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Prodi Farmasi UMY

14 Februari 2018
 Sediaan steril berupa salep, larutan atau suspensi, yang
penggunaannya di mata dengan jalan meneteskan, mengoleskan
pada selaput lendir mata di sekitar kelopak mata dan bola mata
 Steril
 Isotonis dengan air mata
 Isohidris dan tidak iritan
 Untuk larutan harus jernih
 Bebas partikel asing
 Cairan (Single and Multiple Dose)
- Larutan
- Suspensi

 Salep mata
1.Tetes Mata : larutan/suspensi steril
mengandung satu/ bbrp obat dlm air/minyak
2.Salep Mata : sed.semisolid steril, homogen,
mengandung satu/bbrp obat→ /eyelid margin
3.Eye lotions : larutan dalam air steril digunakan
(undiluted) for washing or bathing the eyes
4.Contacs lens products : Larutan dalam air steril
digunakan untuk the cleaning, disinfection ,
storage and wetting of contacts lens
-bacterial,fungal and viral infections of the eye or eyelids

-allergic or infectious conjunctivitis or inflammation

-elevated intraocular pressure and glaucoma

-dry eye due to inadequate production of fluids bathing the eye

* Normal volume of tear fluid : 7-8 µl


*Not blink 30 µl
*Blink 10µl
*A single drop of an ophthalmic sol./susp.,50µl(20drops/ml)
*Eye capacity , 5 – 10 µl
Decreased frequency of dosing,
Increased Ocular retention time and Greater Bioavailability are achieved by
formulations that extend corneal contact time, such as :
*gel systems, *liposomes, *polymeric drug carriers, *Ophthalmic suspensi &
emulsi.

Gels(using viscosity-increasing agents to increase corneal contact time):


1.Pilocarpine( Pilopine HS Gel,Alcon) employs Carbopol 940
2.Timolol maleat(Timoptic-XE,Merck),employs gellan gum(Gelrite) which
forms a gel upon contact with the precorneal tear film.
Anesthetics :tetracaine,cocaine,proparacaine
(to provide pain relief preoperatively,postoperatively,for ophthalmic
trauma, and during ophthalmic examination )

Antibiotic and antimicrobial agents:


(systemically and local to combat ophthalmic infection)
the agents used topically: gentamicin, sulfacetamide,tetracycline,
ciprofloxacin,ofloxacin,kloramfenicol,polymyxin B-bacitracin, and
tobramycin.

Antifungal agents : used topically against fungal endophthalmitis and fungal


keratitis are : amphotericin B, natamycin and flucytosine
Anti-inflammatory agents:to treat inflammation of the eye,as allergic conjunctivitis
*the topical anti-inflammatory steroidal agents: fluorometholone,
prednisolone,dexametasone salt.
*Nonsteroidal anti-inflammatory agents :diclofenac,flurbiprofen, ketorolac ,and
suprofen
Antiviral agents : against viral infections, as that caused by herpes simplex virus,(topically :
trifluridine,idoxuridine and vidarabine )
Astringents: treatment of conjunctivitis,( Zinc sulfate, solution)
Beta-adrenergic blocking agents :-treatment of intraocular pressure and chronic open-angle
glaucoma( betaxolol HCl & timolol maleate)
Miotics and other glaucoma agents:
Miotics : treatment of glaucoma,accomodative esotropia, convergent strabismus, and for local
treatment of myasthenia gravis( pilocarpine, echothiophate iodide, demecarium bromide)
Treatment of glaucoma(carbonic anhydrase inhibitors: acetazolamide(oral))
Beta-blockers, such as timolol, and an ester prodrug analogue of prostaglandine F2a
(lanatoprost)
Mydriatics and cycloplegics : dilating the pupil. Mydriatics having a long duration of
action are termed cycloplegics.
(Atropine,scopolamine,homatropine,cyclopentolate,phenylephrine,
hydroxyamphetamine,tropicamide).
Protectants and artificial tears : Solutions employed as artificial tears
or as contact lens fluids to lubricate the eye
Contain agents such as: CMC,MC,HPMC and PVA.
Vasoconstrictors and ocular decongestants :
Vasoconstrictors applied topically to the mucous membranes of the
eye cause transient constriction of the conjunctival blood vessels.
They are intended to soothe, refresh and remove redness due to
minor eye irritation.(naphazoline,oxymetazoline and
tetrahydrozoline hydrochlorides)
Antihistamines,such as pheniramine maleate,are included in some
products to provide relief of itching due pollen,ragweed, and animal
dander.
 Adalah larutan dalam air atau minyak,
atau suspensi yang digunakan dengan
cara meneteskan ke lapisan conjunctiva
 Termasuk juga cairan irigasi untuk
membersihkan mata
 Tetes mata dapat berisi antara lain:
 antibakteri (antibiotik)
 antiinflamasi (corticosteroid)
 midriatikum
 anestesi lokal
 miotic, dll
PHARMACEUTICAL REQUIREMENTS
The preparation of solutions and suspensions for ophthalmic
use requires special consideration with regard to sterility,
preservation, isotonicity, buffering,viscosity, ocular
bioavailability, and packaging

 STERILITY AND PRESERVATION


Ophthalmic solutions and suspensions must be sterilized for safe use.
Although it is preferable to sterilize ophthalmics in their fi nal containers
by autoclaving at 121°C (250°F) for 15 minutes, this method sometimes is
precluded by thermal instability of the formulation. As an alternative,
bacterial fi lters may be used. Although bacterial filters work with a high
degree of effi ciency, they are not as reliable as the autoclave
In practice, the isotonicity limits of an ophthalmic
solution in terms of sodium chloride or its osmotic
equivalent may range from 0.6% to 2.0% without
marked discomfort to the eye.
Sodium chloride itself does not have to be used to
establish a solution’s osmotic pressure. Boric acid in
a concentration of 1.9% produces the same osmotic
pressure as does 0.9% sodium chloride. All of an
ophthalmic solution’s solutes, including the active
and inactive ingredients, contribute to the osmotic
pressure of a solution.
pH Sediaan Ophthalmic disesuaikan dan di Buffer dengan tujuan :
a.for greater comfort to the eye
b.to render the formulation more stable
c.to enhance the aqueous solubility of the drug
d.to enhance the drug’s bioavailability ( i.e; by favoring unionized
molecular species ),and
e.to maximaze preservative efficacy

The pH of normal tears ± 7,4


Tears have some buffer capacity
Kebanyakan obat Ophthalmic bersifat asam lemah dan hanya
memiliki sedikit buffer capacity
Viscosity and Thickening Agents :
Viscosity is a property of a liquids related to the resistance to flow
The reciprocal of viscosity is fluidity
Pure water at 20C( 68F) 1 centipoise ( 1.0087 cp )
Ethyl alcohol 1,19 cp
Olive oil 100,00 cp
Glycerin 400,00 cp
Castor Oil 1000,00 cp
 Tetes mata dengan pembawa minyak antara
lain digunakan:
 castor steril
 Mikroorganisme yang sering ditemukan
(kontaminant) pada sediaan tetes mata
antara lain :
 Pseudomonas aeruginosa (paling sering)
 Staphylococus aureus
 Proteus vulgaris
R/ Obat/bahan aktif
Bahan Pembawa
Bahan Tambahan

a. Antimikroba/Preservatives
b. Peng-isotonis
c. Viscositay and Thickening Agents
d. pH-Buffer
e. Stabilizer
 Ketorolac Tromethamine 5mg/ml Bahan aktif
 Benzalkonium chloride 0,1 mg/ml Preservative
 Sodium chloride 1 mg/ml Isotonisitas
 Disodium EDTA 7,9 mg/ml Chelating agent
 Hydrochloric Acid Adjust pH Asam
 Sodium Hydroxide Adjust pH Basa
 WFI
Syarat Bahan Tambahan :
1. Kompatibel ( fisika, kimia, terapi ) dengan Obat dan
Zat tambahan lain

2. Kompatibel dengan wadah/pengemas

3. Tidak dipengaruhi metoda sterilisasi yang digunakan

4. Non-toxic dan Non-iritan pada jaringan mata

5. Efektif pada konsentrasi yang digunakan


( product tetap stabil dalam penyimpanan sampai
dipakai)
1. Obat / Zat Aktif, misal : antibiotik, corticosteroid

2. Bahan Pembawa:
a. Air
 Larutan (bebas partikel)
 Suspensi (Serbuk sangat halus)
b. Minyak
 Castor oil
 Sesame Oil (Tetrasiklin HCl Suspensi)

3. Bahan Tambahan / Adjuvants, berfungsi:


a. Mempertahankan sterilitas
b. Menyesuaikan tonisitas
c. Viskositas
d. Menyesuaikan / menstabilkan pH
e. Menaikkan kelarutan obat
f. Menstabilkan sediaan
a. Antimikroba / preservative
 Untuk tetes mata multiple dose
 Untuk tetes mata single dose (dalam
operasi mata) tidak mengandung
preservative
 Contoh preservative :
 Benzalkonium chlorida 0,004 – 0,01%
 Chlorhexidine acetate 0,01%
 Chlorbutol 0,5%
 Garam phenil mercuri 0,002%
 Thiomersal 0,005%-0,01%
 Benzyl alcohol
b. Peng-isotonis
 Perhitungan isotonis antara lain dengan :
 NaCl equivalen
 Faktor disosiasi
 Penurunan Titik Beku(PTB/FPD).
 Contoh zat pengisotonis: NaCl
c. Viskositas dan Thickening agent
 Supaya larutan obat dapat kontak lama dengan
mata sehingga dapat menaikkan bioavailability
 Contoh bahan pengental (Viscositas)
 Cellulose derivate (MC = Metil Cellulose, CMC =
Carboxy Metil Selulose, HPMC = Hidroxy Propil
Metilselulose)
 Polyvinyl alcohol
d. pH-Buffer
 Menaikkan stabilitas
 Menambah kenyamanan pada mata
 Menaikkan efek terapi
 Contoh buffer yang dapat dipakai:
 Buffer borate (Boric acid / Borax)
 Buffer fosfat (Sodium acid phosphate / sodium
phosphate)
 Buffer citrate (asam sitrat / sodium sitrat)
e. Stabilizer
 Mencegah oksidasi (menaikkan stabilitas)
 Contoh antioksidant:
 Sodium metabisulfite (pH asam)
 Sodium bisulfite (pH intermediate)
 Sodium sulfite (pH alkalis)
 Theoretically, a hypertonic solution added to the body’s system will have
a tendency to draw water from the body tissues toward the solution in an
effort to dilute and establish a concentration equilibrium. In the blood
stream, a hypertonic injection can cause crenation (shrinking) of blood
cells; in the eye, the solution can draw water toward the site of the topical
application. Conversely, a hypotonic solution may induce hemolysis of
red blood cells or passage of water from the site of an ophthalmic
application
 through the tissues of the eye.
 Faktor fisiologis
Kondisi kornea dan Conjunctive
 Faktor fisiko kimia
- Tonisitas
- pH
- Konsentrasi bahan aktif
- Viskositas
- Surfaktan
 Tekanan osmosis air mata : 0,9% b/v NaCl dalam Air
 Tetes mata dan salep mata dapat tertekan keluar karena
gerakan pelupuk mata
 Untuk salep mata pelepasan bahan aktif dipengaruhi
kelarutan dan ukuran partikel bahan aktif
 Perlu peningkatan viskositas  distribusi dan waktu
kontak. Perlu penambahan PVP, HPMC atau PVA
 Sebisa mungkin bahannya hidrofil
Tiga tahapan pembuatan:
1. Pembuatan larutan
 Bahan pembawa harus disiapkan sebelum
ditambah zat aktif
 Ditambah preservative, antioksidan, buffer
 pH disesuaikan sebelum  “Final Volume”
2. Penjernihan larutan
 Disaring  bebas partikel
 Suspensi  bahan pembawa (air, minyak)
disaring sebelum zat aktif disuspensikan
3. Pengisian dan sterilitas
 Diisikan ke dalam wadah akhir  STERILISASI
 Sterilisasi yang digunakan:
a. Autoclave, 115C, 30’ atau 121C, 15’
b. Pemanasan dengan bactericide 98-100 der.Celc., 30’
c. Filtrasi
 Teknik aseptis (zat aktif, wadah, pelarut  steril)
 Di ruang kelas I (Laminar Air Flow)
 Filter 0,22 µm
 Aseptik:
 Ruangan (kelas I, LAF)
 Alat-alat steril
 Zat aktif steril
 Bahan pembawa (pelarut) steril
 Wadah steril
 Proses (pembuatan sediaan  pengisi terjaga stabil)
d. Metode lain:
 Sterilisasi panas kering (untuk non-aquaeous)
 Ionizing radiation (untuk heat-labile drugs)
Sterilisasi bahan baku dan bahan kemas
Oven : 120C 2 jam/150C 1 jam
Autoclaf : 121C 15-30 mnt
Bahan aktif dicampur/mixing
Filling
 Kebersihan  Aseptis(kontaminasi dan partikel
asing)
 Formula (Bahan baku dan bahan kemas)
 Teknologi
 Sarana dan prasarana  Desain dan kualitas
Pemilihan metode Sterilitas antara lain:
 Stabilitas terhadap panas
 Bentuk sediaan

Container (Wadah):
 Melindungi isi
 Inert (tidak bereaksi dengan isi)
 Bebas partkel
 Tahan proses sterilisasi

Tipe wadah: Single dose, multiple dose


Komponen wadah : plastik, gelas (+ karet)
EYE OINTMENTS
-therapeutic
-diagnostic
OBAT – OBAT yang digunakan :
-antimikroba ( antibakteri , antiviral )
-corticosteroids
-non-steroidal anti-inflammatory agents
-mydriatic
* Simple Eye Ointment BP 1988

Syarat – syarat Eye Ointment ( EO ):


-Steril
-Bebas partikel( asing )
FORMULATION of EYE OINTMENT
- Bases
-Adjuvants
Bases : -parafin
-wool fat
-yellow soft paraffin
Contoh Alifatic alcohol :- cetyl dan stearyl alcohl

* cholesterol dan beeswax , sering digunakan untuk mengganti


wool fat ( mempermudah pencampuran dengan air )
Adjuvant :
-antimikroba
-antioksidan
-stabilizing agent
Containers for eye ointments : - metal or plastic
Preparation of Eye Ointments
- Aseptic Techniq
-Sterilisasi : Ionizing Radiation

Preparation, Clarification and Sterilisation of Eye ointment basis


Labelling

Eye LOTIONS
Formulation

Containers and Labelling

CONTACT LENS PRODUCTS


-TRADITIONAL CORNEAL DELIVERY SYSTEMS
-ADVANCED CORNEAL DELIVERY SYSTEMs
* Gels
-pilocarpine 9 Carbopol 940 )
* Ocular Inserts
( Ophthalmic Inserts : Lacrisert – Merck ).
* Pilocarpine Insert ( Hydroxy propyl cellulose)
* Particulate(Nanoparticles dan Microparticles)
*Mucoadhesive Polymer
*Liposomes
*Ocular Iontophoresis
Contact Lenses and Care and Use Solutions
1.Hard Contact Lenses
- provide durability and clear, crisp vision
-made of a rigid plastic resin(polymethylmetacrylate/PMMA)
-7 to 10 mmФ,cover only part of the cornea
-PMMA lenses are practically impermeable to oxygen and
moisture
2.Soft contact lenses
-made of hydrophilic transparent plastic(hydroxyethyl
methacrylate/HEMA, with small amount of cross-lingking
agents that provide a hydrogel network )
-13 to 15 mmФ, cover the entire cornea
-contain 30 to 80% water, enables enhanced permeability to
oxygen
-less durable than hard contact lenses
- 2 types : a.daily wear and b.extended wear
3.Disposable Soft lenses

*Rigid gas permeable (RGP) contact lenses


-take advantage of feature of both soft and hard lenses
-oxygen permeable but hydrophobic

CARE of CONTACT LENSES


a.cleaning solution
b.soaking solution
c.wetting solution
d.mixed-purpose solutions
Products for Soft Contact Lenses
1.Cleaners
2.Rinsing and Storage solutions
3.Disinfection and Neutralization

Product for Hard Contact Lenses


1.Cleaners
2.Soaking and Storage solutions
3.Wetting solutions
4.Combination solutions

Product for RGP Contact Lenses


-requires the same general regimen as for hard contact lenses
except that RGP-specific solutions must be used.

Clinical Considerations in the Use of Contact Lenses


Products for Soft Contact Lenses
1.Cleaners
a.surfactants,which emulsify accumulated oils, lipids and
inorganic compounds

b.enzymatic cleaners, which breakdown and remove protein


deposits
The ingredients of Surfactant cleaners including :
* a nonionic detergent,wetting agent, chelating agent, buffer
and preservatives
Enzymatic cleaning( enzyme tablets ).
Enzyme tablets,containing :
*papain,pancreatin, or subtilisin,which causes the
hydrolysis of protein to peptides and amino acids.
2.Rinsing/Storage Splutions
* Saine solutions( neutral pH and Isotonic with human teras ).
a.saline + presevative
b.saline only
3.Disinfection and Neutralization
*Disinfection
- thermal( heat )
- chemical( no heat ) hydrogen peroxide
Thermal disinfection :
* The lenses + saline solution,heated 80 derajat C, 10 menit
Chemical disinfection : Hydrogen peroxide
Untuk mencegah iritasi mata dari sisa peroksida setelah disinfeksi, lensa
dipaparkan dengan salah satu zat penetral:
1.the catalytic type ( an enzyme catalase or a platinum disc)
2.the reactive type(such as sod.pyruvate or sod.thiosulfate)
3.the dilution-elution type.
Products for Hard Contact Lenses
1.Cleaners
* a surfactanc cleaners( solution/gel),….20 second.
2.Soaking/Storage Solution
*Soaking solution
-disinfecting agent(0,01% benzakonium klorida dan
0,01% Na-EDTA)
3.Wetting Solutions
Wetting solutions contain :
- surfactants
- solutions to to facilitate a cushion between the lens
and the cornea and the eyelid.
*a viscosity-inducing agent(HEC)
* a wetting agent(PVA)
*preservatives(benzalkonium-Cl/Na-edetat)
* buff.agent/Salt(to adjust pH & maintain tonist)
4.Combination Solutions
- provide combination effects as
a.cleaning/soaking
b.wetting/soaking
c.cleaning/wetting/soaking

Products for Rigid Gas Permeable (RGP) Contact Lenses


-the same general regimen as for hard contact lenses except that
RGP-specific solution must be used.
Two cleaning methods :
-hand washing ,or
-mechanical washing
Setelah dibersihkan(cleaning), the RGP lenses kemudian dibilas dan
direndam dlm wetting/soaking semalam kmdian paginya gosok/
rubbed dengan lart.wetting/soaking yang baru,baru bisa dipakai(
inserted into the eye)
Clinical Consideration in the Use of Contact Lenses
-soft lenses
-dapat mengabsorpsi obat2 yang digunakan secara topikal
-sed.bentuk salep dan suspensi sukar digunakan
-bentuk salep tdk.hanya mempengaruhi penglihatan tp juga
menyebabkan discoloration pada contact lens.
-solusi : digunakan sed.bentuk larutan atau penggunaan soft
lens ditunda sampai pengobatan selesai
Beberapa obat yang digunakan via berbagai diketahui sampai
cairan lacrimal dan terjadi interaksi drug-contact lens, misal :
1.orange staining by rifamfisin
2.lens clouding by ribavirin
3.ocular imflammation by salicylates
4.refrctive changes by acetazolamide
Lens tidak boleh disimpan dalam Tap water atau saliva
Penggunaan cosmetic harus hati-hati bagi pengguna contac lens.
FORMULATION OF TYPICAL OPHTHALMIC SUSPENSIONS and OINTMENTS
(Pharm.Dosage Forms: Disp.Syst. Vol 2, 387-397 )
A.SUSPENSION
A.Prednisolone Acetate Ophthalmic Suspension
Prednisone acetate,micronized 1.0%
Benzalkonium chloride(preservative) 0.01%
Disodium edetate(chelating agent) qs
Phosphate buffer qs
HPMC(viscosity-increasing agent) qs
Polysorbate 80(dispersing agent) qs
Sodium chloride(osmolality-adjusting agent) qs
Sodium hidroxyde( to adjust pH) qs
and /or Hydrochloric acid(to adjust pH) qs
Purified water qs 100 ml
GELS

B.PILOCARPINE GEL
Pilocarpine hydrochloride 4.0%
Benzalkonium choride(preservative) 0.008%
Disodium edetate(chelating agent) 0.2%
Carbomer 940 (gelling agent ) 20%
Sodium hydroxide(to adjust pH) qs
And /or
Hydrochloric acid( to adjust pH) qs
Purified water ad 100 ml
OINTMENTS

GENTAMYCIN OPHTHALMIC OINTMENT


Gentamicin sulfate( as Gentamicin base ) 0.3%
Methylparaben(preservative) 0.05%
Propylparaben(preservative) 0.01%
White petrolatum ad 100 g
TABLE. SOME SODIUM CHLORIDE EQUIVALENTS
SUBSTANCE MOLECULAR WEIGHT IONS i SODIUM CHLORIDE
 EQUIVALENT
Atropine sulfate.H2O 695.0 3 2.6 0.12
Benzalkonium chloride 360.0 2 1.8 0.16
Benzyl alcohol 108.0 1 1.0 0.30
Boric acid 61.8 1 1.0 0.52
Chlorobutanol 177.0 1 1.0 0.18
Cocaine hydrochloride 340.0 2 1.8 0.17
Ephedrine sulfate 429.0 3 2.6 0.20
Epinephrine bitartrate 333.0 2 1.8 0.18
Ethylmorphine hydrochloride.2H2O 386.0 2 1.8 0.15
Naphazoline hydrochloride 247.0 2 1.8 0.27
Physostigmine salicylate 413.0 2 1.8 0.14
Pilocarpine hydrochloride 245.0 2 1.8 0.24
Procaine hydrochloride 273.0 2 1.8 0.21
Scopolamine hydrobromide.3H2O 438.0 2 1.8 0.13
Tetracycline hydrochloride 481.0 2 1.8 0.12
Zinc sulfate.7H2O 288.0 2 1.4 0.16
ISOTONIC SOLUTIONS PREPARED FROM COMMON OPHTHALMIC DRUGS

DRUG (1.0 G) VOLUME OF ISOTONIC


SOLUTION (mL)

 Atropine sulfate 14.3


 Boric acid 55.7
 Chlorobutanol (hydrous) 26.7
 Cocaine hydrochloride 17.7
 Colistimethate sodium 16.7
 Dibucaine hydrochloride 14.3
 Ephedrine sulfate 25.7
 Epinephrine bitartrate 20.0
 Eucatropine hydrochloride 20.0
 TABLE 17.2 ISOTONIC SOLUTIONS PREPARED FROM COMMON OPHTHALMIC DRUGS
 DRUG (1.0 G) VOLUME OF
ISOTONIC
SOLUTION (mL)
 Fluorescein sodium 34.3
 Homatropine hydrobromide 19.0
 Neomycin sulfate 12.3
 Penicillin G potassium 20.0
 Phenylephrine hydrochloride 35.7
 Physostigmine salicylate 17.7
 Physostigmine sulfate 14.3
 Pilocarpine hydrochloride 26.7
 Pilocarpine nitrate 25.7
 Polymyxin B sulfate 10.0
 Procaine hydrochloride 23.3
 Proparacaine hydrochloride 16.7
 Scopolamine hydrobromide 13.3
 Silver nitrate 36.7
 TABLE. ISOTONIC SOLUTIONS PREPARED FROM COMMON OPHTHALMIC DRUGS
DRUG (1.0 G) VOLUME OF ISOTONIC
SOLUTION (mL)
 Silver nitrate 36.7
 Sodium bicarbonate 72.3
 Sodium biphosphate 44.3
 Sodium borate 46.7
 Sodium phosphate (dibasic,
 heptahydrate)
 32.3
 Streptomycin sulfate 7.7
 Sulfacetamide sodium 25.7
 Sulfadiazine sodium 26.7
 Tetracaine hydrochloride 20.0
 Tetracaine hydrochloride 20.0
 Tetracycline hydrochloride 15.7
 Zinc sulfate 16.7
 FIGURE . Sterilization by fi ltration. The preparation of
 a sterile solution by passage through a syringe affi xed with a
 microbial fi lter. (Courtesy of Millipore Corporation.)
 Kadar  Stabil 3 bln
 pH 7,4 3 month
 Viscosity < 0,1 poise
 Particle size  Microscopic ->
<20 particle 25 μM
<10 particle 50 μM
None 100 μM  3 Month
 Sterilisitas  7 days at 37C
 Stability  3 month at 27C no aglomeration
Labelling :
Identitas produk
Petunjuk penyimpanan
ED
Peringatan
Volume sediaan
Petunjuk penggunaan
FIGURE.Examples of sterilizing filters.(Courtesy of Millipore Corporation.)
 (bacterial fi ltration equipment that may be used in the extemporaneous
preparation of ophthalmic solutions)
谢谢