Formulation and Development of Solid Nano-Emulsifying Drug Delivery System of BCS Class IV Drug Delafloxacin

Abstract

Aqueous solubility of drugs is one of the most important factors that determine their dissolution performance and hence oral absorption and bioavailability. About 70% of new drug substances are poorly water soluble and exhibit slow dissolution rates and often incomplete oral bioavailability. The aim of present investigation is to develop a novel emulsifying drug delivery system (SNEDDS) to enhance the dissolution rate profile by increasing the solubility of Delafloxacin. The oral route is the most commonly used method for administration of drugs, with nearly 80% of the marketed dosage forms being delivered orally. This route of drug administration is the most convenient and non- invasive, leading to better patient compliance. Therefore, different formulation strategies have been investigated for enhancing the solubility of poorly soluble drugs with the aim of improving oral bioavailability. However, the optimized formulation has chosen a suitable emulsifying rate with a quick dissolution rate based on the smaller z-average diameter. The optimized Delafloxacin SNEDDS has exhibited faster dissolution rate as 97±2.07 % drug released which is clearly indicating that developed SNEDDS enhanced the dissolution rate of the drug.

Introduction

1. Introduction

Delafloxacin (DLF) is a fourth-generation fluoroquinolone antibiotic used in treating various infections like gonorrhea and pneumonia. Compared to other fluoroquinolones, a structural change at position C-7 enhances its effectiveness against both gram-positive and gram-negative bacteria. However, its poor water solubility results in low oral bioavailability (58.8%), necessitating formulation strategies like Self-Nanoemulsifying Drug Delivery Systems (SNEDDS) to enhance solubility and absorption.

2. Materials and Methods

a. Preformulation Studies:

• Melting Point: 227°C (within standard range).

• Solubility: High in 0.1 N HCl (8.72 mg/ml), lower in water (0.122 mg/ml).

• Calibration Curve: Linear in the range of 0–50 µg/ml at 298 nm (R² = 0.994).

b. Solubility in Excipients:

• Best solubility: Oil – Capryol 90 (136.72 mg/ml), Surfactant – Poloxamer 188 (307.63 mg/ml), Co-surfactant – Transcutol HP (99.09 mg/ml).

c. SNEDDS Preparation:

• Nine formulations (F1–F9) were made using different combinations of oil, surfactants, and co-surfactants.

• Liquid SNEDDS (L-SNEDDS) were converted to Solid SNEDDS (S-SNEDDS) using adsorption on Aerosil.

3. Evaluation Parameters

a. Transmittance (%): All formulations showed >90% at 1000x dilution, confirming nanoemulsion formation.

b. Particle Size, Zeta Potential, PDI:

• Smallest particle size: F5 (124.68 nm).

• Lowest PDI (best uniformity): F5 (0.125).

• Zeta potential ranged from −2.53 to −6.57 mV (F5: −5.74 mV).

c. Viscosity and Cloud Point:

• F5 showed lowest viscosity (24 cPs) and high cloud point (~77–78°C), suitable for oral formulation stability.

d. Micromeritic Properties (F5):

• Angle of repose: 27.64°, Carr’s Index: 14.22, Hausner’s Ratio: 1.24 – indicating good flowability.

e. Drug Content:

• F5 had highest drug loading efficiency: 99.09%.

f. SEM & DSC:

• SEM: Pure drug showed irregular crystals; S-SNEDDS showed spherical, smooth-surfaced particles.

• DSC: F5 showed reduced crystallinity, indicating possible amorphization and improved solubility.

g. FTIR:

• No significant chemical interaction between drug and excipients, confirming compatibility.

h. In Vitro Drug Release:

• F5 released 97.02% of the drug in 2 hours, outperforming pure drug and marketed product.

• Best release kinetics followed Fickian diffusion (R² = 0.977).

4. Stability Studies

• Formulations stored under 25°C/60% RH and 40°C/75% RH for 3 months showed no significant degradation or performance change.

Conclusion

Delafloxacin is a lipophilic drug as constrained of aqueous solubility, hepatic first-pass metabolism with poor absorption rate thus, formulated to overcome such hindrances. The developed liquid formulations have found appropriate results of thermodynamic stability, emulsifying rate and adequate dissolution rate. Whereas, based on the characterization and evaluation of numerous parameters have revealed that the developed formulations were providing an efficacious therapeutic efficacy of the drug. The optimized Delafloxacin SNEDDS has selected based on the smaller z-average diameter and faster dissolution rate as well as an appropriate emulsification rate as compared with the other formulations. The optimized formulation had exhibited faster dissolution rate as 97±2.07 % drug released which is clearly indicating that developed SNEDDS enhanced the dissolution rate of the drug. Therefore, It reveals that the characterization, evaluation and comparison of various parameters have to reached on the conclusion that S-SNEDDS is a potential drug delivery system of the drug. Finally, we can conclude that S-SNEDDS is a robust and promising nanocarriers to enhance drug bioavailability and therapeutic efficacy.

References

[1] Shah, M.K.; Khatri, P.; Vora, N.; Patel, N.K.; Jain, S.; Lin, S. Lipid Nanocarriers: Preparation, Characterization and Absorption Mechanism and Applications to Improve Oral Bioavailability of Poorly Water-Soluble Drugs. In Biomedical Applications of Nanoparticles; William Andrew Publisher: Norwich, NY, USA, 2019; pp. 117–147, ISBN 9780128165065. [2] Boyd, B.J.; Bergström, C.A.S.; Vinarov, Z.; Kuentz, M.; Brouwers, J.; Augustijns, P.; Brandl, M.; Bernkop-Schnürch, A.; Shrestha, N.; Préat, V.; et al. Successful Oral Delivery of Poorly Water-Soluble Drugs Both Depends on the Intraluminal Behavior of Drugs and of Appropriate Advanced Drug Delivery Systems. Eur. J. Pharm. Sci. 2019, 137, 104967 [3] Kalepu, S., Manthina, M. &Padavala, V. 2013. Oral lipid-based drug delivery systems – an overview. ActaPharmaceuticaSinica B, 3 (6), pp. 361-372. [4] Krishnaiah, Y. S. R. 2010. Pharmaceutical Technologies for Enhancing Oral Bioavailability of Poorly Soluble Drugs. Journal of Bioequivalence & Bioavailability, 2 (2), pp. 028-036. [5] Rajendra C., Harish P. Jain A.K., Himesh S., SaraogiG.K.(2011). Preparation and evaluation of the self-emulsifying drug delivery system containing atorvastatin HMGCOA inhibitor. International Journal of Pharmacy and Pharmaceutical Sciences, 3 (3): 147-152., ISSN- 0975-1491. [6] Lipinski, C. A. (2000).Drug-like properties and the causes of poor solubility and poor permeability. J PharmacolToxicol Methods, 44 (1), 235-249., ISSN: 1056-8719. [7] Ghose, A. K., Viswanadhan, V. N., &Wendoloski, J. J. (1999).A Knowledge-Based Approach in Designing Combinatorial or Medicinal Chemistry Libraries for Drug Discovery. 1. A Qualitative and Quantitative Characterization of Known Drug Databases. Journal of Combinatorial Chemistry, 1 (1), 55-68., ISSN: 2156-8952. [8] Shahba, A. A., Mohsin, K., &Alanazi, F. K. (2012). Novel Self-Nanoemulsifying Drug Delivery Systems (SNEDDS) for Oral Delivery of Cinnarizine: Design, Optimization, and In-Vitro Assessment. AAPS PharmSciTech, 13 (3), 967-977., ISSN: 1530-9932. [9] Sven S., Hassan B., Thilo S., Martin O. (2009). Self-Emulsifying Drug Delivery Systems Facing the bioavailability challenge in drug delivery. Die PharmazeutischeIndustrie, 71(8):1409-1416., ISSN 0031-711X. [10] Gursoy, R. N., & Benita, S. (2004). Self-emulsifying drug delivery systems (SEDDS) for improved oral delivery of lipophilic drugs. Biomed Pharmacother, 58 (3), 173-182. ISSN: 0753-3322. [11] Stegemann, S., Leveiller, F., Franchi, D., de Jong, H., & Linden, H. (2007). When poor solubility becomes an issue: from early stage to proof of concept. Eur J Pharm Sci, 31(5), 249-261., ISSN: 0928-0987. [12] Mangale M. R, Pathak S, Mene H. R, More B. (2015). A nanoemulsion, as pharmaceutical overview. Int. J. Pharm. SCI. Rev. Res., 33 (1), 244-252., ISSN 0976 – 044X [13] Mahmoud, D. B., Shukr, M. H., &Bendas, E. R. (2014). In vitro and in vivo evaluation of self-nanoemulsifying drug delivery systems of cilostazol for oral and parenteral administration. Int J Pharm, 476(1-2), 60-69. [14] Jiajia R., David J. M.(2012). Lemon oil solubilization in mixed surfactant solutions: Rationalizing microemulsion and nanoemulsion formation. Food Hydrocolloids. 26(1), 268-276. [15] Avachat, A. M., & Patel, V. G. (2015). Self nanoemulsifying drug delivery system of stabilized ellagic acid-phospholipid complex with improved dissolution and permeability. Saudi Pharm J, 23(3), 276-289. [16] Dunnhaupt, S., Kammona, O., Waldner, C., Kiparissides, C., &Bernkop-Schnurch, A. (2015). Nano-carrier systems: Strategies to overcome the mucus gel barrier. Eur J Pharm Biopharm, 96, 447-453. [17] Karavasili C, Andreadis I, Tsantarliotou M, Taitzoglou I, Chatzopoulou P, Katsantonis D, Zacharis C, Markopoulou C, Fatouros D. Self-Nanoemulsifying Drug Delivery Systems (SNEDDS) Containing Rice Bran Oil for Enhanced Fenofibrate Oral Delivery: In Vitro Digestion, Ex Vivo Permeability, and In Vivo Bioavailability Studies. AAPS PharmSciTech. 2020; 21(6). [18] Beg S, Swain S, Singh HP, PatraChN, Rao ME. Development, optimization, and characterization of solid self-nanoemulsifying drug delivery systems of valsartan using porous carriers. AAPS PharmSciTech. 2012 Dec;13(4):1416-27. [19] Beg S, Sandhu PS, Batra RS, KhuranaRK, Singh B. QbD-based systematic development of novel optimized solid self-nanoemulsifying drug delivery systems (SNEDDS) of lovastatin with enhanced biopharmaceutical performance, Drug Delivery, 2015; 22(6):765-784. [20] Fayed ND, GodaAE, Essa EA, Maghraby MEI. Chitosan-encapsulated niosomes for enhanced oral delivery of atorvastatin. 2021; 66: 102866. [21] Verma R, Kaushik D, Kumar M, Parmar D. Components of self-microemulsifying drug delivery systems. A Comprehensive Textbook on self-emulsifying Drug Delivery Systems. 2021: 79-94

Copyright

Copyright © 2025 Gokul Pandurang Mali, Dr. Pranav Parekh, Dr. Mrunal Shirsat, Dr. Mahesh Thakare, Apoorv Gholap. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.