Diclofenac Sodium Loaded Nanosized Ethosomes: An Investigation on Z-Average, Polydispersity and Stability

Introduction

Ethosomes are sophisticated vesicular delivery carriers that are capable of delivering various pharmaceutical actives [1, 2, 3]. These novel delivery systems contain soft phospholipid vesicles in the presence of high concentrations of ethanol [4, 5]. Diclofenac sodium is a non-steroidal anti-inflammatory drug (NSAID) [6]. NSAIDs are the most common and extensively used drugs for the management of pain, inflammation, and arthritis [7]. They inhibit Cyclooxygenase-2 (Cox-2) and thereby prostaglandin biosynthesis which is responsible for inflammation. The oral administration of NSAIDs is frequently associated with adverse effects such as gastric ulceration, bleeding and irritation [8]. Thus, ethosomal topical delivery of Diclofenac sodium was thought significant to overcome aforementioned adverse effect. Besides, other toxicities such as nausea, vomiting and diarrhea due to the high concentration of NSAIDs in the alimentary canal can also be circumvented. Also, dose related adverse effects such as acute renal insufficiency can be avoided through topical application.

Methods

Preparation of Diclofenac sodium ethosomes: To prepare ethosomes, initially Diclofenac sodium and soya lecithin was dissolved in ethanol (5mL). To this distilled water was added slowly with constant stirring and the resultant mixture was probe sonicated (PCI Analytics, Mumbai) at an optimized conditions of 5min and 60W.

Z-average, PDI, and zeta potential measurement: Size and PDI (polydispersity index) were determined by dynamic light scattering (DLS) using Malvern Zetasizer Nano ZS (Malvern Instruments, UK). Zeta potential was measured using the same instrument based on the electrophoretic mobility.

Result and Discussion

The obtained results for diclofenac sodium loaded ethosomes are depicted in Figures 1-3.

Click to enlarge

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High power ultrasound was found to be useful method to produce Diclofenac sodium loaded ethosomes based on soya lecithin (Phospholipon 90G). Distinctive applications of dynamic light scattering (DLS) are the characterization of particles, emulsions or molecules, which have been dispersed or dissolved in a liquid [9]. Here, it is necessary to realize that the brownian motion of particles or molecules within suspension results in scattering of laser light with different intensities. Investigation of these intensity variations yields the velocity of the Brownian motion and henceforth the particle size by the Stokes- Einstein relationship. As can be seen from Figure 1, 27.4 (% Mean number) particles had size of 396.1 nm, followed by 25.1(% Mean number) corresponding to 342 nm, 19.6 (% Mean number) particles of 458.7nm. Figure 2 depicts size distribution of diclofenac sodium ethosomes by intensity. Note that Z-Average is an intensity-based calculated value and also known as the cumulants mean. As defined in ISO 13321 and more recently ISO 22412, Z- Average is the best value to report when used in a quality control setting [9]. The designed Diclofenac sodium ethosomes had Z-Average of 440.3nm. Polydispersity index (PDI) is a dimensionless parameter indicative of particle size distribution. In general, PDI value within 0.03-0.06 is indicative of monodisperse system, while PDI within 0.10-0.20 suggest narrow size distribution [10]. Also, to note that PDI value within 0.25-0.50 and above 0.50 is considered to have broad size distribution. Diclofenac sodium loaded ethosomes had PDI of 0.56 indicative of broad distribution of particles. Zeta potential is a prime factor predicting the stability of colloidal dispersion. In general, particles with zeta potentials values more than +30 mV or -30 mV are normally considered stable [11]. As shown in Figure 3, diclofenac sodium loaded ethosomes had zeta potential of -35.2 mV. Significant negative surface charges could be attributed to adsorption of hydroxyl ions of lipid at the interface [12].

Conclusion

Based on the obtained results it can be concluded that with power ultrasound it is feasible to produce nanosized Diclofenac sodium ethosomes with substantial stability as reflected through zeta potential value of -35.2 mV.