FARMASI FISIK 2

DIFFUSION and DISSOLUTION

Iskandarsyah, Kurnia SS Putri,

Raditya Iswandana

Fakultas Farmasi, Universitas Indonesia

2019
 Diffusion
• Free diffusion of substances through liquids, solids, and
membranes is an important process in the pharmaceutical
sciences.
• Diffusion is defined as a process of mass transfer of
individual molecules of a substance brought about by
random molecular motion and associated with a driving
force such as a concentration gradient.
• Example of diffusion process :
- drug transport through a polymeric matrix/ membrane
(includes disintegration and/or dissolution)
- drug transport across biological membrane (skin,
intestine, other organs)  affect absorption and
elimination   efficient drug distribution throughout
the body and into tissues and organs.
Diffusion
Diffusion, Osmosis, Ultrafiltration, Dialysis

• Osmosis : the passage of solvent across a membrane 

application: osmotic-release oral system (OROS)
• Dialysis: The passage of solute and solvent altogether.
• Ultrafiltration : separation of colloidal particles and
macromolecules by the use of a membrane. Hydraulic
pressure is used to force the solvent through the
membrane.
• Hemodialysis : separation of metabolic waste products
(small molecules) from the blood while preserving the
high-molecular-weight components of the blood.
 Fick's Laws of Diffusion

• The amount (gram or moles), M, of material flowing through a

unit area (cm2), S, of a barrier in unit time (sec), t, is known as the
flux, J (g/cm2 sec):

• The flux, in turn, is proportional to the concentration gradient,

dC/dx:

• D is the diffusion coefficient of a penetrant (also called the

diffusant) in cm2/sec, C is its concentration in g/cm3, and x is the
distance in centimeter of movement perpendicular to the surface
of the barrier.
 Fick's Laws of Diffusion

• The negative sign of equation signifies that diffusion occurs

in a direction opposite to that of increasing concentration.

• That is, diffusion occurs in the direction of decreasing

concentration of diffusant; thus, the flux is always a
positive quantity.

• Diffusion will stop when the concentration gradient no

longer exists (i.e., when dC/dx = 0).
 Fick's Laws of Diffusion
• An equation for mass transport that emphasizes the change
in concentration with time at a definite location (rather
than unit area of barrier) in unit time is known as Fick's
second law (Fick II)

• Fick's second law states that the change in concentration

with time in a particular region is proportional to the
change in the concentration gradient at that point in the
system.
 Steady State & Sink Condition

• Fick's first law gives the flux (or rate of diffusion through unit
area) in the steady state of flow.
• The second law refers in general to a change in concentration of
diffusant with time at any distance, x (i.e., a non-steady state of
flow)  however, we can keep the steady state if in diffusion
experiments, the solution in the receptor compartment is
constantly removed and replaced with fresh solvent to keep the
concentration at a low level.  “sink conditions”
• When the system has been in existence a sufficient time, the
concentration of diffusant in the solutions at the left and right of
the barrier (gradient concentration, hence, flux) becomes
constant with respect to time but obviously not the same in the
two compartments  steady state
 Steady State & Sink Condition

• When d2C/dx2 = 0  no change in dC/dx  dC/dx is

constant  dC/dt = 0  steady state  occur after
sufficient time
 Diffusion Driving Force

1. Concentration  in “ordinary diffusion”  occur in passive

diffusion & drug dissolution process
2. Pressure  osmotic drug release, Pressure-driven jets for drug
delivery
3. Temperature:
• Microwave-assisted extraction (MAE)
• Lyophilization  during freeze drying process, water vapor
diffusion across the pore path length of the dry matrix under
low temperature and vacuum conditions  ice–vapor interface
governed by the Clausius–Clapeyron pressure–temperature
relationship,
4. Electric potential  Iontophoretic dermal drug delivery
 Diffusion Through Membranes
and Diffusional Resistance

• A steady state diffusion across a thin film of

thickness h and the diffusion coefficient (D)
is considered constant because the
solutions on both sides of the film are
dilute.
• The concentrations on both sides of the
film, C1 and C2, are kept constant and both
sides are well mixed.
• Diffusion occurs in the direction from the
higher concentration (Cd) to the lower
concentration (Cr). After sufficient time,
steady state is achieved and the
concentrations are constant at all points in
the film  the concentration profile inside
the film is linear, and the flux is constant.
 Diffusion Through Membranes
and Diffusional Resistance

• At steady state (dC/dt = 0), Fick's second law becomes with

integration:

• The term h/D is often called the diffusional resistance,

denoted by R.
 Permeability

• Permeability is a term that is used more often in the

pharmaceutical sciences.
• Resistance and permeability are inversely related.
• The higher the resistance to diffusion, the lower is the
permeability of the diffusing substance.

 Cs  C 
=D dc DA
dt h
• D = diffusion coefficient of the membrane
• K is the distribution or partition coefficient
Multilayer Diffusion
Membrane Control and Diffusion Layer Control
 Procedure and Appartus
for Assesing Drug Diffusion
 Procedure and Appartus
for Assesing Drug Diffusion

FRANZ • (A) – donor compartment

DIFFUSION CELL • (B) – receptor compartment
• (C) - membrane
• (D) - O-ring
• (E) water jacket,
• (F) pengaduk magnetik,
• (G) tempat sampling
 Application of Diffusion
in Pharmaceutical Process

• Biological diffusion
- GIT absorption of drugs  affected by gradient
concentration & pH partition
- Transcorneal Permeation
- Percutaneous Absorption  & Matrix
- Buccal Absorption
- Uterine Diffusion
• Diffusion from Drug system
- Soluble drug in Topical Vehicle
- Drug release from reservoir & matrix
- Lag time
- Osmotic Drug Release
DISSOLUTION
Drug Release & Dissolution
 Drug Release & Dissolution

• Disintegration tests is not sufficient to predict how formulations or

drug products are expected to perform in patients  Dissolution test

• Application of dissolution test:

(a) solid oral dosage forms
(b) rectal dosage forms such as suppositories,
(c) pulmonary (lung delivery) dosage forms,
(d) modified-release dosage forms, and
(e) semisolid products: ointments, creams, and transdermal products.
 Drug Release & Dissolution

Drug release is the process by which a drug leaves a drug product and is
subjected to absorption, distribution, metabolism, and excretion,
eventually becoming available for pharmacologic action.
- Immediate release
- Modified release: Delayed, Extended/ Sustained, Controlled (Pulsatile)

Drug dissolution is the process by which drug molecules are liberated

from a solid phase and enter into a solution phase.
 Dissolution & Diffusion
Noyes-Whitney Fick’s Law
of Dissolution of Diffusion

 Cs  C 
dc DA
dt h
The saturation solubility of a drug is a key factor in the Noyes–
Whitney equation.
The driving force for dissolution is the concentration gradient
across the boundary layer  depends on the thickness of the
boundary layer and the concentration of drug that is already
dissolved.
When the concentration of dissolved drug, C is less than 20% of the
saturation concentration, Cs, the system is said to operate under
“sink conditions.”
The driving force for dissolution is greatest when the system is
under sink condition
Factors affect bioavailability of drugs
Factors affect bioavailability of drugs
 Biopharmaceutical Classification System

Availability of drug in the human body after oral administration depend

on solubility, permeability, and drug release.

Typically, the BCS is used to build an IVIVC (in vitro – in vivo correlation)
 to predict bioavailability of the drug based on in vitro (dissolution)
study
 UJI DISOLUSI KOMPENDIAL
Dilakukan sesuai dengan monografi yang tercantum dalam farmakope
edisi terakhir.
Faktor yang mempengaruhi hasil uji disolusi:
• Pengadukan  kecepatan pengadukan mempengaruhi ketebalan
lapisan difusi  semakin besar intensitas pengadukan, semakin
tipis lapisan difusi, sehingga semakin cepat waktu disolusi
• Kondisi media disolusi: pH, suhu, viskositas, tegangan permukaan
dan komposisi media disolusi
Uji disolusi dilakukan sesuai dengan ketentuan yang tercantum dalam
monografi/farmakope, yang mencakup :
a. Tipe alat & Kecepatan pengadukan
b.Jenis dan volume medium
c. Lama/waktu uji disolusi
d.Toleransi (Q), jumlah obat yang terdisolusi
e. Metode analisis
 UJI DISOLUSI KOMPENDIAL

• Kecepatan rpm harus dikalibrasi secara berkala menggunakan

tachometer. Simpangan rpm ± 4% dari yg tercantum dalam monografi
• Sumbu batang pengaduk posisi vertikal terhadap labu media disolusi
dan cecara berkala diverivikasi menggunakan alat centering check.
Batang pengaduk harus berada tepat di tengah2 labu disolusi sehingga
sumbunya tidak lebih dari 2 mm pada tiap titik dari sumbu vertikal
labu
• Jarak antara bagian bawah pengaduk dayung/keranjang dan dasar
labu harus diverivikasi dalam batas toleransi 25 ±2 mm (kecuali
dinyatakan lain dalam monografi)
• Suhu tangas air harus dikalibrasi: 37 ± 0,50C
 UJI DISOLUSI KOMPENDIAL

MEDIA DISOLUSI
Tercantum dalam monografi masing-masingnsediaan.
Prinsipnya sesuai dengan sifat zat aktif yang akan diuji:
• Air
• Larutan HCL pH 1,2
• Larutan dapar pH 3-5: dapar asetat
• Larutan dapar fosfat pH 5,8; 6,8; 7,2; 7,4
• Larutan netral pH 6-7,5: cairan usus buatan
• Larutan surfaktan dalam air: natrium lauril sulfat 0,00054%
dalam air
UJI DISOLUSI KOMPENDIAL
 UJI DISOLUSI KOMPENDIAL
Perlu diperhatikan adanya gas/ udara pada medium disolusi:
1)Adanya gelembung udara dalam media disolusi akan memperkecil luas
permukaan sediaan yang berkontak dengan media disolusi, sehingga
menghambat proses disolusi.
2)Gelembung udara dapat menutup lubang keranjang sehingga
mengganggu aliran media masuk dan keluar dari keranjang
3) Gas/udara terlarut dapat merubah pH media disolusi

Cara menghilangkan gas/ udara yg terlarut pada medium disolusi:

• Air yang akan digunakan dipanaskan dahulu, kemudian ditutup dan
didinginkan di bawah aliran air
• Menggunakan ultrasonik selama 15 menit
• Media dipanaskan hingga 410C sambil diaduk perlahan, segera
disaring menggunakan saringan dengan lubang pori ≤ 0,45 µm, lalu
aduk kuat dalam hampa udara selama 5 menit
 Pengambilan Contoh
• Dilakukan pada daerah pertengahan antara permukaan media
dengan disolusi dan bagian atas keranjang yang berputar atau alat
dayung dan tidak kurang dari 1 cm terhadap dinding labu disolusi
• Dilakukan pada waktu yang ditentukan sesuai monografi, toleransi ±
2%
• Prosedur pooled sample: contoh diambil dari masing2 labu kemudian
disatukan dan dihomogenkan, digunakan sebagai larutan uji
 Compendial Methods of Dissolution

Apparatus Name Drug Product

Apparatus 1 Rotating basket Tablets
Apparatus 2 Paddle Tablets, capsules, modified drug
products, suspensions
Apparatus 3 Reciprocating cylinder Extended-release drug products
Apparatus 4 Flow cell Drug products containing low-water-
soluble drugs
Apparatus 5 Paddle over disk Transdermal drug products
Apparatus 6 Cylinder Transdermal drug products
Apparatus 7 Reciprocating disk Extended-release drug products
Rotating bottle (Non-USP-NF) Extended-release drug products (beads)
Diffusion cell (Non-USP-NF) Ointments, creams, transdermal drug
(Franz) products
 Rotating Basket Method (Apparatus 1)

• The rotating basket apparatus (Apparatus 1) consists of a

cylindrical basket held by a motor shaft. The basket holds
the sample and rotates in a round flask containing the
dissolution medium.
• The entire flask is immersed in a constant-temperature
bath set at 37°C. The rotating speed and the position of the
basket must meet specific requirements set forth in the
current USP. The most common rotating speed for the
basket method is 100 rpm.
• Apparatus 1 is generally preferred for capsules and for
dosage forms that tend to float or disintegrate slowly.
 Paddle Method (Apparatus 2)
• The paddle apparatus (Apparatus 2) consists of a special, coated paddle
that minimizes turbulence due to stirring
• The paddle is attached vertically to a variable-speed motor that rotates at a
controlled speed. The tablet or capsule is placed into the round-bottom
dissolution flask, which minimizes turbulence of the dissolution medium.
• The apparatus is housed in a constant-temperature water bath maintained
at 37°C, similar to the rotating-basket method. The position and alignment
of the paddle are specified in the USP.
• The paddle method is very sensitive to tilting. Improper alignment may
drastically affect the dissolution results with some drug products.
• The most common operating speeds for Apparatus 2 are 50 rpm for solid
oral dosage forms and 25 rpm for suspensions. Apparatus 2 is generally
preferred for tablets.
• A sinker, such as a few turns of platinum wire, may be used to prevent a
capsule or tablet from floating. A sinker may also be used for film-coated
tablets that stick to the vessel walls or to help position the tablet or capsule
under the paddle. The sinker should not alter the dissolution
characteristics of the dosage form.
Reciprocating Cylinder Method (Apparatus 3)

• The reciprocating cylinder apparatus (Apparatus 3)

consists of a set of cylindrical, flat-bottomed glass vessels
equipped with reciprocating cylinders for dissolution
testing of extended-release products, particularly bead-
type modified-release dosage forms.
 Flow-Through-Cell Method (Apparatus 4)

• The flow-through-cell apparatus (Apparatus 4) consists of a

reservoir for the dissolution medium and a pump that forces
dissolution medium through the cell holding the test sample.
• Flow rate ranges from 4 to 16 mL/min. Six samples are tested
during the dissolution testing, and the medium is maintained at
37°C.
• Apparatus 4 may be used for modified-release dosage forms that
contain active ingredients having very limited solubility.
• There are many variations of this method. Essentially, the
sample is held in a fixed position while the dissolution medium
is pumped through the sample holder, thus dissolving the drug.
 Flow-Through-Cell Method (Apparatus 4)

• Laminar flow of the medium is achieved by using a pulseless pump.

Peristaltic or centrifugal pumps are not recommended.
• The flow rate is usually maintained between 10 and 100 mL/min.
• The dissolution medium may be fresh or recirculated. In the case of
fresh medium, the dissolution rate at any moment may be
obtained, whereas in the official paddle or basket method,
cumulative dissolution rates are monitored.
• A major advantage of the flow-through method is the easy
maintenance of a sink condition for dissolution.
• A large volume of dissolution medium may also be used, and the
mode of operation is easily adapted to automated equipment.
 Paddle-over-Disk Method (Apparatus 5)
• The USP-NF also lists a paddle-over-disk method for
testing the release of drugs from transdermal products.
• The apparatus (Apparatus 5) consists of a sample holder
or disk assembly that holds the product.
• The entire preparation is placed in a dissolution flask filled
with specified medium maintained at 32°C.
• The paddle is placed directly over the disk assembly.
Samples are drawn midway between the surface of the
dissolution medium and the top of the paddle blade at
specified times.
• Similar to dissolution testing with capsules and tablets, six
units are tested during each run. Acceptance criteria are
stated in the individual drug monographs.
 Cylinder Method (Apparatus 6)
• The cylinder method (Apparatus 6) for testing transdermal
preparation is modified from the basket method
(Apparatus 1).
• In place of the basket, a stainless steel cylinder is used to
hold the sample.
• The sample is mounted onto cuprophan (an inert porous
cellulosic material) and the entire system adheres to the
cylinder.
• Testing is maintained at 32°C. Samples are drawn midway
between the surface of the dissolution medium and the top
of the rotating cylinder for analysis.
 Reciprocating Disk Method (Apparatus 7)
• In the reciprocating disk method for testing transdermal
products, a motor drive assembly (Apparatus 7) is used to
reciprocate the system vertically, and the samples are
placed on disk-shaped holders using cuprophan supports.
• The test is also carried out at 32°C, and reciprocating
frequency is about 30 cycles per minute. The acceptance
criteria are listed in the individual drug monographs.
 Alternative Methods of Dissolution Testing
Rotating Bottle Method
• The rotating bottle method was suggested in NF-XIII (National
Formulary) but has become less popular since. The rotating bottle
method was used mainly for controlled-release beads. For this purpose
the dissolution medium may be easily changed, such as from artificial
gastric juice to artificial intestinal juice.
• The equipment consists of a rotating rack that holds the sample drug
products in bottles. The bottles are capped tightly and rotated in a 37°C
temperature bath. At various times, the samples are removed from the
bottle, decanted through a 40-mesh screen, and the residues are assayed.
• To the remaining drug residues within the bottles are added an equal
volume of fresh medium and the dissolution test is continued. A
dissolution test with pH 1.2 medium for 1 hour, pH 2.5 medium for the
next 1 hour, followed by pH 4.5 medium for 1.5 hours, pH 7.0 medium for
1.5 hours, and pH 7.5 medium for 2 hours was recommended to simulate
condition of the gastrointestinal tract.
• The main disadvantage is that this procedure is manual and tedious.
Moreover, it is not known if the rotating bottle procedure results in a
better in-vitro–in-vivo correlation for drugs.
 Peristalsis Method

• The peristalsis method attempts to simulate the

hydrodynamic conditions of the gastrointestinal tract in an
in-vitro dissolution device.
• The apparatus consists of a rigid plastic cylindrical tubing
fitted with a septum and rubber stoppers at both ends.
• The dissolution chamber consists of a space between the
septum and the lower stopper.
• The apparatus is placed in a beaker containing the
dissolution medium.
• The dissolution medium is pumped with peristaltic action
through the dosage form
 Interpretasi Data
• Uji disolusi dapat dilakukan 1 tahap, 2 tahap atau 3 tahap (S1,
S2, S3)
• Kecuali dinyatakan lain dalam masing2 monografi, persyaratan
dipenuhi bila jumlah zat aktif yang terlarut sesuai dengan tabel
penerimaan.
• Lanjutkan uji sampai 3 tahap kecuali bila hasil uji sudah
memenuhi syarat pada tahap S1 dan S2
• Q adalah jumlah zat aktif yang terlarut sesuai dengan
monografi. Angka 5% dan 15% dalam tabel adalah persentasi
kadar pada etiket, yaitu Q
 Interpretasi Data

Tabel Penerimaan

Jumlah
Tahap Batas Penerimaan
yang diuji
S1 6 Tiap unit tidak kurang dari Q+5%

Rata2 dari 12 unit (S1+S2) adalah ≥ Q

S2 6
Tidak 1 unitpun sediaan yang < Q-15%

Rata2 dari 24 unit (S1+S2+S3) adalah ≥ Q

S3 12 Tidak lebih dari 2 unit sediaan < Q-15%
Tidak satu unitpun < Q – 25%
 Methods for Testing
Enteric-Coated Products
• USP-NF lists two methods (Method A and Method B) for testing
enteric-coated products. The latest revision of the USP-NF should
be consulted for complete details of the methods.
• Both methods require that the dissolution test be performed in the
apparatus specified in the drug monograph (usually Apparatus 2 or
Apparatus 1). The product is first tested with 0.1 N HCl for 2 hours
and then changed to pH 6.8 buffer medium. The buffer stage
generally runs for 45 minutes or for the time specified in the
monograph.
• The objective is that no significant dissolution occurs in the acid
phase (less than 10% for any sample unit), and a specified
percentage of drug must be released in the buffer phase.
Specifications are set in the individual drug monographs.
 Interpretasi Data

Tahap Asam

Jumlah
Tahap Batas Penerimaan
yang diuji
A1 6 Tidak satupun > 10%

Rata2 dari 12 unit (A1+A2) tidak > 10%

A2 6
Tidak 1 unitpun sediaan yang > 25%

Rata2 dari 24 unit (A1+A2+A3) tidak > 10%

A3 12
Tidak satu unitpun > 25%
 Interpretasi Data

Tabel Basa

Jumlah
Tahap Batas Penerimaan
yang diuji
B1 6 Tiap unit tidak kurang dari Q+5%

Rata2 dari 12 unit (B1+B2) adalah ≥ Q

B2 6
Tidak 1 unitpun sediaan yang < Q-15%

Rata2 dari 24 unit (B1+B2+B3) adalah ≥ Q

B3 12 Tidak lebih dari 2 unit sediaan < Q-15%
Tidak satu unitpun < Q – 25%
 UJI KESESUAIAN ALAT
Sebelum melakukan uji disolusi alat harus diuji kesesuaian
menggunakan tablet kalibrator disolusi:
- disintregating type
- non disintegrating type
Kondisi pengujian seperti tertera dalam sertifikat kalibrator .
Alat dinyatakan sesuai jika hasil yang diperoleh berada dalam
rentang pada sertifikat kalibrator
 UJI KESESUAIAN ALAT
Tablet Kalibrator Disolusi USP disintegration Type (LOT O0C056): Tablet
Prednison 10 mg, menggunakan 500 ml air sebagai media disolusi, waktu
30 menit, kadar ditetapkan secara UV spektrofotometri pada λ 242 nm.
Syarat kadar zat terlarut:
53-71% untuk Apparatus 1 pada 50 rpm
27-48% untuk Apparatus 2 pada 50 rpm

Tablet Kalibrator Disolusi USP Non disintegration Type (LOT O): Tablet
Asam Salisilat 300 mg, menggunakan 900 ml dapar fosfat 0,05M pH
7,40±0,05 sebagai media disolusi, waktu 30 menit, penetapan kadar secara
spektrofotometri UV pada λ 296 nm.
Syarat kadar zat terlarut
23-29% untuk Apparatus 1 pada 100 rpm
17-26% untuk Apparatus 2 pada 100 rpm
 Tahapan Uji Disolusi
1. Menyiapkan medium disolusi
2. Membuat kurva kalibrasi ZA  y= bx + a (y= serapan, x = kons)
3. Penetapan kadar sediaan
4. Menyiapkan alat disolusi  pasang alat dan biarkan media disolusi
mencapai suhu 370±0,50C
5. Menjalankan proses disolusi: Masukkan satu tablet/kapsul ke masing-
masing labu disolusi, hilangkan gelembung udara dari permukaan dan
jalankan alat pada kecepatan seperti tertera dalam monografi.
6. Pengambilan sample/contoh pada interval waktu yg ditetapkan pada
daerah yg sudah diatur.
7. Melakukan pengukuran kadar ZA terlarut (dengan spektrofotometer
UV-Vis, HPLC,dll) , jika perlu setelah diencerkan
8. Menetapkan kadar ZA terdisolusi, dengan membandingkan dengan
kadar ZA dalam sediaan

Ct = (y – a)
(b . 1000)
 Uji Pelepasan Obat /
Uji Disolusi Kompendial
Drug Release Test

• Dilakukan untuk mengetahui • Dilakukan untuk mengetahui

kesesuaian disolusi sediaan profil pelepasan ZA dari sediaan
dengan persyaratan kompendial • Pengambilan sample dilakukan
• Pengambilan sample dilakukan 1 beberapa kali pada waktu yang
kali pada waktu yg ditentukan di direncanakan
farmakope
 Drug Release Model

• If a dosage form's dimensions diminish proportionally in such a

manner that the geometric shape of the dosage form stays
constant as dissolution is occurring, then dissolution occurs in
planes that are parallel to the dosage form surface and we use
the Hixson–Crowell cube-root model
Drug Release Model

When a powdered drug is homogeneously

dispersed throughout the matrix of an erodible
tablet, the drug is assumed to dissolve in the
polymer matrix and to diffuse out from the
surface of the device  As the drug is released,
the distance for diffusion becomes increasingly
greater  Higuchi model
Drug Release Model

Drug release from the reservoir dosage

form is considered constant due to
constant membrane thickness of
diffusion layer  Zero order
 Intrinsic Dissolution Method

• Most methods for dissolution deal with a finished drug product.

Sometimes a new drug or substance may be tested for dissolution
without the effect of excipients or the fabrication effect of
processing.
• The dissolution of a drug powder by maintaining a constant
surface area is called intrinsic dissolution. Intrinsic dissolution is
usually expressed as mg/cm2/min.
• In one method, the basket method is adapted to test dissolution of
powder by placing the powder in a disk attached with a clipper to
the bottom of the basket.
 Intrinsic Dissolution Test

Wood’s Apparatus
 Intrinsic Dissolution Test
Nelson Constant Surface Method

Dissolution
medium
Rotating
Paddle
Harden wax
or paraffin Tablet surface
 Penutup

• Uji Disolusi adalah uji biofarmasetik yang penting untuk

menjamin efektifitas obat. Parameter ini mempunyai
korelasi yang lebih baik dengan profil farmakokinetik obat
in vivo, dibandingkan dengan uji waktu hancur.
• Untuk mendapatkan hasil uji yang valid dan dapat
dipercaya, perlu diperhatikan faktor yg berhubungan
dengan lingkungan uji antara lain: pengadukan, pH media
disolusi, suhu dan gas terlarut yang terdapat dalam media
disolusi.
THANK YOU