1. QUALITY RISK MANAGEMENT IN SUSTAINED
RELEASE TABLET FORMULATION DEVELOPMENT
Sajan Maharjan
M.Pharm (1st year)

2. Sustained Release Tablets
 a dose for suitable time period is incorporated into one tablet
from which the drug is slowly released.
 helps to prevent peak of high plasma concentration and
trough of low plasma concentration.
 avoid side effects associated with high conc. and
 lack of activity associated to low conc. , giving better overall
therapy.

3. Oral sustained release systems
Matrix
Reservoir
Monolithic
Among all of the above, matrix systems are mostly used

4. Formulation of sustained release tablet of Diltiazem HCl using
Rosin as a matrix system
Proposed formula:
Composition (in mg)
1.
2.
3.
4.
Ingredients
Diltiazem HCl (Active)
Rosin (Polymer)
Talc
Magnesium Stearate
F1(1:1.25)
90
112.5
6
4
F2(1:1.5)
90
135
6
4
F3(1:1.75)
90
157.5
6
4

5. Tablet Compression
• Drug (Diltiazem Hydrochloride), polymer, magnesium stearate
and talc were passed through sieve no. 80 separately and then
mixed properly.
• The matrix tablets of the above formulations were compressed
in a tablet compression machine.

6. Drug-excipient interaction studies
(Preformulation studies)
• Differential Scanning Calorimetry (DSC), Fourier Transform
Infrared (FTIR) Spectroscopy studies and HPTLC were used for
the evaluation of physicochemical compatibility and
interactions.
• helps in the prediction of interaction of the drug with
polymers, diluents and lubricants used in tablet formulations

7. Evaluation of tablet formulations
• Evaluation of characteristics of powder blend (bulk density,
tapped density, angle of repose, particle size) and tablets
(hardness, friability, uniformity of weight and drug content).
• Drug content of formulated tablets (by using a UV
spectrophotometer)
• Release studies (dissolution) performed at 75 rpm in 900 ml
of phosphate buffer pH 7.4 at 37 0.2 C.
Data analysis

8. Results and Risk identification
• DSC, FTIR and HPTLC results revealed that there is no interaction
between the drug and the excipients used in the formulation
• The pre compression parameters like bulk density and
compressibility index reveal that the powder mixture had good
flow properties
• All the tablets were found to pass the uniformity of weight.
• Content of Diltiazem HCl was found in the range of 98.5 to
101.0%.

10. RISK ANALYSIS AND EVALUATION
• The polymer influences the drug release
• release of drug was retarded due to the hydrophobic
nature of the polymer, which prevents the penetration of
the dissolution medium into the matrix tablets leading to
slower dissolution and diffusion of the drug molecules
from the matrix system.

11. Risk Control
• formulation subjected to check the effect of release enhancers
like lactose, MCC, and Mannitol
Composition (in mg)
1.
2.
3.
4.
5.
6.
7.
Ingredients
Diltiazem HCl (Active)
Rosin (Polymer)
Lactose
MCC
Mannitol
Talc
Magnesium Stearate
F4(1:1.75)
90
157.5
37.5
9
6
F5(1:1.75)
90
157.5
37.5
9
6
F6(1:1.75)
90
157.5
37.5
9
6

12. Risk Control ( Contd…)
• The composition was subjected to in vitro release studies
• From the release profile
 the tablets containing MCC as diluent showed significant
increase in the release of drug, this might be due to swelling
behavior of MCC in water and eventually disintegration of the
tablets
 Tablets contain mannitol and lactose as diluent showed
significant higher drug release when compared with MCC.
These might be due the rapid solubility of lactose and
mannitol, tendency to form pores in the matrix which allow the
dissolution medium to penetrate the matrix and dissolve the drug

13. Risk Review and Risk Communication
•The polymer influences to slower dissolution and diffusion of the
drug molecules from the matrix system
•Release of drug from the matrices can be adjusted by using release
enhancers like Lactose, Mannitol, MCC
•These risks are communicated to production department and quality
management department
•The final formula is then submitted to production department:
Ingredients
1. Diltiazem HCl
2. Rosin
3. Lactose
4. Talc
5. Magnesium Stearate
Composition (in mg)
90
157.5
37.5
9
6
Tablet Wt. = 300 mg

14. Risks during
manufacture and
distribution
• Adequate stability
• Uniformity in composition
• Dose variation
• Cross contamination
• Preservation
• Proper packaging
• selection of packing
material
• label control
Risk management throughout
the life cycle of product i.e from
design
development, mfg, distribution
with good quality assurance
procedure
Develop highest quality in the shortest time