Formulation and Evaluation of Self Emulsifying Drug Delivery System of Lopinavir

Authors

  • Oshin Udiwal
  • Narendra Gehlot
  • Garvita Joshi
  • Vikas Jain

Keywords:

Lopinavir, Self-emulsifying drug delivery system, Bioavailability enhancement, Lipid-based formulation, Tablet

Abstract

Lopinavir (LOP) is a poorly water-soluble antiretroviral drug with limited oral bioavailability. The present study aimed to develop and evaluate liquid and solid self-emulsifying drug delivery systems (SEDDS) to enhance the solubility and dissolution behavior of lopinavir. Preformulation studies revealed a melting point of 104–106 °C and confirmed drug purity and compatibility by FTIR spectroscopy. Solubility screening identified Capmul MCM C8 EP as the most suitable oil, exhibiting a solubility of 75–100 mg/g, while Cremophor RH40 and Labrafil M 2125 CS showed superior emulsification efficiency with percentage transmittance values of 98.32% and 100.20%, respectively. Ternary phase diagram studies demonstrated a broad self-emulsifying region for the Capmul MCM C8–Cremophor RH40–Labrafil M 2125 system, maintaining fine emulsification up to 60% oil concentration. The optimized liquid SEDDS (L2) exhibited a mean globule size of 60.19 ± 3.27 nm in distilled water, 65.23 ± 3.15 nm in simulated gastric fluid, and 61.19 ± 3.15 nm in simulated intestinal fluid, with polydispersity indices below 0.45 and positive zeta potential values ranging from +13.12 to +14.23 mV. The formulation showed excellent robustness to dilution with transmittance values exceeding 98% and no drug precipitation for up to 12 h. In vitro dissolution studies demonstrated rapid drug release, with more than 85% lopinavir released within 20 min and complete drug release within 60 min in all dissolution media. The optimized L-SEDDS was successfully converted into tablet SEDDS (T-SEDDS), which complied with pharmacopeial quality parameters, including hardness (4.5 kg/cm²), friability (0.54%), disintegration time (2 min 45 s), and drug content (99.52 ± 2.56%). The T-SEDDS exhibited complete drug release within 120 min, comparable to the liquid formulation. Stability studies conducted at 40 ± 2 °C/75 ± 5% RH for 3 months showed no significant changes in physical appearance, disintegration time, or drug content. These results demonstrate that SEDDS is an effective strategy for enhancing the oral delivery of lopinavir and offers a promising approach for improving the bioavailability of poorly water-soluble drugs..



Downloads

Download data is not yet available.

References

[1] Aungst B. J. Novel formulation strategies for improving oral bioavailability of drugs with poor membrane permeation or presystemic metabolism. J. Pharm. Sci. 1993; 82: 979-986.

[2] Jing-ling Tang, Jin Sun, Zhong-Gui He. Self- emulsifying drug delivery systems: strategy for improving oral delivery of poorly soluble drugs. Curr. Drug Ther. 2007; 2: 85-93.

[3] Anand U. Kyatanwar, Kisan R. Jadhav, Vilasrao J. Kadam. Self-micro emulsifying drug delivery systems (SEDDS): Review. J. Pharm. Res. 2010; 3(1): 75-83.

[4] Patel PA, Chaulang GM, Akolkotkar A, Mutha SS, Handicap SR, Bhosale AV. Self-emulsifying drug delivery system: A review. Research J. Pharm and Tech. 2008; 1(4): 313-323.

[5] Bo Tang, Gang Cheng, Jian-Chun Gu, Cai-Hong Xu. Development of solid self-emulsifying drug delivery systems: preparation techniques and dosage forms. Drug Discov. Today. 2008; 13: 606-612.

[6] Sachan R, Khatri K, Kasture S. B. Self-emulsifying drug delivery system: A novel approach for enhancement of bioavailability. Int J. Pharm Tech Research. 2010; 2(3): 1738-1745.

[7] Ahmed Abdalla, Sandra Klein, Karsten Mader. A new Self emulsifying drug delivery system for poorly soluble drugs: Characterization, Dissolution, in vitro digestion and incorporation into solid pellets. Eur. J. Pharm. Sci. 2008; 35: 457-464.

[8] Parashar AK. Synthesis and characterization of temozolomide loaded theranostic quantum dots for the treatment of brain glioma. J Med Pharm Allied Sci [Internet]. 2021;10(3):2778–82. Available from: http://dx.doi.org/10.22270/jmpas.v10i3.1073

[9] Parashar AK, Tyagi LK, Sethi VA, Bansal K. Advanced nanotheranostics: Evolving strategies in cancer therapy and diagnosis. ijnrph [Internet]. 2025;1–9. Available from: http://dx.doi.org/10.61554/ijnrph.v3i1.2025.170

[10] Tang J.L, Sun J. Guihe Z. Self- Emulsifying Drug Delivery Systems: Strategy for Improving Oral Delivery of Poorly Soluble Drug. Curr. Drug Ther. 2007; 2: 85-93.

[11] Parashar AK, Saraogi GK, Jain PK, Kurmi B, Shrivastava V, Arora V. Polymer-drug conjugates: revolutionizing nanotheranostic agents for diagnosis and therapy. Discov Oncol [Internet]. 2024;15(1). Available from: http://dx.doi.org/10.1007/s12672-024-01509-9

[12] Parashar AK, Tyagi LK, Sethi VA. Histotripsy: A Promising Modality for Cancer Treatment. Curr Cancer Ther Rev [Internet]. 2024 Sep 19;21. Available from: https://doi.org/10.2174/0115733947330950240906075443

[13] Beatriz Zanchetta, Marco Vinícius Chaud, Maria Helena Andrade Santana. Self-Emulsifying Drug Delivery Systems in Pharmaceutical Development. J. Adv. Chem. Eng. 2015; 5(3): 01-07.

[14] Vajpayee D, Parashar AK, Sethi VA. Design and development of topical hydrogel of Centella Asiatica for the treatment of skin burn. ijnrph [Internet]. 2024;229–34. Available from: http://dx.doi.org/10.61554/ijnrph.v2i1.2024.62

[15] Li HQ, Yi T. Preparation and in vitro characterization of berberine hydrochloride self-emulsifying microsphere by membrane emulsification technology. Acta Pharmaceutica Sinica. 2013; 48(4):554-559.

[16] Saraogi GK, Bagri R, Singh S, Parashar AK. Formulation Development and Characterization of Surface Modified Pectin Microspheres for Colon Targeting. Bull Env Pharmacol Life Sci. 2023;12(9):16–23.

[17] Pandey PK, Jain SD, Parashar AK, Gupta AK. Formulation and Evaluation of Hydrogel for the Treatment of Acne. Int J Adv Res Med Chem. 2022;4(1):11–5.

[18] Kanchan Kohli, Sunny Chopra, Deepika Dhar, Saurabh Arora, Roop K. Khar. Self-emulsifying drug delivery systems: An approach to enhance oral bioavailability. Drug Discov. Today. 2010; 15 (21/22): 958-965.

[19] Colin W. Pouton, Christopher J. H. Porter. Formulation of lipid-based delivery systems for oral administration: Materials, Methods and Strategies. Advanced Drug Delivery Reviews. 2008; 60: 625-637.

[20] Parashar AK, Saraogi GK, Shrivastava V, Bagri R, Tyagi LK, Sethi VA, et al. Development of Angiopep-2 targeted dendrimer-based nanotheranostic system for enhanced temozolomide delivery to glioblastoma multiforme. Bull Natl Res Cent [Internet]. 2025;49(1). Available from: http://dx.doi.org/10.1186/s42269-025-01309-3

[21] Keemi Lim, Zuratul A.A. Hamid. Applications of Nanocomposite Materials in Drug Delivery. Polymer nanoparticle carriers in drug delivery systems. 2018.

[22] Abou Assi, R.; M Abdulbaqi, I.; Seok Ming, T.; Siok Yee, C.; A Wahab, H.; Asif, S. M.; Darwis, Y. Liquid and Solid Self-Emulsifying Drug Delivery Systems (SEDDs) as Carriers for the Oral Delivery of Azithromycin: Optimization, In Vitro Characterization and Stability Assessment. Pharmaceutics 2020, 12 (11), 1052, DOI: 10.3390/pharmaceutics12111052

[23] Zaichik, S.; Steinbring, C.; Menzel, C.; Knabl, L.; Orth-Höller, D.; Ellemunter, H.; Niedermayr, K.; Bernkop-Schnürch, A. Development of self-emulsifying drug delivery systems (SEDDS) for ciprofloxacin with improved mucus permeating properties. Int. J. Pharm. 2018, 547, 282– 290, DOI: 10.1016/j.ijpharm.2018.06.005

[24] Parashar AK, Saraogi GK, Sethi VA. Design, formulation, and in vitro evaluation of docetaxel-loaded nanostructured lipid carriers. International Journal of Medical, Pharmaceutical and Health Sciences [Internet]. 2024;1(4):153–62. Available from: http://dx.doi.org/10.62946/ijmphs/1.4.153-162

[25] Mahmood, A.; Khan, L.; Ijaz, M.; Nazir, I.; Naseem, M.; Tahir, M. A.; Aamir, M. N.; Rehman, M. U.; Asim, M. H. Enhanced intestinal permeability of cefixime by self-emulsifying drug delivery system: in-vitro and ex-vivo characterization. Molecules 2023, 28 (6), 2827, DOI: 10.3390/molecules28062827

[26] Cardona, M. I.; Dominguez, G. P.; Echeverry, S. M.; Valderrama, I. H.; Bernkop-Schnürch, A.; Aragón, M. Enhanced oral bioavailability of rutin by a self-emulsifying drug delivery system of an extract of calyces from Physalis peruviana. J. Drug Delivery Sci. Technol. 2021, 66, e102797 DOI: 10.1016/j.jddst.2021.102797

[27] Balakrishnan, P.; Lee, B.-J.; Oh, D. H.; Kim, J. O.; Lee, Y.-I.; Kim, D.-D.; Jee, J.-P.; Lee, Y.-B.; Woo, J. S.; Yong, C. S.; Choi, H.-G. Enhanced oral bioavailability of Coenzyme Q10 by self-emulsifying drug delivery systems. Int. J. Pharm. 2009, 374 (1–2), 66– 72, DOI: 10.1016/j.ijpharm.2009.03.008

[28] Gupta C, Sahu GK, Parashar AK, Singh K, Bukke SPN, Udom GJ. Novel curcumin floating tablets for spatial delivery in peptic ulcer. Biomed Res Int [Internet]. 2025;2025(1):6622146. Available from: http://dx.doi.org/10.1155/bmri/6622146

[29] Zaichik, S.; Steinbring, C.; Caliskan, C.; Bernkop-Schnürch, A. Development and in vitro evaluation of a self-emulsifying drug delivery system (SEDDS) for oral vancomycin administration. Int. J. Pharm. 2019, 554, 125– 133, DOI: 10.1016/j.ijpharm.2018.11.010

[30] Sharma K, Parashar AK, Saraogi GK. Solubility enhancement of BCS-class II drug resveratrol using solid dispersion. ijnrph [Internet]. 2025;184–94. Available from: http://dx.doi.org/10.61554/ijnrph.v3i1.2025.166

[31] Azeem, A.; Rizwan, M.; Ahmad, F. J.; Iqbal, Z.; Khar, R. K.; Aqil, M.; Talegaonkar, S. Nanoemulsion components screening and selection: a technical note. AAPS PharmSciTechnol 2009, 10 (1), 69– 76, DOI: 10.1208/s12249-008-9178-x

[32] Sirvi, A.; Kuche, K.; Chaudhari, D.; Ghadi, R.; Date, T.; Katiyar, S. S.; Jain, S. Supersaturable self-emulsifying drug delivery system: a strategy for improving the loading and oral bioavailability of quercetin. J. Drug Delivery Sci. Technol. 2022, 71, 103289, DOI: 10.1016/j.jddst.2022.103289

[33] Patel, M. J.; Patel, N. M.; Patel, R. B.; Patel, R. P. Formulation and evaluation of self-microemulsifying drug delivery system of lovastatin. Asian J. Pharm. Sci. 2010, 5, 266– 275

[34] Maji, I.; Mahajan, S.; Sriram, A.; Medtiya, P.; Vasave, R.; Khatri, D. K.; Kumar, R.; Singh, S. B.; Madan, J.; Singh, P. K. Solid self emulsifying drug delivery system: Superior mode for oral delivery of hydrophobic cargos. J. Controlled Release 2021, 337, 646– 660, DOI: 10.1016/j.jconrel.2021.08.013

[35] Parashar AK, Hardenia A, Saraogi GK et al. Next-Generation Nucleic Acid Delivery: A Review of Nanobiosystem Design and Applications. Current Gene Therapy (Bentham Science ). 2025; 25: 1-19. DOI: 10.2174/0115665232367377250519114910.

[36] Gao, P.; Jiang, Z.; Luo, Q.; Mu, C.; Cui, M.; Yang, X. Preparation and evaluation of self-emulsifying drug delivery system (SEDDS) of cepharanthine. AAPS PharmSciTech 2021, 22 (7), 245, DOI: 10.1208/s12249-021-02085-9

[37] Neslihan Gursoy, R.; Benita, S. Self-emulsifying drug delivery systems (SEDDS) for improved oral delivery of lipophilic drugs. Biomed. Pharmacother. 2004, 58 (3), 173– 182, DOI: 10.1016/j.biopha.2004.02.001

[38] Yadav N, Parashar AK, Sethi VA. Development and assessment of in-situ gel formulation for ocular pain and inflammation. ijnrph [Internet]. 2024;248–54. Available from: http://dx.doi.org/10.61554/ijnrph.v2i1.2024.71

[39] Galatage ST, Manjappa AS, Salawi A, Desai JL, Kumbar VM, Ghagane S, et al. Palbociclib-letrozole loaded solid self-nano emulsifying drug delivery system for oral treatment of breast cancer: In-vitro and In-vivo characterization. J Drug Deliv Sci Technol [Internet]. 2025;104(106469):106469. Available from: http://dx.doi.org/10.1016/j.jddst.2024.106469

[40] Parashar AK, Tyagi L, Sethi VA. Development and evaluation of raft-forming Rosiglitazone Maleate tablets for enhanced drug delivery. J Adv Sci Res [Internet]. 2025;16(03):24–30. Available from: http://dx.doi.org/10.55218/jasr.2025160305

[41] Bekker A, Yang J, Wang J, Cotton MF, Cababasay M, Wiesner L, et al. Safety and pharmacokinetics of lopinavir/ritonavir oral solution in preterm and term infants starting before 3 months of age. Pediatr Infect Dis J [Internet]. 2024;43(4):355–60. Available from: http://dx.doi.org/10.1097/INF.0000000000004243

[42] Buddhadev SS, C Garala K, S S, Rahamathulla M, Ahmed MM, Farhana SA, et al. Quality by design aided self-nano emulsifying drug delivery systems development for the oral delivery of Benidipine: Improvement of biopharmaceutical performance. Drug Deliv [Internet]. 2024;31(1):2288801. Available from: http://dx.doi.org/10.1080/10717544.2023.2288801

[43] Gowripattapu S, Sathis Kumar D, Selvamuthukumar S. Formulation and statistical evaluation of tablets containing Pitavastatin- self nano emulsifying drug delivery systems. Curr Drug Deliv [Internet]. 2023;20(4):414–32. Available from: http://dx.doi.org/10.2174/1567201819666220517113012

[44] Jain N, Jain N, Parashar AK. Design and development of biosynthetic copper nanoparticles for skin diseases. ijnrph [Internet]. 2025;200–6. Available from: http://dx.doi.org/10.61554/ijnrph.v3i1.2025.143

Downloads

Published

2026-01-05

How to Cite

1.
Udiwal O, Gehlot N, Joshi G, Jain V. Formulation and Evaluation of Self Emulsifying Drug Delivery System of Lopinavir. J Neonatal Surg [Internet]. 2026 Jan. 5 [cited 2026 Jan. 20];14(33S):378-96. Available from: https://jneonatalsurg.com/index.php/jns/article/view/9829

Issue

Vol. 14 No. 33S (2025): Journal of Neonatal Surgery

Section

Original Article

License

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

You are free to:

  • Adapt — remix, transform, and build upon the material for any purpose, even commercially.

Terms:

  • Attribution — You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.
  • No additional restrictions — You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.