Nanopharmaceutical Research Group Department of Pharmaceutical Science

Faculty of Pharmacy USB

More than 75 % all materilas are in particulate form

The particles may be solid, liquid and gaseous

Micromeritics is the science of small particles. It is the study of a number

of characteristics, including

paRticle size and size distribution,

shape, angle of repose, porosity, true

volume, apparent density ANd

bulkiness.

Size and surface area can be related

1. The physical, chemical and

pharmacologial of a drug

2. The partile size of a drug can affect

its release from dosage forms

3. The viewpoints a both physical

stability

Size range and number or

weight particles

Shape and surface area

Polydisperse

The sphere thats very easy

Diameter

The degree of asymmetri particles increases

equivalent spherical diameter

ds, dv, dp, dst

n : the number of particle, d : The equivalent diameter p : index size (p 1 = the particle length, p 2 = surface, p 3 = volume. The value of index : p positive ( arithmetic), p negative (harmonic) and p zero ( geometric)

Edmundson Equation

Arithmetic, Geomteric and Harmonic

Average Particle Size

For a colletion particle : ndf, f : frequency index has value 0, 1,2 and 3

The size frequency distribution is expresed total number, length, surface

and volume particle

Particle Size Distribution

The number or weight vs the size range or mean particle size, so called frequency distribution curve. For example (Sinko (2006), Martins Physical Pharmacy and Pharmaceutical Science, p 444)

The following data at above, we can calculate the average diameter of the particles i.e dln, dsn, dvn, dsl dvs and dwm

Mode

Other method to representing the data is to plot cumulative percentage over or under particular size with particle size

Cont..

When the data in Figure 18-2 (taken from Table 18-6) are plotted as frequency versus the logarithm of the particular diameter, a typicall bell-shaped curve. A size distribution fitting this pattern is spoken as a log normal distribution, in contrast to the normal distribution show in Figure 18-1

The logarithm of the particle size vs the cumulative percent frequency on a probability scale

dg/50 : geometric mean diameter

g : geometric standart deviation

g : 50 %

16 % .

g : 50 %

84% .

Number and Weight Distribution

Hatch and Choate Equation

The number distribution can be convert to a weight distribution and vice versa

0,8791

Particle Number

The number of particles per unit weight (N) or therm dvn

Microscopy, sieving, sedimentation , LD, PCS, SEM, TEM and the determination of particle volume

Methods for Determining Particles Size

Cont.. MICROSCOPIC METHOD(OPTICAL MICROSCOPY)

Uses an ordinary microscope for particle measurement in the range of 0.2 m to 100 m.

Presence of agglomeration and particles of more than one component may be detected

The diameter is obtained only from two dimensions: length and breadth, the thickness/depth in not measured.

The microscopic method can include counting not fewer than 200 particles in a single plane using calibrated ocular on a microscope.

Cont..

SIEVING - uses standard sieves; generally used for grading coarser particles. May be employed for screening materials as fine as 44 m (No. 325 sieve)

A carefully weighed sample of the powder is paced on the top sieve, and after the sieves are shaken for a predetermined period of time. The powder retained on each sieves is weighed

Sieving errors can arise : sieve loading, duration and intensity of agitation

US Sieve Standart

Sedimentation Stokes Law

v :

=

2 0

18 0 or dst =

18 0

Spheres fallin freely and at a constant rate

Irregularly shaped particle s as long as diameter is relative particle size equivalent to that of sphere

The particles mus not be aggregated or clumped

Flow of medium dispersion laminar / streamline

MICROMERITICS FACTORS AFFECTING FLOW PROPERTIES

1. PARTICLE SIZE AND SHAPE 250-2000m = free flowing

75 250 m = flow freely or cause problem depending on shape

Very fine particles (less than 10 m) = do not flow freely as large particles

Particle shape and flow properties

Spherical shape flow better than needle particles

Elongated or flat particles tend to pack resulting to high porosity powders

2. POROSITY AND DENSITY High density, low porosity = FREE FLOWING

3. SURFACE ROUGHNESS Leads to poor flow characteristics

BENTUK PARTIKEL DAN LUAS PERMUKAAN

1. BENTUK PARTIKEL Sferis luas permukaan minimum persatuan volume

Luas permukaan = . d2 dan Volume = 3

6

Dengan konstanta perbandingan maka : luas permukaan = s . dp

2 = . ds2

(s : faktor luas permukaan, ds : diameter permukaan ekivalen)

volume = v . dp3 =

2

6

(v : faktor volume, ds : diameter volume ekivalen)

Jadi sferis s = .ds2/dp2 = 3,142 dan v = .dv3/6dp3 = 0,524

2. LUAS PERMUKAAN SPESIFIK

Permukaan spesifik : luas permukaan per satuan volume (Sv) atau persatuan berat (Sw)

Persamaan diturunkan dari persamaan luas permukaan dan volume, untuk partikel asimetris maka :

Sv =

=

. 2

.3

Sv =

n : jumlah partikel

Sw =

: densitas partikel

substitusi Sv pada Sw , maka Sw =

dvs : diameter volume permukaan

Jika sferis atau mendekati sferis, maka Sw = 6

karena bentuk sferis s / v = 6

Contoh.

SIFAT TURUNAN SERBUK

1. POROSITAS

Volume bulk (ruahan) =Vb

Vb Vb

Serbuk tanpa pori-pori internal atau ruang-ruang kapiler, volume ruahan adl vol sebenarnya + vol ruang antara

partikel (vol kosong= v)

v = Vb - Vp

Vp : volume sebenarnya

Porositas/kekosongan () : rasio volume kosong (V) dengan volume ruahan (Vb), dinyatakan dlm persen x 100. Persamaan :

=

= 1 -

2. PENGATURAN SUSUNAN

Serbuk sferis

terapat/rhombohedral = 26%

renggang/kubik/terbuka = 48%

Serbuk sejati/umumnya serbuk farmasi : 30-50%

Serbuk flokulat/agregat : 30-50%

Serbuk kristalin dg tekanan 100.000 lb/inci2 = < 1%

3. DENSITAS PARTIKEL

Densitas () = massa / volume

Volume partikel padat cukup sulit ditentukan karena

1. partikel mengandung retakan mikroskopis

2. pori-pori dalam

3. ruang kapiler

Ada 3 jenis densitas yaitu :

1. Densitas sebenarnya (). Densitas bahan padat sesungguhnya

dimana terdapat pori-pori intrapartikel dan rongga partikel

yg lebih besar dari dimensi molekuler, atom dan kisi kristal.

Alat : densitometer helium

2. Densitas granul (g). Densitas bahan padat yg ditentukan

dengan pemindahan merkuri yg tidak berpenetrasi ke dalam

pori-pori yang lebih kecil dari 10 m.

Alat : densitometer merkuri

3. Densitas ruahan (b). Massa suatu serbuk dibagi dengan

volume ruahan. Volume ruahan diukur dengan gelas ukur

100 ml tanpa diketuk (untapped volume).

Alat : Tap density tester

densitas ruahan dipengaruhi : PSD, bentuk partikel, agegrasi

Jika volume ruahan dihitung setelah dilakukan ketukan (tapped) disebut densitas mampat/Bj mampat/ tapped density. Standar ketukan adalah 10, 500 dan 1250 ketukan

Tapped density (Bj mampat) =

Porositas intrapartikel (ip). Dihitung dengan mengetahui

densitas sebenarnya dan densitas granul.

inrapartikel = 1 -

= 1-

Porositas antarruang/porositas kosong (k). Vol relatif bagian kosong antarruang terhadap vol ruahan serbuk. Dihitung jika densitas ruahan dan densitas granul diketahui

antarruang= 1 -

= 1-

Porositas total (total). Serbuk berpori tersusun dari bagian kosong antara partikel dan juga pori-pori. Sehingga total :

total =

= 1 -

(Vb : vol bulk, Vp : vol bhn padat)

Dimana Vp = w/ dan Vb = w / b (w : berat/massa serbuk) Substitusi kedua persamaan diatas diperoleh porositas total sbb:

total = 1 -

atau total 1 -

4. KERUAHAN

Merupakan ukuran volume ruahan dan kebalikan densitas

ruahan. Keruahan meningkat dengan bertambahnya ukuran

suatu partikel.

5. SIFAT ALIRAN

Dipengaruhi : ukuran partikel, bentuk partikel, tekstur suatu

partikel dan densitas.

Partikel fine dg ukuran 1-10 m sifat aliran jelek karena gaya

kohesi antara partikel besar atau sama dengan gaya gravitasi.

Kelembaban juga menyebabkan sifat aliran berkurang.

Serbuk dgn densitas tinggi dan porositas dalam rendah akan

lebih mudah mengalir

Tekstur permukaan yg tdk rata /kasar menyebabkan terjadi

gesekan dan perlekatan shg serbuk tdk mengalir bebas.

6. SUDUT DIAM/SUDUT ISTIRAHAT ( = phi)

Sudut maksimum antara permukaan gundukan serbuk dan bidang horisontal. Sebagai fungsi gaya gesek antar partikel yg menghasilkan permukaan dengan sudut berada dala kesetimbangan dg gaya gravitasi .

Tangen sudut diam = koefisien gesekan ()

tan = atau tan = h/r

(h tinggi serbuk, r : jari-jari gundukan serbuk) Sudut diam kecil serbuk mudah mengalir dan sebaliknya.

Semakin kasar/tidak beraturan permukaan partikel , semakin

besar sudut istirahat maka sifat aliran semakin menurun.

Thank you Dreams and Endeavors