6. Dispersi Kasar

7/28/2019 6. Dispersi Kasar

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Disperse systems

Definition:- A substance, the disperse (discontinuous) phase, is

dispersed as particles over the dispersion medium

(continuous phase)

- Phases can be solids, liquids or gasses

Disperse phase

(discontinuous phase)

Dispersie medium

(continuous phase)


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Suspensions

Colloids:

Particle size: 1 nm - 1 mm

No sedimentation by Brownian movement

Suspensions:

Particle size: > 1mmSedimentation


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Suspensions

Pharmaceutical suspensions are uniform dispersions

of solid drug particles in a vehicle in which the drughas minimum solubility. Colloidal suspension 1 nm to 0.5 m Coarse suspension 1 to 100 m

May be for oral, ophthalmic, parenteral, or topical use

Oral suspensions may be aqueous preparations withflavored, sweetened vehicles or powder productsfor oralsuspension

Marketed preparations: ready-to-use dry powders which must be reconstituted before

administration


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SUSPENSIONS

Examples of Pharmaceutical Suspensions:

1. Antacid oral suspensions

2. Antibacterial oral suspension

3. Dry powders for oral suspension (antibiotic) 4. Analgesic oral suspension

5. Anthelmentic oral suspension

6. Anticonvulsant oral suspension

7. Antifungal oral suspension


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B. Amsden CHEE 440

Interfacial Phenomena

flocculation or caking determined by forces of attraction (van der Waals)

versus forces of repulsion (electrostatic)

deflocculated repulsion> attraction

affected by [electrolytes]

flocculated

attraction > repulsion


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B. Amsden CHEE 440

Electrical Properties

particles may become charged byadsorption of ionic species present in soln or

preferential adsorption of OH-

ionization of -COOH or -NH2 group

-----

-solid

+++++

+ hydroxyl ion


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B. Amsden CHEE 440

Electric Double Layer

--

----

++

++++

+

-+

+-

+ --

++

-

+-- ++ -

+

+

gegenion

Nernst potential

zeta potential

tightly

bounddiffuse

electroneutralbulk


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Electrical Double Layer

Surface charge

----

-

---+

+

++

Stern layer (fixed)Zeta potential

Nernst potential

Electroneutral solution


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B. Amsden CHEE 440

Electrical Props contd

Nernst potential potential difference between the actual

solid surface and the electroneutral bulk

Zeta potential

potential difference between the tightly

bound layer and the bulk governs electrostatic force of repulsion

between solid particles


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What are colloids? Colloids are particles of a few mm or smaller suspended in

a liquid

Colloids have high surface areas/mass

When working with colloidal systems it is necessary to control:

Stability controlled by:

Surface charges on the particles

pH and/or ionic strength of the dispersing media

Selective adsorption of ions

Particle size

Colloidal Systems


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If all the particles have a

large negative or positivezeta potential, they willrepel each other becauseof electrostatic repulsionforces -- stable dispersion

Negativezeta potential

Positivezeta potential

+30 mV

-30 mV

0 mV

STABLE

STABLE

NOT STABLE

Zeta Potential and Dispersion Stability


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Zeta Potential & Dispersion Stability

If all the particles have a large negative orpositive zeta potential, they will repel each other

because of electrostatic repulsion force ----

stable dispersion

In general, the higher the zeta potential, the morestable the particle dispersion. The dividing lines

for aqueous dispersion is considered to be

>+30mV or


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Desirable Features

particles should settle slowly

formulation should allow the easyredispersion of sedimented particles

a flocculated suspension is desirablethan a deflloculated suspension

a suspension should not be too viscousto reduce the sedimentation rate


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Well Formulated Suspension

Resuspend easily upon shaking

Settle slowly after shaking

Homogeneous mix of drugPhysicallyand chemically stable during its shelf

life

Sterile (parenteral, ocular) Gets into syringe (parenteral, ocular)


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Untuk cairan obat luar :

Produk tersebut harus cukup cair sehingga dapattersebar dengan mudah ke seluruh daerah yangsedang diobati tapi juga tidak boleh sedemikianmudah bergerak sehingga gampang hilang dari

permukaan dimana obat tersebut digunakan Cairan tersebut harus dapat kering dengan cepat

dan membentuk suatu lapisan pelindung yangelastis sehingga tidak akan mudah terhapus

Mempunyai warna dan bau yang nyaman


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Untuk tujuan farmasi :

Kestabilan fisik suspensi didefinisikan sebagaitidak menggumpal tetap terdistribusi merata diseluruh system.

Karena kondisi ini jarang terjadi maka dapatdikatakan, jika partikel-partikel tersebutmengendap, maka partikel-partikel tersebut harusmudah disuspensi kembali dengan sedikit

pengocokan.


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Pengendapan dalam suspensi

Physical stability


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Theory of Sedimentation

The factors involved in the rate of velocity of settlingof the particles in a suspension are best expressed inthe equation of the Stokes law

Stokes equation applies to uniform, perfectly

spherical particles settling in a very dilute suspensionwith no hindrance or turbulance

FACTORS TO BE CONSIDERED Particle size

Density of the vehicle- -polyethylene glycol -polyvinyl pyrolidone -glycerin -sorbitol -sugar.


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Sedimentation rate (1)

Three forces acting on the falling particle:

- gravity (constant, )

- upwards forces (constant, )- friction (increases with increasing speed, )

Equilibrium of forces constant speed


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Stokes Law

= kecepatan akhir

(cm/dt)

d= diameter partikel sdano= kerapatan

fase terdisper danmedium pendispersi

o= viskositas medium

pendispersi (poise)

v Stability

Particles need to comeinto contact (collide) to

coalesce Therefore, higher

concentrations (viasettling) promotecoalescence or caking


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External Forces Acting onParticles

V(-o)g

2-5 mm

Gravity Brownian Movement

Sedimentationequilibrium:Gravity isneutralized byBrownian movement


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Calculations

Determine the absolute viscosity of syrupusing a ball of radius of 0.2 cm. The densityof the ball is 2.33g/cc and the density of thesyrup is 1.33 g/cc at 250 C. The rate of fallingis 4.35 cm/sec.

Determine the velocity of settling of sulfur inwater. The average particle radius is 5.5 m.The density of sulfur and water at 250 C. is1.96 and 0.997 g/c.c., respectively. Theviscosity of water at 250 C. is 0.00895 poise.


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Calculations

If the height of the bottle is 10 cm how longwill it take to completely settle?

Particle size determination:From the previous example, calculate the

average particle size of sulfur.

What is the necessary viscosity to reduce thesedimentation rate from 0.0071 cm/sec to0.00071 cm/sec?


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State Rate of settling Sedimentation

volume

Nature

Flocculated Fast High Porous, easy toredisperse

Deflocculated Slow Low Compact, difficultto redisperse


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Deflocculated suspension Flocculated suspension

- Low sedimentation rate

- Liquid above sediment

remains turbid (particles of< 1 mm do not sediment due

to Brownian movement)

- Sedimentation is build up

from the bottom

- Compact sediment

difficult to redisperse

- High sedimentation rate

- Liquid above sediment is

clear (also particles< 1 mm sediment)

- Sedimentation is build up

from the top

- Loose sediment easy to

redisperse

Deflocculated is also referred to as peptised

Sedimentation behavior


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Deflocculated suspension Flocculated suspension

Structures sediment

o

u

V

VF==Degree of sedimentation:

Original volume

Volume sediment


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Settling and Aggregation

The suspension shall formloose networks offlocksthat settle rapidly, do not

form cakes and are easyto resuspend.

Settling and aggregation

may result in formation ofcakes(suspension) that isdifficult to resuspend orphase separation

(emulsion)

flock

cake


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Sedimentation Volume

V = Vu /V0 ; ideally, V should be equal to 1.0


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Sedimentation

Stokes law:

Take care:

- Wetting particles (contact angle)

- Shape of the particles (compare: parachute)

- High particle concentration

- Non-Newtonian liquids (yield stress)

- Convection by differences in temperature

18d2(s - f)g

v =


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B. Amsden CHEE 440

Formulation of Suspensions

2 common approaches :

1.use of a structured vehicle

caking still a problem

2.flocculation no cake formation

less common approach is to combineabove


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B. Amsden CHEE 440

Controlled Flocculation

electrolytes

most widely used reduce zeta potential

decrease force of repulsion

change pH

bridge formation

alcohol

reduction in zeta potential

surfactants form adsorbed monolayers on particle surface

efficacy is dependent on charge, concentration

ll d l l


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B. Amsden CHEE 440

Controlled Flocculation

polymers

adsorb to particle surface

bridging

viscosity, thixotropy

protective colloid action

most effective

S d hi l


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B. Amsden CHEE 440

Structured Vehicles

pseudoplastic or plastic dispersion

medium

examples

methylcellulose, bentonitenegatively charged

increase viscosity


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B. Amsden CHEE 440

Combined Approach

possibility of incompatibilities of

suspending agent and flocculatingagent

structured vehicles have negativecharge

incompatible if particle carries anegative charge


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Pertimbangan Rheologi

Prinsip rheologi bisa diterapkan untukpenyelidikan dari factor-faktor berikut :

viskositas dari suatu suspensi apabilamempengaruhi pengendapan dari partikel-partikel zat terdispersi

perubahan dalam sifat-sifat aliran dalamsuspensi bila wadahnya dikocok dan dituangdari botol

kualitas penyebaran dari cairan (lotio) biladigunakan untuk suatu bagian permukaanyang akan diobati

pembuatan suspensi


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Emulsions

Dispersed system - two immiscible liquid phases,one of which is dispersed as globules in theother o/w - oleaginous internal phase and an aqueous

external phase

w/o - aqueous internal and an oleaginous externalphase

Microemulsion: Droplets size range 0.01 to 0.1m

Macroemulsion: Droplets size rangeapproximately 5 m.


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dispersion

B phase A phase Emulsion solution

Definition

An emulsion is a dispersion in which the dispersed phase

is composed of small globules of a liquid distributed

throughout a vehicle in which it is immiscible.


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O/W W/O

Types of emulsions

W/O/W O/W/O

Internalphase

Externalphase

oil-in-water water-in-oil

Water in-oil-in-water

Oil-in-water-

in-oil

Internalphase

Externalphase

Basic types multiple


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Types of Emulsion

Oil-in-water emulsion Water-in-oil emulsion

Water

Oil

mm


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Multiple Emulsions

Water-in-oil-in-water emulsion Oil-in-water-in-oil emulsion

Water

Oil

mm


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Instability emulsions

Sedimentation Floating

Combined with coalescence

cracking of breaking

Possibly combined with floccu-

lation (secondary minimum)

Sedimentation Creaming


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Settling & Creaming

Stokes Law

v Stability

Particles need to come into contact(collide) to coalesce

Therefore, higher concentrations(via settling) promote coalescenceor caking


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Schematic of the emulsion breakdownprocesses.


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Contoh Soal

Suatu emulsi o/w mangandung minyakmineral dengan BJ 0,9 terdispers dalam suatufase air yang mempunyai BJ 1,05. Jikapartikel minyak mempunyai diameter rata-

rata 5 m, fase luar mempunyai viskositas0,5 poise berapakah kecepatan creamingdalam cm per hari ?


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Physical Stability -> Phase Separation

Phases separation starts with growth in particle size

Physical contact -> first step in coalescence Flocculation and aggregation

Come together but do not fuse No disruption of interface Surfactants slow process Fusion of particles -> next step

Coalescence Come together & fuse Disruption of interface

Surfactants slow process

Phase separation (final endpoint) Result of continued coalescence


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Surfactants adsorb at interfaces Interfacial energy decreases(interfacial energy: energy required to create new interface)

Improvement stability emulsions

hydrophobic

hydrophilic

oil

water


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Emulsification

Emulsifier


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Theories of Emulsification:

1) Surface Tension Theory:- lowering of interfacial tension.

2) Oriented-Wedge Theory:

- mono molecular layers of emulsifying agentsare curved around a droplet of the internalphase of the emulsion.

3) Interfacial film theory:

- A film of emulsifying agent prevents thecontact and coslescing of the dispersedphase.


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Surfactants and Micelles

Surface active agents have a certain affinity for bothpolar & nonpolar solvents

Amphiphilic nature adsorb at interfaces

At a concentration that is characteristic of eachamphiphile, these molecules will aggregate to producemicelles


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Viscositas dari fase luar dapat ditingkatkan tanpamelewati batas-batas konsistensi yang dapat diterimadengan menambah suatu zat pengental (viscosityimprover atau thickening agent)

Ukuran partikel dari bola-bola bisa dikurangi denganmenghomogenkannya.

Ini merupakan dasar untuk kestabilan terhadap creamingdari corpus yang homogen.


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Stability

Phase Inversion O/W W/O

Change water washable, etc. E.g. divalent salts Ca++, Mg++ in hard water

Inversi juga bisa dihasilkan dengan mengubah perbandingandengan penambahan volume fase internal.


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Sifat Rheologi Emulsi

Kebanyakan emulsi, kecuali emulsi encer,menunjukkan aliran Non Newton

Faktor-faktor prinsip yang mempengaruhi sifat-sifataliran dari emulsi adalah sifat viskositas yangberhubungan dengan fase terdispers, fase kontinu

dan zat pengemulsi


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Pengurangan ukuran partikel rata-rata akanmenaikkan viskositas.

Makin luas distribusi ukuran partikel, makin rendahviskositasnya jika dibandingkan dengan system yangmemiliki ukuran partikel rata-rata serupa tetapi dengandistribusi ukuran partikel yang lebih sempit.

Makin tinggi konsentrasi zat pengemulsi, akan makintinggi pula viskositas produk tersebut.


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Example:

Determine the absolute viscosity of syrup using a

ball of radius of 0.2 cm. The density of the ball is2.33g/cc and the density of the syrup is 1.33 g/cc at250 C. The rate of falling is 4.35 cm/sec.

v = 2r2 (D - d) g/9n

n= 2r2 (D - d) g/9v

= 2 (0.2)(0.2) [2.33 - 1.33] 980/9(4.35)

= 2.0 poise


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If the height of the bottle is 10 cmhow long will it take to completelysettle?

1/x = 7.1*10-3/10

x = 1408 sec = 23.5 appprox. 24minutes

It sediment too fast. Increase viscosityto reduce the sedimentation.


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Particle size determination:

From the previous example, calculate theaverage particle size of sulfur.

v = 2r2 (D - d) g/9n

r2= v9n /2 (D - d) g

= (0.0071)(9)(0.00895)/2(1.96 -0.997)980

r = 5.5*10-4 cm

diameter = 11*10-4 cm


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What is the necessary viscosity to reduce thesedimentation rate from 0.0071 cm/sec to0.00071 cm/sec?

v = 2r2 (D - d) g/9n

= 2r2 (D - d)g/9v

= 2 (5.5*10-4)2 (1.96 - 0.997)(980)/9(0.00071)

= 0.0894 poise

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6. Dispersi Kasar