Oliveira et al.

Effervescent vitamin C tablets and its quality control

Scientific Electronic Archives

Issue ID: Sci. Elec. Arch. Vol. 13 (5)
May 2020
DOI: http://dx.doi.org/10.36560/13520201055
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Effervescent vitamin C tablets and its quality control

M. S. Oliveira, M. P. R. Torres, A. L. Raiser, E. B. Ribeiro, C. R. Andrighetti, D. M. S. Valladão

Federal University of Mato Grosso - Campus Sinop

Author for correspondence: deniavalladao@gmail.com

______________________________________________________________________________________
Abstract. Ascorbic acid (vitamin C), a potent antioxidant, is not synthesized by the human body and is obtained from
food and pharmaceutical formulations. As a pharmaceutical product, it is available as a solution, powder, granules and
tablets. Effervescent tablets are the most consumed since the isolated form or associated with other substances. It is
commercially available from several suppliers, which makes its evaluation fundamental to ensure the quality, efficacy and
safety of the patient in face of over-the-counter medication. Quality control is essential in the final product, as many
products do not have the desired quality, compromising its validity and action. The present study aimed to evaluate
effervescent vitamin C tablets from three different brands. The quality tests were carried out according to the parameters
recommended by the Brazilian Pharmacopeia. The content was determined by the titrimetric and spectrophotometric
method, as there is no official methodology for effervescent vitamin C tablets. All brands were approved in the quality
tests used, guaranteeing and demonstrating the company's commitment to the population that consumes it.
Keywords: ascorbic acid, quality control, effervescent tablets
______________________________________________________________________________________

Introduction other hand, depending on the active substance, it

Oral dosage forms are the most used for contributes to the stability of the product during the
medication administration due to their ease of shelf life (CRISTINA, 2012).
administration, transport and greater stability, when Quality control of pharmaceutical forms is an
compared to liquid and semi-solid forms. Among oral indispensable condition, since it is the sector
solids, tablets are more common due to the responsible for guaranteeing the quality and
relatively simple manufacturing process, with high effectiveness of the medicine, which will be
productivity and low cost (LACHMAN et al., 2010). marketed (GIL, 2010; PINTO et al., 2010; UNITED
However, when the tablet requires a large amount of STATES PHARMACOPEIA, 2007).
active substance, its administration is difficult due to For effervescent drugs, in addition to the
its size and an option for these cases is effervescent tests for identification, purity, drug content and those
tablets (ANSEL, 2007). inherent to the pharmaceutical form, such as
Effervescent tablets are prepared by hardness, friability, average weight, uniformity of unit
compacting granulated effervescent salts that doses, two tests stand out: the disintegration test /
release carbon dioxide in contact with water. dissolution, and the pH of the solution obtained after
Therefore, it is necessary to be dissolved or the disintegration (GIL, 2010; UNITED STATES
dispersed in water before administration. PHARMACOPEIA, 2007). This test also collaborate
(BRANYFIELD, c2017; CAMPOS, ALVES and to verify the release of carbon dioxide into the
SILVA, 2012). The use of these effervescent solution functioning as a buffer system, due to the
formulations has been growing due to advantages balance generated between the acid component and
such as: good stability, masking of unpleasant taste, the corresponding salt. (ANSEL, 2007; WORLD
possibility of working with high doses, efficient HEALTH ORGANIZATION, 2011). Also, the
administration in patients with difficulty in disintegration and dissolution happen
swallowing, in addition to increasing the simultaneously.
bioavailability of the drug (ASLANI e SHARIFIAN, The pH after disaggregation must be
2019; CRISTINA, 2012; LINDBERG, 2007). As a constant or with slight variations between tablets in
disadvantage, we can mention the need for the same batch. Heterogeneity or large variations in
packaging to be impervious to moisture and light, values during the tests probably suggest that there
which makes the medicine more expensive. On the is heterogeneity in the distribution of raw materials

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 Oliveira et al. Effervescent vitamin C tablets and its quality control

before compression, which may influence the containing about 1–2 % vitamin C, which were
stability and flavor of the final product (ANSEL, recorded at room temperature in the range of 2000 -
-1
2007; GENNARO, 2014). 500 cm . For each sample, 20 scans were recorded
-1
Among the effervescent drugs sold, are with a resolution of 4 cm . The test is considered
tablets containing ascorbic acid (Vitamin C). Vitamin positive if the samples showed absorption
C is water-soluble and has low stability against maximums at the same wavelengths and with the
oxidation, requiring care in its production, storage same relative intensities as those observed in the
and use (ALVES, JAIME, GONÇALVES, SUZUKI, ascorbic acid (RCS) spectrum, prepared in an
2008; DELVIN, 2011). As vitamin C is a widely identical manner.
marketed product not only under medical guidance,
it is expected that the proposed trust will exist, Measurement of average weight
regardless of the brand or supplier company. Loss of Twenty effervescent tablets from each
quality interferes with the success of the treatment supplier were individually weighed to calculate the
and / or exposes users to exacerbation of adverse or average weight, standard deviation and coefficient of
undesirable events, since the active substance can variation. According to the Brazilian Pharmacopeia
be altered during storage, by the action of light, (BRASIL, 2010), tablets containing more than 250
moisture and heat (PRISTA et al., 1995). mg, can have a maximum of two tablets outside the
Thus, due to the concern with health, the specified limits of +/- 5.0%, and no sample can
ease of marketing vitamin supplements, the wide contain unit weight above or below double of the
variety of suppliers and prices, the work aimed to percentage indicated (BRASIL, 2010).
verify the quality of effervescent tablets from three
brands available in the market in 2019 Hardness
. Ten units were submitted to the test, using
Methods the durometer, in order to verify their resistance
Samples against a force applied diametrically. According to
Samples from three brands that produce the Brazilian Pharmacopoeia, the minimum
effervescent vitamin C at a dose of 1 g were acceptable is 3 kgf (BRASIL, 2010).
analyzed. The tablets were purchased in the
municipality of Sinop - MT, in 2019. The tablets of Friability
each supplier were from the same manufacturing Ten tablets of each pharmaceutical product
batch and, for ethical reasons, the names of the were weighed and placed in a friabilometer. After
manufacturers of the drugs were not informed, being 100 rotations carried out for 4 minutes (25 rpm), the
called products, X, Y and Z. tablets were removed from the equipment and any
residue or dust will be removed and weighed again.
Reference chemical substance (RCS) Friability was calculated by the difference between
The RCS used was 99.7% pure ascorbic the initial weight and the final weight of the tablets.
acid (Proquimios). Tablets with losses of less than 1.5% of their weight
are considered acceptable. Chipped or split-layer
Reagents tablets were not considered for calculating the
All reagents used were of analytical grade: percentage of friability (BRASIL, 2010).
soluble starch (Synth), sulfuric acid (Proquimios),
hydrochloric acid (Synth), resublimated iodine Disintegration time
(Isofar), potassium iodide (Neon), sodium thiosulfate To perform the test, a tablet was added to a
(Isofar), potassium dichromate (Isofar), 1,10- beaker containing 200 mL of water at a temperature
0
Phenanthroline (Vetec) and iron sulfate of 15 – 25 C. The test was performed in six times.
heptahydrate (Dynamic). According to the World Health Organization (WHO),
gas bubbles must be released and when the gas
Equipments release ends, the granules must be disaggregated
The equipment used was: analytical balance and dissolved or dispersed in water in less than five
(Shimadzu - model AUY220), durometer (Logen - minutes (WORLD HEALTH ORGANIZATION, 2011).
model LSD-DI), infrared spectrophotometer with
Fourier transform (FTIR) (Affinity - 1 - Shimadzu), Determination of pH
digital pH meter (Del lab - model DLA -PH), The pH was determined in the six solutions
stopwatch (Dinloo - XL-009A), UV-visible resulting from the effervescence test, using a pH
spectrophotometer (PG Instruments - model T80). meter previously calibrated with buffer solutions
Vitamin C tablets were analyzed according (BRASIL, 2010).
to the tests described below.
Dosing and uniformity of unit doses
Drug identification test Effervescent tablets containing ascorbic acid
Infrared absorption spectrophotometry with do not have an official monograph, therefore, dosing
Fourier transform (FTIR) was used. The spectra was carried out following two methods: titrimetric
were obtained using potassium bromide tablets

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 Oliveira et al. Effervescent vitamin C tablets and its quality control

and spectrophotometric. The tests were performed complex with strong absorption in the wavelength of
in triplicate. 510 nm.
The dosage performed by the titrimetric For both methods, the acceptance value of
method is that indicated by the Brazilian 90 to 110% was adopted as established for the
Pharmacopeia for tablets and that was used for pharmaceutical form of ascorbic acid tablets
effervescent tablets (BRASIL, 2010). For the test, 20 (BRASIL, 2010)
tablets were totally powdered and weighed. Then, The uniformity assay for unit doses was the
0.2 g of weight equivalent of ascorbic acid was same as for dosing, only being performed
dissolved in a mixture of 100 ml of water and 25 ml individually with 10 effervescent tablets.
-1
of sulfuric acid 1 mol.L , which was then titrated with
-1
0.05 mol.L iodine solution using starch solution as Results and discussion
indicator. (BRASIL, 2010). The identification test performed by FTIR
The spectrophotometric method was showed that all products contain vitamin C (Figure
performed according to Silva et al (2019), in which 1), as they as they presented the same absorption
an iron (III) and 1.10-phenanthroline complex is bands as SRQ ascorbic acid.
reduced by ascorbic acid, resulting in a red-orange

Ascorbic Acid (CRS)

Product Z
Product Y
100
Product X

75
% Transmitance

50

25

0
4000 3500 3000 2500 2000 1500 1000 500
-1
Wavenumber (cm )

Figure 1. Spectrometry of the RCS ascorbic acid infrared region and samples of effervescent tablets containing vitamin
C (X, Y and Z product).

The average weights of the samples are limit can break down too quickly (ANSEL, 2007).
shown in Table 1. All samples showed values
according to the established by the Brazilian Both situations can result in an ineffective
Pharmacopeia (BRASIL, 2010). The product named drug release and action. The results of the hardness
X had the lowest relative standard deviation test are shown in Table 2, where it was found that all
(0.53%), while product Y the largest deviation products passed the hardness test because they
(2.43%), showing a greater dispersion of weights had values above 3.0 kgf.
from one tablet to another. The friability test reflects the resistance of
The hardness test allows to verify the the tablet to wear when subjected to mechanical
resistance of the tablet to crushing or even rupture shocks resulting from industrial processes and
under a subjected pressure and its result is everyday actions, such as production, packaging,
expressed in kgf (kilogram-force). The Brazilian storage, transport and distribution, and even
Pharmacopeia (BRASIL, 2010) establishes only the handling by the patient (LACHMAN et al. , 2001).
minimum value of 3.0 Kgf that the tablets must have. There is usually a relationship between hardness
It is an important test for tablets that can interfere and friability, where a high hardness can result in
with production, packaging, transport and handling reduced friability and vice versa (STORPIRTIS,
operations. A tablet with a very high hardness can 2009). The Brazilian pharmacopoeia (BRAZIL, 2010)
break down very slowly or even not break down, on and the American pharmacopeia (UNITED STATES
the other hand, a tablet with a hardness below the PHARMACOPEIA, 2007) reported that effervescent
tablets may have different specifications regarding

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 Oliveira et al. Effervescent vitamin C tablets and its quality control

friability, which makes it essential to choose the disintegrate and dissolve completely in the water.
packaging material to ensure quality, stability and This type of tablet is prepared by compacting some
the shelf life of tablets with high friability. salts that release carbon dioxide in contact with
water (BRANYFIELD, c2017). Thus, the
Table 1. Individual weight, average weight and relative disintegration and dissolution of the effervescent
standard deviation of effervescent vitamin C tablets tablets occurs by the release of carbon dioxide and,
(products X, Y and Z). when the gaseous release ends, the granules must
be disaggregated and dissolved in water in less than
Tablet Individual Individual Individual 5 minutes.
weight weight weight Tablets not disintegrated or incompletely
(g)X (g)Y (g)Z dissolved in water after effervescence suggest
1 3.970 3.809 3.336 manufacturing flaws, such as, for example, a very
2 3.949 3.729 3.308 high hardness, which makes the tablet not fully
3 3.929 3.810 3.273 disintegrate in water, which may influence the
4 3.952 3.791 3.259 content and action of the drug (ÓRFÃO, 2016).
5 3.964 3.716 3.298 The water temperature influences
6 3.956 3.758 3.290 disintegration and dissolution. Low temperatures
7 3.944 3.645 3.226 result in an increase in time, so it is set at a
8 3.992 3.704 3.230 temperature between 15 to 25 ° C for the
9 3.966 3.815 3.284 disintegration and dissolution process to occur
10 3.949 3.799 3.238 (LINDBERG, 2007).
11 3.997 3.785 3.170 The three products (X, Y and Z) at the temperature
12 3.939 3.845 3.205 0
of 20 C disintegrated and dissolved within the
13 4.016 3.768 3.227 established limit of 5 minutes (Table 3). The results
14 3.972 3.775 3.263 found are similar to those of Aslani (2014). This
15 3.969 3.709 3.177 author evaluated Amoxicillin effervescent tablets and
16 3.988 3.601 3.181 found that the analyzed samples disintegrated in
17 3.937 3.733 3.261 less than 5 minutes, a condition for effervescent
18 3.971 3.602 3.270 tablets. The disintegration and dissolution time for
19 3.973 3.558 3.280 this type of pharmaceutical form is essential for its
20 3.997 3.934 3.240 administration, since they are ingested right after the
Average 3.966 3.744 3.251 total disintegration / dissolution.
weight
Standard 0.023 0.091 0.045 Table 3. Disintegration and dissolution time of samples of
deviation effervescent vitamin C tablets of products X, Y and Z at
0
R.S.D (%) 0.58 2.43 1.38 20 C .
R.S.D. (%) = Relative standard deviation. Tablet X Y Z
1 2 min 10 s 1 min 57 s 1 min 28 s
Table 2. Hardness of the samples of effervescent tablets 2 2 min 15 s 1 min 46 s 1 min 27 s
of vitamin C of products X, Y and Z. 3 2 min 10 s 1 min 56 s 1 min 22 s
Tablet X (kgf) Y (kgf) Z (kgf) 4 1 min 57 s 1 min 53 s 1 min 37 s
1 8.25 > 20.38 17.08 5 2 min16 s 1 min 59 s 1 min 23 s
2 6.06 15.19 > 20.38 6 2 min 04 s 1 min 51 s 1 min 18 s
3 12.82 > 20.38 > 20.38 Average 2 min 02 s 1 min 54 s 1 min 26 s
4 17.51 11.54 19.07
5 7.47 > 20.38 > 20.38
The pH must remain constant or with small
6 15.37 15.95 17.75
variations between tablets in the same batch.
7 18.61 13.98 15.37
Vitamin C has a slightly acidic characteristic, since it
8 10.81 17.21 > 20.38
is a weak acid (pKa = 4.04 at 25 ºC) (DAMODARAN,
9 > 20.38 12.49 14.51
2010) and must be maintained to maintain its
10 17.88 18.17 17.77
stability (ROSA, 2007).
The maintenance of pH is important so that
The results corroborated with Andrade
the vitamin does not degrade when exposed to
(2017), where the analysis of the tablets showed a
variations such as a very acidic pH, hydrolysis or a
loss greater than 1.5% in the friability test, showing
basic pH may occur, resulting in oxidation of
that the loss of material may be related to the
ascorbic acid, in addition to light, humidity,
excipients, which are sensitive to mechanical action
temperature, oxygen, resulting in chemical
due to their effervescent mechanism that it should
transformations to the tablet that become dangerous
dissolve quickly. To prevent loss and breakage of
under these conditions (ROSA, 2007; SURINI,
the tablets, the packages are tubes. The
2017). The pH is one of the main factors that affect
effervescence time allows you to check the time (in
the stability of ascorbic acid (PATHY, 2018)
minutes) that effervescent tablets take to

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 Oliveira et al. Effervescent vitamin C tablets and its quality control

In addition, the pH must be in balance with the quality in the drug's production stages
the pH of the stomach (pH = 1.4) and the intestine (LACHMAN et al., 2010).
(pH = 7.5) (BRUNTON, 2012) to favor its absorption.
An interesting aspect is the buffering capacity of Table 6. Content and relative standard deviation of
excipients of effervescent forms, since gastric pH samples of effervescent tablets of vitamin C of products X,
tends to increase after ingestion of this type of Y and Z obtained by titration..
pharmaceutical form (LEE, 2012; IPCI, 2016). X Y Z
The pH results after the disintegration / dissolution of Ascorbic acid (%) 98.1 100.4 98.8
the tablets are shown in Table 5. All products R.S.D. (%) 0.57 1.55 1.36
showed a pH between 4.5 to 5.0, which is suitable R.S.D. (%) = Relative standard deviation.
for this type of formulation to guarantee the stability
of the solution at the time of its administration. Table 7. Content and relative standard deviation of
samples of effervescent tablets of vitamin C, products X, Y
and Z obtained by spectrophotometry in the visible region.
Table 5. The pH values and relative standard deviation of
effervescent tablets containing vitamin C from products X, X Y Z
Y and Z.. Ascorbic acid (%) 104.6 105 105.7
Tablet X Y Z R.S.D. (%) 0.43 0.118 0.773
R.S.D. (%) = Relative standard deviation.
1 4.63 4.49 4.72
2 4.59 4.47 4.80
For the uniformity test of unit doses, the
3 4.65 4.50 4.90
titrimetric method was chosen since there was no
4 4.60 4.52 4.95 difference between the methods used. The test was
5 4.63 4.53 4.74 performed by weight variation and the results are
6 4.58 4.54 4.87 shown in Table 8. The three products had an
Average 4.61 4.51 4.83 acceptance value of less than 15, which is the limit
R.S.D. (%) 0.58 0.57 1.90 established by the Brazilian Pharmacopeia (BRASIL,
R.S.D. (%) = Relative standard deviation. 2010), ensuring that all products have the declared
amount of vitamin C and the homogeneity of the
The dosage of medications is essential for pharmaceutical form in each tablet.
the administration of correct doses, in order to
ensure that the quantity of the declared active Table 8. Uniformity and relative standard deviation of
samples of effervescent vitamin C tablets of products X, Y
ingredient is within the established after being
and Z.
subjected to all stages of production (GIL, 2010). Tablet X (%) Y (%) Z (%)
The drug content must respect the limits
established by the Pharmacopeia (BRASIL, 2010) 1 95.0 96.4 96.4
2 97.5 95.9 95.9
because levels above the established may cause
3 96.7 99.7 96.3
adverse effects such as overdose, toxicity, on the
other hand, a level below the minimum will not result 4 98.0 93.4 96.8
in the expected action of the medication. 5 98.0 97.2 97.6
It is worth mentioning that two tests were 6 97.6 98.0 98.0
performed to determine the dosage (titrimetric and 7 97.5 100.0 93.4
spectrophotometric), whose objective was to 8 97.0 101.7 94.6
analyze the possible difference between the 9 97.9 97.6 95.1
methods, since there is no official methodology for 10 97.8 95.9 93.8
this dosage form, in addition to ensuring the Average 97.30 97.58 95.79
reliability of the results obtained. R.S.D. (%) 0.94 2.47 1.61
The results of the analyzes are shown in AV 3.39 6.69 6.41
Table 6 and 7, verifying that all products had an R.S.D. (%) = Relative standard deviation.
ascorbic acid content between 98.1 and 105.7%. AV = Acceptance value
The results found were similar to Andrade (2017),
who reported levels between 97.51% and 101.67%, Therefore, the batches of the three brands
using the titrimetric method. According to the were approved in the quality tests, showing
parameters adopted for ascorbic acid tablets, pharmacotechnical efficacy, product stability and
effervescent tablets were within the limit. guarantee of safety to the user during its validity
There was no difference between the period.
methods used (p <0.05), showing that effervescent Complying with quality standards is
tablets can be evaluated by both methods. The data essential for any medication to result in an effective
corroborated with the study by Silva et al. (2019). treatment, in addition to guaranteeing the quality of
The uniformity of the tablets represents the the product, contributing to the safety and reliability
guarantee of the quantity of active ingredient in each of the patient.
unit. Factors such as hardness, excipients used,
homogeneity, weight, loss of tablet powder influence Conclusion
the efficiency of the drug, that is, uniformity checks
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 Oliveira et al. Effervescent vitamin C tablets and its quality control

The analyzes to determine the quality of CRISTINA, HPD. Formas farmacêuticas

effervescent tablets containing ascorbic acid from efervescentes uma abordagem alternativa. 91p.
three companies met all the necessary requirements (Dissertação de Mestrado) – Universidade de
for approval in the quality tests, as there is no Lisboa, Lisboa, Portugal, 2012.
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Pharmacopoeia. In addition, the assay tests were DAMODARAN, S., PARKIN, KL., FENNEMA, RO.
similar, showing the possibility of using two methods Química de alimentos de Fennema. (4 ed.) Artmed,
that are simple and low cost. Porto Alegre, p. 366-367, 2010.
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