ArticlePDF Available

Abstract and Figures

Ascorbic acid (vitamin C) is extensively used in a variety of formulations including creams. It is an ingredient of anti-aging cosmetic products alone or along with alpha-tocopherol (vitamin E). In solutions and creams, ascorbic acid is susceptible to air and light and undergoes oxidative degradation to dehydroascorbic acid and further to inactive products. The degradation is influenced by oxygen, temperature, viscosity and pH of the medium and is also catalyzed by metal ions, particularly Cu2+, Fe2+, and Zn2+. This review highlights the stability and modes of stabilization of ascorbic acid in both the cosmetic and pharmaceutical preparations. A number of approaches involved in the stabilization of the vitamin such as the use of antioxidants, stabilizers, synergists, other vitamins, and formulation of multiple emulsions, nanosuspensions, microencapsulation, etc. have been discussed (16) Stability and Stabilization of Ascorbic Acid. Available from: [accessed Jan 28 2018].
Content may be subject to copyright.
KEYWORDS: Ascorbic acid; stability; stabilization, cosmetic and pharmaceutical preparations.
AbstractAscorbic acid (vitamin C) is extensively used in a variety of formulations including creams. It is an
ingredient of anti-aging cosmetic products alone or along with alpha-tocopherol (vitamin E). In
solutions and creams, ascorbic acid is susceptible to air and light and undergoes oxidative degradation to dehydroascorbic
acid and further to inactive products. The degradation is influenced by oxygen, temperature, viscosity and pH of the medium
and is also catalyzed by metal ions, particularly Cu2+, Fe2+, and Zn2+. This review highlights the stability and modes of stabilization
of ascorbic acid in both the cosmetic and pharmaceutical preparations. A number of approaches involved in the stabilization of
the vitamin such as the use of antioxidants, stabilizers, synergists, other vitamins, and formulation of multiple emulsions,
nanosuspensions, microencapsulation, etc. have been discussed.
Stability and Stabilization of Ascorbic Acid
A Review
Ascorbic acid (AA) is known to play an important role as
an antioxidant due to its presence in the body  uids (1). It
causes an increase in the rate of absorption of iron, calcium
and folic acid and hence reduces allergic reactions,
boosts the immune system, stimulates the formation of bile
in the gallbladder and facilitates the excretion of various
steroids (2). In the body AA plays an essential role in the
production of collagen tissue around bones, teeth, cartilage,
skin and damaged tissue (3). It has shown a prominent
pharmacological effect in a number of disease conditions
such as scurvy, common cold, osteoarthritis, hypertension,
heart diseases, cancer, diabetes mellitus, asthma, wound
healing, pregnancy, gout and eye diseases (4). Because
of all these favourable effects, AA has been used in a
variety of cosmetic and pharmaceutical formulations (5). It
is highly soluble in water and alcohol, and is easily oxidised
to dehydroascorbic acid in its solubilised form (1). The rapid
degradation of AA in aqueous media is still a major factor
in the formulation of its products. It is also reported that AA
oxidation occurs rapidly in an alkaline environment especially
at higher temperatures (>50°C) (6) and its reaction with
oxygen is strongly catalysed by metal ions, particularly cupric
and ferric ions (7, 8). The degradation of AA proceeds both by
aerobic and anaerobic pathways and depends upon many
factors such as oxygen, temperature, light, pH and storage
conditions (1, 3, 9–12).
The stability of a pharmaceutical formulation, particularly,
the semisolid dosage form depends on its formulation
characteristics and the nature of the active ingredients.
These characteristics are in uenced by the nature and
amount of the excipients to be added and their sensitivity to
the environmental factors to which these dosage forms are
exposed. In the semisolid dosage forms a careful selection
of bases including oil-in-water (o/w) and water-in-oil (w/o)
emulsifying agents, humectants, emollients, etc. would
provide physical stability to the formulation and enhance the
shelf-life of the product. In the selection of these ingredients
the formulator has to take into consideration the nature of
the active ingredient and the possible effect of formulation
ingredients on its stability pro le. The stability of AA and
various modes of its stabilization are discussed in the following
Vegetables and Fruits
AA is a white crystalline organic compound and can be
synthesized from glucose or extracted from certain natural
sources such as fruits and vegetables to meet the nutrient
requirements of a healthy diet. Plants and most animals
synthesize their own AA but humans lack this ability due to the
de ciency of an enzyme known as L-gulono-gamma-lactone
oxidase (13).
AA along with its derivatives is added to foods and fruit
*Corresponding author
Baqai Institute of Pharmaceutical Sciences, Baqai Medical University, 51, Deh Tor, Toll Plaza,
Super Highway, Gadap Road, Karachi-74600, Pakistan
H&PC Today - Household and Personal Care Today Vol. 10(3) May/June 2015
the studies
related to the
stabilization of
In order to
achieve maximum
stability of AA in
various foods,
cosmetics and
formulations, different strategies have been employed, some
of which are briey described below:
Use of Other Vitamins in Combination with AA
AA is known to be one of the important members of the
water-soluble vitamin group. It has been reported that AA
acts synergistically with other water- and fat-soluble vitamins
including alpha-tocopherol (vitamin E) (TP) (31). In recent
years, AA has been successfully used in a number of cosmetic
and dermatological formulations along with TP. They are
specically indicated for topical applications such as skin
depigmentation and ability to take part in proline and lysine
hydroxylation in collagen biosynthesis (3). The stabilizing
effect of TP on the photodegradation of AA has been studied
using UV spectrometry. Similarly, the stability of AA in o/w
creams in the presence of vitamins including riboavin (RF),
nicotinamide (NA) and TP has been investigated by Ahmed
et al. (31), Jung et al. (37), Kim et al. (38) and the results
showed the highest stability of AA with TP.
Use of Stabilizers / Preservatives / Synergists
The photosensitivity of AA makes it highly unstable for use
in cosmetic (9) and pharmaceutical preparations (26) and
hence it requires the use of appropriate stabilizing agents. As
mentioned above, TP acts as a synergist with AA, by acting as
an electron donor to restore the tocopheroxyl radical (7, 39).
TP rst functions as the primary antioxidant that reacts with
an organic free ascorbyl radical in the physiological system
and is then converted back to ascorbate through the redox
cycle (40). The interaction of AA with a redox partner such as
TP has been found to be useful to slow down its oxidation and
prolong its physiological action (3, 41, 42).
The instability of AA in various formulations also leads to the
use of stabilizers or preservatives such as citric acid (CT),
boric acid (BA) or tartaric acid (TA). A study was designed
to determine the effects of CT, TA and BA on the stabilization
of AA in various o/w cream formulations in the light and
in the dark. The results indicated a marked decrease in
the rate of degradation of AA by these stabilizers both
in the light and in the dark. The order of stabilization was
found as CT>TA>BA (20). Similarly, a decrease in the rate
of degradation of AA in w/o creams has been observed
in the presence of CT indicating that the change of phase
does not affect the efcacy of the stabilizer (21). In the AA
formulations, these agents act simultaneously as antioxidants
(29, 43, 44), preservatives or synergists (45) that may lead to
the stabilization of the formulations. CT has been found to
be a naturally occurring antioxidant in carcinogenesis (46)
and lipid peroxidation (47) whereas BA acts as a complexing
agent for hydroxyl compounds including AA (9, 20, 48–52)
juices for the improvement of nutritional quality (14, 15).
The degradation of AA in orange, grape, pomegranate
juices and sour cherry nectar with or without the addition of
hydrogen peroxide (H2O2) has been studied at 20, 30 and
40°C (16). In another stability study for the determination of
the retention of AA in homogenized raw fruits and vegetables
stored under routine conditions, raw collard greens (Brassica
oleracea var. viridis), clementine (Citrus clementina hort. ex
Tanaka) and potatoes (Solanum tuberosum) were selected
as the representatives of foods to be sampled in a USDA’s
National Food and Nutrient Analysis Program (NFNAP) (17).
The retention of AA was also studied in dried guava during
storage at 30, 40 and 50°C and with different water activity
values that resulted in the degradation of AA by a pseudo-rst
order reaction (18).
Cosmetic and Pharmaceutical Formulations
AA has found wide applications in the eld of cosmetics
and pharmacy. In cosmetic preparations AA is used for its
anti-ageing, depigmentation (19) and antioxidant properties
(20–22) along with its ability to reduce wrinkles by promoting
collagen synthesis (23). Because of these favourable effects,
AA has long been used in cosmetic preparations (5, 24).
AA is sensitive to light (9, 25–30) and is degraded to form
dehydroascorbic acid and 2,3-diketogulonic acid on UV
irradiation by photooxidation and subsequent hydrolysis (27)
(Figure 1).
Similarly, chemical oxidation has also been found as a
major cause of AA degradation in the dark (9, 20, 21,
31) thus making it difficult to be used in cosmetics and
pharmaceutical formulations. The contact of AA with
metals in solution form has been reported to form free
radicals which are then converted to molecular oxygen
that oxidizes AA in solution. The rate of oxidation has
been found to increase with pH, oxygen content and
concentration of metal ions in the solution (32, 33). In
an attempt to study the stability of AA in pure water
solutions (without buffers), it has been observed that the
rate of oxidation is pH dependent, showing a minimum
at pH 2.5 to 3.0 and a maximum at pH 4.0. The pH
adjustment is necessary to preserve the physical, chemical
and therapeutic properties of AA because fruit juices
containing this vitamin have pH values ranging from 2.5 to
5.0 (34).
A number of derivatives of AA such as sodium ascorbate
and ascorbyl palmitate are used as antioxidants in
cosmetics and pharmaceutical preparations (29, 35).
However, they lack the biological activity similar to that of
AA (5, 36); therefore, this review particularly emphasizes
Figure 1. Degradation of ascorbic acid (AA) upon UV irradiation by photooxidation and subsequent hydrolysis.
H&PC Today - Household and Personal Care Today Vol. 10(3) May/June 2015
to use the latter in dermocosmetic products (71). It has
been stated that the stability of AA may be achieved by
preparing a solid-in-oil-nanosuspension (SONS) having
medium chain triglycerides such as sucrose erucate (i.e.
lipophilic surfactant) and sucrose monolaureate (i.e.
hydrophilic surfactant) stored at 25°C, protected from light.
A lipase-based enzymatic technique has been used to
degrade a formulation phase making it easier for AA to be
extracted. The results showed that the entire encapsulated
AA (95.3%) has been successfully extracted from the SONS
with the addition of a medium-chain triglyceride. Hence
the SONS showed increased stability of AA due to low
moisture contents (65).
Use of Solvents
In aqueous solution AA undergoes rapid oxidation (1)
but its stability is increased in acidic and weakly alkaline
media upon the addition of acetonitrile. It has been
observed that acetonitrile decreases the rate of AA
degradation to four fold at a concentration of 0.2%
while at a concentration of 2.0% the rate of reaction
reaches to the least value and remains unchanged upon
further addition of acetonitrile (58). This may be due to
a change in the polarity of the medium to inhibit the
rate of degradation of ionized AA. The effect of ethanol
on the stabilization of AA was also studied and the
results indicated a markedly lower effect of this solvent
compared to acetonitrile (58).
Effect of Viscosity, Dielectric Constant and pH
The rate of a chemical reaction may be affected by a
number of factors including the pH, viscosity and dielectric
constant of the medium which can greatly influence the
stability of oxidisable substances (72, 73). A study has been
performed to determine the effect of different humectants
such as ethylene glycol, propylene glycol and glycerine
in cream formulations containing AA. The humectants
showed stabilizing effect on the degradation of AA,
depending upon their viscosity, in the order of ethylene
glycol>propylene glycol>glycerine (9). A study of the rate
of photolysis of AA in aqueous and organic solvents has
been carried out using UV irradiation. It has been observed
that there is a linear relation between the rate of photolysis
and the solvent dielectric constant or the reciprocal
of viscosity. Hence an increase in the solvent dielectric
constant or a decrease in solvent viscosity leads to an
increase in the rate of photolysis. This should be taken into
consideration during the formulation of pharmaceutical
preparations containing AA (50). As stated earlier the rate
of photolysis of AA in cream formulations is also affected
by pH and redox potential of AA (e.g. E° at pH 5.0 = +0.127
V and at pH 7.0 = +0.058 V) and is due to the change in
the ionization of AA. An increase in the viscosity of creams
is also known to affect the physical stability of AA in cream
formulations. It has been reported that the higher the
viscosity of the medium the lower will be the degradation
of AA. Therefore, a careful selection of excipients including
emollients and humectants is of utmost importance to
improve the stability of AA (21).
Microencapsulation and emulsification are the widely
used techniques for the stabilization of AA in formulations
particularly at a concentration of 1–5% (18, 69, 74).
and enhances its level in plasma (53). Stabilization of AA
is also achieved by using other antioxidants such as DL-
methionine, mannitol, sorbitol, sucrose, dextrose, sodium
thiosulphate, halide salts, triplet quenchers, metal-
complexing agents and various viscosity enhancing agents
(54, 55). For the maximum stability of AA in solutions the
use of metaphosphoric acid is also reported (56, 57) with
greater efficacy than that of CT, perchloric, acetic, and
orthophosphoric acids (57, 58). In another study palmitic
acid (PA), an emulsifier, has been observed to exert a
greater stabilizing effect against the degradation of
AA in creams than the myristic and stearic acid (9). The
drugs prepared in the form of extruded granules with low
substituted hydroxyl propyl cellulose (L-HPC) and water
have been investigated using AA and thiamine nitrate
(TN) as model drugs. D-Mannitol is used as the control
additive for a comparison with L-HPC. The percentage of
AA remaining after a storage period of 14 days at 60°C in
a closed glass bottle was 57% in D-mannitol granules and
89% in L-HPC granules, showing higher stability of AA in
L-HPC granules (33).
Formulation of Multiple Emulsions
Multiple w/o/w emulsions are vesicular systems in which small
water droplets are entrapped within oil drops, and then
dispersed in the aqueous phase (59). They may be used as
a potent drug and cosmetic vehicles to prolong the action
after administration (60–63). The w/o emulsions containing
AA complexed with surfactants have been reported
(64–66). In a separate formulation, AA is added into the
inner aqueous phase of the w/o/w emulsion using parafn
oil at a concentration of 1% and a two step method for the
preparation of the emulsion. Stability studies on AA have been
performed at different temperatures, such as 8°C (refrigerator),
25°C (oven) and 40°C (oven) at 75% RH (stability cabin) for a
period of 28 days to foresee the changes in these formulations.
Different parameters, such as pH, globule size, electrical
conductivity and effect of centrifugation (simulating gravity)
have been evaluated during the stability studies. Multiple
emulsion formulations have been found to be stable at lower
temperatures (i.e. 8° and 25°C) during the study period with
no phase separation in all the samples (67). Another study has
been conducted using a high concentration of AA up to 30%
in the dispersed phase of w/o emulsions, with their continuous
phase containing rened soybean oil or Moringa oleifera oil
and a food-grade hydrophobic emulsier. All the w/o emulsions
appeared stable for more than 30 days at 4°C or 25°C with
slight increase in the average droplet diameter and without
any phase separation. AA retention ratio of these emulsions
followed rst-order kinetics showing good stability (68).
In order to study the effect of composition on AA
formulations such as surfactant/co-surfactant associations
and the use of different oils on the physicochemical
characteristics of the system, a polyglycoside
microemulsion has been developed which showed
good stability. It can protect AA from degradation with
enhanced penetration ability into the skin for topical
application. The study also revealed that the control of
pH and electrolyte concentration is necessary for the
stabilization of AA in the formulations (69, 70).
Formulation of Nanosuspensions
Since AA is not as stable as its derivatives such as tetra-
isopalmitoyl ascorbic acid (IPAA), it is often, recommended
H&PC Today - Household and Personal Care Today Vol. 10(3) May/June 2015
“Controlling temperature and water loss to maintain ascorbic
acid levels in strawberries during postharvest handling”, J.
Food Sci. 63, 1033–1036 (1998).
11. Roig, M. G., Rivera, Z. S., Kennedy, J. F. “A model study on rate
of degradation of L ascorbic acid during processing using
home-produced juice concentrates”, Int. J. Food Sci. Nutr. 46,
107–115 (1995).
12. Satoh, K., Sakagami, H., Terasaka, H., Ida, Y., Fujisawa, S.
“Interaction between hydroquinone and ascorbic acid
derivatives: quenching effects of organic solvents”,
Anticancer Res. 20, 1577–1581 (2000).
13. Nishikimi, M., Fukuyama, R., Minoshima, S., Shimizu, N., Yagi, K.
“Cloning and chromosomal mapping of the human
nonfunctional gene for L-gulono-gamma-lactone oxidase, the
enzyme for L-ascorbic acid biosynthesis missing in man”, J.
Biol. Chem. 269, 13685–13688 (1994).
14. Freedman, L., Francis, F. J. “Effect of ascorbic acid on color of
jellies”, J. Food Sci. 49, 1212–1213 (1984).
15. Starr, M. S., Francis, F. J. “Oxygen and ascorbic acid effect on
the relative stability of four anthocyanin pigments in cranberry
juice”, Food Tech. 22, 91–93 (1968).
16. Ozkan, M., Kırca, A., Cemeroglu, B. “Effects of hydrogen
peroxide on the stability of ascorbic acid during storage in
various fruit juices”, Food Chem. 88, 591–597 (2004).
17. Phillips, K. M., Tarrago-Trani, M. T., Gebhardt, S. E., Exler, J.,
Patterson, K. Y., Haytowitz, D. B., Pehrsson, P. R., Holden, J. M.
“Stability of vitamin C in frozen raw fruit and vegetable
homogenates”, J. Food Comp. Anal. 23, 253–259 (2010).
18. Uddin, M. S., Hawlader, M. N. A., Ding, L., Mujumdar, A. S.
“Degradation of ascorbic acid in dried guava during
storage”, J. Food Eng. 51, 21–26 (2002).
19. Zhai, H. Z., Maibach, H. L. “Skin whitening agents”, Cosmet.
Toilet. 116, 20–25 (2001).
20. Ahmad, I., Sheraz, M. A., Ahmed, S., Shad, Z., Vaid, F. H. M.
“Photostabilization of ascorbic acid with citric acid, tartaric
acid and boric acid in cream formulations”, Int. J. Cosmet.
Sci. 34, 240–245 (2012).
21. Sheraz, M. A., Khan, M. F., Ahmed, S., Kazi, S. H., Khattak, S. U.
R., Ahmad, I. “Factors affecting formulation characteristics
and stability of ascorbic acid in water-in-oil creams”, Int. J.
Cosmet. Sci. 36, 494–504 (2014).
22. Spiclin, P., Homer, M., Zupancic, A., Gasperlin, M. “Sodium
ascorbyl phosphate in topical microemulsions”, Int. J. Pharm.
256, 65–73 (2003).
23. Murad, S., Grove, D., Lindberg, K. A., Reynolds, G., Sivarajah,
A., Pinnell, S. R. “Regulation of collagen synthesis by ascorbic
acid”, Proc. Natl. Acad. Sci. 78, 2879–2882 (1981).
24. Kameyama, K., Sakai, C., Kondoh, S., Yonemoto, K.,
Nishiyama, S., Tagawa, M., Murata, T., Ohnum, T., Quigley, J.,
Dorsky, A., Bucks, D., Blanock, K. “Inhibitory effect of
magnesium l-ascorbyl-2 phosphate (VC-PMG) on
melanogenesis in vitro and in vivo”, J. Am. Acad. Dermatol.
34, 29–33 (1996).
25. Monograph on Ascorbic Acid, British Pharmacopoeia, Her
Majesty’s Stationary Office, London, UK (2013) Electronic
26. DeRitter, E. “Vitamins in pharmaceutical formulations”, J.
Pharm. Sci. 71, 1073–1096 (1982).
27. Homann, P., Gaffron, H. “Photochemistry and metal catalyzes:
Studies in a flavin sensitized oxidation of ascorbic acid”,
Photochem. Photobiol. 3, 499–515 (1964).
28. Monograph on ascorbic acid (819), Edited by O’ Neil, M. J.
The Merck Index, 15th ed., Royal Society of Chemistry, Merck
& Co., Inc., White House Station, NJ, USA, pp. 142–143 (2013).
29. Handbook of Pharmaceutical Excipients, Edited by Rowe, R.
C., Sheskey, P. J., Quinn, M. E. 4th ed., Pharmaceutical Press,
London, UK, (2009) pp. 43–47, 181–183, 625–627.
30. Martindale: The Complete Drug Reference, Edited by
Sweetman, S. C. 36th ed., Pharmaceutical Press, London, UK
Both w/o and w/o/w emulsification methods have
been used for encapsulation of AA (3, 67–69, 74–76). In
order to improve AA microencapsulation by complex
coacervation, both gelatine and gum arabic have
been used as encapsulating agents. In a w/o emulsion
using corn oil, a 30% solution of AA and polyglycerol
polyricinoleate (PGPR 90) as surfactant has been made for
making coacervation of a hydrophilic core material. The
encapsulation was carried out successfully in the double
emulsion with the complex coacervation thus confining
AA to a more stable microcapsule form rather than in
solution. It suggests the option of controlled release
under specific conditions and masking the acidic taste
of AA (77). Microencapsulated AA is also reported to
be more stable to colour change (18). Starch and beta-
cyclodextrin encapsulated AA delays its degradation
during storage at a temperature of 38°C and relative
humidity of 84% (18).
The stability of air sensitive drugs such as AA has always
been a problem for the formulator. Various approaches
have been adopted to achieve stabilization of AA in
cosmetic preparations. These include the use of stabilizers,
antioxidants, preservatives, synergists, emulsifiers etc. The
techniques of entrapment of AA in multiple emulsions and
encapsulation in nanosuspensions have shown significant
improvement in the stabilization of AA. The control of
medium pH, polarity and viscosity also prolong the shelf-life
of AA in cosmetic preparations.
1. Tsao, C. S., Young, M. A. “Stabilized ascorbic acid solution”,
Med. Sci. Res. 24, 473–475 (1996).
2. Abbasi, A., Niakousari, M. “Kinetics of ascorbic acid
degradation in un-pasteurized Iranian lemon juice during
regular storage conditions”, Pak. J. Biol. Sci. 11, 1365–1369
3. Gallarate, M., Carlotti, M. E., Trotta, M., Bovo, S. “On the
stability of ascorbic acid in emulsified systems for topical and
cosmetic use”, Int. J. Pharm. 188, 233–241 (1999).
4. Sheraz, M. A., Khan, M. F., Ahmed, S., Ahmad I:
Pharmacological effects of ascorbic acid, in Vitamin C:
Dietary Sources, Technology, Daily Requirements and
Symptoms of Deficiency, Edited by Guine, R. P. F., Ed. Nova
Science Publishers, Inc., New York, USA (2013).
5. Pinnell, S. R., Yang, H., Omar, M., Monteiro-Riviere, N., DeBuys,
H. V., Walker, L. C., Wang, Y., Levine, M. “Topical L-ascorbic
acid: percutaneous absorption studies”, Dermatol. Surg. 27,
137–142 (2001).
6. Yuan, J. P., Chen, F. “Degradation of ascorbic acid in
aqueous solution”, J. Agr. Food. Chem. 46, 5078–5082 (1998).
7. Buettner, G. R., Jurkiewicz, B. A: Chemistry and biochemistry of
ascorbic acid, in Handbook of Antioxidants, Edited by
Cadenas, E., Paker, L., Eds. Marcel Dekker, New York, USA
8. Niki, E. “Vitamin C as an antioxidant”, World. Rev. Nutr. Diet.
64, 1–30 (1991).
9. Ahmad, I., Sheraz, M. A., Ahmed, S., Shaikh, R. H., Vaid, F. H.
M., Khattak, S. U. R., Ansari, S. A. “Photostability and
interaction of ascorbic acid in cream formulations”, AAPS
PharmSciTech. 12, 917–923 (2011).
10. Nunes, M. C. N., Brecht, J. K., Morais, A. M. M. B., Sargent, S. A.
H&PC Today - Household and Personal Care Today Vol. 10(3) May/June 2015
... [7][8][9] However, formulating ascorbic acid is difficult due to its instability in the bulk aqueous system. [10] Several approaches have been adopted to preserve its stability and enhance its delivery to the target site, such as formulation of multiple emulsion, and microparticles including nanoparticles. [10][11][12] Furthermore, nanoparticulate systems have been reported to improve drug accumulation, drug uptake, and drug absorption across biological barriers. ...
... [10] Several approaches have been adopted to preserve its stability and enhance its delivery to the target site, such as formulation of multiple emulsion, and microparticles including nanoparticles. [10][11][12] Furthermore, nanoparticulate systems have been reported to improve drug accumulation, drug uptake, and drug absorption across biological barriers. [13,14] Poly(lactic-co-glycolic acid) (PLGA) is a biodegradable synthetic hydrophobic polymer frequently employed to develop various therapeutic devices including drug delivery systems. ...
Full-text available
Background: Chemotherapy is commonly used in oral cancer therapy, especially as the disease advances. However, it is associated with terrible adverse effects and the occurrence of chemoresistance which causes treatment failure. Thus, discovering a new potential anticancer agent and developing a safe, effective, and non-invasive drug delivery are necessary. Objective: The objective of the current study is to develop ascorbic acid-loaded poly(lactic-co-glycolic) acid (AA-PLGA) nanoparticles incorporated into polyacrylic acid gel intended to treat oral cancer. Materials and methods: Double emulsion solvent evaporation method was used to fabricate AA-PLGA nanoparticles. Optimization was carried out in the primary emulsion based on multilevel factorial design by testing at varying surfactant types and concentrations. The optimized nanoparticles formulation was further incorporated into different concentrations of polyacrylic acid gel, and compared with a mucoadhesive polyacrylic acid-based commercial product (Kin Care) as a reference. The optimized AA-PLGA nanoparticles were subjected to cytotoxic assay against the SCC-25 cell line. Results: For the optimized formulation, we observed particle size of 252 ± 2.98 nm, polydispersity index (PDI) of 0.151 ± 0.02, zeta potential of −20.93 ± 0.87 mV, and encapsulation efficiency of 69.73 ± 1.07%. Polyacrylic acid polymer with a strength of 1% was chosen as the optimum gelling agent for AA-PLGA nanoparticles-in-gel formulation. Cytotoxicity study of the optimized nanoparticle demonstrated significant (P < 0.05) reduction of cancer cell viability in a dose-dependent manner with a half-maximal inhibitory concentration value of 2.42 mg/mL. Conclusion: The results of the present study support the feasibility of AA-PLGA nanoparticles-in-gel formulation for oral cancer therapy.
... For the crystallization of ascorbic acid, water has been used as a prominent solvent because of its high solubility and easy availability. However, many studies have reported the degradation of ascorbic acid in aqueous solutions [6,7]. In addition to water, the effects of other solvents such as methanol, ethanol, isopropanol, and their compositions have been studied on various aspects of the crystallization process [8][9][10][11][12][13]. ...
... substituting Equations (4)- (6) in Equation (2), ...
Full-text available
This work investigates the effect of different solvent systems on solubility, thermodynamics, metastable zone width (MSZW), and crystal habit of ascorbic acid, in order to help optimize its crystallization process. The solubility curves and metastable zone (MSZ) limits were determined experimentally using the polythermal method in pure solvents: water and alcohols (methanol/ethanol/isopropanol), as well as water-alcohol binary solvent systems. The solubility decreases with increasing alcohol composition for all solvent systems. The solubility data were well correlated using the Jouyban–Acree model as a function of two variables: temperature and solvent composition. The dissolution enthalpy (ΔHdiss), dissolution entropy (ΔSdiss), and Gibbs free energy (ΔGdiss) were determined using Van’t Hoff and Jouyban–Acree models. The thermodynamic properties increase with increasing alcohol composition. The lowest and highest values of enthalpy were obtained for water (20.52 kJ mol −1) and isopropanol (35.33 kJ mol−1), respectively. Pure alcohols as solvents widen the metastable zone width, indicating high supersaturation required for the nucleation. Crystal images captured during cooling crystallization in water confirm the cubic crystal habit formation, whereas increasing alcohol composition in the solvent system promotes preferential growth along one crystallographic axis, leading to elongated prism-shaped crystals in methanol and ethanol and needle-shaped crystals in isopropanol.
... Supplemental ASA (25-2000 mg/kg) has been reported to have a positive impact on growth performance and immunological responses in various aquatic animals, thereby enhancing their resistance to stressors [8][9][10]. However, ASA is unstable, its oxidation is accelerated in alkaline environments, and the rate of its loss is influenced by factors such as temperature, oxygen, light, and pH [11,12]. Even when provided with 4-5 times the recommended dosage of ASA, its efficacy still cannot be guaranteed [13]. ...
Full-text available
L-ascorbic acid (ASA) is a micronutrient that is essential for reproduction, growth, and immunity in animals. Due to the loss of enzyme L-gulono-1,4-lactone oxidase (GLO), most aquatic animals lack the capacity for ASA biosynthesis and therefore require supplementation with exogenous ASA. Recent studies have shown that 2-keto-L-gulonic acid (2KGA), a novel potential precursor of ASA, can enhance plant growth and improve stress resistance by promoting the synthesis and accumulation of ASA. Our hypothesis is that 2-keto-L-gulonic acid (2KGA) plays a similar role in aquatic animals. To investigate this, we conducted an in vivo trial to examine the effects of exogenous 2KGA supplementation on ASA metabolism and growth of zebrafish (Danio rerio). Zebrafish were categorized into groups based on their dietary intake, including a basal diet (CK group), a basal diet supplemented with 800 mg/kg ASA (ASA group), and 800 mg/kg 2KGA-Na (2KGA group) for a duration of three weeks. The results demonstrated a significant increase in ASA content in zebrafish treated with 2KGA (34.82% increase, p < 0.05) compared to the CK group, reaching a consistent level with the ASA group (39.61% increase, p < 0.05). Furthermore, the supplementation of 2KGA significantly improved growth parameters relevant to zebrafish (specific growth rate increased by 129.04%, p < 0.05) and enhanced feed utilization (feed intake increased by 15.65%, p < 0.05). Positive correlations were observed between growth parameters, feed utilization, whole-body chemical composition, and ASA content. Our findings suggest that supplementation with exogenous 2KGA can serve as a novel approach for elevating ASA synthesis in aquatic animals, and further investigation of its underlying mechanism is required.
... This problem may be overcome by combining ascorbic acid with α-tocopherol, a lipid-soluble antioxidant in low-density lipoprotein and lipid membrane oxidation, due to their synergistic interactions. In fact, ascorbic acid has been suggested as a regenerator of α-tocopherol from its radicals by several studies which reported an increase of antioxidant effects of α-tocopherol in the presence of ascorbic acid [4,6,[11][12][13]. Therefore, in skin care formulations, the combined utilization of both ingredients has been suggested [4,9]. ...
Full-text available
The main function of vitamin C, as an antioxidant, is to combat free radicals and prevent premature aging, smoothing wrinkles and expression lines. In addition, it acts directly on depigmentation and prevention of blemishes on the skin. In this study, natural oils (30 wt.%) and α-tocopherol (2.5 wt.%) containing oil-in-water (O/W) emulsions stabilized with the bacterial fucose-rich polysaccharide FucoPol were formulated, adding L-ascorbic acid as an antioxidant. The optimized formulations were obtained with 8.0 wt.% L-ascorbic acid for the Olea europaea oil formulation (C1) with a ƞ value of 2.71 Pa.s (measured at shear rate of 2.3 s−1) and E24 = 96% and with 15 wt.% L-ascorbic acid for the Prunus amygdalus dulcis formulation (C2) with a ƞ value of 5.15 Pa.s (at a shear rate of 2.3 s−1) and E24 = 99%. The stability of the FucoPol-based formulations was investigated over 45 days at 4 °C, 20 °C, and 30 °C. The results showed that all formulations maintained the organoleptic characteristics, with pH variations (5.7–6.8 for C1, and 5.5–6.03 for C2) within the regulations for cosmetic products (4 ≤ pH ≤ 7). The accelerated stability tests proved the formulations’ stability at 4 °C with EI = 95% for C1 and EI = 100% for C2. The rheological assessment demonstrated that the formulation presents a shear-thinning and liquid-like behavior. Regarding textural parameters, formulations C1 and C2 displayed an increase in firmness and consistency with similar spreadability during the shelf life. These findings further demonstrate FucoPol’s functional properties, acting as an emulsifier and stabilizer polysaccharide in cosmetic formulations containing L-ascorbic acid.
... Effect on Phenolic compounds : Generally, some factors like, pH, air, temperature, metallic ions affect the degradation of phenolic compounds (Sheraz et al, 2015). In freeze drying technique, degradation of phenolic compounds is less due to less processing temperature. ...
Drying is the earliest technique of food preservation which inhibits enzymatic activity and microbial growth in food with extended shelflife without altering the quality. Among all the drying techniques, freeze drying has emerged as one of the most crucial procedures for the preservation of food. Freeze-drying, often referred to as lyophilization is a method to remove water from a substance in the form of ice through a vacuum system called sublimation. The principles of freeze-drying are covered in this review, along with the principle & application in food preservation and current research works related to freeze-drying procedures. It is feasible to draw certain inferences about the benefits and drawbacks of freeze-drying foods and to get a sense of how things could be developed in the future by assessing the sufficient data represent in the manuscript.
Full-text available
The global market of food, cosmetics, and pharmaceutical products requires continuous tracking of harmful ingredients and microbial contamination for the sake of the safety of both products and consumers as these products greatly dominate the consumer’s health, directly or indirectly. The existence, survival, and growth of microorganisms in the product may lead to physicochemical degradation or spoilage and may infect the consumer at another end. It has become a challenge for industries to produce a product that is safe, self-stable, and has high nutritional value, as many factors such as physical, chemical, enzymatic, or microbial activities are responsible for causing spoilage to the product within the due course of time. Thus, preservatives are added to retain the virtue of the product to ensure its safety for the consumer. Nowadays, the use of synthetic/artificial preservatives has become common and has not been widely accepted by consumers as they are aware of the fact that exposure to preservatives can lead to adverse effects on health, which is a major area of concern for researchers. Naturally occurring phenolic compounds appear to be extensively used as bio-preservatives to prolong the shelf life of the finished product. Based on the convincing shreds of evidence reported in the literature, it is suggested that phenolic compounds and their derivatives have massive potential to be investigated for the development of new moieties and are proven to be promising drug molecules. The objective of this article is to provide an overview of the significant role of phenolic compounds and their derivatives in the preservation of perishable products from microbial attack due to their exclusive antioxidant and free radical scavenging properties and the problems associated with the use of synthetic preservatives in pharmaceutical products. This article also analyzes the recent trends in preservation along with technical norms that regulate the food, cosmetic, and pharmaceutical products in the developing countries.
Conference Paper
There exists a need for high temperature fracturing fluids as we expand exploration into deeper, lower permeability, and hotter formations. Fracturing fluid stability depends on two main bonds: the crosslinker to polymer bond and the monomer to monomer bond. To preserve the crosslinker to polymer bond, a proper crosslinker with a suitable delay additive is typically utilized. On the other hand, the monomer to monomer bond is challenging to protect since it’s susceptible to a variety of factors with the main culprit being oxygen radical attacks. Consequently, the most common high temperature stabilizers used are oxygen scavengers such as sodium thiosulfate or sodium sulfite. Unfortunately, both additives create their own issues. Sodium thiosulfate is known to degrade at high temperature to generate H2S, while sulfites generate sulfates that end up causing inorganic scale precipitation or feeding sulfate reducing bacteria creating another source of H2S in the reservoir. Additionally, Sodium thiosulfate is a high pH additive which can cause formation damage through fines migration and precipitation of hydroxides. Vitamin C is renowned for its antioxidative and oxygen scavenging properties throughout many industries. It is commonly used as an extremely cheap supplement to boost the immune system and as a food preservative to increase shelf life. Moreover, it has an acidic pH and offers a chemical structure capable of delaying crosslinking reactions. For that reason, this work aims to study the influence of Vitamin C as a multifunctional additive in fracturing fluids. The tests mainly utilized the high-pressure/high-temperature (HPHT) rheometer. The performance of Vitamin C was assessed with a guar derivative at temperatures between 250-300°F for 1.5 hours. Moreover, zeta potential and coreflood were used to evaluate the formation damage tendencies of using this additive. The results showed that the use of Vitamin C was able to provide a pH reduction, crosslinking delay, and enhance the high temperature stability of fracturing fluids. Zeta potential and coreflood experiments showed that clays were more stable at lower pH conditions minimizing fines migration. Vitamin C is a cheap and readily manufactured environmentally friendly additive that offers solutions to the use of fracturing fluids at high temperatures. Utilizing it not only offers oxygen scavenging ability, but also replaces additives that lower pH and provides crosslinking delaying properties.
Full-text available
Background: Reactive oxygen species generated by ultraviolet light result in photocarcinogenic and photoaging changes in the skin. Antioxidants protect skin from these insults. Objective: This study defines formulation characteristics for delivering L-ascorbic acid into the skin to supplement the skin's natural antioxidant reservoir. Methods: L-ascorbic acid or its derivatives were applied to pig skin. Skin levels of L-ascorbic acid were measured to determine percutaneous delivery. Results: L-ascorbic acid must be formulated at pH levels less than 3.5 to enter the skin. Maximal concentration for optimal percutaneous absorption was 20%. Tissue levels were saturated after three daily applications; the half-life of tissue disappearance was about 4 days. Derivatives of ascorbic acid including magnesium ascorbyl phosphate, ascorbyl-6-palmitate, and dehydroascorbic acid did not increase skin levels of L-ascorbic acid. Conclusions: Delivery of topical L-ascorbic acid into the skin is critically dependent on formulation characteristics.
Full-text available
Ascorbic acid degradation in orange, grape and pomegranate juices, and sour cherry nectar was studied at 20, 30 and 40 °C, with or without the addition of hydrogen peroxide (H2O2). Analysis of kinetic data suggested that the degradation fitted better to a zero-order model than a first-order model. Rate constants increased slightly in the presence of 0.5 ppm H2O2. However, increasing H2O2 concentration from 0.5 to 5 ppm caused a substantial increase in the degradation rates of ascorbic acid. Anthocyanins markedly accelerated the degradation of ascorbic acid in sour cherry nectar and pomegranate juice, especially at 5 ppm H2O2 concentration. Degradation was slowest in orange juice, with or without the addition of H2O2. Activation energies were lowest for grape juice (26.2 kJ mol−1) and highest for pomegranate juice (71.0 kJ mol−1) in the presence of 0.5 ppm H2O2.
Ascorbic acid (vitamin C) is an essential nutrient involved in many physiological functions. In addition to its vitamin activities, the use of ascorbic acid has extended to other medical and industrial applications. Most of these make use of its reducing properties. In animals and plants, ascorbic acid can provide protection against oxidative damage from environmental chemicals, ionising radiation and ultraviolet light. However, ascorbic acid in solution is very unstable. It may undergo auto-oxidation and decompose rapidly to produce many degradation products. Some of these oxidation and degradation products have destructive pro-oxidant effects, including lipid peroxidation, cytotoxicity, mutagenesis and adduct formation with proteins and nucleic acid. Various methods have been attempted to stabilise ascorbic acid in solution. An isotonic ascorbic acid solution stabilised by a borate-EDTA buffering system has been prepared. This solution is very stable with respect to ascorbate content, colouring, clearness, and pH value. It contains ascorbate: 5 mM, berate: 320 mM, EDTA: 3 mM, and sodium ion: 155 mM, and has a pH value of 7.4. Results from in vitro and in vivo experiments indicate that this solution is not toxic to cultured cells or laboratory animals. It is suitable for nutritional, biochemical, and medical applications.
Sodium ascorbyl phosphate is a hydrophilic derivative of ascorbic acid, which has improved stability arising from its chemical structure. It is used in cosmetic and pharmaceutical preparations since it has many favorable effects in the skin, the most important being antioxidant action. In order to achieve this, it has to be converted into free ascorbic acid by enzymatic degradation in the skin. In the present work, o/w and w/o microemulsions composed of the same ingredients, were selected as carrier systems for topical delivery of sodium ascorbyl phosphate. We showed that sodium ascorbyl phosphate was stable in both types of microemulsion with no significant influence of its location in the carrier system. To obtain liquid microemulsions appropriate for topical application, their viscosity was increased by adding thickening agents. On the basis of rheological characterization, 4.00% (m/m) colloidal silica was chosen as a suitable thickening agent for w/o microemulsions and 0.50% (m/m) xanthan gum for the o/w type. The presence of thickening agent and the location of sodium ascorbyl phosphate in the microemulsion influenced the in vitro drug release profiles. When incorporated in the internal aqueous phase, sustained release profiles were observed. This study confirmed microemulsions as suitable carrier systems for topical application of sodium ascorbyl phosphate.
Objective The present investigation is based on the formulation of different water-in-oil (w/o) creams of ascorbic acid (AA) as a potential topical or cosmetic preparation for anti-aging purpose. The effect of different excipients, medium pH and viscosity on the chemical as well as physical stability of AA during storage has been evaluated.Methods Several water-in-oil (w/o) cream formulations of AA have been prepared at pH 4–6 using different emollients and humectants. The creams were stored in the dark at 30°C for a period of three months and were studied for AA loss and change in physical characteristics.ResultsThe pH of the creams appeared to influence the stability of AA as the degradation was found to increase with an increase in pH by first-order kinetics. The stability of AA is increased with an increase in the viscosity of the medium. The creams that showed the highest rates of degradation (i.e. at pH 6) were also compared with the creams at the same pH by adding citric acid (CT) as a stabilizer. CT was found to decrease the rates of degradation of AA in all the formulations.Conclusion Among all the formulations, the creams containing castor oil as emollient and glycerin as humectant showed minimum degradation as compared to the creams containing other excipients. FTIR studies indicated that there is no significant interaction between AA and CT in physical mixtures.This article is protected by copyright. All rights reserved.
An HPLC method, for the simultaneous determination of the degradation products of ascorbic acid, was employed to investigate the degradation of ascorbic acid in aqueous solution at different pH values. After ascorbic acid aqueous solutions were heated at 100 °C for 2 h, four main degradation products, furfural, 2-furoic acid, 3-hydroxy-2-pyrone, and an unidentified compound, were separated and determined. In an acid aqueous solution, ascorbic acid was converted to 2-furoic acid and 3-hydroxy-2-pyrone via dehydroascorbic acid under aerobic conditions, whereas under anaerobic conditions, ascorbic acid degraded to furfural. Low pH conditions favored the formation of furfural, 2-furoic acid, and 3-hydroxy-2-pyrone; at extremely low pH (i.e., pH 1), the formation of furfural dominated. In an alkaline aqueous solution, the unknown compound became the main degradation product of ascorbic acid; at pH 10, only very small amounts of furfural and 3-hydroxy-2-pyrone with no 2-furoic acid were detected. Our results suggest that, in a hydrogen-ion-catalyzed environment, the anaerobic degradation of ascorbic acid to furfural is the main degradation pathway in an aqueous solution. Keywords: Ascorbic acid; dehydroascorbic acid; degradation; furfural; 2-furoic acid; 3-hydroxy-2-pyrone; HPLC
Jellies, prepared from strawberry, blackberry, apple and orange juice, were fortified with ascorbic acid at 0, 35, and 70 mg/100 mL. After storage at room temperature, the jellies were sampled at intervals up to 32 wk for color measurement. The ascorbic acid did produce lighter products as shown by higher Hunter L values. The hues were shifted towards the yellow as shown by higher theta values. The ascorbic acid was well retained in the jellies. Whether the lightness and hue changes are desirable is probably a matter of individual preference.
This paper constitutes a study of the interaction between ascorbate, diketogulonate, manganous ion, oxygen and illuminated flavins (or other sensitizers). When ascorbate is chosen as the substrate, the resulting photoxidation assumes a peculiar two-step course. This happens because traces of ascorbate inhibit the photoxidation of diketogulonate and oxygen retards the photoxidation of small amounts of ascorbate. Sensitized photo-reactions which are inhibited by high concentrations of oxygen are affected by the addition of various organic compounds. Of these, the herbicides 3-(p-clilorophenyl)-1,1-dimethylurea (CMU) and 3-(3, 4-dichlorophenyl)-1,1-dimethylurea (DCMU) interfere nearly exclusively with flavin sensitized photoreactions, while other inhibiting compounds tested, such as tryptophane and tyrosine, do not display a similar selectivity for only one dye. A second even more rigid specificity concerns the role of manganous ions. Diketogulonate is oxidized through the action of light excited flavin or of traces of alkali in the dark only when Mn⁺⁺ is available. No other metal tested had this ability.
Retention of ascorbic acid (vitamin C) in dried guava during storage was studied. The effects of storage temperature: 30°C, 40°C, 50°C and water activity (aw): 0.43, 0.75, 0.84, 0.97 were investigated. The degradation of ascorbic acid follows a pseudo-first-order reaction. The rate constant increased about four to six fold when storage condition was changed from aw=0.43–0.97. The rate constants and corresponding water activities are related by a second-order polynomial equation. The effect of temperature on the rate constant followed the Arrhenius relationship. The activation energy of ascorbic acid degradation is found to be in the range 3.4–11.0 kcal/mol. An empirical equation, based on temperature, water activity and rate constant, is developed to predict shelf life of dried guava in respect of ascorbic acid retention.