MATRIKS SANDINGAN BAHAN BAKU

POVIDONE K30
SPESIFIKASI

Specification CoA (ex. Specification In House

No. Parameters Huangshan Bonsun) Specification USP NF 2021 Specification EP 10 Pr-S3.1-05-SP-K.01/03 Spesifikasi yang diajukan Justifikasi
(Referensi: USP43/EP10) (Referensi: USP 42)
White hygroscopis powder White to slightly creamy white or yellowish-white, Serbuk putih atau sedikit Serbuk putih atau sedikit
1 Pemerian white powder. Is hygroscopic powder krem, higroskopis. krem, higroskopis.
hygroscopic. or flakes.
Freely soluble in water, in Freely soluble in water, in freely soluble in water, in Mudah larut dalam air, Mudah larut dalam air,
ethanol (96%), methanol. methanol, and in alcohol; ethanol (96 per cent) and metanol, dan alkohol. Sukar metanol, dan alkohol. Sukar
Very slightly soluble in slightly soluble in acetone; in methanol, very slightly larut dalam aseton. Praktis larut dalam aseton. Praktis
2 Kelarutan
acetone practically insoluble in ether. soluble in acetone tidak larut dalam eter. tidak larut dalam eter.

Identifikasi
A Positive Positive Positive Pengujian dengan raman Pengujian dengan raman
B Positive An orange-yellow precipitate A pink colour is produced. -spektroskopi. -spektroskopi.
3 Positive is
A formed.
pale blue precipitate is - - -
C
Positive formed.
A deep red color is produced A red colour is produced.◊ - -
D

E Positive The substance dissolves. The substance dissolves. - -

Clear and coloration NMT Clear and coloration NMT
4 Appearance of solution - - -
B6, BY6 or R6 B6, BY6 or R6
5 pH 3,0 - 5,0 3,0 - 5,0 3,0 - 5,0 3,0 - 5,0 3,0 - 5,0
Viscosity as K value 27,0 - 32,4 27,0 - 32,4 27,0 - 32,4 27,0 - 32,4 27,0 - 32,4
Aldehydes as ≤ 500 ppm ≤ 0,05 % ≤ 500 ppm ≤ 0,05 % ≤ 0,05 %
acetaldehyde
Peroxide as H2O2 ≤ 150 ppm ≤ 400 ppm ≤ 400 ppm ≤ 400 ppm ≤ 400 ppm
Hydrazine ≤ 1 ppm ≤ 1 ppm ≤ 1 ppm ≤ 1 ppm ≤ 1 ppm
Impurity A ≤ 5,0 ppm ≤ 0,001 % ≤ 10,0 ppm ≤ 0,001 % ≤ 0,001 %
Impurity B ≤ 2,0 % ≤ 3,0 % ≤ 3,0 % ≤ 3,0 % ≤ 3,0 %
Lead ≤ 5 ppm ≤ 10 ppm - ≤ 10 ppm ≤ 10 ppm
Cd ≤ 0,5 ppm - - - -
As ≤ 0,5 ppm - - - -
Hg ≤ 3 ppm - - - -
Co ≤ 5 ppm - - - -
Ni ≤ 20 ppm - - - -
Kadar air ≤ 5,0 % ≤ 5,0 % ≤ 5,0 % ≤ 5,0 % ≤ 5,0 %
Sisa pijar ≤ 0,1 % ≤ 0,1 % ≤ 0,1 % ≤ 0,1 % ≤ 0,1 %
Formic acid ≤ 0,2 % ≤ 0,5 % ≤ 0,5 % ≤ 0,5 % ≤ 0,5 %
Kadar nitrogen 11,5 - 12,8% 11,5 - 12,8% 11,5 - 12,8% 11,5 - 12,8% 11,5 - 12,8%
11 Mikrobiologi
ALT ≤ 100 CFU/g - - ≤ 200 CFU/g ≤ 200 CFU/g
AKK ≤ 100 CFU/g - - ≤ 20 CFU/g ≤ 20 CFU/g
Escherichia coli negative/g - - - -
Pseudomonas
negative/g - - - -
aeruginosa
Salmonella negative/10g - - - -

Staphylococcus aureus negative/g - - -

-

Keterangan :
*General chapter
**Pemilihan syarat didasarkan pada jumlah bahan baku yang digunakan pada produk jadi, yaitu sebesar 0,005 g dalam tiap gram produk jadi. Dari nilai tersebut didapatkan kemungkinan nilai ALT dan AKK yang
dibawa bahan baku adalah 5 cfu/g dan 0,5 cfu/g bila menggunakan syarat USP. Nilai tersebut memenuhi spesifikasi produk jadi sehingga digunakan syarat berdasarkan USP.
Hasil uji mengacu dari hasil CoA Manufakture

Kesimpulan : ≤ 5 ppm
Spesifikasi in house tidak melakukan pengujian identifikasi KLT dan komposisi Bacitracine.
Spesifikasi Mikrobiologi Sesuai dengan USP NF 2021 untuk ALT AKK dan CoA untuk identifikasi Staphylococcus aureus
dan Pseudomonas aeruginosa dengan menimbang persyaratan produk jadi (USP NF 2021).

Pengujian yang akan dilakukan mengacu ke spesifikasi inhouse metode Pr-S3.1-05-SP-A.31/00, sesuai dengan FI VI.

Dibuat Oleh, Direview Oleh,

Nama : Yusticio D.S. Nama : Kelvina Gemilang Nama : Ferry Endra T.N. Nama : Meti Christina
Tanggal : Tanggal : Tanggal : Tanggal :
 MATRIKS SANDINGAN BAHAN BAKU
POVIDONE K30
METODE PENGUJIAN

Parameters USP NF 2021 EP 10

Identifikasi B Larutan uji 20 mg/mL of Povidone Dissolve 2.5 g in carbon dioxide-free water R and dilute to 25 mL with the same solvent. Add the
Prosedur To 10 mL of the Sample solution, add 20 mL of 1 to 1 mL of solution S1 (see Tests) add 0.2 mL of
N hydrochloric acid VS and 5 mL of potassium dimethylaminobenzaldehyde solution R1 and 0.1
dichromate TS. mL of
sulfuric acid R. A pink colour is produced.

Identifikasi C Larutan A Dissolve 75 mg of cobalt nitrate and 300 mg of

Larutan uji ammonium
20 mg/mL ofthiocyanate
Povidone in 2 mL of water.
Prosedur Combine Solution A and 5 mL of the Sample
Identifikasi D Larutan uji solution,
5 mg/mL and render the resulting solution acidic
of Povidone
by
To 5 mL of the of
the addition 3 N hydrochloric
Prosedur Sample solution, addacid.
a few drops
of iodine TS.
Identifikasi E larutan uji 50 mg/mL of Povidone in water
Larutan uji Dissolve 1.0 g in carbon dioxide-free water R and
dilute to 20.0 mL with the same solvent. Add the
substance to
Appearance of be examined to the water in small portions,
solution stirring using a
magnetic stirrer

pH 50 mg/mL in water
Viscosity as K Larutan uji 5 g/100 mL air 5 g/100 mL air
value
 Larutan A Transfer 8.3 g of potassium pyrophosphate to a
500-mL volumetric flask and dissolve in 400 mL
Aldehydes as of water. Adjust, if necessary, with 1 N
acetaldehyde hydrochloric acid VS to a pH of 9.0, and dilute
with water to volume.

Larutan B Transfer a quantity of lyophilized aldehyde

dehydrogenase, equivalent to 70 units, to a glass
vial, and dissolve in 10.0 mL of water.
Larutan C Transfer 40 mg of nicotinamide adenine
dinucleotide to a glass vial, and dissolve in 10.0
mL of Solution A.
Larutan standar Dissolve 0.140 g of acetaldehyde ammonia trimer
trihydrate in water to make 200.0 mL. Dilute 1.0
mL of the solution with Solution A to 100.0 mL

Larutan uji 10 mg/mL of Povidone in Solution A. Insert a

stopper into the flask, heat at 60° for 1 h, and cool
to room temperature.
Metode Spektrofotometer UV
Panjang gelombang 340 nm
 Prosedur Pipet 0.5 mL each of the Standard solution,
Sample solution, and water (used for blank test)
into separate cells. Add 2.5 mL of Solution A and
0.2 mL of Solution C to each cell. Cover the cells
to exclude oxygen. Mix by inversion and allow to
stand for 2–3 min at 22 ± 2°. Determine the
absorbances of the solutions using the water as the
reference. Add 0.05 mL of Solution B to each cell.
Cover the cells to exclude oxygen. Mix by
inversion and allow to stand for 5 min at 22 ± 2°.
Determine the absorbances of the solutions, using
the water as the reference

Peroxide as Larutan uji 40 mg/mL of Povidone in water, calculated on the

H2O2 anhydrous basis
Blangko To 25 mL of the Sample solution, add 2 mL of
13% sulfuric acid.
Metode Spektrofotometer UV
Panjang gelombang 405 nm
Prosedur To 25 mL of the Sample solution, add 2 mL of
titanium trichloride–sulfuric acid TS, and allow to
stand for 30 min. Measure the absorbance of a
portion of this solution against the Blank.

Hydrazine Larutan standar 9 µg/mL of salicylaldazine in toluene

 Larutan uji Transfer 2.5 g to a 50-mL centrifuge tube, add 25
mL of water, and mix to dissolve. Add 500 µL of
a solution (1 in 20) of salicylaldehyde in
methanol. Swirl and heat in a water bath at 60° for
15 min. Allow to cool and add 2.0 mL of toluene.
Insert a stopper in the tube, shake vigorously for 2
min, and centrifuge. Use the clear upper toluene
layer in the centrifuge tube as the Sample
solution.

Metode KLT
Adsorbent 0.25-mm layer of dimethylsilanized
chromatographic silica gel with fluorescent
indicator
Volume uji 10 µL
Diluent Methanol and water (2:1)
Penampak bercak UV 365 nm
Impurity A Metode HPLC
Detektor UV 235 nm
Kolom 4.6-mm × 15-cm; 5-µm packing L1
Suhu kolom 40°C
Laju alir 1.0 mL/min
Volum injeksi 20 µL
Fase gerak Water and acetonitrile (90:10)
Larutan SST Transfer 10 mg of vinylpyrrolidinone and 500 mg
of vinyl acetate to a 100-mL volumetric flask, and
dissolve in and dilute with methanol to volume.
Transfer 1.0 mL of this solution to a 100-mL
volumetric flask, and dilute with Mobile phase to
volume

Larutan stok standar 5 µg/mL of vinylpyrrolidinone in Mobile phase

 Larutan standar 0.25 µg/mL of vinylpyrrolidinone diluted from the
Standard stock solution in Mobile phase
Larutan uji 25 mg/mL of Povidone in Mobile phase
Impurity B Metode HPLC
Detektor UV 205 nm
Kolom 4.6-mm × 15-cm; 5-µm packing L1
Suhu kolom 40°C
Laju alir 0,8 mL/min
Volum injeksi 50 µL
Fase gerak Water and methanol (19:1)
Larutan standar 30 µg/mL of 2-pyrrolidinone in Mobile phase
Larutan uji 5 mg/mL of Povidone in Mobile phase
Lead Larutan uji 1.0 g in 25 mL of water

Cd
As
Hg
Co
Ni
Kadar air
Sisa pijar
Formic acid Metode HPLC
Detektor UV 210 nm
Suhu kolom 40°C
Laju alir 1,0 mL/min
Volum injeksi 50 µL
Fase gerak Diluted perchloric acid (1 in 700)
Larutan standar 10 µg/mL of formic acid in water
Larutan stok uji 20 mg/mL of Povidone in water
Larutan uji Transfer a suspension of strongly acidic ion-
exchange resin (use the hydrogen form of ion-
exchange resin) in water to a column of about 8
mm in inside diameter to give a packing depth of
about 20 mm in length. Keep the strongly acidic
ion-exchange resin layer constantly immersed in
water. Pour 5 mL of water and adjust the flow rate
so that water drops at a rate of about 1 mL/min.
When the level of the water is near the top of the
strongly acidic ion-exchange resin layer, introduce
100 mL of the Sample stock solution into the
column. Disregard the first 2 mL of the eluate,
then collect 1.5 mL of the solution, and use this as
the Sample solution.
 Weigh 1g Sample accurately and place in a
Kjeldahl flask. Add 5 g of a powdered mixture of
33 g of potassium sulfate, 1 g of cupric sulfate,
and 1 g of titanium dioxide. Wash down any
adhering sample from the neck of the flask with a
small amount of water. Add 7 mL of sulfuric acid
allowing it to flow down the inside wall of the
flask. Heat the flask gradually until the solution
has a clear, yellow-green color and the inside wall
of the flask is free from any carbonized material
and then heat for an additional 45 min. After
cooling, cautiously add 20 mL of water, and
connect the flask to the distillation apparatus
previously washed by passing steam through it.
To the absorption flask add 30 mL of a solution of
boric acid (1 in 25), 3 drops of bromocresol
Kadar nitrogen green-methyl red TS, and sufficient water to
immerse the lower end of the condenser tube. Add
30 mL of a solution of sodium hydroxide (2 in 5)
through the funnel, rinse the funnel cautiously
with 10 mL of water, immediately close the clamp
attached to the rubber tube, and then start the
distillation with steam to obtain 80–100 mL of the
distillate. Remove the absorption flask from the
lower end of the condenser tube, rinsing the end
part with a small quantity of water, and titrate the
distillate with 0.025 mol/L sulfuric acid VS until
the color of the solution changes from green
through pale grayish blue to pale grayish red-
purple. Perform a blank determination in the same
manner, and make any necessary correction.
Kesimpulan :

Dibuat Oleh, Direview Oleh,

Nama : Yusticio D.S. Nama : Kelvina Gemilang Nama : Ferry Endra T.N.
Tanggal : Tanggal : Tanggal :
 In House
Pr-S3.1-05-SP-K.01/03 Spesifikasi yang diajukan Justifikasi
Referensi : USP 42
nd dilute to 25 mL with the same solvent. Add the substance to be examined to the water in small portions, stirring using a magnetic stirrer
Nama : Meti Christina
Tanggal :