Structural Properties of Non Aqueous Ethyl cellulose
Systems Used In Topical Drug Delivery
L. Bruno1, S Kasapis2, B Jiang1, K T Chow3, P.W.S Heng3
1
Department of Chemistry, National University of Singapore, Block S8, Level 5, Science
Drive 3, Singapore 117543
2
School of Applied Sciences, RMIT University, Bundoora West Campus, Melbourne, Victoria
3083, Australia
3
Department of Pharmacy, National University of Singapore, 18 Science Drive 4, Singapore
117543
Aqueous gels are much better studied than non aqueous gels because hydrophilic gelling
agents are readily available. However water poses a risk of hydrolytic reactions and the
alternative formulations of hydro alcoholic compounds (e.g. ethanol) can neither eliminate the
possibility of drug hydrolysis nor prevent undesirable variation in formulation owing to high
evaporative potential1. Non-aqueous gel system of ethyl cellulose and propylene glycol
dicaprylate was reported to be a good delivery system for water-sensitive drugs showing
good rheological and mechanical properties for different formulations and different storage
time2.
The structural properties of this gel system intended for topical drug delivery was
investigated using small deformation dynamic oscillation in combination with other
techniques like time temperature superposition, micro and modulated differential scanning
calorimetry, wide angle X ray diffraction, infrared spectroscopy and optical profile analysis to
determine gel particle roughness.
The effect of temperature on the gel system was determined by dynamic oscillation testing
comprising of heating followed by a cooling cycle of 25 to 90 to 25˚C. The heating profile
showed a gradual reduction in G’ and the cooling profile shows that the material restructures
but it requires an isothermal run at 25˚C for 48 hours for a complete recovery which indicates
thermal hysteresis in the molecular network dynamics. This heating, cooling and isothermal
run was repeated twice and in doing so specific features of tan  shows the involvement of
two distinct molecular processes. At subzero temperatures it was seen that the time
temperature equivalence was active in the system producing a master curve of rubbery
viscoelasticity. A time sweep lasting 6 days carried out on the gel system shows a
continuous increase in rigidity as a function of time of observation at ambient temperature,
thereby showing that there are dynamic structures present in the system developing
continuously. This was further supported by the results of the optical profile analysis which
recorded the gel roughness of the fresh gel over 27days. The nature of these molecular
rearrangements were further assessed using wide angle X ray diffraction and ATR-FTIR.
From the experimental observations it can be concluded that solvent diffusion and
consequent particle swelling is followed by particle erosion as a function of aging at ambient
temperature or thermal processing, resulting in the release of polymeric strands that are able
to form a three dimensional structure. The outcome of these two molecular mechanisms is a
composite mixture of individual ethyl cellulose species supporting particle remnants, which is
based on a balance of topological particle disentanglements and polymeric entanglements in
solution.
References:
1 Agrawal, A.M, Manek, R.V, Kolling, W.M, Neau, S.H.(2003). Studies on the Interaction of Water with
Ethylcellulose: Effect of Polymer Particle Size, AAPS PharmSciTech,4,1-11
2 P. W. S. Heng, L. W. Chan, and K. T. Chow (2005). Development of novel non aqueous ethyl
cellulose gel matrices: Rheological and mechanical characterization. Pharmaceutical Research 22 (4),
676-684