QUALITY BY DESIGN FOR PROCESS OPTIMISATION OF A NOVEL ORAL

SOLID DOSAGE FORM

ICH Q8 Pharmaceutical Development

Pharmaceutical Development

Quality cannot be tested into products; quality should be built-in by design
Introduces a new (optional) development paradigm, Quality by Design (QbD),
a systematic approach to pharmaceutical development.

What is QbD?

Quality by Design is: 1) a scientific,risk based,holistic and proactive approach to
pceutical development. 2) a deliberate design effort from product conception through
commercialization. 3)a full understanding of how product attributes and process relate to
product performance
Active pharmaceutical
ingredient
General
Stress testing
Selection of batches
Container closure system
Specifi cation
Testing frequency
Storage conditions
Stability commitment
Evaluation
Statements and labelling
Ongoing stability studies
Finished pharmaceutical product
General
Selection of batches
Container closure system
Testing frequency
Storage conditions
Stability commitment
Evaluation
Statements and labelling
In-use stability
Variations
Ongoing stability studies
ICH Guidelines for Active pharmaceutical
ingredient And Finished pharmaceutical product :
Dosage Form Design: Traditional Vs Systematic
Approach
Current Approach
Quality assured by testing and
inspection

Data intensive submission disjointed
information without big picture


Specifications based on batch history

Frozen process, discouraging changes

Focus on reproducibility often
avoiding or ignoring variation
QbD Approach
Quality built into product & process
by design, based on scientific
understanding
Knowledge rich submission
showingproduct knowledge &
process Understanding
Specifications based on product
performance requirements
Flexible process within design space,
allowing continuous improvement
Focus on robustness
understanding and controlling
variation

General
principels
of QbD
API partical
size polymorphism
stability
bioavability and
solubility
process
variables
Compression
range,physical
character, Blending
uniformity
finished
product testing
stingfformulatio
optimisation,
stability, Drug
release, packaging
exipients
polymer to control
release,flow
compression
character copatibility
with API stability
Enhancement of Solubility of Digoxin using QbD Principle
What is Solubility ?
Solubility may be defined as the amount of a substance that dissolves in a
given volume of solvent at a specified temperature. More specifically,
compound solubility can be defined as unbuffered, buffered, and intrinsic
solubility. Unbuffered solubility, usually in water, means solubility of a saturated
solution of the compound at the final pH of the solution (which may be far from
pH 7 due to self-buffering).
By enhancement of solubility we can enhance the Bioavailability of Drug.
Enhancement Of Bioavilability
Enhancement Of Bioavilability
Many poorly soluble and slowly dissolving drugs currently are
marketed in microcrystalline form.
The bioavailability of digoxin increased from 40% to approximately
80% to 97% by reducing the particle size from 100 to approximately
10 nm. .
Chloramphenicol palmitate and ritonavir provide good examples of
how polymorphism can influence drug dissolution and, thus,
drug solubility.
Therefore, many poorly soluble and slowly dissolving drugs
currently are marketed in a micronized or microcrystalline form
Enhancement Of Bioavilability
Increase in solubility of Benzathin using salt form


Plot of Dissolved Drug Concentration versus Time