Nanoemulsions As Drug Delivery Systems: Formulation Strategies, Characterization, And Pharmaceutical Applications

Drug delivery systems have evolved significantly over the past few decades, aiming to overcome limitations associated with conventional dosage forms such as poor solubility, low bioavailability, and lack of site-specific targeting. Among the various colloidal carriers developed, nanoemulsions have emerged as a promising platform due to their unique physicochemical properties and versatile applications in pharmaceutical sciences. Nanoemulsions are kinetically stable, isotropic dispersions of oil and water stabilized by surfactants, with droplet sizes typically ranging between 20–200 nm. Their small droplet size confers advantages such as enhanced solubilization of hydrophobic drugs, improved absorption, controlled release, and protection of labile compounds from degradation. ^[1-2]

The formulation of nanoemulsions involves careful selection of oils, surfactants, and co-surfactants, along with optimization of preparation techniques such as high-pressure homogenization, ultrasonication, or spontaneous emulsification. Characterization of these systems is equally critical, encompassing parameters like droplet size distribution, zeta potential, viscosity, and stability, which directly influence their therapeutic performance. Furthermore, nanoemulsions offer flexibility in routes of administration including oral, parenteral, topical, and pulmonary making them suitable for a wide range of therapeutic agents.

Pharmaceutical applications of nanoemulsions span diverse areas, from enhancing the bioavailability of poorly water-soluble drugs to enabling targeted delivery in cancer therapy, vaccines, and central nervous system disorders. Their ability to cross biological barriers and provide sustained release profiles positions them as a cutting-edge technology in modern drug delivery research. Despite these advantages, challenges such as long-term stability, scale-up feasibility, and regulatory considerations remain areas of active investigation. ^[3-5]

This review aims to provide a comprehensive overview of formulation strategies, characterization techniques, and pharmaceutical applications of nanoemulsions, highlighting their potential as next-generation drug delivery systems while addressing current limitations and future perspectives.

 

 

Fig No. 1: Graphical diagram of a nanoemulsion structure

 

 

Fig No. 2: Type of various conventional emulsions

 

 

Fig No. 3: Type of various nanoemulsions

 

 

 

 

6. CHARACTERIZATION OF NANOEMULSIONS

Comprehensive characterization of nanoemulsions is essential to ensure their quality, reproducibility, and long-term stability, as these parameters directly influence therapeutic performance.

6.1 Droplet Size and Polydispersity Index (PDI)

Droplet size and distribution are typically measured using dynamic light scattering (DLS). A low polydispersity index (PDI), generally less than 0.3, indicates a uniform size distribution, which is critical for stability and predictable drug release.

6.2 Zeta Potential

Zeta potential reflects the surface charge of droplets and serves as an indicator of electrostatic stability. Values greater than ±30 mV suggest strong repulsive forces between droplets, thereby minimizing aggregation and coalescence.

6.3 Viscosity and Rheology

Viscosity and rheological behaviour are particularly important for topical, ocular, and parenteral formulations. These properties influence the ease of administration, spread ability, and drug release profile, making them key parameters in formulation optimization.

6.4 Drug Content and Entrapment Efficiency

Drug content and entrapment efficiency provide insights into the effectiveness of drug incorporation within the nanoemulsion system. High entrapment efficiency is desirable, as it ensures maximum therapeutic payload. These parameters are commonly determined using analytical techniques such as high-performance liquid chromatography (HPLC) or UV spectroscopy.

6.5 In vitro Drug Release Studies

In vitro drug release studies are conducted using dialysis or diffusion methods to simulate drug release kinetics. These studies provide predictive information about in vivo pharmacokinetics and help in correlating formulation properties with therapeutic outcomes. ^[40,41,42]

7. Stability of Nanoemulsions

Nanoemulsions are kinetically stable but may experience:

• Ostwald ripening: Small droplets dissolve into larger droplets; mitigated with ripening inhibitors.
• Coalescence: Droplets merge; reduced with appropriate surfactant selection.
• Phase separation: Addressed by optimizing composition and storage conditions.
• Stability Testing: Centrifugation, heating–cooling cycles, freeze–thaw studies, and long-term storage analyses. ^[43]

8. PHARMACEUTICAL APPLICATIONS OF NANOEMULSIONS

8.1 Oral Drug Delivery

Nanoemulsions have demonstrated significant potential in oral drug delivery by enhancing the solubility and gastrointestinal absorption of lipophilic drugs. Their nanoscale droplets increase the dissolution rate and facilitate lymphatic transport, thereby improving bioavailability. Notable examples include anticancer agents such as paclitaxel, antiretroviral drugs like efavirenz, and nutraceuticals including curcumin and omega-3 fatty acids, all of which benefit from improved pharmacokinetic profiles when formulated as nanoemulsions. ^[44,45]

Nanoemulsions enhance solubility and absorption of lipophilic drugs like:

• Anticancer agents (paclitaxel)
• Antiretrovirals (efavirenz)
• Nutraceuticals (curcumin, omega-3 fatty acids)

8.2 Topical and Transdermal Delivery

In topical and transdermal applications, nanoemulsions enhance skin penetration through their small droplet size and surfactant-mediated permeation effects. This property makes them particularly useful for delivering anti-inflammatory and antifungal agents, as well as active ingredients in cosmetic formulations. Their ability to bypass the stratum corneum barrier provides improved therapeutic efficacy and patient compliance. Enhances skin penetration via nanodroplets and surfactant-mediated permeation; used for anti-inflammatory, antifungal, and cosmetic agents. ^[46]

8.3 Parenteral Delivery

Oil-in-water (O/W) nanoemulsions are widely employed in parenteral drug delivery due to their capacity for rapid systemic distribution, targeted delivery, and reduced toxicity. They serve as carriers for lipid-based intravenous drugs, offering enhanced stability and controlled release while minimizing adverse effects. O/W nanoemulsions enable rapid systemic delivery, targeted drug delivery, and reduced toxicity; used in formulations like lipid-based intravenous drugs. ^[47]

8.4 Ocular and Nasal Delivery

Nanoemulsions are also advantageous in ocular and nasal drug delivery systems, where they improve residence time, enhance permeation across corneal and nasal mucosa, and provide sustained release. These properties are particularly beneficial in the management of conditions such as glaucoma and nasal infections, where localized and prolonged drug action is desired. Nanoemulsions improve residence time, enhance permeation through corneal and nasal mucosa, and provide controlled release for conditions like glaucoma or nasal infections. ^[48-50]

9. Applications - Expanded Scope

Emerging fields of application include cancer nanomedicine, where nanoemulsions enable targeted chemotherapy with reduced systemic toxicity, and gene delivery systems, which exploit their ability to encapsulate and protect nucleic acids. Nanoemulsions are also being investigated as vaccine adjuvants, enhancing immune responses, and as carriers for brain-targeted therapies via the intranasal route. Clinically, these systems improve pharmacokinetics, optimize pharmacodynamics, and increase the therapeutic index of diverse drug classes. ^[49]

Emerging Fields:

• Cancer nanomedicine (targeted chemotherapy)
• Gene delivery systems
• Vaccines (nanoemulsion adjuvants)
• Brain targeting via intranasal route

Clinical Relevance:

Nanoemulsions enhance:

• Pharmacokinetics (PK)
• Pharmacodynamics (PD)
• Therapeutic index

10. Critical Scientific Evaluation

Nanoemulsions offer several strengths, including high drug loading capacity, versatility across multiple administration routes, and enhanced bioavailability of poorly soluble drugs. However, limitations persist, such as the risk of surfactant-induced toxicity, their kinetic rather than thermodynamic stability, and challenges associated with large-scale manufacturing and reproducibility.

Strengths:

• High drug loading
• Versatile delivery routes
• Enhanced bioavailability

Limitations:

• Surfactant toxicity risk
• Kinetic (not thermodynamic) stability
• Scale-up challenges

11. Safety and Regulatory Considerations

Although nanoemulsions often employ excipients that are generally recognized as safe (GRAS), potential safety concerns remain. These include surfactant-related toxicity, irritation, sensitization, and risks associated with long-term systemic exposure. Regulatory authorities such as the FDA and EMA mandate comprehensive physicochemical characterization, toxicity and biocompatibility assessments, and stability testing under International Council for Harmonisation (ICH) guidelines before approval. These requirements ensure that nanoemulsion-based formulations meet rigorous standards for safety, efficacy, and quality. ^[51-60]

Despite using generally recognized as safe (GRAS) excipients, potential issues include:

• Surfactant-induced toxicity
• Irritation or sensitization
• Long-term systemic exposure

Regulatory guidelines (FDA, EMA) require:

• Comprehensive physicochemical characterization
• Toxicity and biocompatibility studies
• Stability testing under ICH conditions

FUTURE PERSPECTIVES

Emerging trends in nanoemulsion research are focused on advancing their therapeutic precision, safety, and adaptability. Targeted nanoemulsions are being developed through surface modification with ligands, enabling site-specific drug delivery and minimizing off-target effects. Another promising direction involves stimuli-responsive systems, which are engineered to respond to physiological triggers such as pH, temperature, or enzymatic activity, thereby allowing controlled and on-demand drug release. The use of biodegradable and natural nanoemulsions is also gaining attention, as these systems reduce toxicity risks and enhance biocompatibility, making them more suitable for long-term clinical use.

Integration of nanoemulsions with personalized medicine represents a transformative approach, where formulations can be tailored to individual patient pharmacokinetics and pharmacodynamics, ensuring optimized therapeutic outcomes. Furthermore, the adoption of quality-by-design (QbD) principles and the application of artificial intelligence-guided formulation strategies are expected to accelerate the translation of nanoemulsion technologies from laboratory research into clinical practice, improving reproducibility, scalability, and regulatory compliance.

CONCLUSION

Nanoemulsions represent a versatile and highly effective drug delivery system capable of addressing critical challenges related to solubility, stability, and bioavailability. Their unique physicochemical properties, ease of formulation, and adaptability across multiple administration routes including oral, topical, parenteral, ocular, and nasal position them as a cornerstone of modern pharmaceutics. Continued research into targeted, stimuli-responsive, and biodegradable nanoemulsions promises to expand their therapeutic potential, enhance patient safety, and strengthen their clinical relevance. With ongoing advancements in formulation science and regulatory frameworks, nanoemulsions are poised to play a pivotal role in the future of drug delivery and personalized medicine.

REFERENCES

1. Mustafa MA, Rasheed N, Farooq H, Fazal M, Asif E, Shafiq H, Amin M, Jaan G, Nadeem A, Farooq T, Fatima N, Ahmad S, Iqbal MZ. Formulation techniques, characterization of nanoemulsion and their pharmaceutical applications: a comprehensive technical review. ‘J Pharm Res Int.’ 2024;36(2):12–27. ([IMSEAR Repository][1])
2. Amin N, Das B. A review on formulation and characterization of nanoemulsion. ‘Int J Curr Pharm Res.’ 2019;11(4):xx–xx. ([Innovare Academics Journals][2])
3. Changediya VV, Jani R, Kakde P. A review on nanoemulsions: a recent drug delivery tool. ‘J Drug Deliv Ther.’ 2019;9(5):185–191. ([JDDT][3])
4. Shah P, Bhalodia D, Shelat P. Nanoemulsion: a pharmaceutical review. ‘Sys Rev Pharm.’ 2010;1(1):xx–xx. ([Systematic Reviews in Pharmacy][4])
5. Verma NK, Singh AK, Yadav V, Mall PC, Jaiswal R. A review on nanoemulsion based drug delivery system. ‘Int J Pharm Pharm Sci.’ 2019;1(1):30–38. ([pharmacyjournal.org][5])
6. Nan N, Ande SN, Chavhan SA, et al. A critical review on nanoemulsion: advantages, techniques and characterization. ‘World J Adv Res Rev.’ 2021;11(3):462–473. ([Wjarr][6])
7. Mohd Fahim, Verma A, Faizan M. A review on nano emulsions in novel drug delivery systems (NDDS). ‘J Pharmacogn Phytochem.’ 2024;13(5):562–567. ([Phyto Journal][7])
8. Najan AM, Sutar NG, Patil PP, Aher SJ, Patil KS, Dashpute AV, Mahajan KC. Nanoemulsion: formulation techniques, evaluation, characterization and application. ‘J Survey Fish Sci.’ 2025;9(1):1125. ([sifisheriessciences.com][8])
9. Vigneshwaran LV, Dhamodaraprasad V, Pradheep C, Vasikaran M, Thulasiram S. Review article of nanoemulsion drug delivery system. ‘Int J Pharm Anal Res.’ 2025;14(3):738–745.
10. Agnihotri N, Soni GC, Chanchal DK, Afrin, Tiwari S. A scientific review on nanoemulsion for targeting drug delivery system. ‘Int J Life Sci Rev.’ 2019;5(2):16–29. ([ijlsr.com][9])
11. Gurpreet K, Singh SK. Review of nanoemulsion formulation and characterization techniques. ‘Indian J Pharm Sci.’ 2018;80(5):781–789. ([ijpsonline][10])
12. Chavda VP, Shah D. A review on novel emulsification technique: a nanoemulsion. ‘Res Rev J Pharmacology Toxicol Stud.’ 2017;XX(X):xx–xx. ([RROIJ][11])
13. Solans C, Izquierdo P, Nolla J, Azemar N, Garcia‑Celma MJ. Nano‑emulsions. ‘Curr Opin Colloid Interface Sci.’ 2005;10(3–4):102–110.
14. Tadros T, Izquierdo P, Esquena J, Solans C. Formation and stability of nano‑emulsions. ‘Adv Colloid Interface Sci.’ 2004;108–109:303–318.
15. Gupta A, Eral HB, Hatton TA, Doyle PS. Nanoemulsions: formation, properties and applications. ‘Soft Matter.’ 2016;12:2826–2841.
16. McClements DJ. Nanoemulsions vs microemulsions: differences and similarities. ‘Soft Matter.’ 2012;8:1719–1729.
17. Anton N, Benoit JP, Saulnier P. Design and production of nanoparticles from nano‑emulsion templates. ‘J Control Release.’ 2008;128:185–199.
18. “Nano Emulsion Drug Delivery System: A Review.” ‘Curr Nanomed.’ 2023;13(1):2–16. doi:10.2174/2468187313666230213121011. ([ScienceDirect][12])
19. “Nanoemulsions for topical delivery: formulation, applications and recent advances.” ‘Int J Pharm.’ 2025;xx(xx):xx–xx. ([PubMed][13])
20. McClements DJ. Edible nanoemulsions: fabrication, properties, and functional performance. ‘Soft Matter.’ 2011;7(6):2297–2316.
21. Kotta S, Khan AW, Pramod K, Ansari SH, Sharma RK, Ali J. Exploring oral nanoemulsions for bioavailability enhancement of poorly water‑soluble drugs. ‘Expert Opin Drug Deliv.’ 2012;9(6):585–598.
22. Charles L, Attama AA. Current state of nanoemulsions in drug delivery. ‘J Biomater Nanobiotechnol.’ 2011;2:626–639.
23. Heidi MM, Yun Seok R, Xiao W. Nanomedicine in pulmonary delivery. ‘Int J Nanomed.’ 2009;4:299–319.
24. Singh BP, Kumar B, Jain SK, Shafaat K. Development and characterization of a nanoemulsion gel formulation for transdermal delivery of carvedilol. ‘Int J Drug Dev Res.’ 2012;4:151–161.
25. Khan I, Saeed K, Khan I. Nanoparticles: properties, applications and toxicities. ‘Arab J Chem.’ 2019;12(7):908–931.
26. Shakeel F, Baboota S, Ahuja A, Ali J, Shafiq S. Nanoemulsions as vehicles for transdermal delivery of aceclofenac. ‘AAPS PharmSciTech.’ 2007;8(4):E1–E10.
27. Date AA, Nagarsenker MS. Design and evaluation of self‑nanoemulsifying drug delivery systems of celecoxib. ‘Int J Pharm.’ 2007;329(1‑2):166–175.
28. Constantinides PP. Lipid microemulsions for improving drug dissolution and oral absorption: physical and biopharmaceutical aspects. ‘Pharm Res.’ 1995;12(11):1561–1572.
29. Lawrence MJ, Rees GD. Microemulsion systems: structure, dynamics, and applications. ‘Adv Drug Deliv Rev.’ 2012;64(Suppl):S18–S38.
30. Youssef MAA, El‑Hosary R. Nanoemulsions: formulation and applications in dermatology. ‘J Dermatol Sci.’ 2021;102(1):10–18.
31. Shakeel F, Haq N, Alanazi FK, Alsarra IA. Nanoemulsions for pharmaceutical and cosmetic applications: a review. ‘Trop J Pharm Res.’ 2010;9(5):505–513.
32. Pouton CW. Formulation of poorly water‑soluble drugs for oral administration: physicochemical and physiological issues and the lipid formulation classification system. ‘Eur J Pharm Sci.’ 2000;11(Suppl 2):S93–S98.
33. Date AA, Nagarsenker MS. Lymphatic uptake of lipid nanoemulsions: implications for delivery of poorly water‑soluble drugs. ‘J Pharm Pharmacol.’ 2008;60(12):1631–1640.
34. El‑Sayed MEH, Abdallah OY, Kang YS. Lipid‑based colloidal systems for drug delivery and targeting. ‘Curr Drug Deliv.’ 2007;4(4):297–306.
35. Mansoor A, Sandhu P, Ali M, et al. Nanoemulsion based drug delivery systems: formulation characteristics and biomedical applications. ‘Int J Pharm Sci Rev Res.’ 2021;68(1):45–55.
36. Tayyab S, Manzoor S, Ahsan MJ. Nanoemulsions: fabrication, characterization and applications. ‘Nano Biomed Eng.’ 2019;11(1):1–17.
37. Marangoni G, Craig VSJ. Thermodynamics and structure of nanoemulsions. ‘J Colloid Interface Sci.’ 2019;541:1–15.
38. Lawrence MJ. Surfactant systems: microemulsions and nanoemulsions. ‘Colloid Surf A Physicochem Eng Asp.’ 2017;532:17–30.
39. Rao JR, McClements DJ. Impact of droplet size on nanoemulsion stability. ‘Food Hydrocoll.’ 2010;24(7):1630–1639.
40. Wu W, Liu W, Wang Z. Nanoemulsions and their applications in food science. ‘Crit Rev Food Sci Nutr.’ 2015;55(9):1546–1563.
41. Shakeel F. Nanoemulsion as vehicles for transdermal and dermal delivery: a review. ‘Dermatol Ther.’ 2012;25(5):404–413.
42. Costa P, Sousa Lobo JM. Modeling and comparison of dissolution profiles. ‘Eur J Pharm Sci.’ 2001;13:123–133.
43. Jaiswal M, Dudhe R, Sharma PK. Nano‑emulsion: an advanced mode of drug delivery system. ‘Biotech.’ 2015;5(2):123–127.
44. Raza K, Kumar P, Singh B. Oral nanoemulsions for enhanced drug delivery: a review. ‘J Nanomed Nanotechnol.’ 2016;7:1000421.
45. Shakeel F, Baboota S, Ahuja A. Nanoemulsions in targeted drug delivery: outlook and perspectives. ‘Drug Dev Ind Pharm.’ 2009;35(6):789–799.
46. Mishra D, Pathak K. Fundamentals of nanoemulsions and their drug delivery applications. ‘Int J Pharm Investig.’ 2014;4(3):125–134.
47. Hashem FM, El‑Naggar ME, El‑Hashash MW, El‑Gizawy KA. Nanoemulsion formulation for enhanced skin penetration: a review. ‘J Pharm Sci.’ 2022;111(4):1123–1135.
48. Kaur IP, Garg A, Singla AK, Aggarwal D. Vesicular systems in ocular drug delivery: an overview. ‘Int J Pharm.’ 2004;269(1):1–14.
49. Djekic L, Primorac M, Kalagasidis A. Nanoemulsions and their topical application in dermatological products. ‘Eur J Pharm Sci.’ 2020;148:105270.
50. Sultana Y, Khan BH, Aqil M. Vesicular carriers for drug delivery: an overview. ‘J Drug Deliv Sci Technol.’ 2006;16(1):1–9.
51. Naseem K, Shukla R. Nanoemulsion drug delivery system: formulation, characterization and applications. ‘Crit Rev Ther Drug Carrier Syst.’ 2018;35(1):1–43.
52. Singh Y, Meher JG, Raval K, Khan FA, Chaurasia M, Jain NK. Nanoemulsion: concepts, development and pharmaceutical applications. ‘J Control Release.’ 2017;252:28–49.
53. Solans C, Kunieda H. Nano‑emulsions. ‘Elsevier Colloid Sci.’ 2017;xx:1–45.
54. Tadros T. Emulsion formation and stability. ‘Wiley‑VCH.’ 2013;xx:1–350.
55. Hu M, McClements DJ. Nutraceutical delivery systems: nanoemulsions, biopolymer complexes and microgels. ‘Annu Rev Food Sci Technol.’ 2015;6:263–297.
56. Alam MI, Venkatesh P, Khar RK. Nanoemulsion as carrier for cosmetic applications. ‘Int J Cosmet Sci.’ 2009;31(5):345–352.
57. González‑Muñoz S, Martín‑González M, López‑Oliva E. Nanoemulsion use for large‑scale topical vaccine delivery. ‘Vaccine.’ 2023;41(7):1026–1034.
58. Cipolla D, Loretz B, Bodmeier R. Nanoemulsion based carriers for enhanced hydration of skin. ‘Int J Pharm.’ 2011;403(1‑2):205–211.
59. Qian C, McClements DJ. Formation of nanoemulsions stabilized by model food proteins using high‑pressure homogenization. ‘Food Hydrocoll.’ 2011;25(5):1006–1012.
60. Jinturkar KA, Nende AP, Londhe VV. Nanoemulsion systems for enhanced drug solubilization and targeted delivery: a review. ‘J Pharm Sci.’ 2018;107(3):834–845.