1. Physical Testing Solutions Disperse systems Aerosols Powders Tablets
Sustained release products
Coated tablets
Hard & soft shell capsules
Microcapsules

2. Physical Testing Sustained release products
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. Saturated drug solution
Coated beads and granules
Dissolution medium
Saturated drug solution

5. Coated beads and granules
There are three stages in the dissolution
0 < t < ti : penetration of medium into the pellet, ti is the time it takes for this to complete (lag time)
ti < t < 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 > tf : slow dissolution
It is difficult to get the last 5-10% of drug to release

6. Coated beads and granules
Factors affecting dissolution:
Film thickness
time
% released
Thin coat
Thick coat

7. Coated beads and granules
Factors affecting dissolution:
Film thickness
Amount of soluble filler in the film
time
% released
↑ filler
↓ filler

8. Coated beads and granules
Kinetics of dissolution: ? ?
time
ln %remaining
Thick coat
Thin coat
M mass not dissolved, Mo total dose, K dissolution constant, ti lag time

9. Coated beads and granules
Kinetics of dissolution:
time
ln %remaining
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: 50–100) 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: Substance type
Drug to substance ratio
Tablet dimensions

15. Erosion tablets Hixon-crowel Dissolution Kinetics
time
3√ remaining
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. Created by dissolved drug (A/ρ)
Insoluble matrices
Tablets made of porous insoluble matrix
Factors affecting dissolution:
Surface area through which diffusion takes place
Drug loading
Porosity
Inherent
Created by dissolved drug (A/ρ)
A Drug dose, ρ 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
√ time
% remaining

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 > 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.
time
% remaining
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=
Tablets made of gel forming substances
Release is a hybrid of diffusion and erosion

29. Release mechanism krosmear peppas
Log time
Log % remaining
krosmear peppas
n an exponent that characterized the release mechanism.
n ≤ 0.5 Fickian diffusion
0.5 < n > 1 non-Fickian model (anomalous transport)
n ≥ 1 zero order

30. Coated tablets
sugar
film
enteric

31. Coated tablets sugar Barrier coat (polymer) Sub-coat (talc+gelatin)
film
enteric
Barrier coat (polymer)
Sub-coat (talc+gelatin)
Dye coat (sucrose syrup+dye lake)
Finishing coat
Polish coat (Beeswax)

32. (Improper drying between coats)
Coated tablets
sugar
film
enteric
Stability problems on storage (during stability program)
Chipped tablets
Split tablets in the periphery
Improper barrier coat
trapped moisture
(Improper drying between coats)

33. Coated tablets sugar Required tests during stability program
film
enteric
Required tests during stability program
Appearance
Gloss (subjectively, glossmeter)
SEM
Friability (for chipped tablets)
Disintegration
Dissolution

34. Coated tablets
film
sugar
enteric
Aqueous film coat
(HMC, HPMC)

35. Coated tablets film Advantages of film coat over sugar coat
enteric
Advantages of film coat over sugar coat
Less labor intensive
Allow engraving to show through
Allow appearance of deep color with little dye

36. (not noticeable initial defective procedures)
Coated tablets
film
sugar
enteric
Stability problems on storage (during stability program)
Dislodging or rupture of film
Change of appearance
Formula
(film and tablet core)
Method of preparation
(not noticeable initial defective procedures)

37. Coated tablets film Required tests during stability program Appearance
sugar
enteric
Required tests during stability program
Appearance
Gloss (subjectively, glossmeter)
SEM
Measure force necessary to strip film from tablet (Tensile tester machine eg. Instron tester)
Disintegration
Dissolution

38. Coated tablets enteric Acid resistance coat (CAP, Shellac)
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 Required tests during stability program
sugar
film
Required tests during stability program
Appearance
Gloss (subjectively, glossmeter)
SEM
Measure force necessary to strip film from tablet (Instron tester)
Disintegration
Dissolution of drug in sugar coat
Dissolution of drug in tablet

41. Coated tablets enteric Required tests during stability program
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)
Cross-linking of gelatin and pellicle formation
Check in simulated gastric fluid

43. Capsules Stability problems on storage (during stability program)
Cross-linking of gelatin and pellicle formation
Moisture shift
Percent relative humidity
Moisture content (mg/g)
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
Loss in polymer weight by gel permeation chromatography
Detection of polymer degradation products (eg. Lactic acid in case of poly(L-lactide) polymer)
Decrease in weight averaged molecular weight
SEM
Time (days)
Mol. weight