ID Design Press, Skopje, Republic of Macedonia

Open Access Macedonian Journal of Medical Sciences. 2019 Nov 30; 7(22):3841-3846.
https://doi.org/10.3889/oamjms.2019.516
eISSN: 1857-9655
Herbal Medicine in Pharmaceutical and Clinical Sciences

Formulation and Quantitative Analysis of Betamethasone

Valerate and Neomycin Sulfate Cream by High Performance
Liquid Chromatography and Spectrophotometry

1 1* 2 2
Yade Metri Permata , Muchlisyam Bachri , Julia Reveny , Fitri Mardiyanti Sibuea

1
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Sumatera Utara, Medan 20155, Indonesia;
2
Department of Pharmaceutical Technology, Faculty of Pharmacy, Universitas Sumatera Utara, Medan 20155, Indonesia

Abstract
Citation: Permata YM, Bachri M, Reveny J, Sibuea FM. BACKGROUND: Combination of betamethasone valerate and neomycin sulfate in cream is used to treat the
Formulation and Quantitative Analysis of Betamethasone
Valerate and Neomycin Sulfate Cream by High
itching, redness, dryness, scaling, inflammation and discomfort of various skin conditions caused by infection. The
Performance Liquid Chromatography and combination of active ingredients has side effects which can cause dry skin, thinning of the skin, hypertrichosis,
Spectrophotometry. Open Access Maced J Med Sci. 2019 and stretch marks.
Nov 30; 7(22):3841-3846.
https://doi.org/10.3889/oamjms.2019.516
AIM: The purpose of this study was to make a formula containing vitamin E and quantitative analysis of
Keywords: Betamethasone valerate; Neomycin sulfate;
Cream; Spectrophotometry; Area under curve betamethasone valerate and neomycin sulfate in creams using High Performance Liquid Chromatography and
*Correspondence: Muchlisyam Bachri. Department of
Spectrophotometry Area Under Curve methods.
Pharmaceutical Chemistry, Faculty of Pharmacy,
Universitas Sumatera Utara, Medan 20155, Indonesia. E- METHODS: Cream preparation includes smelting and emulsification processes, with oil phases namely stearic
mail: muchlisyam@usu.ac.id acid and vitamin E as well as water phases are glycerin, sodium bi-borate, tri-ethanolamine. Physical tests for the
Received: 25-Sep-2019; Revised: 17-Oct-2019; cream were organoleptic, homogeneity, pH, evaluation of dispersion, and viscosity. HPLC analysis for cream was
Accepted: 18-Oct-2019; Online first: 14-Nov-2019
carried out using C18 column, and the mobile phase of methanol: water with comparison optimization beforehand.
Copyright: © 2019 Yade Metri Permata, Muchlisyam
Bachri, Julia Reveny, Fitri Mardiyanti Sibuea. This is an
Spectrophotometry analysis for cream was carried out using application of Area Under Curves methods.
open-access article distributed under the terms of the
Creative Commons Attribution-NonCommercial 4.0 RESULTS: The formula used was betamethasone valerate 5 mg, neomycin sulfate 25 mg, stearic acid, glycerin,
International License (CC BY-NC 4.0) sodium bi-borate, tri-ethanolamine, vitamin E and distilled water. The obtained cream was in the form of semi-
Funding: This work was supported by the Universitas solid, odorless, white (colorless), homogeneous, pH 7, the dispersion power of 500 mg cream is 4.0-4.3 cm in
Sumatera Utara grant numbers 447/UN5.2.3.1/PPM/ KP-
TALENTA USU 2018. diameter and viscosity is 7500 Cps. Analysis of the determination of the levels of the two components was carried
Competing Interests: The authors have declared that no
out by the HPLC method C-18 column with the mobile phase of methanol: water (90: 10). Betamethasone
competing interests exist valerate and neomycin sulfate levels in formulas made HPLC methods were 94.15%, and 136.56%, respectively
and using AUC spectrophotometry methods were 107.98% and 94.81%.
CONCLUSION: Cream that made by new formula with vitamin E shows good result in physical evaluation. HPLC
methods with a mobile phase of methanol: water (90:10) was not recommended, while the AUC
spectrophotometry method shows the valid result of quantitative analysis of betamethasone valerate and
neomycin sulfate in cream.

Introduction levels in tablet preparations have been developed [3].

The spectrophotometric method had been
modified so that it can be used for mixed drug
The UV spectrophotometry is drug analysis analysts that have more than two maximum
method that able to determine the levels of multi- wavelengths. The spectrophotometric technique
component compounds which have overlapping applied in the manufacture of quantitative calibration
problems in UV spectra [1], [2]. Multi-component drug curves in adjacent spectral analysis is very important
products are increasingly distributed to patients, and in the quality control. The multi-component product
the determination of each substance level in the consisting of 2 or more drug components usually had
mixture of drug components is need to find simple, an adjacent wavelength when the spectrum overlaps.
fast, validated and safe method for researchers. In addition, the spectrophotometric technique can be
Various methods for determining multi-component
_______________________________________________________________________________________________________________________________

Open Access Maced J Med Sci. 2019 Nov 30; 7(22):3841-3846. 3841
Herbal Medicine in Pharmaceutical and Clinical Sciences
_______________________________________________________________________________________________________________________________

applied to analyze multi-component drug [4]. this study included a set of Ultra Violet
Spectrophotometer instruments, complete High-
The High Performance Liquid
Performance Liquid Chromatography (Shimadzu
Chromatography (HPLC) method can be used to
Prominence series) Whatman Cellulose Nitrate
determine the concentration of drug combinations in
membrane filter 0.45 μm, Cellulose Nitrate 0.2 μm and
preparations or product [5]. In the implementation of
PTFE 0.5 μm; analytical balance (Boeco BBL31); pH
this method, optimization must be done by using
meter (Hanna) and glassware.
columns that correspond to the mobile phase that can
separate the mixture. By using the mobile phase with The material used were analytical grade from
a variety of mixtures and comparisons of the mobile Merck, namely ethanol, methanol, phosphate buffer
phase mixture of water methanol it is expected that pH 7.2, sodium hydroxide, distilled water (PT
the HPLC method can produce a separation system Ikapharmindo Putramas), stearic acid, vitamin E,
with high speed and efficiency while being supported glycerin, sodium bi-borate, triethanolamine,
by advances in column technology, high pressure betamethasone valerate and neomycin sulfate
pump systems, and highly sensitive and diverse standard obtain from PPOM Jakarta.
detectors, analyze various samples qualitatively and
The preparation of cream includes the
quantitatively, both in single and mixed components
smelting process and the emulsification process.
[6].
Immiscible components with water are thawed
The analysis method for determining the together in a water bath at a temperature of 70-75°C,
mixture content of betamethasone valerate and while all aqueous solutions that are heat-resistant and
neomycin sulfate with the HPLC and components that dissolve in water were heated at the
spectrophotometric methods has never been done. To same temperature as the fat component. Then the
be able to determine the content of the mixture by the aqueous solution is slowly added to the liquid fat
application method of spectrophotometry and HPLC is mixture and stirred constantly, the temperature is
influenced by the success of simultaneous analysis maintained for 5-10 minutes to prevent crystallization
and type of solvent, absorption wavelength, from the material. Next the mixture is slowly cooled
optimization and flow rate to obtain results that meet with continuous stirring until the mixture thickens.
the validation requirements with levels that meet the After thickening, betamethasone valerate and
requirements of Indonesian Pharmacopoeia. neomycin sulfate, the active compounds were added
to be mashed little by little and slowly so that the
Betamethasone valerate is white powder,
cream did not separate until homogeneous. The
difficult to dissolve in water, rather difficult to dissolve
evaluation of cream preparations carried out was
in ethanol, and is an active semi-synthetic
organoleptic, including odor, color, texture of
pharmaceutical raw material which is glucocorticoid.
preparation, and consistency using respondents. Then
Betamethasone can be determined using
an evaluation of pH, evaluation of dispersion, and
spectrophotometry methods, betamethasone valerate
viscosity conducted to the cream.
in ethanol has a maximum wavelength of 240 nm
(A11 = 390a) [7]. Neomycin sulfate is a sulfate salt Analysis of the active compound by using
from neomycin sulfate, which has usually use as spectrophotometry method procedure started by
antimicrobial agent. Based on Indonesian making of standard spectrum. The standard of
pharmacopeia, the analysis on neomycin sulfate is betamethasone valerate was weighed 50 mg, into a
using microbial testing [5]. Another study shown that 100-ml flask, and dissolve using 70% ethanol so that
absorption ration and chemometric spectrophotometry a solution with concentration 500 µg/ml was obtained.
methods was valid for determination betamethasone This solution then diluted to obtain a concentration of
valerate and neomycin sulfate in cream [8], [9]. 11 µg/ml. While for neomycin sulfate, the standard
was weighed 100 mg into a 100 ml flask, and dissolve
Thus, the present study aimed to make a
using 70% ethanol so that a solution with
formula containing vitamin E and make a comparison
concentration 1000 µg/ml was obtained. This solution
of determine levels of betamethasone valerate and
then diluted to obtain a concentration of 170 µg/ml.
neomycin sulfate in creams using High Performance
The calibration curve was made by measuring
Liquid Chromatography and Spectrophotometry Area
absorption from various concentrations of standard by
Under Curve methods.
diluting the standard solution to a concentration of 5.5;
11.5; 15.5; 20.5 µg/ml for betamethasone valerate and
85; 170; 255; 340 µg/ml for neomycin sulfate. Then
the determination of the maximal absorption spectrum
Material and Methods of betamethasone valerate and neomycin sulfate was
carried out by making a mixture of betamethasone
valerate and neomycin sulfate standard mixtures. The
The present study was conducted at area under curve (AUC) absorption spectrum was
Research laboratory in Faculty Pharmacy Universitas carried out using the UV probe 2.42 software to obtain
Sumaera Utara, Medan, Indonesia. The tools used in the spectrum. This software operated calculation of
the area value at the maximum length of the two
_______________________________________________________________________________________________________________________________

3842 https://www.id-press.eu/mjms/index
 Permata et al. Formulation and Quantitative Analysis of Betamethasone Valerate and Neomycin Sulfate Cream
_______________________________________________________________________________________________________________________________

active compounds. The absorption spectrum

produced was then made into a spectrum of ratios for
each betamethasone valerate and neomycin sulfate,
then the making of the AUC spectrum and carried out
with the level determination as in the sample.
The method is validated with validation
parameter accuracy, precision, linearity, limit of Figure 1: Maximum absorption spectrum of neomycin sulfate (170
µg/ml) and betamethasone valerate (11 µg/ml)
detection (LOD) and limit of quantization (LOQ).
Accuracy test is done by standard addition method
[10]. The precision determination was done based on
relative standard deviation (RSD) values with relative The absorption spectrum of neomycin sulfate
standard deviation requirements is worth less than 2% and betamethasone valerate in different
[11]. Linearity was the ability of the analytical method concentrations were shown in Figure 2 and Figure 3.
to obtain the results that are in accordance with the
range of concentrations of certain analytes. The
regression used in the calibration curve is obtained
from the equation y = ax + b. This equation will
produce a relation coefficient (r). This coefficient of
relations is used to determine the linearity, LOD and
LOQ of an analytical method used [10], [11].
The HPLC method for cream analysis was
done by using C18 column, and the mobile phase of
methanol: water with comparison optimization first.
The HPLC analysis procedure includes conditioning Figure 2: Absorption spectrum of Neomycin sulfate at
the HPLC, determining the mobile phase composition concentrations 85 µg/ml-340 µg/ml
between methanol and water, determining the
optimum flow rate of methanol and water, determining
the levels of betamethasone valerate and neomycin Measurement of the absorption spectrum of
sulfate and calculating the respective levels. betamethasone valerate and neomycin sulfate
standard mixture was carried out based on a
comparison of sample concentration (drug). Where
the concentration of neomycin sulfate and
betamethasone valerate was in ratio 1 to 5. Neomycin
Results sulfate standard reach maximum absorption that
meets the law of Lambert-beer, in the concentration of
170 µg/ml.
The formula of cream was made based on the
Table 1. It shows good result of physical evaluation of
cream.

Table 1: Formula of cream

No. Formula
1 Betamethasone valerate 5 mg
2 Neomycin sulfate 25 mg
3 Stearic acid 0.7061 g
4 Glycerin 0.4972 g
5 Na biborate 0.0124 g
6 TEA 0.0497 g
7 Vitamin E 0.0049 g
8 Water 3.7294 g
Total 5g
Oil phase Stearic acid and vitamin E Figure 3: Absorption spectrum of Betamethasone valerate at
Water base Glycerin, Na bi-borate, TEA, water concentration 5.5 µg/ml-20.5 µg/ml

The organoleptic test was intended to see the

physical appearance of the cream, which included The standard mixture of neomycin sulfate and
shape, color and smell where the results obtained betamethasone valerate concentration were 170
were in the form of semi-solid, odorless, white µg/mL and 11 µg/mL produces a spectrum similar to
(unchanged), homogeneous, pH 7 with spread power the betamethasone valerate spectrum because
4.0-4.3 cm and viscosity 7500 Cps. neomycin sulfate has insignificant absorption so that
the mixture does not affect the shape of the standard
The maximum absorption spectrum of absorption spectrum. The standard and cream mixture
neomycin sulfate and betamethasone valerate can be spectrum can be seen in Figure 4.
seen in Figure 1.
The sample solution preparation was done by
_______________________________________________________________________________________________________________________________

Open Access Maced J Med Sci. 2019 Nov 30; 7(22):3841-3846. 3843
Herbal Medicine in Pharmaceutical and Clinical Sciences
_______________________________________________________________________________________________________________________________

the standard addition method until it reaches the Table 3: Level of neomycin sulfate and betamethasone valerate
in cream
maximum concentration. Addition of neomycin sulfate
carried out with a ratio of 1: 5, where the measured No.
Active compounds Level of active Composition of Requirements
compounds active compounds
Neomycin sulfate uptake did not meet the Lambert- 1 Neomycin sulfate (94.81 2 58) 25 mg (90-135)%
2 Betamethasone valerate (107. 8 1.6491)% 5 mg (90-110)%
beer law (absorption is not in the range 0.2-0.6), so
that it is added until it reaches maximum
concentration. A number of samples were analyzed by Chromatogram of each raw compound with
addition of the analytes mixed, and analyzed, again. the mobile phase of methanol: water with a ratio of 90:
The difference between the two results is compared 10 for optimal results after optimization.
with the actual level.

Figure 4: The Absorption Spectrum of Neomycin sulfate and

Betamethasone valerate standard mixture in cream

The prepared sample was then measured at a Figure 6: The chromatogram of betamethasone valerate at
wavelength of 200-400 nm. The absorption spectrum concentration 11 μg/ml and retention time 5.3 minutes
of the samples obtained was a mixture of the
spectrum of neomycin sulfate and betamethasone
valerate to obtain the area under curve by the Chromatogram samples of cream
wavelength 244-254 nm for neomycin sulfate and preparations can be seen in Figures 6 and 7.
240-250 nm for betamethasone valerate, then the
concentration is calculated using equations.
Spectrum of AUC neomycin sulfate and
spectrum of AUC Betamethasone valerate in cream is
seen in Figure 5.

Figure 7: The chromatogram of neomycin sulfate at concentration

Figure 5: AUC Spectrum of Neomycin sulfate and Betamethasone 50 μg/ml and retention time 2.7 minute
valerate in Cream

Figure 8 is the chromatogram of a cream. The

The value of the area under the neomycin retention time used for testing was 5.3 minutes for
sulphate and betamethasone valerate curves in cream betamethasone valerate and 2.7 minutes for
can be seen in Table 2 and the levels of the active neomycin sulfate.
compounds in cream preparations can be seen in
Table 3.

Table 2: Area under curves of neomycin sulfate and

betamethasone valerate
Area under curves of neomycin Area under curves of betamethasone
No. sulfate valerate
244 nm 240 nm 250 nm 254 nm
1 0.235 0.189 0.300 0.327
2 0.236 0.189 0.299 0.327
3 0.236 0.189 0.299 0.328
4 0.236 0.189 0.299 0.327
5 0.236 0.189 0.299 0.327
6 0.236 0.189 0.300 0.328

Figure 8: The chromatogram of cream

Determination of the maximum wavelength
that has been done shows that each compound has a
different maximum wavelength. The maximum The results of betamethasone valerate and
wavelength of the research results for betamethasone neomycin sulfate levels in cream were describe in
valerate and neomycin sulfate is 240 nm. Table 4.
_______________________________________________________________________________________________________________________________

3844 https://www.id-press.eu/mjms/index
 Permata et al. Formulation and Quantitative Analysis of Betamethasone Valerate and Neomycin Sulfate Cream
_______________________________________________________________________________________________________________________________
Table 4: The betamethasone valerate and neomycin sulfate measuring and calculating the absorbance of the area
levels in cream
under the curve of 2 wavelengths around the
No Name Sample Betamethasone valerate Neomycin Sulfate maximum absorption wavelength of one component of
1 Standard 100 μg/ml 46,71983 11 μg/ml 411,6
109.46 % 91.96 % the drug, and this method is called the measurement
119.70 % 181.37 %
79.92 % 117.32 %
method in the area under curve and abbreviated by
2 Cream
83.98 % 149.41 % the name of the AUC method. This method is one of
83.70 % 148.93 %
88.12 % 130.37 % the prevailing spectrophotometric methods which
Level of active 0. 415 0.1338 mg/g 6.827 11.8105
3
compound 94.15 % 136.56 %
have no valid curve where no sharp peaks or spectra
are a parabolic or broad spectrum. This method has a
The levels of neomycin sulfate and calculation of the integrated absorbance value
betamethasone valerate in cream were 90-135% and between the two selected wavelengths λ1 and λ2.
90-110%, respectively. The relative standard deviation Single form determination of betamethasone
(RSD) for neomycin sulfate and betamethasone valerate and neomycin sulfate levels can be
valerate were 1.73% and 0.92%. Neomycin sulfate determined by ultra-violet spectrophotometry method.
and betamethasone valerate have good precision Betamethasone valerate has maximum absorption at
because both RSD values are less than 2%. The 240 nm wavelength (A11 = 390a) in ethanol while
validation parameters tested were accuracy, neomycin sulfate has the maximum absorption at 285
precision, linearity, limit of detection (LOD), and limit nm (A11 = 39b) in water [7]. In other literature state
of quantization (LOQ). Accuracy tests are expressed that determination of levels of neomycin sulfate by
in percent recovery which is determined by the ultraviolet spectrophotometric method has insignificant
standard addition method. In this study validation tests absorbance, with wavelengths of 230-360 nm [12].
were carried out with a standard addition method in
cream samples. Because the conditions for measuring multi-
component levels are using the same solvent, the
Accuracy tests were carried out by making orientation of the solvent done to find the solvent that
three concentrations of samples with a specific range can dissolved the active compounds. The orientation
of 80%, 100%, and 120% calculated from the equality was carried out by trying 2 treatments, namely
of weighing on sample concentration, each specific treatment one dissolved the two-active compound with
range consisted of three repetitions containing 70% 50% ethanol and the second treatment dissolved the
analyte and 30% standard. The spectrum absorption two-active compound with 70% ethanol. Based on the
of neomycin sulfate and betamethasone valerate for orientation results showed that 70% ethanol can
the recovery test can be seen in Figure 9. dissolve the two active substances of the drug.
Determination of the maximum absorption spectrum of
neomycin sulfate and betamethasone valerate was
made in a wavelength range of 200-400 nm. Based on
the results of the qualitative absorption spectrum, the
maximum wavelength of neomycin sulfate
Figure 9: The spectrum absorption of neomycin sulfate and
betamethasone valerate for the recovery test (concentration 170 µg/ml) was obtained at 244 nm
and for betamethasone valerate (concentration 11
µg/ml) at 240 nm.
The percent recovery was eligible for method The second absorbance point of the
validation with an average of 98%-102% for neomycin wavelength was not the wavelength point which has
sulfate was 99.44% and betamethasone valerate was maximum absorptions, but the point that was bound to
100.07%. The relative standard deviation (RSD) the curve is the wavelength point on the left and right
meets the precision requirements because each was side of the peak area. The calculation of area was by
less than 2% with 1.54% for neomycin sulfate and calculates the area bound by the curve and horizontal
0.87% for betamethasone valerate. The limit of axis. The axis is chosen by entering the wavelength
detection and limit of quantization was illustrated in range where the area must be calculated. This
table 5. wavelength range is chosen based on repeated
observations so that it gets linearity between the area
Table 5: The validation methods parameters
under the curve and concentration. The spectrum
No Active Compounds % Recovery RSD LOD LOQ mentioned was used to calculate AUC. Thus, a
1 Neomycin sulfate 99.44% 1.54% 11.2184 µg/ml 37.3 4 µg/ ml
2 Betamethasone valerate 100.07% 0.87%. 0. 481 µg/ ml 2.1 04 µg/ ml calibration curve can be constructed by plotting
concentration versus AUC.
High Performance Liquid Chromatography
(HPLC) is a separation system with high speed and
Discussion efficiency, because it is supported by advancements
in column technology, high pressure pump systems
and very sensitive and diverse detectors so as to be
Area under curve spectrophotometry is a able to analyze various samples qualitatively and
method that performs the determination of levels by
_______________________________________________________________________________________________________________________________

Open Access Maced J Med Sci. 2019 Nov 30; 7(22):3841-3846. 3845
Herbal Medicine in Pharmaceutical and Clinical Sciences
_______________________________________________________________________________________________________________________________

quantitatively, both in single components or mixture. 9(2):118-26.

HPLC is a method often used to analyze drug 2. Rivai H, Astuty W, Asra R. Pengembangan dan Validasi Metode
compounds. HPLC can be used to check the purity of Analisis Betametason dalam Tablet dengan Metode Absorbansi
active compounds, supervise the process of synthesis dan Luas Daerah di Bawah Kurva Secara Spektrofotometri
Ultraviolet. J Sains dan Teknol Farmasu. 2017; 19(1):s52-7.
and quality control [5], [13]. Among the ratio of mobile
phase that had identified, (90: 10) is the best mobile 3. Bendre SD, Ghule PJ. Analytical Method Development,
Validation, and Assay of Betamethasone Dipropionate Craem by
phase for betamethasone valerate and neomycin HPLC Method. Int Res J Pharm. 2016; 7(12):74-83.
sulfate. https://doi.org/10.7897/2230-8407.0712151
In conclusion, cream that made by new 4. Muchlisyam, Pardede TR. Spectrofotometri dan Analisis
Multikomponen Obat. Medan: USU Press, 2017.
formula with vitamin E shows good result in physical
evaluation. HPLC methods with various ratio of 5. Ditjen POM RI. Farmakope Indonesia [Internet]. 4th ed.
Departemen Kesehatan Republik Indonesia. Jakarta: Departemen
methanol: water was conducted to obtain the best Kesehatan RI, 1995. Available from:
mobile phase for betamethasone valerate and https://doi.org/10.6066/jtip.2013.24.2.121
neomycin sulfate analysis. The best mobile phase of
methanol: water (90: 10), but this method not 6. Harahap Y, Amalia GA, Maggadani BP. Analysis of Rifampicin in
recommended, while the AUC spectrophotometry Dried Blood Spots Using High Performance Liquid
method shows the valid result for quantitative analysis Chromatography. Asian J Sci Res. 2018; 11(2):232-9.
https://doi.org/10.3923/ajsr.2018.232.239
of betamethasone valerate and neomycin sulfate in
cream. 7. Moffat AC, Osselton MD, Widdop B. Clarke's Analysis of Drug
and Poisons. 4th ed. London: Pharmaceutical Press; 2011.
8. Bachri M, Reveny J, Permata YM, Situmorang CEA. Validation
of Intersection Absorption Spectrum For Simultaneous
Determination of Betamethasone Valerate and Neomycin Sulfate in
Cream. Rasayan J Chem. 2019; 12(1):232-9.
Acknowledgment https://doi.org/10.31788/RJC.2019.1215013
9. Bachri M, Permata YM, Permadi R. Validation and Simultaneous
Estimation of Betamethasone Valerate and Neomycin Sulfate
Cream By Absorbance Ratio Spectrophotometry Methods. Int Res
We are gratefully Rector of Universitas J Pharm. 2019; 10(2):48-52. https://doi.org/10.7897/2230-
Sumatera Utara and Chairman of the USU Research 8407.100240
Institutes for financial support in order to carried out 10. Harmita. Petunjuk pelaksanaan validasi. Maj Ilmu Kefarmasian.
this research. 2004; 1(3):117-35. https://doi.org/10.7454/psr.v1i3.3375
11. Satiadarma K, Mulja M, Tjahyono DH, Kartasasmita RE. Asas
Pengembangan Prosedur Analisis. 1st ed. Surabaya: Airlangga
University Press, 2004.
12. Sweetman SC. Martindale The Complete Drug Reference. 36th
References ed. New York: Pharmaceutical Press; 2009.
13. Jasprica I, Mršić N, Dragić T, Cetina-Čižmek B. Determination
of meglumine in pharmaceutical formulations using high
1. Asra R, Rivai H, Astuty W. Pengembangan dan Validasi Metode performance liquid chromatography. Die Pharmazie-An
Analisis Betametason Tablet dengan Metode Absorbansi dan Luas International Journal of Pharmaceutical Sciences. 2011;
Daerah di Bawah Kurva Secara Spektrofotometri Ultraviolet 66(12):916-9.
Pengembangan dan Validasi Metode Analisis Betametason Tablet
dengan Metode semi sintetis aktif yang me. J Farm Higea. 2017;

_______________________________________________________________________________________________________________________________

3846 https://www.id-press.eu/mjms/index