The main objective of this study was to optimize the stability of cetyl alcohol/stearyl alcohol emulsions in terms of percentage of internal phase volume, emulsifier type and concentration, and amount of external phase (water). Creams (o/w emulsions) were prepared by phase inversion and physical properties as particle size of the internal phase, apparent viscosity, and sedimentation volume evaluated. Stability was performed at room temperature, 40°C, 50°C, and under stress conditions. High hydrophilic lipophilic balance (HLB) nonionic surfactants as tween 80, tween 20, Myrj 52, Brij 35, and low HLB span 60 were used as emulsifying agents. The percentage of internal phase components (cetyl alcohol and stearyl alcohol), percentage of emulsifying agents, and percentage of aqueous external phase were varied, and stability was investigated. As the level of emulsifier agent (tween 80 and span 60) increased from 3% to 15%, and the percent of the internal phase remained constant at 30%, the particle size of the internal phase decreased and the cream became more stable. Formulations of the same composition, but prepared using Myrj 53 and tween 20 as emulsifiers, showed a larger particle size than formulations prepared using tween 80 and Brij 35. As the level of the internal phase volume increased and consequently the amount of water decreased, emulsion viscosity increased. The best formulation containing 30% internal phase (50% cetyl alcohol, 35% stearyl alcohol), 15% emulsifying agents (tween 80/span 60 ratio of 3:1), and 70% water was selected, and effects of process temperature and cooling rate on emulsion stability investigated. This formulation was further investigated in terms of stability of a 1% hydrocortisone addition by varying the percentage (30%, 35%, 40%, and 45%) of internal phase and percentage of water (70%, 65%, 60%, and 55%). The best formulation contained 45% internal phase (22.5 g cetyl alcohol, 15.75 g stearyl alcohol, 15% emulsifying agent, which is equivalent to 5 g tween 80 and 1.7 g span 60), and 55% w/w water, was manufactured under different manufacturing processes. Emulsions prepared by homogenization at the beginning of the process of emulsification were stable with small internal phase particle diameter. This study demonstrates that at every cetyl alcohol/stearyl alcohol ratio there is a phase volume/emulsifier HLB ratio, which results in optimum stability.
[1]
N. Realdon,et al.
Influence of processing conditions in the manufacture of O/W creams: II. Effect on drug availability.
,
2002,
Farmaco.
[2]
G. Flynn,et al.
Release of Hydrocortisone from a Cream Matrix: Dependency of Release on Suspension Concentration and Measurement of Solubility and Diffusivity
,
2001,
Pharmaceutical development and technology (Print).
[3]
Marjan Tušar,et al.
Lipophilic semisolid emulsion systems: viscoelastic behaviour and prediction of physical stability by neural network modelling
,
1998
.
[4]
J. Richardson,et al.
Correlation of physical parameters of an oil in water emulsion with manufacturing procedures and stability
,
1995
.
[5]
B. B. Sheth,et al.
Particle size reduction of emulsions by formulation design-II: effect of oil and surfactant concentration.
,
1995,
PDA journal of pharmaceutical science and technology.
[6]
U. T. Lashmar,et al.
Correlation of rheological properties of an oil in water emulsion with manufacturing procedures and stability
,
1993
.
[7]
P. Kahela,et al.
The influence of ageing on the release of hydrocortisone from o/w creams.
,
1990,
Acta pharmaceutica Nordica.
[8]
F. Ishii,et al.
Physicopharmaceutical characteristics of an oil-in-water emulsion-type ointment containing diclofenac sodium.
,
1984,
Journal of Pharmacy and Science.
[9]
T. Fredriksson.
A comparative study of dithranol cream, 0.25% and 0.1%, and dithranol ointment 0.25% in the treatment of psoriasis.
,
1983,
Pharmatherapeutica.