474X.62240
13. Shah RS. Shah RR. Nitalikar MM. Magdum CS. Microspheres by Spray Drying: An Approach to Enhance Solubility of Bicalutamide. Asian J. Pharm. Res. 2017; 7(3): 183-188.
14. Meena KP. Choudhary P. Karri T. Samal P. Preparation and Characterization of Rutin Loaded Microparticles for the treatment of Diabetes. Research J. Pharm. and Tech. 2023; 16(10):4867-4. doi: 10.52711/0974-360X.2023.00789
15. Sonawale P. Patil A. Kamble A. Bhutkar M. Solubility Enhancement of Lipophilic Drugs - Solid Self Micro-Emulsifying Drug Delivery System. Asian J. Pharm. Tech. 2016; 6 (3): 155-158.
16. Suxam. Bharti N. Sharma P. Kumari N. Microwave Generated Bionanocomposites for Solubility and Dissolution Enhancement of Poorly Water-Soluble Drug. Asian J. Pharm. Res. 2022; 12(3):192-8. DOI: 10.52711/2231-5691.2022.00031
17. Syed IA. Rao YM. Dendrimers Based Drug Delivery Systems. Research J. Pharm. and Tech. 2012; 5(3): 307-316.
18. Kumar GP. Kumar SK. Drug Dissolution Enhancement by Salt Formation: Current Prospects. Research J. Pharma. Dosage Forms and Tech. 2011; 3(6): 251-259.
19. Kunchanur M. Mannur VK. Raghuwanshi L. Mastiholimath V. Design Characterization and Stability studies of Mesalamine Loaded Solid Lipid Nanoparticles. Research J. Pharm. and Tech. 2023; 16(10):4767-3. doi: 10.52711/0974-360X.2023.00773
20. Gardouh A. Gamal Al. Gad S. Formulation and pharmacokinetic evaluation of rifampicin solid lipid nanoparticles. J Res Pharm. 2020; 24: 539-551.
21. Hussain A. Singha SK. Singha N. Verma PRP. In vitro-in vivo-in silico simulation studies of Anti-tubercular drugs doped with Self Nanoemulsifying Drug Delivery system. RSC Adv. 2016; 6:93147-93161. doi.org/10.1039/C6RA14122F
22. Alshamsan A. Kazi M. Badran MM. Alanazi FK. Role of Alternative Lipid Excipients in the Design of Self-Nanoemulsifying Formulations for Fenofibrate: Characterization, in vitro Dispersion, Digestion and ex vivo Gut Permeation Studies. Front. Pharmacol. 2018; 9:1219. doi.org/10.3389/fphar.2018.01219
23. Mohsin K. Alamri R. Ahmad A. Raish M. Alanazi FK. Hussain MD. Development of self-nanoemulsifying drug delivery systems for the enhancement of solubility and oral bioavailability of fenofibrate, a poorly water-soluble drug. Int J Nanomedicine. 2016; 11: 2829-2838. doi.org/10.2147/IJN.S104187
24. Shinde VR. Pore YV. Rao JV. A Novel Co-crystallization Technique to enhance the Physicochemical property of BCS Class-II drugs using Efavirenz as a model drug. Research J. Pharm. and Tech. 2022; 15(4):1603-9. doi: 10.52711/0974-360X.2022.00268
25. Makadia HA. Bhatt AY. Parmar RB. Paun MJS. Tank HM. Self-nano Emulsifying Drug Delivery System (SNEDDS): Future Aspects. Asian J. Pharm. Res. 2013; 3(1): 20-26.
26. Abushal AS. Aleanizy FS. Alqahtani FY. Shakeel F. Iqbal M. Haq N et al. Self-Nanoemulsifying Drug Delivery System (SNEDDS) of Apremilast: In Vitro Evaluation and Pharmacokinetics Studies. Molecules. 2022; 27:3085. doi.org/10.3390/molecules27103085
27. Morakul B. Self-nanoemulsifying drug delivery systems (SNEDDS): an advancement technology for oral drug delivery. Pharm Sci Asia. 2020; 47:205-220. doi.org/10.29090/psa.2020.03.019.0121
28. Kazi M. Alhajri A. Alshehri SM. Elzayat EM. Meanazel OTA. Shakeel F et al. Enhancing Oral Bioavailability of Apigenin Using a Bioactive Self-Nanoemulsifying Drug Delivery System (Bio-SNEDDS): In Vitro, In Vivo and Stability Evaluations. Pharmaceutics. 2020; 12: 749. doi.org/10.3390/pharmaceutics12080749
29. Kim DS. Cho JH. Park JH. Kim JS. Song ES. Kwon J et al. Self-microemulsifying drug delivery system (SMEDDS) for improved oral delivery and photostability of methotrexate. Int J Nanomedicine 2019; 14:4949-4960. doi.org/10.2147/IJN.S211014
30. Al-Qushawi A. Rassouli A. Atyabi F. Peighambari SM. Esfandyari-Manesh. Shams GR et al. Preparation and Characterization of Three Tilmicosin-loaded Lipid Nanoparticles: Physicochemical Properties and in-vitro Antibacterial Activities. Iran J Pharm Res. 2016; 15: 663-676.
31. van Staden D. du Plessis J. Viljoen J. Development of a Self-Emulsifying Drug Delivery System for Optimized Topical Delivery of Clofazimine. Pharmaceutics. 2020; 12: 523. doi.org/10.3390/pharmaceutics12060523
32. Fatouros DG. Ghoneim AM. Abdel‑Mageed HM. Osman R. Shaker DS. Structural Development of Self Nano Emulsifying Drug Delivery Systems (SNEDDS) During In Vitro Lipid Digestion Monitored by Small-angle X-ray Scattering. Pharmaceutical Research. 2017; 24:1844-1853. doi.org/10.1186/s43094-022-00418-4
33. Ogbole OO. Ajaiyeoba EO. Traditional management of tuberculosis in Ogun state of Nigeria: The practice and ethnobotanical survey. Afr. J. Trad. Cam. 2010; 7: 79-84.
34. Pouton CW. Lipid formulations for oral administration of drugs: non-emulsifying, self-emulsifying and ‘self-microemulsifying’ drug delivery systems. Eur. J. Pharm. Sci. 2000; 2: S93-8. doi.org/10.1016/s0928-0987(00)00167-6
35. Craig DQM. Barker SA. Banning D. Booth SW. An investigation into the mechanisms of self-emulsification using particle size analysis and low frequency dielectric spectroscopy. Int. J. Pharm. 1995; 114: 103-110. doi.org/10.1016/0378-5173(94)00222-Q
36. Swamy N. Basavaiah K. Vamsikrishna P. Stability-indicating UV-spectrophotometric Assay of Rifampicin. Insight Pharm. Sci. 2018; 8: 1-12.
37. Podder M. Ahmed MF. Moni MR. Rahman ML. Biswas B. Sharmin N. Effect of metal ions on structural, morphological and optical properties of nano-crystallite spinel cobalt-aluminate (CoAl2O4). Arab. J. Chem. 2023; 16:104700. doi.org/ 10.1016/j.arabjc.2023.104700
38. Hoque AA. Dutta D. Paul B. Kumari L. Ehsan I. Dhara M et al. ΔPSap4#5 surface-functionalized abiraterone-loaded nanoparticle successfully inhibits carcinogen-induced prostate cancer in mice: a mechanistic investigation. Cancer Nano. 2023; 14:73. doi.org/10.1186/s12645-023-00223-5
39. Szulczyk D. Woziński M. Koliński M. Kmiecik S. Głogowska A. Augustynowicz-Kopec E et al. Menthol‑ and thymol‑based ciprofoxacin derivatives against Mycobacterium tuberculosis: in vitro activity, lipophilicity, and computational studies. Scientifc Reports.2023; 13:16328. doi.org/10.1038/s41598-023-43708-4
40. Getahun M. Blumberg HM. Ameni G. Beyene D. Kempker RR. et al. Minimum inhibitory concentrations of rifampin and isoniazid among multidrug and isoniazid resistant Mycobacterium tuberculosis in Ethiopia. PLoS ONE. 2022; 17: e0274426. doi.org/10.1371/journal.pone.0274426
41. Preeti. Sambhakar S. Malik R. Bhatia S. Harrasi AA. Rani C et al. Nanoemulsion: An Emerging Novel Technology for Improving the Bioavailability of Drugs. Scientifica. 2023; 6640103 pp 25. doi.org/10.1155/2023/6640103
42. Izham MNM. Hussin Y. Aziz MNM. Yeap SK. Rahman HS. Preparation and Characterization of Self Nano-Emulsifying Drug Delivery System Loaded with Citral and Its Antiproliferative Effect on Colorectal Cells In Vitro. Nanomaterials (Basel). 2019; 9: 1028. doi.org/ 10.3390/nano9071028
43. Al-Tamimi DJ. Hussein AA. Formulation and Characterization of Self-Microemulsifying Drug Delivery System of Tacrolimus. Iraqi J Pharm Sci. 2021; 30:91-100. doi.org/10.31351/vol30iss1pp91-100
44. Shah K. Chan LW. Wong TW. Critical physicochemical and biological attributes of nanoemulsions for pulmonary delivery of rifampicin by nebulization technique in tuberculosis treatment. Drug Delivery. 2017; 24:1631-1647. doi.org/10.1080/10717544.2017.1384298
45. Mehta SK. Kaur G. Bhasin KK. Tween-Embedded Microemulsions-Physicochemical and Spectroscopic Analysis for Antitubercular Drugs. AAPS PharmSciTech. 2010; 11:143-153. doi.org/ 10.1208/s12249-009-9356-5
46. Elshall AA. Ghoneim AM. Abdel‑Mageed HM. Osman R. Shaker DS. Ex vivo permeation parameters and skin deposition of melatonin-loaded microemulsion for treatment of alopecia. Futur J Pharm Sci. 2022; 8:28. doi.org/10.1186/s43094-022-00418-4
47. Wang J. Wang X. Li J. Chen Y. Yang W. Zhang L. Effects of Dietary Coconut Oil as a Medium-chain Fatty Acid Source on Performance, Carcass Composition and Serum Lipids in Male Broilers. Asian Australas. J. Anim. Sci. 2015; 28: 223-230. doi.org/ 10.5713/ajas.14.0328
48. Kommuru TR. Gurley B. Khan MA. Reddy IK. Self-emulsifying drug delivery systems (SEDDS) of coenzyme Q10: formulation development and bioavailability assessment. Int J Pharm. 2001; 212:233-46. doi.org/10.1016/s0378-5173(00)00614-1
49. Schwarz C. Mehnert W. Lucks JS. Müller RH. Solid lipid nanoparticles (SLN) for controlled drug delivery. I. Production, characterization and sterilization. Journal of Controlled Release. 1994; 30:83-96. doi.org/10.1016/0168-3659(94)90047-7
50. Ke Z. Hou X. Jia X. Design and optimization of self-nanoemulsifying drug delivery systems for improved bioavailability of cyclovirobuxine D. Drug Des Devel Ther 2016; 10:2049-60. doi.org/ 10.2147/DDDT.S106356
51. Rehman FU. Shah KU. Shah SU. Khan IU. Khan GM. Khan A. From nanoemulsions to self-nanoemulsions, with recent advances in self-nanoemulsifying drug delivery systems (SNEDDS). Expert Opin Drug Deliv. 2016; 14: 1325-1340. doi.org/10.1080/17425247.2016.1218462
52. Monwar M. Ranjan BK, Bytul RM, Iwao Y, Imam WMI. Preparation and Characterization of Azithromycin Loaded Solid Dispersion: A New Approach to Enhance in vitro Antibacterial Activity. Indian J of Pharmaceutical Education and Research. 2022; 56: s432-s443. doi.org/ 10.5530/ijper.56.3s.151