FORMULASI

DAN
EVALUASI
SEDIAAN
INHALASI /
AEROSOL
Dhadhang Wahyu Kurniawan
Department of Pharmaceutics
School of Pharmacy Universitas Jenderal
Soedirman Purwokerto
 Definisi
 Aerosol adalah bentuk sediaan yang
mengandung satu atau lebih zat aktif dalam
wadah kemas tekan, berisi propelan yang dapat
memancarkan isinya berupa kabut hingga
habis, dapat digunakan untuk obat dalam atau
obat luar dengan menggunakan propelan yang
cocok.
 Propelan adalah bagian bahan dari aerosol yang
berfungsi mendorong sediaan keluar dari
wadah lewat saluran katup sampai habis.
 Propelan juga dapat berfungsi sebagai solven
atau kosolven.

12/7/2020 2
AEROSOL
menurut FI IV

• Adalah sediaan yang dikemas di

bawah tekanan, mengandung zat
aktif terapeutik yang dilepas pada
saat sistem katup yang sesuai
ditekan
• Sediaan ini digunakan untuk
pemakaian topikal pada kulit dan
juga pemakaian lokal pada hidung
(aerosol nasal), mulut (aerosol
lingual), atau paru-paru (aerosol
inhalasi)
 Kandungan, Formula, &
Pewadahan
 Selain mengandung zat aktif, ke dalam
formula aerosol dapat ditambahkan zat
penstabil (pengemulsi, pensuspensi) dan
pelarut pembantu.
 Formula aerosol secara umum terdiri dari
 konsentrat (zat aktif )
 propelan,
 pelarut
 zat penstabil (pensuspensi, pengemulsi)
 Wadah aeosol dapat berupa wadah kaca,
wadah logam, dan wadah plastik.

12/7/2020 4
 • Particle size distribution.
• Uniformity of dose for metered
valve.
Delivery rate
Aerosol
•
• Wetness and temperature of
characteristics: •
the spray
Spray pattern
• Velocity of spray
• Foam density.
• Fluid viscosity.

;
 Propelan

• Adalah bagian aerosol yang umumnya berupa gas cair.

Umumnya propelan adalah:
• Halogenated derivative of hydrocarbons
• Low molecular weight hydrocarbons: butane, pentane
• Compressed gas

Test for propellants

• Vapor pressure
• Density
• Gas chromatography test for purity
• Moisture, halogen, non-volatile residue
▪ An equilibrium is quickly established between that portion of propellant
which remains liquefied and that which vaporizes
▪ The vapor phase exerts pressure in all directions--against the walls of the
container, the valve assembly, and the surface of the liquid phase
▪ It is this pressure that upon actuation of the aerosol valve forces the liquid
phase up the dip tube and out of the orifice of the valve into the atmosphere.

❖ As the propellant meets the air, it immediately evaporates due to the drop
in pressure, leaving the product concentrate as airborne liquid droplets or
dry particles, depending upon the formulation.
❖ As the liquid phase is removed from the container, equilibrium between the
propellant remaining liquefied and that in the vapor state is reestablished.

▪ Thus, even during expulsion of the product from the aerosol package, the pressure
within remains virtually constant, and the product may be continuously released at
an even rate and with the same propulsion.
▪ However, when the liquid reservoir is depleted, the pressure may not be
maintained, and the gas may be expelled from the container with diminishing
pressure until it is exhausted.
 Features of the Aerosol Dosage Form
Some features of pharmaceutical aerosols that may be considered advantages over
other types of dosage forms are as follows:
1. A portion of medication maybe easily withdrawn from the package without contamination
or exposure to the remaining material.
2. By virtue of its hermetic character, the aerosol container protects medicinal agents
adversely affected by atmospheric oxygen and moisture.
• Being opaque, the usual aerosol container also protects drugs adversely affected by light.
• If the product is packaged under sterile conditions, sterility may also be maintained during the
shelf-life of the product.

3. Topical medication may be applied in a uniform, thin layer to the skin, without touching the
affected area.
• Reduce the irritation
• The rapid volatilization of the propellant also provides a cooling, refreshing effect.
Some features of pharmaceutical aerosols that may be considered advantages over
other types of dosage forms are as follows:
4. By proper formulation and valve control, the physical form and the particle size of
the emitted product may be controlled which may contribute to the efficacy of a
drug.
• Through the use of metered valves, dosage may be controlled.
5. Aerosol application is a “clean” process, requiring little or no “wash-up” by the
user
6. Have an immediate effect and can distributing the medicaments to the certain
tissues of the region.
• Bigger absorption area; abundant blood circulation; smaller resistance of
penetration.
7. Drug can avoid to be destroyed or inactivated by the pH or enzymatic activity of
the stomach or intestines, also can avoid the first pass effect.
 Disadvantages of the pharmaceutical aerosol:

❖ High cost.

❖ Because of the volatility, the propellants has the refrigeration

effect which can irritate the skin.

❖ To certain individuals, who may be sensitive to the propellant

agent and who utilize an inhalation aerosol, the fluorinated
hydrocarbons may exhibit cardiotoxic effects following rapid and
repeated use of the aerosol product.
 Aerosol Systems
TWO-PHASE SYSTEMS
This system is comprised of the liquid
phase, containing the liquefied
propellant and product concentrate,
and the vapor phase.
THREE-PHASE SYSTEMS
This system is comprised of a layer
of water-immiscible liquid
propellant, a layer of highly
aqueous product concentrate, and
the vapor phase.
Emulsion or
suspension
 The Aerosol principle
An aerosol formulation consists of two component parts, the
product concentrate and the propellant

1 The product concentrate is the active 2 the propellant

ingredient of the aerosol combined with the
required adjuncts, such as antioxidants,
surface-active agents, and solvents, to
prepare a stable and efficacious product.
➢ When the propellant is a liquefied gas
or a mixture of liquefied gases, it
frequently serves the dual role of
propellant and solvent or vehicle for
the product concentrate.
➢ In certain aerosol systems, no liquefied
compressed gases, as carbon dioxide,
nitrogen, and nitrous oxide, are
employed as the propellant.
 ➢Chlorofluorocarbons (CFCs)

❑ The most used propellant in aerosol Among the chlorofluorocarbons

products used as propellants in
pharmaceuticals are:
❑ However, these propellants are being
phased out and will be prohibited due to ❖dichlorodifluoromethane,
scientific recognition that they reduce the
❖dichlorotetrafluoroethane,
amount of ozone in the stratosphere,
which results in an increase in the amount ❖trichloromonofluoromethane.
of ultraviolet radiation reaching the earth,
an increase in the incidence of skin cancer,
and other adverse environmental effects.
 How to determine the vapor pressure of a
certain mixture?
Example 1: What is a vapor pressure of a 60:40 mixture of
propane and isobutane. Information on two propellants is as follows:

Property propane isobutane

Molecular formula C3H8 C4H10
Molecular weight 44.1 58.1
Boiling point(℉ ) -43.7 10.9
Vapor pressure(psig@70℉ ) 110 30.4
Liquid density(g/ml @70℉ ) 0.50 0.56
Flash point(℉ ) -156 -117
❖ Assume an ideal solution.
❖ For Raoult’s law, we need to determine the number of
moles of each propellants:

60
n propane = = 1.36 ❖From Raoult’s law, the partial
44.1 pressure exerted by the propane is:

40 n propane
n isobu tane = = 0.69 Ppropane = 
• P propane
58.1 n propane + n isobu tane
1.36
= 110 = 72.98 psi
1.36 + 0.69
❖The partial pressure exerted by the isobutane is:
n isobu tane 
Pisobu tane = • Pisobu tan e
n propane + n isobu tane
0.69
=  30.4 = 10.23 psi
1.36 + 0.69
❖The vapor pressure exerted by both gases, PT, is:
Dalton’s PT=72.98+10.23=83.21psi at
law 70℉
❖ The vapor pressure required for a specific application
can be calculated in a similar manner and different
ratios of propellants may be used to obtain that pressure.
 Pressurized containers
Various materials have been used in
the manufacture of aerosol containers,
including:
• glass, uncoated or plastic coated;
• metal, including tin-plated steel,
aluminum, and stainless steel;
• plastics
The selection of the container for an
aerosol product is based on:
➢ its adaptability to production methods
➢ compatibility with formulation
components
➢ ability to sustain the pressure intended
for the product
➢ the interest in design
➢ aesthetic appeal on the part of the
manufacturer
➢ cost
 Valve assembly
❖ The function of the valve assembly is to
permit the expulsion of the contents of
the can in the desired form, at the desired
rate, and, in the case of metered valves, in
the proper amount or dose.
❖ Among the materials used in the
manufacture of the various valve parts are
plastic, rubber, aluminum, and stainless
steel.
 To regulate the flow of the
therapeutic agent and propellant
from the container.
 Materials used for the
manufacturing of valve should be
inert to the formulations used.
 Plastic, rubber, aluminum, stainless
steel valve components are used.
 Continuous spray valve:
used on topical products.
 Metered-dose valve: must deliver
an accurate dose within specified
tolerance.
 Filling Operations
COLD FILLING & PRESSURE FILLING
❖COLD FILLING
❑ both the product concentrate and the ❑ When sufficient propellant has been
propellant must be cooled to temperatures added, the valve assembly is
of -30℉to -40℉ immediately inserted and crimped into
place
❑ the chilled product concentrate is
quantitatively metered into an equally ❑ Notice:
cold aerosol container
➢ because of the low temperatures required,
❑ the liquefied gas is added, the heavy aqueous systems cannot be filled by this
vapors of the cold liquid propellant process, since the water turns to ice.
generally displace the air present in the
➢ in the process, some of the propellant
container
vapors are also lost
 ❖PRESSURE FILLING

❑ the product concentrate is

quantitatively placed in the aerosol
container
❑ the valve assembly is inserted and
crimped into place
❑ the liquefied gas, under pressure, is
metered into the valve stem from a
pressure burette
❑ Pressure filling is used for most
pharmaceutical aerosols.
❑ It has the advantage over the cold
filling method in that there is less
danger of moisture contamination
of the product, and also less
propellant is lost in the process.
Aerosol (MDI)
• 3 tipe bentuk sediaan untuk saluran
pernafasan, yaitu :
• metered-dose Inhaler (MDIs),
• dry-powder Inhaler (DPI), dan
• nebulizers.
• MDIs adalah sistem yang paling umum
digunakan selama lebih dari 50 tahun.
• Volume produk biasanya 25-100 µm, yang
dikemas dalam wadah kaleng kecil (canister).

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 Keuntungan
• Mudah dibawa (baik untuk
penanganan pada saat kondisi
pernafasan akut misalnya pada
pasien asma)
• Lebih murah
• Tersegel baik dan meminimalkan
oksidasi terhadap bahan
terapeutik dan kontaminasi
mikroba.
• Efektif untuk penanganan
gangguan pernafasan.

12/7/2020 24
 Kerugian

• MDI biasanya mengandung

bahan obat terdispersi dan
masalah yang sering timbul
berkaitan dengan stabilitas
fisiknya.
• Seringnya obat menjadi kurang
efektif.
• Efikasi klinik biasanya tergantung
pada kemampuan pasien
menggunakan MDI dengan baik
dan benar.

12/7/2020 25
 There are two types of MDI formulations:

1. Suspension formulations, in  CFC-containing MDIs contain CFC-12

which micro particulate drug and CFC-11 and sometimes CFC-
114. HFCs 134a and 227.
(typically micronized material) is
 Hydrofluroalkane propellants (HFA
dispersed in a combination of 134a, HFA227.
propellants.
2. Solution formulations, in which
the drug freely dissolves in either
the propellant or a combination of
propellant and an acceptable co-
solvent, typically ethanol.
 Zat aktif (dan eksipien) dicampur dengan sebagian
propelan yang mempunyai titik didih relatif tinggi dan
tekanan uap rendah, seperti
trikloromonofluorometana (23°C dan 89 kPA) pada
atau di bawah 20°C.

Pembuatan Campuran obat/propelan ini selanjutnya diisikan ke

dalam canister (kaleng kecil) dan canister itu kemudian
MDI → berkerut dengan katup/valve terpasang.

Pengisian Propelan yang menguap selanjutnya diisikan ke dalam

tekanan canister melalui valve di bawah tekanan sampai
campuran propelan didapatkan dengan benar.

Meskipun teknik ini mudah, tergantung pada

penggunaan propelan yang menguap sedikit yang titik
didihnya lebih tinggi daripada temperatur dalam area
pencampuran.
12/7/2020 28
Pembuatan MDI →
Pengisian dingin
• Obat (dan eksipien) dan propelan dicampur di
bawah kondisi dingin (sekitar -30°C) dan
diisikan ke dalam canister (yang diikuti kerutan
dengan valve yang terpasang).
• Propelan selanjutnya diisikan ke dalam canister
melalui valve pada temperatur rendah ini
sampai massa yang ditambahkan benar.

12/7/2020 29
Gambar Aerosol Cara Penggunaan
(MDI) Aerosol (MDI)

12/7/2020 30
Contoh Formula:

• Aerosol Inhalasi

12/7/2020 31
 Dry Powder Inhalers (DPI)

• Bentuk sediaan untuk saluran

pernafasan dimana serbuk yang
mengandung bahan terapeutik di
hisap/hirup ke dalam saluran
pernafasan.
• Aliran serbuk aktif saat dihirup
oleh pasien dan penggunaan
propelan tidak dibutuhkan.

12/7/2020 32
 Gambar DPI

12/7/2020 33
DPIs
• Formulasi dan pembuatan serbuk kering
merupakan bagian dari sistem penghantaran obat
secara inhalasi.
• Dispersi serbuk ini terikat secara tertutup
terhadap kinerja perangkat inhaler.
• Penemuan terkini tentang perangkat serbuk
inhaler adalah tercapainya peningkatan efisiensi
dispersi inhaler dan pengurangan resistensi
perangkat serta decoupling dispersi serbuk supaya
dapat memberikan dosis secara akurat dan
fleksibel untuk kebutuhan pasien yang berbeda.

12/7/2020 34
DPIs → Innova™

• The Innova ™ (Inhale Therapeutic Systems, San Carlos, California, U.S.A.)

merupakan inhlaer dosis unit yang didesain untuk penggunaan jangka lama.
• Sistem ini diperkuat dengan bolus tersimpan dari udara yang dikompresi dan
didesain untuk menghasilkan aerosol yang tidak tergantung dari inisiatif pasien.
• Wadah transparan memungkinkan pasien untuk melihat aerosol untuk
mengetahui dosisnya.
• Lebih jauh, perangkat didesain untuk mempunyai kapasitas mengalirkan dan
mengekstrak hingga 90% dosis dari reservoir, meminimalkan limbah, dan
meningkatkan akurasi dan presisi dosis sediaan.

12/7/2020 35
Diagram skematik Innova™ dari Inhale
Therapeutic Systems

12/7/2020 36
DPIs → Solo™

• The Solo™ merupakan perangkat inhaler dosis unit dari Inhale

Therapeutic Systems patient-drive
• Sistem ini kontrol alirannya built-in untuk memaksimalkan
reprodusibilitas dosis terhadap pasien.
• Sistem ini didesain untuk penggunaan jangka pendek dan ketika
diinginkan dosis sediaan dalam jumlah besar.

12/7/2020 37
SkyePharma mDPI
• Merupakan inhaler dosis multi pocket-sized yang dilengkapi fitur dosis
tunggal “intelligent” untuk menghitung dosis yang didispensikan dan
sisanya di dalam inhaler.
• Mekanisme penguncian built-in tidak menghasilkan efek “tailoff”
terhadap dosis terakhir dari inhaler.

12/7/2020 38
Gambar SkyePharma mDPI. (Courtesy of
SkyePharma, PLC, Switzerland)

12/7/2020 39
 • Nebulisasi meliputi
penggunaan energi (gas atau
ultrasonik sistem) pada
NEBULIZER larutan bahan terapeutik dan
menghasilkan tetesan-tetesan
larutan, yang kemudian akan
dihirup oleh pasien melalui
masker.
• Nebulizer umumnya
digunakan untuk penanganan
kondisi akut atau pasien
kesulitan untuk menggunakan
bentuk sediaan saluran
pernafasan lainnya.

12/7/2020 41
 Formulations for Nebulization
•Physicochemical parameters such as pKa, log P,
isoelectric pH (proteins and peptides), and solubility (vs.
pH, ionic strength, buffer, and co-solvent level) are all
important.

•Tonicity and solution pH, though typically regarded as

formulation issues, must be investigated during
preformulation to ensure selection of an appropriate salt
form for development.

•For example, acidic ( pH <2) hypertonic and hypotonic

aerosols have been demonstrated to induce broncho
constriction in asthmatic subjects.
 It is important to profile the solution stability of
the drug candidate as early as possible to identify
the pH of optimum stability.
 The influence of light, oxygen, and trace metals
on compound degradation also needs to be
considered to assess the requirement for
antioxidants (sodium metabisulfite, ascorbic acid,
etc.) or chelating agents (EDTA, citric acid, etc.).
 Inclusion of such agents, though required to
improve the chemical stability, must be weighed
against the potential for adverse effects on the
lung.
 Drug stability in solution should be monitored
using a stability-indicating assay, following stress
storage as a function of elevated temperature.
 As a guide to formulation development,
studies should be undertaken to evaluate
the contribution of candidate excipients,
including preservatives, antioxidants,
chelating agents, co- solvents, and buffers
on compound stability and solubility. This
is particularly important in the development
of suspensions for nebulization.
 Compatibility with packaging components
also needs to be considered as a matter of
priority. Peptides and proteins in particular
are notorious in their ability to adsorb onto
a variety of surfaces, particularly plastic.
 Nebulizers are designed primarily for use with aqueous solutions or
suspensions.
 Typically the drug suspensions use primary particles in the range of 2–
5 microns.
 Pharmaceutical solution technology, consistent with that used for
parenteral products, may be applied to nebulizer solution or
suspension formulation and processing.
 Nebulizer solutions are usually formulated in water, although other co-
solvents, for example, glycerin, propylene glycol, and ethanol, may
be used.
 However, it is important to note that any excipients with possible airway
toxicological implications might compromise a drug product
 Thus, such additional excipients should not be introduced unless
essential and, if so, formulated at the lowest feasible concentration.
 The range of suspending agents in approved products is limited.
 Nebulizer solution pH may be an
important factor in determining
compound physical or chemical stability.
It has been recommended that solution
pH be greater than 5.0, because there is
considerable evidence to show that
bronco constriction is a function of
hydrogen ion concentration.
 Nevertheless, the formulation “buffer
capacity” and “titratable acid content,” in
addition to the nature of the acid
present, are perhaps the most important
factors for nebulizer solutions of greater
than pH 2.0.
 Nebulizer solutions are typically filled
as unit dosages in plastic containers.
The latter uses blow-fill-seal
technology . Thus drug formulation
compatibility with plastics is an
important factor.
 Characterization of any sorption
processes of plasticizer, monomer,
and “extractables” or “leachables” is
critical during long-term product-
evaluation studies.
 Such sterile unit-dose formulations, in
essence, do not require chemical
preservation.
 Contoh Formula:

• Aerosol Foam (Kosmetik/Personal care)

12/7/2020 47
 Why Pulmonary Delivery?
Route Advantages Disadvantages
Oral Safe Unpredictable and slow absorption
Convient Emzymatic degradation
Inexpensive Not localized delivery

Needle Predictable response Requires special training

Rapid absorption Improver administration can lead to embolism
Not localized delivery
Painful
Infection possible
Unpredictible deposition
Inhaled Safe
Convient
Rapid absorption
Localized delivery
The influencing factors of absorption

• The air current of breath: the amount of inspiration and frequency of

breath.
• Particle size: most 5μm, must be smaller than 10μm.
• The features of drug: solubility; molecular weight, oil-solubility (Ko/w),
moisture absorption.
 Testing the Filled Containers
❖The aerosol container is tested under
various environmental conditions for
leaks or weakness in the valve
assembly or container.
❖The valve discharge rate is
determined by discharging a portion
of the contents of a previously
weighed aerosol during a given
period of time and calculating.
❖Aerosols may be tested:
➢for their spray patterns
➢for particle size distribution of the
spray: most 5μm, must be smaller
than 10μm.
➢for accuracy and reproducibility
of dosage when using metered
valves.
 Section 2: Sprays

❖ Sprays may be defined as aqueous or oleaginous

solutions in the form of coarse droplets or as finely
divided solids to be applied topically, most usually to
the nasal-pharyngeal tract or to the skin.

❖ For example: medicinal atomizers, which are employed

for the issuance of a medicated solution to the patient in
the form of fine droplets
 Section 3: Inhalations

❖Inhalations are drugs or solutions of drugs administered

by the nasal or oral respiratory route. The drugs may be
administered for their local action on the bronchial tree
or for their systemic effects through absorption from the
lungs.
❖A unique form of powder administration involves the
inhalation of a micronized powder directly into the lungs
using a special breath-activated device
Preformulation aspects on inhalation drug
delivery system design

Particle Engineering:
• Micronization → 1.0 to 3.0 microns
• Supercritical fluid recrystallization
• Spray-drying
• Controlled precipitation (in which size control could be achieved
and other desirable properties, e.g., extended release of the drug
may be realized)
 Inhalation drug delivery system Design
NEBULIZED DRUG DELIVERY
 In ultrasonic nebulizers, ultrasound waves
are formed in an ultrasonic nebulizer chamber by
a ceramic piezoelectric crystal that vibrates.
 when electrically excited, these set up high-
energy waves in the solution, with in the device
chamber, of a precise frequency that generates
an aerosol cloud at the solution surface.
Schematic of an ultrasonic nebulizer
 The aerosol produced by an air-jet nebulizer is generated
by a completely different principle.
 When compressed air is forced through an orifice, an area
of low pressure is formed where the air jet exists.
 A liquid may be withdrawn from a perpendicular nozzle,
(the Bernoulli effect) to mix with the air jet to form droplets.
 A baffle (or baffles) within the nebulizer is often used to
facilitate the formation of the aerosol cloud.
 Carrier air (oxygen) can be used to generate the “air jet.”
 Alternatively, compressors may be used to generate the
air stream
Schematic of an air-jet nebulizer
It Includes the testing of :
» 1. Propellents
» 2. Valves, Actuator, Dip Tubes
» 3. Containers
» 4. Weight Checking
» 5. Leak Testing
» 6. Spray Testing

14
 Vapor pressure and density of the propellant are
determined and compared to specification sheet

Parameter Tested by
Identification Gas Chromatography
IR spectroscopy
Purity Moisture, halogen, non-volatile
residue determination

15
 Sampling is done according to standard procedures as found in
Military Standars “MIL-STD-105D”
 For metered dose aerosols test methods was developed by
 ‘Aerosol Specification Committee’
 ‘Industrial Pharmaceutical Technical Section’
 ‘Academy Of Pharmaceutical Sciences'

 The object of this test is to determine magnitude of valve

delivery & degree of uniformity between individual valves.
 Standard test solutions were proposed to rule out variation in
valve delivery.

16
Ingredients % w/w Test Solutions ‘A’ Test Solutions ‘B’ Test Solutions ‘C’
Iso propyl myristate 0.10% 0.10% 0.10%
Dichloro difluoro 49.95% 25.0% 50.25%
methane
Dichloro tetrafluoro 49.95% 25.0% 24.75%
ethane
Trichloro - - 24.9%
monofluoro methane
Alcohol USP - 49.9% -
Specific gravity @25c 1.384 1.092 1.388

17
▪ Take 25 valves and placed on containers filled with specific
test solution
▪ Actuator with 0.020 inch orifice is attached
▪ Temperature -25±1°C
▪ Valve is actuated to fullest extent for 2 sec and weighed
▪ Difference between them represents delivery in mg
▪ Repeat this for total 2 individual delivery from each of 25
test units.

soln

Valve Acceptance: Deliveries Limit's

54µL or less 15%
55 to 200 µL 10%
18
 Of 50 delivery

 If 4 or more are outside limits: valves are rejected

 If 3 delivery are outside limits: another 25 valves are teste

Lot is rejected if more than 1 delivery outside the

specification

 If 2 delivery from 1 valve are beyond limits: another 25

valves are tested

Lot is rejected if more than 1 delivery outside specification

19

 Containers are examined for defects in
lining.
 Q.C aspects includes degree of
conductivity of electric current as
measure of exposed metals.
 Glass containers examined for Flaws.
4. Weight Checking
 Is done by periodically adding
tared empty aerosol container to
filling lines which after filling with
concentrate are removed and
weighed.
 Same procedure is used
for checking weight of
Propellents.
20

 It is means of checking crimping of
the valve and detect the defective
containers due to leakage
 Is done by measuring the Crimp‟s
dimension and comparing.
 Final testing of valve closure is done by
passing filled containers through water
bath.
6. Spray Testing
 Most pharmaceutical aerosols are
100% spray tested.
 This serves to clear dip tube of pure
propellant and concentrate
 To check for defects in valves &
spray pattern.
21
A. Flammability & combustibility:
1. Flash point
2. Flash projection

B. Physicochemical characteristics:
1. Vapour pressure
2. Density
3. Moisture content
4. Identification of propellents

22
C. Performance:
1. Aerosol valve discharge rate
2. Spray pattern
3. Dosage with metered valves
4. Net contents
5. Foam stability
6. Particle size determination

D. Biological testing:
1. Therapeutic activity
2. Toxicity studies

23
1.Flash point:
Apparatus: Open Cup Tag Apparatus
Product is chilled to -25°F and test liquids
temperature is allowed to increase slowly
and temperature at which vapors Ignite is
called as Flash Point .

2.Flame Projection:
Product is sprayed for 4 sec
onto flame and exact length
is measured with ruler.

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 Property Method
Vapor pressure - Pressure gauge
- Can puncturing device
Density - Hydrometer
- Pycnometer
Moisture - Karl Fischer method
- Gas Chromatography
Identification of propellants - Gas chromatography
- IR spectroscopy

25
 1. Aerosol valve discharge rate:
 Aerosol product of known weight is discharged for
specific time.
 By reweighing the container, the change in the wt. per
time dispensed is the Discharge rate in gm/sec.

2. Spray pattern:
 The method is based on the
impingement of spray on piece of
paper that has treated with Dye-Talc
mixture.
 The particles that strike the paper
cause the dye to go into solution and
to be adsorbed onto paper giving a
record of spray for comparison
purpose
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 Reproducibility of dosage determined by:
 Assay techniques
 Accurate weighing of filled container followed by dispensing
several dosage.
 Containers are then reweighed and difference in weight
divided by number of dosage dispensed gives average dose.

4. Net Contents
 Tared cans than have been placed onto the filling lines are reweighed
and the difference in weight is equal to the
net contents.
 In Destructive method: weighing a full container and then
dispensing as much of the content as possible.
 The contents are then weighed. This gives the net content
Various Methods:
▪ Visual Evaluation,
▪ Time for given mass to penetrate the foam,
▪ Time for given rod to fall which is inserted
into the foam,
▪ Rotational Viscometer.

6. Particle Size Determination

Methods:
▪ Cascade Impactor,
▪ Light Scattering Decay.

28
Principle:
Stream of particle projected through
a series of nozzle and glass slides
at high velocity, larger particle are
impacted on low velocity stage, and
smaller particle are collected at higher
velocity stage.

b). Light Scattering Decay

As aerosol settles under turbulent condition, the

changes in the light of a Tyndall beam is
measured.

29
1.Therapeutic Activity :
» For Inhalation Aerosols : is depends on the particle size.
» For Topical Aerosols : is applied to test areas &
adsorption of therapeutic
ingredient is determined.

2.Toxicity :
» For Inhalation Aerosols : exposing test animals to vapor
sprayed from Aerosol container.
» For Topical Aerosols : Irritation and Chilling effects
are determined.

30
Referensi:
 Aerosol dan permasalahannya,
http://food_drugs_info.blogspot.com/2005/01/aerosol-atau-erosol-dan.html,
diakses 6 maret 2010.
 Laurier L. Schramm, 2005, Emulsions, Foam and Suspensions, Wiley-VCH
Verlag GmBH & Co., Weinheim.
 David Jones, 2008, Fast Track : Pharmaceutical Dosage Form and Design,
Pharmaceutical Press, London.
 Sarfaraz K. Niazi, 2004, Handbook of Pharmaceutical Manufacturing
Formulations : Liquid Products, CRC Press LLC, Florida.

12/7/2020 75
THANK
YOU…