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Sekolah Tinggi Farmasi Indonesia 2017/ 2018


Salman Umar1 Fifi Harmely2 dan Aulia Hayati Syafnur
Sekolah Tinggi Farmasi Indonesia Yayasan Perintis Padang


A thermal analysis of solid dispersion of irbesartan with polyvinylpyrrolidone

K-30 and its relation to solubility and dissolution have been performed. Irbesartan is an
antihypertensive drug of the angiotensin receptor blocker group. The irrants solid
dispersion was prepared by using a PVP K-30 carrier with a dissolution method
prepared in three ratios Irbesartan: PVP K-30 that is F1 (1: 0,5), F2 (1: 1) and F3 (1: 3).
The three formulas are tested, they are thermal analysis, solubility test and dissolution
test. Based on the characterization of physics using DTA instrument shows the decrease
of melting point and decrease of energy marked by the formation of endothermic peak
of irbesartan. Based on the solubility test results obtained on the formula F1, F2, F3
have increased the level with the change of solubility classification from practically
insoluble to very soluble in F3 and the dissolution test of formula F3 has the highest
dissolution efficiency value indicated by solid dispersion F3 that is 72,65%. From the
data obtained the relationship between thermal analysis with solubility and dissolution.
The more ΔH decreases the heat, the more solubility and dissolution of the solid
dispersion of irbesartan-PVP K-30. Based on ANOVA one way statistical analysis there
were significant differences in solubility test, dissolution test and dissolution efficiency
at (P <0,005).

Keywords : Thermal analysis, Solubility, Dissolution, Solid Dispersion, Irbesartan and PVP

INTRODUCTION Irbesartan is one of the antihypertensive

Irbesartan is an angiotensin II drugs belonging to BCS II
receptor antagonist (Angiotensin II (Biopharmaceutical Classification System
receptor antagonist / ARB) used in the II) with low solubility but high
treatment of hypertensive diseases. In permeability. Drugs with low solubility
general, angiotensin II receptor but high permeability often exhibit low
antagonists such as irbesartan bind to gastrointestinal absorption due to poor
angiotensin II type 1 (AT1) receptor with drug solubility in gastrointestinal fluids
high affinity which causes inhibition of resulting in low oral bioavailability of the
angiotensin II action in smooth muscle of oral drug (Kumar, et al., 2011).
blood vessels, thus causing a decrease in According to BCS the drug is considered
arterial blood pressure (Sweetman, 2009). to be highly soluble when the rate of
The availability of pharmaceuticals absorption in humans is over 90% of the
is related to the Biopharmaceutics given dose (Chawla & Bansal, 2007).
Classification System (BCS), most of Various approaches are being made
which are classified into BCS class II. to increase the solubility and speed of

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Sekolah Tinggi Farmasi Indonesia 2017/ 2018

drug dissolution, one of which is the most The temperature of the sample may be
practical solid dispersion technology to below (if the change is endothermic) or
improve the solubility of insoluble drugs. above (if the change is exothermic) the
The solid dispersion is a dispersion reference temperature (Grega Klančnik,
system comprising one or more active 2010).
substances dispersed in a solid state on a DSC and DTA analyzes are
carrier. The solid dispersion is obtained typically used to study phase transitions,
by melting, dissolving and by means of a such as melting, glass transition
combined method of melting and dilution temperature (Tg), or exothermic
(Fudholi, 2013). decomposition, as well as analyzing the
During the process of solid stability of oxidation, the heat capacity of
dispersion formation it is possible to a material, and changes in the envelope of
change the properties and parameters of the material (Yang & Wolcott, 2005).
both physical and chemical preparations, Solubility is one of the
causing differences in properties between physicochemical properties of drug
irbesartan and polyvinylpyrrolidone. The compounds that are important in
differences in properties and parameters predicting the degree of absorption of
may include differences in solubility, drugs in the gastrointestinal tract. Drugs
particle size, melting point and that have poor soluble drugs often show
decomposition. Some differences in low bioavailability and dissolution rate is
properties and parameters can be the rate limting step in the drug
thermally analyzed (Purnawan et al., absorption process (Shargel & Yu, 1999).
2008). In general, water soluble drugs (poorly
To know the thermal properties of a soluble drugs) are a challenge in the
material required a method of pharmaceutical industry (Ansel, 1989).
measurement called thermal analysis. Dissolution is the process of
Thermal analysis can be defined as a dissolving an active substance or drug in
measurement of the physical properties of a dissolution medium where its velocity
a material that is a function of is affected by the surface area of the
temperature. This analysis can determine active substance particles, the particle
specific properties such as enthalpy, heat size, the dosage form, and the auxiliary
capacity, and material thermal materials used (Banakar 1991). The rate
coefficients (Dodd et al., 1987). of dissolution is the number of dissolved
One of the techniques for thermal drugs of time union. Drugs given in solid
analysis is Differential Thermal Analysis dosage form should be soluble in the
(DTA) and Differential Scanning gastrointestinal tract before absorption
Calorimetry (DSC). Differential Thermal into the blood circulation to the receptor
Analysis is a thermal analysis that works and will provide the desired therapeutic
according to temperature changes. That is effect (Abdou, 1989).
by comparing the temperature between Based on the above, the present
the reference material and the sample study will analyze an existing formula
material. The sample temperature and the that is practically insoluble in water,
referent will always remain the same until soluble in ethanol using a hydrophilized
some thermal event occurs such as polyvinyl pyrrolidone (PVP) K-30 in the
melting, decomposing or altering the form of solid dispersion by a method
crystal structure of the sample. Both dissolution. Interaction results were
temperature differences continue to be characterized using thermal analysis,
detected and recorded as a curve peak.

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solubility and dissolution profile Making of Irbesartan Solid Dispersion

determination. - Polivinil Pirolidon K-30 (Novinda,
METHODOLOGY Table2.Comparison of Powdered
Tools Soybean DispersionFormulation
The tools used in this research are Irbesartan- Polivinil Pirolidon K-
laboratory standard equipments, digital 30
analytical scales (Adventurer OHAUS),
desiccator, vacuum oven (DAIHAN No Material F1 F2 F3

Scientific), sieve (The Tyler Standard 1. Irbesartan 1 1 1

Screen Scale), Differential Thermal
Analysis (Shimadzu TG 60, 2. Polivinil Pirolidon 0,5 1 3
Simultaneous DTA -TG Apparatus),
Orbital Shaker (VRN-480 GEMMY Orbit
Shaker), UV-Vis Spectrophotometer The solid dispersion of irbesartan -
(SHIMADZU UV-1700 Pharma Spec), polyvinyl pyrrolidone K-30 is prepared
capillary tubes and dissolution test kits by dissolution method. Weigh each
(Hanson SR8PLUS). material according to the composition.
Material The irrantsartan powder - polyvinyl
Pure powder (Dr.Reddy's), Polyvinyl pyrrolidone K-30 was each diluted with
Pirolidon (PVP) K-30 (Nanhang ethanol p.a. until a clear solution is
Industrial Co., Ltd), Ethanol 96% (CV formed. To the solution of irbesartan, the
Akamasada), HCl 0.1 N, Aqua Bidestilata solution of polyvinyl pyrrolidone K-30 is
(Novalindo CV), Aquades ( CV added slowly while stirring. The resulting
Novalindo) and Whatman no.42 filter solution is then evaporated and dried in a
paper. vacuum oven at a temperature of 40 ° C
to 50 ° C to dry. The resulting solid is
Research procedure scraped and crushed and then passed to a
Preparation of Physical Mixture mesh screen of 60 and stored in the
Irbesartan - Polivinilpirolidon K-30 desiccator.

Table 1. Comparison of Physical Mixture Determination of Differential

Formulas Irbesartan - Polivinil Thermal Analysis (DTA) Analysis of
Pirolidon K-30 Irbesartan, PVP, Physical mixture and
Solid Dispersion
Material Comparison The thermal analysis test of the
sample is done by using DTA tool. A 5-
Irbesartan 1
10 mg sample is placed on an aluminum
polivinil pirolidon K-30 1
pan. The DTA device is programmed in a
heating temperature range from 30- 500 °
The physical mixture of irbesartan - C with a heating rate of 10 ° C per
polyvinyl pyrrolidone K-30 was crushed minute. In DTA heat is absorbed or
with mortar for 15 min until emitted by chemical systems of materials
homogeneous, then passed to a mesh performed by inert comparators
sieve 60 and stored in a desiccator. (Alumina, Silicon, Carbide or glass
beads) and both temperatures are added at
. a constant rate. Irbesartan thermogram,

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PVP and solid dispersion irbesartan - curve (the relationship between

PVP is measured as a function of concentration and absorption).
temperature (Gennaro, 1985). c. Determination of levels of irradiant
recovery in physical mixture and
Determination of Solubility Test solid dispersion
The solubility test was performed on Weighed Physical Mixture, F1, F2
the physical mixture of irbesartan-PVP and F3 equivalent to 150 mg irbesartan ie
K-30, solid dispersion F1, F2, and F3. 300 mg CF, 225 mg F1, 300 mg F2 and
The physical mixture, solid dispersions 600 mg F3. Then dissolve with 0.1 N HCl
F1, F2, and F3 were weighed as much as in a 100 mL measuring flask until the
50 mg then into a 100 mL erlemeyer, boundary marks. Then pipette 0.5 mL
then add aqua bidestylata ad 100 mL. then put in a 50 mL measuring flask,
This test is done for 6 hours using orbital simply volume up to the limit mark with
shaker tool. After that the sample was 0.1 N HCl. Measure uptake at maximum
filtered using Whatman filter paper absorption wavelength. The concentration
no.24. The filtrate solution was taken 2 of irbesartan in the powder is determined
mL then diluted into a 10 mL measuring using the calibration curve and calculate
flask. Then measure the level using UV- the level of each formula and determine
Vis spectrophotometer using maximum the percent of recovery gain.
absorption wavelength.
Determination of Dissolution Profile of
Determination of Irbesartan Retrieval Physical Mixture and Solid Dispersion
Level (Novinda, 2016) Irbesartan-Polyvinyl Pyrrolidone K-30
a. Determination of the maximum Determination of irbesartan
absorption wavelength of irbesartan dissolution profile based on Farmakope
in 0.1 N HCl. Indonesia V was done using method 2
A total of 50 mg irbesartan is with paddle. The container is filled with
weighed inserted in a 100 mL measuring water and the temperature is set to 37 ° C.
flask, add a bit of 96% stirring ethanol The flask was filled with 1000 mL of
until dissolved then simply volume up to HCL 0.1 N medium at a speed of 50 rpm,
the limit marker with 0.1 N HCl. From then the physical mixture of irrantsartan-
the mother liquor, dipipet 0.8 mL insert polyvinylpyrrolidone K-30 and solid
into a 50 mL measuring flask is sufficient dispersion F1, F2 and F3 were weighed
volume up to the limit marker with 0.1 N equivalent to 150 mg irbesartan and then
HCl. Furthermore, the maximum inserted into the capsule. The capsule is
absorption wavelength was measured inserted into a rowing container and
using UV-Vis spectrophotometers at rotated. The dissolution solution is plated
wavelength range 200-400 nm. 5 mL at 5, 10, 15, 30, 45, and 60 minutes.
b. Making irbesartan calibration curve In each piping it is replaced with medium
Dilutions of the 500 μg / mL of dissolution medium (same volume and
irrantsartan parent solution in 0.1N HCl temperature at the time of insertion).
each with a concentration of 8, 10, 12, 14, Each of the dipped liquid samples is then
16 μg / mL in a 25 mL measuring flask fed into a 25 mL measuring flask and it is
were performed. Each solution was sufficient until the boundary marks, then
measured uptake at maximum absorption the absorption is measured at the
wavelength by using a UV maximum absorption wavelength
spectrophotometer. Create a calibration obtained (Departemen Kesehatan RI,

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RESULTS AND DISCUSSION by a rise in temperature during the

In this research, firstly, the reaction took place.
manufacture of physical mixture and The thermal change of interaction
solid dispersion powder. The physical between the physical mixture and the
mixture is a mixture of two or more solid dispersion of Irbesartan and PVP K-
solids prepared by grinding the material 30 is shown in Appendix 6. According to
up homogeneously. This physical mixture Pharmacopeia Indonesia Edition V,
was made by mixing irrants and Irbesartan has a melting distance between
polyvinylpyrrolidine K-30 with a ratio of 180°C-181°C,while polyvinylpyrrolidone
1: 1 then crushed to homogeneous. has a melting range of 150 ºC. In
The solid dispersion powder is irbesartan and PVP K-30 which have
prepared in 3 formulas in the ratio of each been made in the form of solid dispersion
of the respective formulas 1: 0.5; 1: 1 and with various comparisons a slight
1: 3 using the dissolution method. The decrease of melting point from the
solvent used is ethanol p.a. wherein each melting point of irbesartan.
irbesartan and a polyvinylpyrrolidone K- From the results of irregular amber
30 were dissolved with ethanol p.a. DTAs requiring heat of -10.37 kJ / g to
separately in a beakerglass until a clear melt at a temperature of 191.52 ° C,
solution is formed. The K-30 whereas in the K-30 PVP it melts at
polyvinylpyrrolidone solution is added to 102.49 ° C with a heat flow of -44 , 32 kJ
the irrational solution slowly while / g. Then on the physical mixture formed
stirring. The solution mixture is endothermic peak at 105.73 ° C with a
evaporated and dried in the vacuum oven heat flow of -5.52 kJ / g. In irbesartan and
at 40 ° C-50 ° C to dry. The solid PVP K-30 which have been made in the
obtained is scraped and crushed, then form of solid dispersion with various
passed to a mesh screen of 60 and stored comparisons experienced a slight
in the desiccator. Then the physical decrease of melting point from the
mixture and solid dispersion formulas melting point of irbesartan.
that have been formed are evaluated to In solid dispersion F1 forms an
see the nature and character of the solids. endothermic peak at a temperature of
Evaluation includes thermal analysis, 185.80 ° C with a heat flow of -2.15 kJ /
solubility, determination of irradiant g. For solid dispersion F2 also forms an
recovery rate and dissolution test. endothermic peak at 176.15 ° C with a
First evaluates the thermal analysis heat flow of -1.67 kJ / g. As well as on
test of the physical mixture and solid solid dispersion F3 formed endothermic
dispersion formulas F1, F2 and F3 using peak at a temperature of 95.23 ° C with a
DTA-TG tools. Differential Thermal heat flow of -28.88 kJ / g. From the data
Analysis Analysis (DTA) is used to obtained the heat flow on solid dispersion
evaluate the change in thermodynamic F3 is greater than other solid dispersion
properties occurring at a given sample of formulas this may be due to the formula
heat energy, indicated by an endothermic F3 there has been a merging of irbesartan
or exothermic peak on a DTA with PVP so that the peak obtained wider
thermogram. Where on the endothermic and melting temperature closer to the
occurrence of heat absorption is melting temperature in PVP.
characterized by a decrease in In the data thermogram of the solid
temperature whereas in the exothermic dispersion preparation there are formed
occurrence of heat release characterized several other peaks such as exothermic,
this is due to the process of heat release

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in the preparation marked by the uV
occurrence of temperature rise during
Thus, in the solid dispersion 0
produced by various comparisons, the
presence of wide peaks at temperatures
between 95.23 ° C to 176.15 ° C. In
general, from this DTA data it can be 100 200 300 400 500
seen that the PVP K-30 component in the Temperatur °C
solid dispersion system affects the
endothermic peak position and the Figure 3. Physical Mixed Thermogram
endothermic peak sharpness. The more (1: 1)
PVP K-30 is used, the endothermic peak uV

shifts to a lower melting point. This 100

indicates that there is a physical

interaction between the dispersed drug 0
(irbesartan) in the PVP carrier K-30. This
possibility is also based on studies found
in the study of glycosidic solid dispersion
systems using polyvinyl pyrrolidone K- 100 200 300 400 500

30 (PVP K-30) and tween 80 (Halim et Temperatur °C

al., 2011).
Figure 4. Thermogram F1 (1: 0.5)
Figure Thermogram DTA
100 uV




100 200 300 400 500 -200
100 200 300 400 500

Temperatur °C Temperatur °C

Figure 1. Pure Irbesartan Thermogram Figure 5. Thermogram F2 (1:1)





-300 -200
100 200 300 400 500 100 200 300 400 500
Temperatur °C
Temperatur °C

Figure 2. Pure PVP Thermogram Figure 6. Thermogram F3 (1:3)

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Determination of solubility, the amount of soluble irbesartan, ie from

dissolution and recovery rate begins with 5.129 mg, 7.935 mg, 8.585 mg and
determination of the maximum 10.591 mg. In F3, it is found that
absorption wavelength of irbesartan in irrarsartan has undergone a change of
HCL medium 0,1 N and in aquabidest solubility classification from practically
media. Based on the result of insoluble to very soluble. This is because
determination of the maximum the manufacture of solid dispersions will
absorption wavelength of irbesartan, on lead to the formation of molecular
0.1 N HCl medium obtained maximum dispersions compared to just the usual
absorption wavelength of 245.8 nm; physical mixing so that the dissolved
while in aquabidest media obtained content in the solvent can increase.
maximum absorption wavelength of 209
nm. This is very different from the Table 4. Solubility test results
maximum absorption wavelength of
Sampel Absorban Level (mg) % Level Soluble Clasification
irbesartan in 0.1 N HCl. Due to the
considerable difference, we used the Campuran 1:19496,9
maximum absorption wavelength of Fisik 0,437 5,129 10,26 (Practical Not Soluble)

irbesartan in 0.1 N HCl in testing the F1 (1:0,5) 1:12602,3

irbesartan solubility. 0,5883 7,935 15,87 (Practical Not Soluble)

F2 (1:1) 1:11648,2
Table3.The maximum absorption 0,624 8,585 17,17 (Practical Not Soluble)

wavelength data of irbesartan in F3 (1: 3) 1:9441,9

0.1 N HCl at a concentration of 0,7343 10,591 21,18 Very dificult to dissolve)

8 μg / mL

Furthermore, the determination of

irradiant recovery rate in the physical
mixture and solid dispersion is made.
Each formula was weighed equivalent to
150 mg then dissolved with 0.1 N HCL in
a 100 mL measuring flask. After that
dipipet as much as 0.5 mL and put in a 50
mL measuring flask then enough with
HCL 0.1 N and measured by using UV
spectrophotometry. There was an
irradiant recovery rate in the physical
mixture, and solid dispersion of F1, F2,
and F3 in HCl 0.1 N medium were
83.68%; 80.8%; 85.04% and 89.26%
Figure7. The maximum absorption
wavelength spectrum of
irbesartan in HCl 0.1

From the results of the irrarsartan

solubility test in the physical mixture and
in the solid dispersion formula obtained

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Table5. Results of determination of Table 6. Results of dissolution of physical

reacquisition rate mixture and solid dispersion F1,
F2, F3
Level of % zat terdisolusi
Sam Absor %
Dilution substance
ple ban Recovery Waktu
aktif (mg) CF F1 F2 F3
CF 5 15,90 32,43 27,18 45,83
0,497 100 x (50/0,5) 125,527 83,68
34,33 38,59 36,39 62,85
F1 0,485 100 x (50/0,5) 121,2 80,8 15 51,73 49,27 45,17 72,52
F2 0,501 100 x (50/0,5) 127,56 85,04 70,69 57,73 58,96 76,58
45 78,85 68,06 67,90 84,47
F3 0,520 100 x (50/0,5) 133,89 89,26
60 85,07 90,01
85,66 87,12

The dissolution rate was then In Pharmacopoeia Indonesia Edition

performed with dissolution medium of V stated that in the 20th minute irbesartan
0.1 N HCl of 1000 mL, at a temperature must be dissolute not less than 80%. In
of ± 37 ºC with a rotation speed of 50 each formula was obtained dissolution
rpm and tested for 60 min using a rowing percentage at minute 30 amount of
method. Interpretation of dissolution data physical mixture 70,69%, F1 57,73%, F2
can be done by observing the profile of 58,96% and F3 76,58%. In this study at
irradiant dissolution, physical mixture the 30th minute it was seen in the best
and solid dispersion in 0.1 N HCl formula of F3 percentage of dissociated
medium. Prior to dissolution, a content of 76.58%, this means that the
calibration curve of 8 μg / mL, 10 μg / dispersionirbesartanpolyivinylpyrrolidone
mL, 12 μg / mL, 14 μg / mL and 16 μg / K-30 in F3 formula is almost closer to the
mL, we get the equation of line y = requirements listed in the literature.
0,0275x + 0,1518 and r = 0,9996. Where the percentage yield from the
The dissolution profile obtained initial minutes has already shown a larger
through the relationship between the percentisable percentage of the other
percentage of dissolved substances in the formulas.
60th minute was as follows the physical Another parameter used for
mixture 85.66%, solid dispersion F1 (1: dissolution evaluation is the efficiency of
0,5) 87.12%, F2 (1: 1) 85.07% and F3 (1: dissolution (ED) (Abdou, 1989). The
3) 90.01%. The complete data can be efficiency of the irradiation dilution is
seen in table 5. From the dissolution obtained from the area under the curve,
profile obtained, the percentage increase where the dissolution efficiency results
of the highest dissolution is in solid from the physical mixture and solid
dispersion F3 where irbesartan is as much dispersions F1, F2 and F3 are 60,9%,
as 90,01%. This increase occurs because 56,46%, 54,57% and 72,65%
the formation of solid dispersion can respectively. Similarly with the
reduce the particle size, increase the dissolution rate, the solid dispersion F3
ability of wettability and solubility and has the greatest dissolution efficiency
the drug can be dispersed molecularly in because it is well-disisolved in its
the form of amorphous particles, resulting disolutions medium. In the literature, the
in an increase in the dissolution rate of an irrantsartan tolerance within 20 minutes
active substance (Craig, 2002). should dissolve not less than 80%, it is
proved that the dispersion of the
irbesartan solid - polyvinylpyrrolidone K-

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30 meets the requirements as stated in the The data obtained were analyzed by
literature ( Departemen Kesehatan RI, one-way anova followed by duncan test
2014). using SPSS 16 application. The result
showed that the influence of solid
Table 7. Results of Dissolution Efficiency dispersion formula of irbesartan to
solubility there was a significant
Dissolution Efficiency difference where the sig value was
(%) obtained 0,00 (P <0,005) and clarified
Campuran fisik 1:1 60,90
with presence of duncan test.
Furthermore, the results obtained on the
Dispersi Padat 1:0,5 (F1) 56,46 influence of solid dispersion formula of
Dispersi Padat 1:1 (F2) 54,57
irbesartan to dissolution seen from the
analysis of dissolution test and
Dispersi Padat 1:3 (F3) 72,65 dissolution efficiency are significant
differences where the sig value obtained
After the data obtained from all test 0.00 (<0.005) and clarified the result in
experiments it can be seen the the presence of duncan test.
relationship between thermal analysis
with solubility and dissolution. Where CONCLUSION
from the solubility data compared with 1. From the research that has been done
the thermal analysis data that is ΔH the can be concluded that: 1. From the
heat decreases while the solubility data obtained, the manufacture of a
increases. Likewise with the dissolution solid dispersion of Irbesartan-PVP
seen from the results of the efficiency of K-30 leads to a physical interaction
dissolution where the value of ΔH heat as shown in the DTA thermogram.
decreases while the disolusinysemakin The influence of thermal properties
increases. on solid dispersion signifies a
decrease in melting point or a
Table 8. Data Recapitulation of Thermal decrease in HH of heat characterized
Analysis, Solubility and Dissolution by the formation of endothermic
2. From the data can be seen the
Sam Peak (°C) ∆H Soluble Classification Dissolution
pel Efficiency relationship between thermal
analysis with solubility and
CF 105,73 -5,52 kJ/g 19496,9
Practical Not Soluble
dissolution, the decreasing ΔH heat
then the increasing solubility and
F1 185,80 -2,15 kJ/g 12602,3 56,46 dissolution of the solid dispersion
Practical Not Soluble
irbesartan - PVP K-30. In soluble
F2 176,15 -1,67 kJ/g 11648,2 54,57
dispersion solubility test, there was
Practical Not Soluble an increase in the level indicated by
the change of solubility classification
F3 95,23 -28,88kJ/g 9441,9 72,65 from practically insoluble to very
Very dificult to
dissolve difficult to dissolve on solid
dispersion F3 (1: 3), and in
dissolution test seen from the highest
dissolution efficiency value indicated
by solid dispersion F3 ie amounted to

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SUGGESTION Grega Klančnik. (2010). Differential

It is suggested to further investigators to Thermal Analysis (DTA) and
carry out further research related to solid Differential Scanning Calorimetry
dispersion of irbesartan - polyvinyl (DSC) as a Method of Material
pyrrolidone K-30 using another method Investigation. Materials and
Geoenvironment, 57(1), 127–142.
Halim, A., Shilvi, A., & Erizal. (2011).
Abdou, H. M. (1989). Dissolution, Studi Sistem Dispersi Padat
Bioavaibility and Bioequivalence. Gliklazid menggunakan Polivinil
Mark Publishing Company Easton: Pirolidon K-30 dan Tween 80.
Pennsylavania. Jurnal Sains Dan Teknologi
Farmasi, 16(2), 95–103.
Ansel, H. C. (1989). Pengantar Bentuk
Sediaan Farmasi Edisi IV, , Kumar, G. A., Ram, K. C & CH. C.,
Penerjemah: Farida Ibrahim. 2011, Enhancement of Solubility
Jakarta: Universitas Indonesia. and Dissolution Rate of Irbesartan
by Solid Dispersion Technique.
Chawla, G., & Bansal, A. . (2007). A
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dan Makanan. Kimia, 2(2), 44–52.
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Zaini, E., Halim, A., Soewandhi, S.N., &
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melalui Metode Kokristalisasi
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