A key goal in pharmaceutical development of oral dosageform

Bioavailability is defined as the rate and extent to which the active

ingredient or active moiety is absorbed for a drug product and becomes
available at the site of action.
Factors Influencing Bioavailability:
1. Physicochemical attributes of Drug
substances
Drug solubility and dissolution rate
Particle size and effective surface area
Bulk and tapped density, Powder flow
characterization
Polymorphism, amorphism and
hygroscopicity
Pseudopolymorphism (hydrates/solvates)
Salt form of the drug
Lipophilicity
pKa of the drug and pH
Drug stability (% volatile, LOD, moisture
content)
2. Dosage Form Characteristics and
Pharmaceutical Ingredients


Disintegration time (tablets/capsules)
dissolution time
Manufacturing variables (method of
granulation, compression force, intensity of
packing of capsule contents)
Pharmaceutical ingredient
(excipients/adjuvants)
Nature and type of dosage form
Product age and storage condition


Pharmaceutical factors
QUALITY BY DESIGN FOR PROCESS OPTIMISATION OF A NOVEL ORAL SOLID
DOSAGEFORM
Dosage Form Design: Traditional Vs Systematic Approach

Design and development of an immaculate drug product or pharmaceutical process usually
involves multiple objectives under its ambit. For decades, this task has been endeavored through
trial and error, supplemented by the previous experience, knowledge and wisdom of the formulator.
The modification of a formulation is carried out by the analysis of its composition and influence of
process factors on dosage form characteristics, changing any one at a time. Using this approach,
the solution of a specific problematic property can be achieved, but attainment of the true optimum
composition or process can never be guaranteed. The final product may be satisfactory but sub-
optimal, as a better formulation might still exist for the studied conditions. Thus, in the traditional
approach the primary aim of the formulator may not be in designing the best formulation, but finding
a suitable solution under the given set of restrictions. The aforementioned drug product
inconsistencies are generally due to inadequate knowledge of causal factor and response
relationship. Nowadays, systematic approaches, usually called as optimization techniques, are
being widely practiced to alleviate such inconsistencies. These encompass experimental designs,
mathematical equations and graphic outcomes, depicting a complete picture of variation of the
response as a function of the factor. Systematic approaches are thus far more advantageous,
possess greater benefits and overcome various pitfalls inherent to the traditional approaches as
these are require fewer experiments to achieve an optimum formulation, reveal interactions, yield
the best solution in the presence of competing objectives, make problem tracing and rectification
quite easier, simulate the product or process performance using model equation, comprehend the
process to assist in formulation development and subsequent scale-up.

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).
General
principels
of QbD
API partical
size
polymorphism
stability
bioavability
and solubility
process
variables
dissolution
disintegration
finished product
testing drug
relaes stability
testing
exipients
partical size
flow property
copatibility with
API stability
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
Guidelines
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