Topical delivery of niacinamide, encapsulated in niosome and proniosome carriers
Abstract
Niacinamide, better known as vitamin B3, is water soluble and takes part in oxidation-reduction
reactions in the mitochondria of the skin (Bissett, 2009:438). This active possesses antiinflammatory
action, decreases transepidermal water loss (TEWL) and prevents the loss of
dermal collagen (Mohammed et al., 2013:192). For this reason niacinamide is an ideal product
to be applied topically for the treatment of ageing, hyperpigmentation, melasma and rosacea
(Gehring, 2004:88).
Considering niacinamide for topical application, the physicochemical characteristics of the active,
as well as the physicochemical properties of the skin must be brought into account (Barry,
2007:566). Since the skin is the outermost organ of the human body; it protects the body by
acting as a barrier against the penetration of agents from the external environment (Bolzinger et
al., 2012:156). This barrier function of the skin resides in the stratum corneum, which is the
outermost layer of the epidermis (Feingold & Denda, 2012:263). Thus, for this reason, the barrier
function of the stratum corneum makes the delivery through the skin a challenge.
For an active to penetrate through the skin and concentrate in the underlying layers; the molecular
size, solubility, partition coefficient and ionisation is of importance (Benson, 2012). According to
Barry (2001:102), the molecular size must be less than 500 Dalton in order to penetrate the skin.
The molecular size of niacinamide is 122.1 Dalton (Dollery, 1999:N62), indicating that the size of
the active will be ideal for topical penetration. The solubility of niacinamide was determined in the
study as 112.70 mg/ml, which according to Naik et al. (2000:319), is the ideal solubility, since it is
higher than 1 mg/ml. The partition coefficient was e -0.43. This value indicates that the active is
not ideal for topical penetration; since it does not possess both lipophilic and hydrophilic properties
(Donnelly & Sing, 2015:13). For the active to penetrate the skin the ideal partition coefficient must
be between one and three. When considering the ionisation of the active, the ionised form of a
molecule is less likely to penetrate the skin than the unionised form (Donnelly and Sing, 2015:15).
Niacinamide is 99.99% ionised at a pH of 7.4, causing the active to pass through the stratum
corneum with difficulty. For these reasons niacinamide was encapsulated into a vesicle system
in order to “mask” the physicochemical characteristics which cause a challenge to penetration
through the skin.
Vesicle systems are hollow particles composed of a protective layer consisting of a hydrophilic
head and a hydrophobic tail (Honeywell-Nguyen & Bouwstra, 2008:206). These systems are
ideal for topical delivery of actives, since they can entrap both hydrophilic and hydrophobic
substances. They deliver the entrapped substance at a specific location and are non-toxic (Honeywell-Nguyen & Bouwstra, 2008:206). These systems are known as niosomes and
proniosomes and the difference between them is the method of preparation (Seleci et al., 2016:4).
Proniosomes are prepared to form a dry powder in order to have a longer storage life than the
niosomes (Yeom et al., 2014:83), consequently, proniosomes are hydrated (just before use) to
form niosomes. Although both the niosomes as well as the proniosome systems present with
excellent properties, their low viscosity can be a drawback when trying to apply the dosage form.
During this study, the viscosity was determined as 4.036 cP and 3.616 cP for the niosomes and
proniosomes, respectively. According to Barry (2007:595), designing a product for maximum
topical effect is important, but designing a product to be acceptable to the consumer is of more
importance. Consumers prefer a product that can be transferred from the container easily,
spreads readily and is not difficult to remove from the skin, thus, a product with poor appearance
will lead to non-patient compliance (Barry, 2007:595). In order to increase the viscosity and
enhance compliance only the niosomes were incorporated into a gel and a cream, since
proniosomes become niosomes once hydrated.
Franz cell diffusion studies were performed on the pre-formulations (niosomes and proniosomes)
and on the formulations (niosome gel and niosome cream). First, the membrane diffusion studies
were performed to determine if any release of the active occurred from the formulation. The
preparation which presented with the highest median flux were the proniosomes
(1 163.58 μg/cm2.h), followed by the niosomes (1 162.58 μg/cm2.h), then the niosome gel
(1 042.08 μg/cm2.h) and lastly, the niosome cream (469.72 μg/cm2.h). During the skin diffusion
studies, all the preparations presented with niacinamide in the receptor phase. The preparation
with the highest median flux value in the skin diffusion studies were niosomes (0.844 μg/cm2.h),
followed by the niosome gel (0.692 μg/cm2.h), the proniosomes (0.462 μg/cm2.h) and lastly, the
niosome cream (0.172 μg/cm2.h). All the preparations presented with niacinamide in the stratum
corneum-epidermis (SCE) and epidermis-dermis (ED). The preparation with the highest median
concentration in the SCE was the niosome (2.13 μg/ml), followed by the niosome gel (1.94 μg/ml),
the niosome cream (1.05 μg/ml) and lastly, the proniosomes (0.71 μg/ml). The niosomes
(5.02 μg/ml) were the dispersion with the highest median concentration in the ED, followed by the
niosome cream (2.86 μg/ml), the proniosomes (2.04 μg/ml) and lastly, the niosome gel
(1.94 μg/ml). Since the aim of this study was to deliver the active topically, all four the
preparations were successful.
Stability tests were performed on the niosome gel and niosome cream for a period of three
months. According to ICH (2006:3) guidelines, the formulations were stored at ± 25° C/60% RH
(relative humidity), ± 30° C/65% RH and ± 40° C/75% RH to determine if any change in the
physicochemical properties of the formulations occurred. The chemical stability (concentration of the active) as well as physical properties (pH, conductivity, viscosity, light microscopy changes,
visual changes, mass loss and zeta-potential) were determined initially (t=0) as well as after 1, 2
and 3 months respectively. Both the formulations were stable regarding the stability of
niacinamide, the pH, mass loss (only the niosome gel), light microscopy, visual appearances and
zeta-potential
Collections
- Health Sciences [2060]