Physical Testing

1
Physical Testing

1. Solutions
2. Disperse systems
3. Aerosols
4. Powders
5. Tablets
6. Sustained release products
7. Coated tablets
8. Hard soft shell capsules
9. Microcapsules

2
Physical Testing
a. coated beads and granules b. erosion
tablets c. insoluble matrices d. osmotic
pump e. gel forms
Sustained release products
3
Coated beads and granules
Sugar crystal
Drug in sugar matrix
film
Semi-permeable
Impermeable soluble filler
4
Coated beads and granules
Dissolution medium
Saturated drug solution
5
Coated beads and granules
There are three stages in the dissolution
0 lt t lt ti penetration of medium into the
pellet, ti is the time it takes for this to
complete (lag time)
ti lt t lt tf dissolution takes place under
constant conc. gradient (drug solubility in the
medium) tf is the time where all drug inside is
dissolved but not yet diffused
t gt tf slow dissolution It is difficult to get
the last 5-10 of drug to release
6
Coated beads and granules
Factors affecting dissolution

1. Film thickness

Thin coat
Thick coat
7
Coated beads and granules
Factors affecting dissolution

1. Film thickness
2. Amount of soluble filler in the film

? filler
? filler
8
Coated beads and granules
Kinetics of dissolution
?
?
M mass not dissolved, Mo total dose, K
dissolution constant, ti lag time
9
Coated beads and granules
Kinetics of dissolution
M mass not dissolved, Mo total dose, K
dissolution constant, ti lag time
10
Coated beads and granules
Stability of dissolution profile on storage
(during stability program)
Tracing of k and ti at different time intervals
Calculating Similarity Factor
It is a logarithmic reciprocal square root
transformation of the sum squared error
11
Coated beads and granules
Stability of dissolution profile on storage
(during stability program)
Tracing of k and ti at different time intervals
Calculating Similarity Factor
Where Rt and Tt are the cumulative percent of
drug released for reference and test assay at
time t, respectively, n is the number of time
points. Generally, a value of f2 close to 100
(range 50100) ensure sameness between the
profiles.
12
Coated beads and granules
Stability of dissolution profile on storage
(during stability program)
Tracing of k and ti at different time intervals
Calculating Similarity Factor
Accelerated testing is not of much use
13
Erosion tablets
Tablets made of substances which does not
dissolve or disintegrate but erode away (eg. Waxy
substances).
Non-eroded (undissolved drug)
Eroded portion (dissolved drug)
14
Erosion tablets
Factors affecting dissolution

1. Substance type
2. Drug to substance ratio
3. Tablet dimensions

15
Erosion tablets
Dissolution Kinetics
Hixon-crowel
M mass not dissolved, Mo total dose, Ke erosion
constant, ti time required for tablet wetting
16
Erosion tablets
Stability of dissolution profile on storage
(during stability program)
Tracing of ke and ti at different time intervals
Calculating Similarity Factor
Accelerated testing is not of much use
17
Insoluble matrices
Tablets made of porous insoluble matrix
Factors affecting dissolution

1. Surface area through which diffusion takes place
2. Drug loading
3. Porosity

Inherent
Created by dissolved drug (A/?)
A Drug dose, ? drug density
Some tablets are not porous but depend on the
dissolution of the drug to create porous network
18
Insoluble matrices
Dissolution Kinetics
Dissolution occurs by diffusion from the
insoluble matrix and the release rate is given by
Higuchi square root law
19
Insoluble matrices
Stability of dissolution profile on storage
(during stability program)
Tracing of ki and ti at different time intervals
Calculating Similarity Factor
Accelerated testing could be used if the physical
properties of both drug and polymer do not change
at elevated temperatures.
20
Osmotic pump
Impervious coat
Laser drilled hole
21
Osmotic pump
Saturated solution of osmotic pressure gt outer
pressure
Dissolution medium
22
Osmotic pump
Difference in osmotic pressure is the driving
force that forces the liquid out through the
hole. It is independent of remaining drug conc.
Release follows zero order kinetics.
Mt Mo - k t
This dosage form is less prone to change in
dissolution on storage than other types of dosage
forms.
23
Osmotic pump
Stability of dissolution profile on storage
(during stability program)
Tracing of k0 and t0 at different time intervals
Calculating Similarity Factor
Accelerated testing is not of much use
24
Gel forms
Tablets made of gel forming substances
Dissolution medium
25
Gel forms
Tablets made of gel forming substances
Drug dissolve and diffuse out through gel
Dissolution medium
26
Gel forms
Tablets made of gel forming substances
Gel layer becomes thicker diffusion path
becomes longer
Dissolution medium
27
Gel forms
Tablets made of gel forming substances
Gel erosion could occur
Dissolution medium
28
Gel forms

Tablets made of gel forming substances
Release is a hybrid of diffusion and erosion
29
Release mechanism
krosmear peppas
n an exponent that characterized the release
mechanism. n 0.5 Fickian diffusion 0.5 lt n gt 1
non-Fickian model (anomalous transport) n 1
zero order
30
Coated tablets
sugar
enteric
film
31
Coated tablets
sugar
enteric
film
Barrier coat (polymer)
Sub-coat (talcgelatin)
Dye coat (sucrose syrupdye lake)
Finishing coat
Polish coat (Beeswax)
32
Coated tablets
sugar
enteric
film
Stability problems on storage (during stability
program)

1. Chipped tablets
2. Split tablets in the periphery

Improper barrier coat
trapped moisture (Improper drying between coats)
33
Coated tablets
sugar
enteric
film
Required tests during stability program

1. Appearance
2. Gloss (subjectively, glossmeter)
3. SEM
4. Friability (for chipped tablets)
5. Disintegration
6. Dissolution

34
Coated tablets
film
sugar
enteric
Aqueous film coat (HMC, HPMC)
35
Coated tablets
film
sugar
enteric
Advantages of film coat over sugar coat

1. Less labor intensive
2. Allow engraving to show through
3. Allow appearance of deep color with little dye

36
Coated tablets
film
sugar
enteric
Stability problems on storage (during stability
program)

1. Dislodging or rupture of film
2. Change of appearance

Formula (film and tablet core)
Method of preparation (not noticeable initial
defective procedures)
37
Coated tablets
film
sugar
enteric
Required tests during stability program

1. Appearance
2. Gloss (subjectively, glossmeter)
3. SEM
4. Measure force necessary to strip film from tablet
   (Tensile tester machine eg. Instron tester)
5. Disintegration
6. Dissolution

38
Coated tablets
enteric
sugar
film
Acid resistance coat (CAP, Shellac)
Sugar coat for immediate dose
39
Coated tablets
enteric
sugar
film
Stability problems on storage (during stability
program)
Polymerization of coating polymer
40
Coated tablets
enteric
sugar
film
Required tests during stability program

1. Appearance
2. Gloss (subjectively, glossmeter)
3. SEM
4. Measure force necessary to strip film from tablet
   (Instron tester)
5. Disintegration
6. Dissolution of drug in sugar coat
7. Dissolution of drug in tablet

41
Coated tablets
enteric
sugar
film
Required tests during stability program
Dissolution of drug in tablet
1 h in SGF at 37oC
2 h in SIF at 37oC
No disintegration, softening or cracking
Disintegration at the end point
42
Capsules
Stability problems on storage (during stability
program)

1. Cross-linking of gelatin and pellicle formation

Check in simulated gastric fluid
43
Capsules
Stability problems on storage (during stability
program)

1. Cross-linking of gelatin and pellicle formation
2. Moisture shift

Capsule shell
Capsule content
Soft shell
Brittle shell
44
Microcapsules
Stability problems on storage (during stability
program)
Loss of intact polymer (microcapsule
decomposition)
45
Microcapsules
Required tests during stability program

1. Loss in polymer weight by gel permeation
   chromatography
2. Detection of polymer degradation products (eg.
   Lactic acid in case of poly(L-lactide) polymer)
3. Decrease in weight averaged molecular weight
4. SEM