Journal of Food Engineering 178 (2016) 60e70

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Journal of Food Engineering

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Dissolution profiling and its comparison of natural fruit powder

effervescent tablets
M. Saifullah a, Y.A. Yusof a, *, N.L. Chin a, M.G. Aziz a, b, M.A.P. Mohammed a, N.A. Aziz a
a
Department of Process and Food Engineering, Faculty of Engineering, Universiti Putra Malaysia, Serdang, Selangor, 43400, Malaysia
b
Department of Food Technology and Rural Industries, Bangladesh Agricultural University, Mymensingh, 2202, Bangladesh

a r t i c l e i n f o a b s t r a c t

Article history: The aims of the study were to observe the dissolution profile of four types of selected fruit powder fast
Received 29 April 2015 dissolve tablet and apply different dissolution profile comparison methods, in order to select most
Received in revised form applicable method. Spray dried powder of pitaya, pineapple, guava and mango were used as raw ma-
6 January 2016
terial. Each type of fruit powder tablet has identical dissolution profile. Dissolution profiles and disso-
Accepted 6 January 2016
Available online 8 January 2016
lution rate of fruit powder tablets were different at different dissolution environment. In model-
independent and statistical method pairwise comparison was performed and in model dependent
method profile comparison was carried out based on best fitting of mathematical model equation.
Keywords:
Fruit powder tablet
Dissolution Profile comparison methods represented that model independent method use wide range of
Dissolution profiling value for profile comparison and it was direct and easy; model dependent method was indirect and
Profile comparison complex and for critically compare the dissolution profile statistical method was the most suitable
Model dependent method method.
Model independent method © 2016 Elsevier Ltd. All rights reserved.
Statistical method

1. Introduction
Like any other agricultural produce plenty of different fruits are
available in the market at the peak season, and due to market
saturation the producers do not get their desired price and some-
times postharvest losses occur. On the other hand, people usually
would like to consume fruits fresh all the year round, but practically
it is quite impossible to provide fresh fruits all the year round. So,
people are usually deprived of the natural taste of fruits in the off
season and producers face financial losses at the peak season. All
fruits are not grown in all areas of the world, and most of the fruits
are produced in the tropical and sub-tropical zones. Hence, people
of the temperate zones are deprived of most of the fruits grown in
the world. Fresh fruits may be exported to temperate zones, but it
will be costly and the risk of spoilage is high. To reduce these
problems fruits are processed into different types of products,
through a number of processing and preservation techniques such
as drying, special packaging and chemical treatments. Among all
the processing and preservation methods, drying of fruit juice in
the powder form is unique technique, which increases the shelf life
* Corresponding author.
E-mail address: yus.aniza@upm.edu.my (Y.A. Yusof).
of the products (Chen and Mujumdar, 2009; Kha et al., 2010; Quek
et al., 2007). In the powder form the moisture content is at
microbiologically safe levels as the water activity becomes very low.
Fruit powder is amorphous dry granular material and it is highly
hygroscopic in nature. Therefore, careful handling and special
packaging is required during marketing, transportation and stor-
age. It is bulky in nature and more space is also required for
transportation and storage, which may increase the price of end
products. However, alternative technique like compaction of fruit
powder in the shape of tablets is more suitable to overcome the
post processing problems regarding storage, transportation and
quality degradation (Zea et al., 2013). Tableting results in the
reduction of surface area and bulk volume of the powder. The ad-
vantages of tableting includes good chemical and physical stability;
and it shows prolonged shelf life, competitive unit production cost
as well as reduction in transportation and storage cost, elegant
appearance and greater acceptance in terms of presentation (Yusof
et al., 2012). Normally people like to take fruit powder tablets in the
juice form after dissolving it in water or as candy. Hence, fast dis-
solving fruit powder tablets will be more acceptable to consumers.
However, the major drawback of fruit powder tablets is poor
dissolution rate. To make the tablets dissolve fast, super dis-
integrants or effervescent agents are necessary during tableting
(Ong et al., 2014; Zea et al., 2013).

http://dx.doi.org/10.1016/j.jfoodeng.2016.01.007
0260-8774/© 2016 Elsevier Ltd. All rights reserved.
 M. Saifullah et al. / Journal of Food Engineering 178 (2016) 60e70
The demand for ready-to-eat or ready-to-serve food and drinks
is increasing day-by-day. Tableting of fruit powder into ready-to-
drink juice tablets will be able to meet consumer demands.
Though fast dissolve fruit powder tablet production is more
beneficial than other products but, it is not available in local market.
Therefore, based on the demands and benefits of fruit powder
tablets, there is a need for large scale production. This requires
dissolution information of the fruit powder tablets for quality
control/checking, product development, and scale up in production
capacity. Dissolution profiles show dissolution pattern of tablets.
Dissolution test of fruit powder tablets is very important from the
point of large scale production and quality checking of finished
products. In vitro dissolution tests are usually used to: (1) assess the
batch-to-batch quality of product; (2) develop new formulations,
and (3) ensure continued product quality and performance after
certain changes, such as changes in the formulation, manufacturing
process, the site of manufacture, and the scale-up of the
manufacturing process (Yuksel et al., 2000).
The Center for Drug Evaluation and Research at the Food and
Drug Administration (FDA, 1997a) reported three types of dissolu-
tion test specifications for fast dissolve products; (1) single point
specifications, (2) two-point specifications, and (3) dissolution
profile comparison. Among them the dissolution profile compari-
son is a more exact technique to specify the product (Sathe et al.,
1996; Shah et al., 1998). The methods for comparison of in vitro
dissolution profiles can be divided into three groups: (1) Statistical
methods (Analysis of variance (ANOVA) based method or pair-t
test) (Costa and Sousa Lobo, 2001; Dash et al., 2010; Mauger
et al., 1986; Polli et al., 1997), (2) Model-dependent methods
(zero order, first order, Higuchi, KorsmeyerePeppas model, Hixson
Crowell, Weibull mode, etc.) (Dash et al., 2010; Polli et al., 1997;
Sathe et al., 1996; Shah et al., 1992), and (3) Model-independent
methods (Costa and Sousa Lobo, 2001; Dash et al., 2010; Polli
et al., 1997; Shah et al., 1992). Based on above reason, the study
was carried out to investigate the dissolution profiles of individual
types of fruit powder tablet, and choose most suitable method to
compare the dissolution profiles of fast dissolving fruit powder
tablets.
2. Materials and methods
Four types of fruit powders (pitaya, pineapple, guava and
mango) and two dissolution media (distilled water and simulated
saliva) were used in this study.
2.1. Materials for preparing fruit powder tablets
The fruit powders used in this research were bought from
Syarikat Sains Maju, Petaling Jaya, Selangor. Each type of powder
was produced by a spray drying process with addition of 10%
maltodextrin. Citric acid (Chem Pure®, R&M Marketing, Essex, UK),
sodium carbonate (Merck KGaA, 64271 Darmstadt, Germany) and
stevia (Botanical Essence Marketing Sdn Bhd) were used for tablet
preparation. Citric acid and sodium carbonate are the common
effervescent agents used in pharmaceutical and nutraceutical in-
dustries to produce fast dissolve effervescent tablet (Lee, 2008).
Stevia was used as a natural sweetener.
2.2. Particle size
The particle size and size range of powder samples were
measured by using a particle size analyzer (Malvern Mastersizer
2000 Instrument Ltd., U.K.) using a dry dispersion method. The
Mastersizer 2000 utilizes the laser light diffraction technique to
analyze the size of particles. For this experiment, powder samples
61
were put into the particle size analyzer and the data was recorded
automatically.
2.3. Crystallinity
The crystallinity of powder sample was identified by powder X-
ray diffraction method. The powder samples were placed into a
sample holder and the surface was smoothed with a glass slide. The
analysis was carried out with X'PertX-ray diffractometer (PRO-P-
Analytical, PW3040MPD, Philips, Japan) by using Ni Ka (1.54059Ao).
The operating voltage and current was 40kv and 40 mA respec-
tively, the samples were scanned between 4 and 90
(2q angle
range) with a step-by-step increase of 0.033
2q/19.67 s. The
crystalline-to-amorphous ratio of materials was determined using
the following equation (Thygesen et al., 2005; Simone et al., 2012).
Ih  Iam
CIR ¼  100 (1)
Ih
where, CIR is the percent crystallinity. Ih is height of height peak,
which represents both crystalline and amorphous material and Iam
is the height of lowest peak, which represents amorphous material
only.
2.4. Solubility time
Solubility rate test of the samples was carried out in dissolution
tester (Pharma Test D-63512, Germany) at 100 rpm paddle speed
and at room temperature in water and at 37
C temperature in
simulated saliva fluid. 0.25gm powder sample was put in 100 ml
solvent and stopwatch was used to measure the total require time
require for complete dissolution of powder sample.
2.5. Formulation and mixing
Each tablet contains fruit powder (47.3%), sodium carbonate
(32.7%) as alkalizing agent, citric Acid (10%) as acidifying agent and
stevia (10%) as natural sweetener (Saifullah et al., 2014). All in-
gredients were measured on a weight to weight ratio and put in a
plastic container, then mixed through a mixing machine (Glas-Col,
S/N 477625, USA) for 30 min at 15 rpm (15 min clockwise and
15 min anticlockwise) to make it as uniform as possible. The mixed
samples were measured into 2.5 gm portions and placed in small
plastic containers for further use in tablet preparation and disso-
lution tests.
2.6. Tableting process and checking few properties of tablet
Tableting of fruit powders were carried out according to a direct
compaction method (Yusof et al., 2012). A 2.5 (±0.01) gm sample
was poured into the cylindrical uniaxial die of size 20 (±0.01) mm.
The universal testing machine (Instron Universal Testing Machine-
5566, Canton MA, UK) was used to compress the powder into tablet
form. The machine was operated using Bluehill software (Canton
MA USA) which was maintained at a compaction speed of 0.1 mm/
min at 9.8 kN force. Upon compression the tablets were ejected
from the die and kept in air tight containers for further study. The
dimensions of the tablets were measured by using digital slide
calipers. The moisture content of the tablets was determined by
using oven drying method. The density of the tablets was calculated
from the ration of mass over volume of the tablet.
2.7. Porosity
The porosity of the tablets was calculated from tablet density
62 M. Saifullah et al. / Journal of Food Engineering 178 (2016) 60e70
€ m,
and true density of the tablet ingredient (Adolfsson and Nystro
1996). It may be calculated using the following equation:


rt
ε¼ 1  100
rtrue
where, ε is porosity, rt density of the tablet and rtrue is the true
density of the tablet ingredients.
2.8. Dissolution test
To measure the dissolution time and observe the dissolution
profile, dissolution tests were carried out in a dissolution tester
(Pharma Test D-63512, Germany) at 100 rpm paddle speed. Two
types of dissolution medium were used during the test, namely
distilled water and simulated saliva fluid. The dissolution test in the
distilled water was carried out at room temperature, while in the
simulated saliva fluid it was carried out at 37.5
C temperature. This
is because people usually take the fruit powder tablet in drink form
after dissolving in water or directly like candy.
2.8.1. Dissolution test in water
At the initial stage of the dissolution test, the dissolution
chamber was filled with 500 ml of distilled water and the tem-
perature of the dissolution medium was maintained at room tem-
perature. Then 5 tablets were placed into the chamber and the
machine was switched on. A 25 ml sample was collected from the
chamber after 1 min intervals and the chamber was filled with fresh
dissolution medium simultaneously until complete dissolution of
the tablets occurs. The samples were kept in 50 ml centrifugal tubes
for further analysis.
2.8.2. Dissolution in simulated saliva
Formulation of the simulated saliva fluid was prepared accord-
ing to Fusayama et al. (1963) and Mareci et al. (2010). It is composed
of 0.400 g NaCl, 0.400 g KCl, 0.795 g CaCl2e2H2O, 0.780 g NaH2-
PO4e2H2O, 0.005 g Na2Se9H2O, 1.000 g NH2CONH2 and distilled
water up to 1000 mL. All chemicals were from R & M Marketing,
Essex, U.K. The pH value of the solution was reduced to 5.6 and
continuously checked using a pH meter (PH-200, Korea). Dissolu-
tion test in simulated saliva was carried out at 37.5
C. Initially the
dissolution chamber was filled with 500 ml dissolution medium
and the temperature of the dissolution medium was checked using
a digital thermometer. Then 5 tablets were placed into the chamber
and the machine paddle and stopwatch were switched on. Samples
(25 ml) were collected from the chamber after 1 min intervals and
the chamber was filled with fresh dissolution medium at 37.5
C
temperature simultaneously until complete dissolution of the
tablet occurred. The samples were kept in 50 ml centrifugal tubes
for further analysis.
2.9. Measurement of percent solute released/percent dissolved
An Ultra Violet spectrophotometer (HACH DR 2800, United
State) was used to analyze the amount of solute present in the
samples collected from the dissolution chamber. Absorbance of
light by the sample solutions was measured at 560 nm wave length.
The percent dissolution/solute released was calculated using the
following equation:
Percent dissolution=percent solute release at any time
At  A0
¼  100
Af
where, A0 ¼ Absorbance of control sample (fresh medium),
At ¼ Absorbance of sample any time, Af ¼ Absorbance of sample
when complete dissolution occurs.
(2)
2.10. Dissolution profiling
To create dissolution profiles of individual fruit powder tablets,
in-vitro dissolution data were plotted on a graph. Time versus
percent dissolution/released graphs show the dissolution profiles
(Abdullah et al., 2008; Yuksel et al., 2000).
2.11. Analysis of dissolution data for model dependent method
To understand the dissolution kinetics and select the best fit
mathematical model the dissolution test data were analyzed using
“Kinet DS” V: 3 an open source software (http://sourceforge.net/
projects/kinetds/files/) (Dorozy _ n ski et al., 2011; Mendyk et al.,
2012; Nayak and Pal, 2013). The software analyzes the dissolution
data according to each model equation (Table 1). The best fit
mathematical model was selected based on the value of the coef-
ficient of determination (R2), Akaike Information Criterion (AIC) and
root mean square error (RMSE) (Costa and Sousa Lobo, 2001; Dash
et al., 2010; Yuksel et al., 2000).
2.12. Dissolution profile comparison
The dissolution profiles of the fruit powder tablets were
compared using model dependent, model independent method
and statistical method. In the model dependent method, dissolu-
tion profile comparison of the different fruit powder tablets were
performed based on selection of the best fit mathematical model
(Yuksel et al., 2000). The model equations are presented in Table 1.
In the model-independent method pair-wise comparison was car-
ried out to compare dissolution profiles. The empirical equation of
similarity factor (f2) and dissimilarity factor (f1) were determined
(Costa and Sousa Lobo, 2001). In the statistical method paired t-test
was used to assess the difference between the mean of the disso-
lution data set in a single time point dissolution of two types of
tablet. During the paired t-test, fruit powder tablets were consid-
ered as reference and test product with respect to each other at
every time point (Yuksel et al., 2000). Paired t-test was carried out
using a software (SPSS version 20).
Table 1
Mathematical model equations.
Dissolution kinetics model name Equation form
Zero-order model Qt ¼ Q0 þ k0 t
First-order model lnQ1
t  lnQ
1
0 ¼ k1 t
HixsoneCrowell model (Hixson and Crowell, 1931) w30  w3t ¼ ks t
1
Higuchi model (Higuchi, 1961) ft ¼ KH t 2
KorsmeyerePeppas model (Korsmeyer et al., 1983) ft ¼ Kt n
Qt is the amount of solute dissolve in time t; Q0 is the initial amount of solute content
in solvent; k0 is the zero order release constant; k1 is the first order release constant;
(3)
w0 is the initial amount of solute in tablet; wt is the remaining amount of solute at
specific time t; ks is constant; ft is amount of solute release at time t; KH is Higuchi
dissolution constant; K is constant; n is release exponent; t is for time.
 M. Saifullah et al. / Journal of Food Engineering 178 (2016) 60e70 63

82 30:5
<
X
4 1 n  2

Similarity factor ðf2 Þ ¼ 50  log 1þ R  Tj 5
: n j¼1 j
9
= (XRD) curve for fruit powders contained large and non-defined
 100
; reported similar findings for mango powder. The amorphous na-
Pn  

j¼1 Rj  Tj
Difference factor ðf1 Þ ¼ Pn  100
R
j¼1 j
where, Tj and Rj are the present dissolution of the test and reference
tablet at each time point j. n is the sampling number.
3. Results and discussion
3.1. Properties of tablet ingredients and tablets
The properties of individual ingredients are very important for
the tablet's physical and dissolution properties. Table 2 shows that
the particle size of fruit powders are different from each other.
However, pitaya and mango powder contained similar and the
lowest sizes of particles among the fruit powders. Guava powder
contained moderate size of particles (29.36 mm), whereas the par-
ticle size of pineapple was the highest (38.30 mm). Taufiq et al.
(2014) reported that nearly similar particle sizes of spray dried
pineapple powder. Particle size of fruit powder depends upon the
drying conditions (i.e., air flow rate, feed flow rate, atomizer speed
and drying temperature), amount and type of career agents
(Chegini and Ghobadian, 2005, 2007; Tonon et al., 2008; Jittanit
et al., 2010; Yousefi et al., 2011; Tze et al., 2012; Suzihaque et al.,
2015). It is noticeable that particle sizes of additives (citric acid,
sodium carbonate and stevia) added to fruit powder tablets are
quite bigger than that of fruit powder. It is known that higher
particle size resulted in higher porosity and it helps to dissolute the
tablet faster (Table 2). It is also noticeable that smaller particle re-
sults in more compact tablet and it prevents particles to come in
contact of dissolution media. However, the tablet ingredients
including additives resulted in new particle distribution, which
affects the dissolution kinetics of fruit powder tablet. Powder
having similar particle size also show different in dissolution rate
and it depends on the chemical composition of the powder particle.
Barbosa-C anovas et al. (2005) reported the presence of free fat in
the particle surface reduce the wettability of powder. Hence,
chemical composition of powder particles can affect the dissolution
of tablet. Finally the presence of bigger sizes additives particles
with small fruit powder particles favors to increase the tablet
dissolution rate. X-ray diffraction result shows the crystallinity of
tablet ingredients. In general, crystalline material exhibit a series of
sharp peaks, while amorphous product produces a broad
background pattern with no specific peak. The stevia, citric acid and
sodium carbonate powder show higher degree of crystallinity and
the values were very closed (approximately 100%). However, fruit
powders were amorphous and hence an X-ray powder diffraction
peaks with abundant noises (Fig. 1). Cano-Chaucaa et al. (2005)
ture of mango powder produced from different drying methods
(4)
was also reported by Caparino et al. (2012). Solubility test repre-
sents the solubility rate of ingredients that is different from each
other and also varies according to dissolution environment. In the
(5)
dissolution chamber when fruit powder was added into the
dissolution medium, a layer was formed at the interface between
the powder and the dissolution medium and caused lump forma-
tion; which caused lower solubility rate of fruit powders compared
to other ingredients. All the ingredients dissolved faster in water
compared to simulated saliva.
The basic properties of fruit powder tablets were different from
each other. The level of compression was also different for different
types of fruit powder tablet. Table 3 shows that the thickness (or
height) of the pitaya powder tablet was high among the tablet,
which resulted in low density and high porosity. On the other hand,
the thickness of guava powder tablet was low and its density was
high and porosity was low as well. Higher degree of compression
results in lower tablet height and porosity causing increased tablet
density.
3.2. Dissolution profiles
Dissolution profiles characterize the dissolution pattern of a
solid dosage form. It may contain two or more data points (time) to
explain the dissolution curve depending on the type of product and
length of time interval. In a fast dissolve tablet, the length of time
interval and number of data points (time) become less compared to
prolong release/less dissolve tablets. The position of time points
defines the pattern of dissolution profile. Figs. 2 and 3 represent the
dissolution profiles of effervescent fruit powder tablets in distilled
water and simulated saliva, respectively. They were obtained by
plotting percent dissolved against time.
Dissolution profiles of all types of tablet look similar, although
the percent dissolved was not the same at all time-points. The total
dissolution time varied with the type of fruit powder tablet dis-
solved. Pitaya and pineapple tablets were the fastest a complete
dissolution process of 7 min. Guava powder tablet took the longest
duration for complete dissolution at 10 min, while the mango
powder took 8 min to dissolve. From the dissolution profiles it was
clear that for all types of tablets the amount of solute released from
the tablet/percent dissolved was low at the first time step (1 min);
about 10% (pitaya tablet) to 30% (pineapple tablet). However,
maximum amount of solutes were released at the second time step
(2 min). Subsequently, the percent dissolved was decreased again
and the amount of solute released was reduced with time. There

Table 2
Properties of individual ingredients.

Name Particle size D[4,3]mm Crystallinity (%) Solubility time (min)

In water In simulated saliva

Pitaya powder 25.072 Amorphous 8 ± 0.5 9 ± 0.38

Pineapple powder 38.30 Amorphous 6 ± 0.23 8 ± 0.26
Guava powder 29.36 Amorphous 10 ± 0.27 12 ± 0.31
Mango powder 25.07 Amorphous 9 ± 0.13 11 ± 0.23
Stevia 289.74 99.91 7 ± 0.19 9 ± 0.34
Citric acid 538.71 99.79 2 ± 0.33 4 ± 0.11
Sodium carbonate 421.36 99.70 5 ± 0.10 5 ± 0.47
64 M. Saifullah et al. / Journal of Food Engineering 178 (2016) 60e70

Fig. 1. X-ray diffraction analysis result.

was little variation observed from tablet to tablet. In the sink con- and as by-product release carbon dioxide and other solute in the
dition the water molecules diffused into the tablet and in presence dissolution medium; which enhanced the dissolution rate and
of water molecule effervescent agent start one directional reaction outer layer of the tablet become rupture by the action of
 M. Saifullah et al. / Journal of Food Engineering 178 (2016) 60e70 65

Table 3
Properties of tablets.

Tablet Dimension Moisture content (%) Density (kg/m3) Porosity (%)

Height (mm) Diameter (mm)

Pitaya tablet 6.80 ± 0.04 20 ± 0.01 2.87 ± 0.12 1170.25 ± 0.09 28.9 ± 0.48
Pineapple tablet 6.56 ± 0.10 20 ± 0.01 2.89 ± 0.25 1213.07 ± 0.14 27.1 ± 0.77
Guava tablet 6.24 ± 0.11 20 ± 0.01 3.06 ± 0.09 1275.28 ± 0.21 24.79 ± 0.65
Mango tablet 6.35 ± 0.17 20 ± 0.01 2.71 ± 0.28 1253.19 ± 0.18 25.48 ± 0.34

Fig. 2. Dissolution profiles in water.

Fig. 3. Dissolution profiles in simulated saliva.

effervescent agent and CO2 production (Kro €gel and Bodmeier,
1999). The outer layer of the tablet is more compacted, and
therefore it initially took more time for the water to diffuse into the
tablet. This is known as lag time.
In the case of simulated saliva, all fruit powder tablets exhibited
similar trends in dissolution profiles and showed maximum
amount of solute released in the first step (1 min) of dissolution,
which was continued up to the second step. In the first minute the
mango powder tablet released the highest amount of solute
(47.46%), while the pitaya powder tablet released the lowest
amount (31.33%). In simulated saliva, temperature of dissolution
medium might help to initiate reaction immediately after putting
the tablet in the dissolution chamber. Dissolution medium tem-
perature also influenced the dissolution rate of fruit powder tablet.
Each type of tablet dissolved faster in simulated saliva than in
distilled water. In the simulated saliva pitaya and pineapple powder
tablets took 6 min to complete dissolution, however guava and
mango powder tablets took 9 min and 7 min respectively.
3.3. Dissolution profile comparison of fruit powder tablet
3.3.1. Model dependent method
In model dependent method dissolution profiles were
compared by using established release kinetics mathematical
66 M. Saifullah et al. / Journal of Food Engineering 178 (2016) 60e70

model. Model dependent methods were based on different math-
ematical functions, which used to describe and compare dissolu-
tion profile of tablets (Dash et al., 2010).
For comparison of dissolution profiles dissolution data were
analyzed and fitted models were selected according to the value of
coefficient of determination (R2), Akaike Information Criterion (AIC)
and Root Mean Square Error (RMSE). Dissolution data were
analyzed according to models and results are presented in Table 4
(for distilled water) and Table 5 (for simulated saliva).
In this research, when distilled water was used as dissolution
medium then pitaya powder tablet dissolution data were fitted
very well with zero order kinetics model. However pineapple,
guava and mango powder tablet dissolution curve fitted with
Higuchi square root of time model. On the other hand, when
simulated saliva fluid was used as dissolution medium, pitaya
powder tablet dissolution curve was fitted with Higuchi model and
dissolution profile of other three types of tablet fitted with Kors-
meyerePeppas Model. The fitted results are bolded in Tables 4 and
5. This change in dissolution data fitting may cause due to change in
dissolution medium and temperature. Curley et al. (2004) reported
alteration of dissolution pattern owing to change in temperature
and dissolution environment. The model fitting were selected
based on highest R2 value and lowest value of AIC and RMES.
Goodness of fit is measured by Akaike Information Criterion (AIC)
based on maximum likelihood. The smallest value of AIC represents
the best fitting of data to a specific model (Costa and Sousa Lobo,
2001).
Each model makes some specific assumption and due to this
assumption different model is suitable for different types of tablets
(Siepmann et al., 2000). Zero order kinetics model is usually used to
describe dissolution of active ingredients from modified release
dosage forms, dissolution of water soluble matrix tablet or when
any tablet act as osmotic system (Costa and Sousa Lobo, 2001;
Freitas and Marchetti, 2005; and Sharma et al., 2005). According
to zero order kinetics model, solute release rate is independent of
solute concentration in tablet (Sharma et al., 2005). Thus the
amount of solute release from the pitaya tablet at any time was not
dependent of solute concentration in the tablet.
The Higuchi model is also applicable to define dissolution of
modified release dosages form, matrix tablet with water soluble
drug. According to Higuchi model, solute release is proportional to
square root of dissolution time (Costa and Sousa Lobo, 2001; Desai
et al., 1966a, 1966b; Higuchi, 1962 and Shoaib et al., 2006). Kors-
meyerePeppas model describes the drug release from polymeric
system. This model is also used to predict the solute or release
mechanism of active ingredients from the tablets. Ong et al. (2014)
and Zea et al. (2013) reported use of KorsmeyerePeppas model to
explore the vitamin C release mechanism from fruit powder tablet
during dissolution. In this model equation the release exponent n
value characterize the release mechanism. For the case cylindrical
tablets, 0.45 n correspond to Fickian diffusion mechanism,
0.45 < n < 0.89 anomalous (Non-Fickian) transport, n ¼ 0.89 case-II
(relaxational) transport, higher than 0.89 Super case-II transport
(Peppas, 1984, 1985). In this study when distilled water was used as
dissolution medium then for pitaya powder tablet solute release
mechanism was super case-II transport and for other three types of
tablet include pineapple, guava and mango; the transport mecha-
nism was anomalous (Non-Fickian). However, in case of simulated
saliva for pitaya powder tablet solute release mechanism was
anomalous (Non-Fickian) transport, and for pineapple, guava and
mango powder tablet that was Fickian diffusion.
From dissolution profile comparison result it is clear that pine-
apple, mango and guava powder effervescent tablet dissolution
profiles were similar in both dissolution mediums according to
model dependent method. However, pitaya powder tablet disso-
lution profile was not similar with other three types of fruit powder
tablet in both medium. This difference may occur due to difference
in dissolution solute release pattern or release exponent value.
3.3.2. Model-independent method (similarity and difference factor)
The difference factor (f1) is the measure of average difference
between two curves at over time points; whereas, the similarity
factor (f2) is a logarithmic transformation of the sum-squared error
of difference between two profiles above all time points. These
factors are usually used in industry to check dissolution profile.
Food and Drug Administration (FDA) also recommend these
methods of profile comparisons. According to FDA guidelines if the
difference factor value below 15 (0e15) and similarity factor value
more than 50 (50e100) then the two products shows equivalence
in dissolution profile (Costa and Sousa Lobo, 2001; Dash et al., 2010;
Yuksel et al., 2000; FDA, 1995, 2007a,b). The similarity factor and
difference factor was calculated from the mean value of percent
dissolve at each point by using the equations (5) and (4) respec-
tively. According to Shah et al. (1998), for the reason of sensitivity of
these factors after 85% dissolution of the product, the number of
sample point should be limited to not more than one; once any
product reached up to dissolution of 85%. In this research for that
reason, the value of f1 and f2 was calculated from minute 4 and
minute 3 for the case of dissolution mediums using distilled water
and simulated saliva, since in water at minute four pineapple

Table 4
Model dependent analysis of dissolution profiles of fruit powder tablets in distilled water.

Dissolution kinetics model Statistics Fruit powder tablet

Pitaya powder tablet Pineapple powder tablet Guava powder tablet Mango powder tablet
2
Zero order kinetics model R 0.911 0.823 0.809 0.831
AIC 48.18 49.09 75.66 58.24
RMSE 8.87 9.47 11.37 10.48
First order kinetics model R2 0.699 0.708 0.610 0.670
AIC 60.10 53.77 85.99 65.75
RMSE 22.15 13.22 19.07 16.77
HixsoneCrowell model R2 0.781 0.748 0.683 0.728
AIC 55.61 51.88 81.32 62.54
RMSE 15.09 11.55 15.10 13.72
Higuchi model R2 0.682 0.909 0.864 0.893
AIC 57.11 44.54 72.29 55.23
RMSE 16.79 6.84 9.61 8.69
KorsmeyerePeppas model R2 0.903 0.908 0.865 0.883
AIC 54.45 46.68 77.86 58.39
RMSE 13.95 7.97 12.70 10.59
n 1.0 0.57 0.76 0.71
 M. Saifullah et al. / Journal of Food Engineering 178 (2016) 60e70 67

Table 5
Model dependent analysis of dissolution profiles of fruit powder tablets in simulated saliva.

Dissolution kinetics Model Statistics Fruit powder tablet

Pitaya powder tablet Pineapple powder tablet Guava powder tablet Mango powder tablet
2
Zero order kinetics model R 0.892 0.894 0.776 0.793
AIC 39.42 37.58 63.02 47.03
RMSE 7.81 6.71 8.84 8.17
First order kinetics model R2 0.790 0.811 0.669 0.729
AIC 44.85 41.87 66.89 49.85
RMSE 12.29 9.58 10.97 9.99
HixsoneCrowell model R2 0.827 0.841 0.706 0.751
AIC 42.79 40.29 65.31 48.77
RMSE 10.35 8.404 10.04 9.25
Higuchi model R2 0.951 0.954 0.727 0.711
AIC 36.58 33.19 64.79 49.39
RMSE 6.17 4.64 9.76 9.67
KorsmeyerePeppas model R2 0.933 0.962 0.899 0.926
AIC 37.23 32.55 57.47 42.05
RMSE 6.51 4.41 6.50 5.72
n 0.65 0.45 0.41 0.38

powder tablet reached dissolution 88.58% and in simulated saliva at

minute three the mango powder tablet reached dissolution level at Table 7
87.47%. In this study, the dissolution profiles of fruit powder tablets Difference factor in distilled water.

were compared through similarity and difference factor in model Sample Difference factor (f1)
independent method. The dissolution data of all types of fruit Reference Test 4 min 5 min 6 min 7 min 8 min 9 min 10 min
powder tablets were analyzed and compared with each other as
Pitaya Pineapple 14.85 9.41 3.93 0
considering reference produce and test product.
e e e
Guava 3.02 4.05 3.69 7.01 5.41 2.81 0
Tables 6 and 7 represents the result of f2 and f1 respectively. In Mango 5.47 3.55 0.04 1.54 0 e e
distilled water at minute four similarity factor value of profiles of Pineapple Guava 15.57 12.30 7.71 7.01 5.41 2.81 0
pitaya and pineapple was slightly lower than minimum standard Mango 8.17 5.36 4.13 1.52 0 e e
value of 50. The values are in bold to indicate that the values are Guava Mango 8.76 7.92 3.88 5.90 5.71 2.89 0

slightly over or below the standard value. The similarity factor

value was 46.96. On the other hand, the difference factor value was
14.85; which was close to the lowest range of difference factor. Table 8
Similarity factor in simulated saliva.
Pineapple and guava powder tablets also showed difference in
dissolution profile at time points of four and 5 min; f1 and f2 value Sample Similarity factor (f2)
was 15.57 and 42.96 for minute four respectively; however the Reference Test 3 min 4 min 5 min 6 min 7 min 8 min 9 min
difference factor value and similarity factor value was 12.30 and
Pitaya Pineapple 83.77 93.45 93.77 100
46.46 at min five respectively. The dissolution profile exhibited the
e e e
Guava 99.73 75.66 60 68.24 65.09 75.79 100
value of f1 and f2 represents that dissolution profiles was similar to Mango 51.64 71.38 90.10 95.77 100 e e
each other at all the time points, except these time points, minute Pineapple Guava 82.35 70.23 63.21 56.16 65.09 75.79 100
four and minute five. Mango 56.45 71.38 81.67 95.77 100 e e
Guava Mango 51.27 59.1 56.19 58.24 65.08 75.79 100
Model-independent method of dissolution profile comparison,
difference and similarity factor analysis result presented in Tables 9
and 8 accordingly in case of dissolution medium simulated saliva.
The result shows that at all-time points, the comparison value was method, similarity of dissolution profile at certain points were
within range of f1 and f2 value; that it can be treated as dissolution determined according to reference range from literature (Costa and
profiles are similar. However there was huge variation in similarity Sousa Lobo, 2001). To compare the dissolution profiles of fruit
level among the fruit powder tablet dissolution profile at same time powder tablets at every time step pair t-test was used. Yuksel et al.
point. (2000) reported pairwise comparison of dissolution profile com-
mercial film-coated tablets. In this test pairwise comparison was
3.3.3. Statistical method carried out by considering fruit powder tablets as reference and test
In model dependent method the dissolution data was analyzed such as pitayaepineapple, pitayaeguava, pitayaemango,
according to specific model equations and in model in-dependent pineapple-guava, pineapple-mango and guavaemango. The mean

Table 6
Similarity factor in distilled water.

Sample Similarity factor (f2)

Reference Test 4 min 5 min 6 min 7 min 8 min 9 min 10 min

Pitaya Pineapple 46.96 54.15 68.88 100 e e e

Guava 79.79 71.77 72.18 57.49 62.97 76.27 100
Mango 68.14 74.42 99.98 87.00 100 e e
Pineapple Guava 42.96 46.46 55.97 57.49 62.98 76.27 100
Mango 56.81 64.17 69.09 87.00 100 e e
Guava Mango 58.94 58.71 71.94 62.67 62.98 76.27 100
68 M. Saifullah et al. / Journal of Food Engineering 178 (2016) 60e70

Table 9 Table 11
Difference factor in simulated saliva. Pair t-test result for dissolution of fruit powder tablets in simulated saliva.

Sample Difference factor (f1) Time Paired sample (fruit Mean difference Sig. 95% confidence
powder tablets) interval of the mean
Reference Test 3 min 4 min 5 min 6 min 7 min 8 min 9 min
difference
Pitaya Pineapple 2.37 1.02 0.91 0 e e e
Lower Upper
Guava 0.20 3.24 6.46 7.46 4.89 2.88 0
Mango 11.78 4.03 1.26 0.69 0 e e 1 min Pitaya Pineapple 8.7400* .038 16.2490 1.2310
Pineapple Guava 2.52 4.22 5.59 7.46 4.89 2.88 0 Pitaya Guava 6.6833 .088 15.8560 2.4893
Mango 9.32 2.98 2.18 0.69 0 e e Pitaya Mango 16.3500* .017 25.7240 6.9760
Guava Mango 12.01 7.51 8.25 7.32 5.14 2.97 0 Pineapple Guava 2.0567 .177 2.2610 6.3743
Pineapple Mango 7.6100* .020 12.3672 2.8528
Guava Mango 9.6667*** .000 10.1127 9.2207
2 min Pitaya Pineapple 4.9400 .060 10.4074 .5274
Table 10 Pitaya Guava 4.6000* .046 8.9774 .2226
Pair t-test result for dissolution of fruit powder tablets in distilled water. Pitaya Mango 9.7700* .021 15.9848 3.5552
Pineapple Guava .3400 .589 1.9531 2.6331
Time Paired sample (fruit Mean difference Sig. 95% confidence
Pineapple Mango 4.8300* .044 9.3147 .3453
powder tablets) interval of the mean
Guava Mango 5.1700 .069 11.3131 .9731
difference
3 min Pitaya Pineapple 1.8600 .121 4.9340 1.2140
Lower Upper Pitaya Guava .1600 .820 2.4956 2.8156
Pitaya Mango 9.2200*** .000 10.0701 8.3699
1 min Pitaya Pineapple 22.0900** .001 25.3812 18.7988
Pineapple Guava 2.0200 .086 .7023 4.7423
Pitaya Guava 4.3800** .002 5.1501 3.6099
Pineapple Mango 7.3600* .010 10.6289 4.0911
Pitaya Mango 10.6733** .004 13.7466 7.6001
Guava Mango 9.3800** .007 12.8084 5.9516
Pineapple Guava 17.7100** .002 14.4815 20.9385
4 min Pitaya Pineapple .9100 .615 7.5481 5.7281
Pineapple Mango 11.4167* .012 5.9563 16.8770
Pitaya Guava 3.2533 .183 3.7369 10.2435
Guava Mango 6.2933** .009 8.8206 3.7661
Pitaya Mango 3.7367 .129 10.1413 2.6680
2 min Pitaya Pineapple 22.9367** .007 31.1630 14.7103
Pineapple Guava 4.1633* .037 .5977 7.7289
Pitaya Guava 3.7967 .113 9.8140 2.2207
Pineapple Mango 2.8267 .086 6.6549 1.0016
Pitaya Mango 11.4600** .003 14.3129 8.6071
Guava Mango 6.9900** .001 7.7307 6.2493
Pineapple Guava 19.1400** .005 13.1971 25.0829
5 min Pitaya Pineapple .8800 .194 1.0829 2.8429
Pineapple Mango 11.4767* .012 5.9104 17.0430
Pitaya Guava 6.2300** .005 4.2516 8.2084
Guava Mango 7.6633* .026 13.0466 2.2801
Pitaya Mango 1.2200 .313 5.1412 2.7012
3 min Pitaya Pineapple 15.7000** .003 19.5782 11.8218
Pineapple Guava 5.3500** .001 4.7410 5.9590
Pitaya Guava 1.1700 .407 5.9980 3.6580
Pineapple Mango 2.1000 .061 4.4425 .2425
Pitaya Mango 9.8467** .004 12.5661 7.1272
Guava Mango 7.4500* .004 9.4415 5.4585
Pineapple Guava 14.5300*** .001 12.1933 16.8667
6 min Pitaya Guava 7.4600* .002 5.8785 9.0415
Pineapple Mango 5.8533* .010 3.3228 8.3839
Pitaya Mango .6900 .075 .1695 1.5495
Guava Mango 8.6767** .004 10.9164 6.4369
Pineapple Guava 7.4600** .002 5.8785 9.0415
4 min Pitaya Pineapple 8.3800* .032 14.9734 1.7866
Pineapple Mango .6900 .075 .1695 1.5495
Pitaya Guava 2.3300 .099 1.0830 5.7430
Guava Mango 6.7700** .004 8.5372 5.0028
Pitaya Mango 4.2233 .093 10.1747 1.7280
7 min Pitaya Guava 4.8867* .011 2.7037 7.0696
Pineapple Guava 10.7100* .014 5.1790 16.2410
Pineapple Guava 4.8867* .011 2.7037 7.0696
Pineapple Mango 4.1567* .022 1.4700 6.8434
Guava Mango 4.8867* .011 7.0696 2.7037
Guava Mango 6.5533* .016 10.1551 2.9516
8 min Pitaya Guava 2.8833* .036 .4491 5.3176
5 min Pitaya Pineapple 8.2000* .034 14.8615 1.5385
Pineapple Guava 2.8833* .036 .4491 5.3176
Pitaya Guava 3.5267* .013 1.7868 5.2665
Guava Mango 2.8833* .036 5.3176 .4491
Pitaya Mango 3.0867* .036 5.6856 .4878
Pineapple Guava 11.7267* .012 6.1941 17.2592 Difference between over-all dissolve profile of fruit powder tablet. *P < 0.05;
Pineapple Mango 5.1133* .038 .7180 9.5087 **P < 0.01 and ***P < 0.001.
Guava Mango 6.6133** .008 9.1080 4.1186
6 min Pitaya Pineapple 4.0733* .023 6.7875 1.3592
Pitaya Guava 3.4633 .071 .7386 7.6653 In case of dissolution in distilled water, at 1 min (first contrast
Pitaya Mango .0433 .923 1.7529 1.6663
Pineapple Guava 7.5367* .021 2.7891 12.2842
point), the dissolution profile of the pairs pitayaepineapple, pit-
Pineapple Mango 4.0300* .004 2.9723 5.0877 ayaeguava, pitayaemango, pineapple-mango and guavaemango
Guava Mango 3.5067 .067 7.6107 .5974 pairs showed significant difference in level of P < 0.01. On the other
7 min Pitaya Guava 7.0067* .012 3.6989 10.3144 hand, the dissolution profile of pineapple-mango pair was signifi-
Pitaya Mango 1.5167*** .000 1.3941 1.6392
cantly different in the level of P < 0.05. There was no significant
Pineapple Guava 7.0067* .012 3.6989 10.3144
Pineapple Mango 1.5167*** .000 1.3941 1.6392 difference present between the dissolution profiles of pit-
Guava Mango 5.4900* .020 8.8676 2.1124 ayaeguava pair at two, three, four, six and 9 min. The dissolution
8 min Pitaya Guava 5.4133** .002 4.5073 6.3194 profiles of pitayaemango pair also showed no significant difference
Pineapple Guava 5.4133** .002 4.5073 6.3194 at four and 6 min. The dissolution profiles of pineapple-guava and
Guava Mango 5.4133** .002 6.3194 4.5073
9 min Pitaya Guava 2.8100 .093 1.1583 6.7783
guavaemango was not significantly different at minute nine.
Pineapple Guava 2.8100 .093 1.1583 6.7783 In case of dissolution in simulated saliva, dissolution profile of
Guava Mango 2.8100 .093 6.7783 1.1583 pitaya powder effervescent tablet was not significantly different
Difference between over-all dissolve profile of fruit powder tablet. *P < 0.05; from pineapple powder effervescent tablet at two, three, four, and
**P < 0.01 and ***P < 0.001. 5 min. Pitaya and guava powder effervescent tablet profiles were
shown no significant difference at one, three and 4 min; same
phenomenon was also happened in case of pitaya powder and
difference value of percent dissolve at certain point was used for mango powder effervescent tablet for four, five and 6 min steps; in
comparison. The test results are presents at in Table 10 (for disso- case of pineapple and guava powder effervescent tablet at one, two
lution medium water) and Table 11 (for dissolution medium and 3 min steps; in case of pineapple and mango powder effer-
simulated saliva). vescent tablet at four, five and 6 min steps; and for guava and
 M. Saifullah et al. / Journal of Food Engineering 178 (2016) 60e70
mango powder effervescent tablet at two and 5 min steps. How-
ever, the dissolution profiles of fruit powder effervescent tablets
were significantly different from each other to the other at the time
steps, excluding these time steps in individual case. In both disso-
lution mediums, a pairwise dissolution profile comparison shows
that the dissolution profiles were not different or same at all the
time steps. O'Hara et al. (1998) reported the dissolution profile may
be considered to differ significantly from each other if the error bars
at each dissolution time point do not overlap. Dissolution profiling
results from, Figs. 2 and 3 it is observed that at most of the disso-
lution time points error bars were not overlapped. So, according to
statistical method dissolution, profiles were significantly different
from each other at most of time points.
4. Conclusion
Dissolution profiling showed that, pitaya, pineapple, mango and
guava powder effervescent tablet was dissolved faster in simulated
saliva rather than water. In both mediums, pitaya and pineapple
powder effervescent tablets showed the lowest total dissolution
time. However, their dissolution profile was different from each
other. In water, initially a lesser amount of solute release/dissolu-
tion of tablet was occurred. On the other hand, for simulated saliva
the dissolution medium temperature influenced to initiate the re-
action of effervescent agent and penetrate medium into the tablet.
So, the dissolution profile in simulated saliva demonstrates that the
major part of the tablet was dissolved within very short time after
putting the tablet into the medium. However, due to dissolution
medium saturation and reduced amount of solute, dissolution rate
became low with increasing time. From the results of dissolution
profile comparison, it was observed that different methods gave
different results regarding the similarity of dissolution profiles. In
model dependent method, all the dissolution data point was
analyzed at a same time and output was presented as model fitting
tool. According to the model dependent method, only the pitaya
powder tablet showed a difference in dissolution profile from other
three types of fruit powder tablets, while pineapple, guava, and
mango powder dissolution profile showed similarity. To compare
dissolution profiles of fruit powder tablets according to model in-
dependent method similarity factor and difference factor was
determined and compared on a point basis. This demonstrates that
at most points, the dissolution profiles were similar and only few
points were not similar, thought their similarity percentage did not
reach 100%. Finally, using statistical method, a pairwise comparison
was carried out. The results showed by comparing the dissolution
profile at every time step, there is a significant difference observed
at most of the time steps through the dissolution profile of fruit
powder tablets. According to the dissolution profile, it is clear that
each type of fruit powder tablet has unique dissolution profile.
Dissolution profiles can be used as a standard for a large scale
production in terms of quality control and improvement in
formulation (i.e., addition of food additives and other vitamins and
minerals). In food processing industry, it can be very helpful for
monitoring and quality assurance during production by comparing
the dissolution profile of individual product with the standard
dissolution profile. Among the dissolution profile comparison
methods, the model dependent method is complicated and indi-
rect, while the model independent method is easier to apply and
interpret. However, the model independent method has considered
wider range of value for profile comparison which describes the
closeness of the two dissolution profile. A statistical pairwise
comparison method is more discriminative than the other two
methods. Statistical methods may be used to analyze the all data
points and compare critically. It is therefore more informative and
useful for a dissolution profile comparison. The dissolution profile
69
comparison results show the pros and cons of each method.
However, the selection of the best method for comparing the
dissolution profile and quality of tablet depends upon the nature
and importance of tablet and its ingredients.
Acknowledgment
The authors would like to acknowledge the Ministry of Educa-
tion Malaysia for granting the Fundamental Research Grant Scheme
(FRGS) with the project code: 03-02-13-1289FR.
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