Design and Development of Self-Emulsifying Drug Delivery System to Improve the Solubility and Bioavailability of Ciprofloxacin

Summary

This study presents and describes the formulation of Ciprofloxacin Self-Emulsifying Drug Delivery Systems.

Abstract

Ciprofloxacin, a potent fluoroquinolone antibiotic, is used to treat various bacterial infections. This drug has low aqueous solubility and limited oral bioavailability. To overcome these limitations, this study focused on developing a Self-Emulsifying Drug Delivery System (SEDDS) for Ciprofloxacin, aiming to enhance its solubility and bioavailability. The formulation process involved selecting silicone oil, Tween 80, propylene glycol (PG), and polyethylene glycol (PEG) as the core components based on solubility studies. The optimization of SEDDS formulations was guided by pseudo-ternary phase diagrams, which helped in identifying the effective self-emulsifying regions and determining the optimal ratios of surfactant and co-surfactant. Evaluation of the SEDDS formulations involved droplet size and zeta potential measurements alongside Fourier-transform infrared (FT-IR) spectroscopy, confirming drug-excipient compatibility and successful drug incorporation. The F2 and F5 formulations exhibited droplet sizes of 320 nm and 202 nm, respectively, with corresponding zeta potentials of -11.4 mV and -13.38 mV, indicative of stability. Release studies showed an initial rapid release, with 88.2% released from F5 within the first 2 h, followed by a sustained release, reaching 93.1% after 5 h. The current formulations significantly improve the drug's solubility and bioavailability.

Introduction

Ciprofloxacin is a fluorinated quinolone with significant activity against both Gram-negative and Gram-positive bacteria, largely due to the presence of a fluorine atom at position 6 of its naphthyridine ring structure. This modification enhances its spectrum of antibacterial activity^1,2. As a synthetic fluoroquinolone antibiotic, it targets bacterial DNA gyrase or topoisomerase II, making it an effective treatment for various bacterial infections. Despite its broad-spectrum efficacy and generally safe profile, it faces challenges with low aqueous solubility and oral bioavailability, hindering its clinical app....

Protocol

NOTE: The details of the reagents and equipment used in this study are listed in the Table of Materials.

1. Solubility studies

1. Measure and mix an excess amount of drug (Ciprofloxacin) with the following selected oil combination: oleic acid oil (2 mL), olive oil (2 mL), castor oil (2 mL), sunflower oil (2 mL), mygliol oil (2 mL), surfactant like T-80 (2 mL), T-20 (2 mL), and co-surfactant including PG (2 mL), PEG200 (2 mL), PEG400 (2 mL), and PEG600 (2 mL).
2. Vortex the mixture thoroughly using the vortex mixer. Incubate the mixed samples at a constant temperature of 25 ± 2 °C u....

Results

Solubility study and Pseudo-ternary phase diagram
The solubility of pure drug in the chosen components is highest in silicone oil at 85 mg/mL, followed by Tween 80 at 70 mg/mL, PG at 50 mg/mL, and PEG at 30 mg/mL. The derived pseudo-ternary phase diagram revealed a constant ratio of surfactants to co-surfactants (Smix). In the diagram, a system composed of PG/PEG 600 and T-80 at a ratio of 1:6 demonstrated a large area capable of emulsification featuring silicone oil. Figure 1

Discussion

Approximately 40% of new chemical entities exhibit poor solubility in water, which results in reduced oral bioavailability²². This challenge significantly hampers the clinical application of many potential therapeutic compounds. It is a wide-ranging synthetic fluoroquinolone antibiotic categorized under BCS IV, exemplifying such drugs with solubility issues³. To overcome these solubility challenges, it is employed in research as a novel approach⁵. It.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Ciprofloxacin	Feroze-Son Pharma (Nowshera 24,110, Pakistan	NA	Standard drug
Mygliol oil,	Dow Chemical Ltd, Bangkok 10,110, Thailand	NA
Oleic acid oil, silicone oil, olive oil, castor oil, and sunflower oil	Gaziantep (Gunedogu Anadolu 34,810, Turkey)	NA	Oil phase
Polyethene oxide 200	Sigma Aldrich (Saint Louis, Missouri 63,101, United States	8.17001	Co-surfactant
Polyethene oxide 400	Sigma Aldrich (Saint Louis, Missouri 63,101, United States	182028	Co-surfactant
Polyethene oxide 600	Ahad International Pharmaceutical, Dera Ismail Khan, 29,050, Pakistan	NA	Co-surfactant
Polyethylene Glycol (PG)	Sigma Aldrich (Saint Louis, Missouri 63,101, United States	1546401	Co-surfactant
Tween 20	Sigma Aldrich (Saint Louis, Missouri 63,101, United States	11332465001
Tween 80	Sigma Aldrich (Saint Louis, Missouri 63,101, United States	P8074	Surfactant