CONCISE PHARMACEUTICAL INDUSTRY RUN UP THOUGHTS FOR NEW COMERS

1. Pharmaceutical
preformulation and
formulation
SUCHANDRA BAGCHI
M.S.(PHARMACEUTICS)
NIPERA1517PE10

2. Flow of seminar
 Introduction
 Candidate drug selection
 Pharmacological characterization
 Early of candidate drug selection
 Biopharmaceutical consideration
 Early drug development and product design
 Product optimization
 Post product optimization
 conclusion

3. Introduction
 To be successful and competitive, research based pharmaceutical companies
must ensure that new discoveries are frequently brought to the market to
generate cash flow. This is required to find the next generation compounds, to
meet the therapeutic needs of patients and of course, to benefit the
shareholders. This cycle of events is sometimes referred to as Product Life
Cycle.
 Unsuccessful compounds should be removed at R&D level only to minimise
expenses of clinical research.
 In spite of high risk and high cost involved, there is still a huge incentive for
pharmaceutical companies to seek financial rewards such as “blockbuster”(I
billion US$ per year).
 Hence the importance of accelerating and optimizing drug discovery and
development, and getting to the market first with a new therapeutic class
medicinal product, cannot be underestimated.

5. To avoid backtracking along the way with long life years
investments a forward planning should provide opportunity for a
well throughout and efficient approach to product development
• Product design
• Process design
• Product optimization
• Process optimization
• Scale up
• Clinical trials
• Scale up for commercial production
• Process validation
The development
process can be
broken down into
several key
defined stages
such as

6. Rational for work
For successful
product
development which
is often associated
with
Good team work
Multidisciplinary
process
By in to the plansStrategies
Descisions
Project
management
system

7. Candidate drug selection
Depending on potency, specificity, duration, safety and pharmaceutical aspects candidate drugs are nominated
for development after being passed through “combinatorial chemistry” and automated “high throughput
screenings”. To ease this burden some rational drug design and quantitative structure activity relationships
(QSAR) are often introduced. Representative libraries of compounds are also present along with genomics.
During CD selection molecular lead is optimized by testing in vitro and in vivo studies with range of
compounds.

8. Selection of candidate drug substance to form
candidate drug product is crucial

10. Depending upon the type of molecule the
preformulation studies varies

11. Early development to candidate drug
selection
Drug
discovery
Lead
generation
Lead
optimization
Hit to leadActive to hit

12. 100 mg approach
Elemental analysis -4mg
HPLC methodology-2mg
NMR spectroscopy-5mg
Mass spectroscopy-5mg
IR/UV-Visible spec -5mg
Karl Fisher -20mg
Pka -10mg
Log P/Log D -10mg
Initial solubility/stability-10mg
Crystallinity-20-30mg
Hygroscopicity-5-10mg
Initial solid stability-10mg
Salt selection-10-50mg of each salt
Initial polymorphism-100mg
DSC/TGA/HSM-2mg per technique
XRPD/RH-10mg
microscopy-/SEM/light-10mg
Stability -100 mg

13. To check the solid state characteristics
of the drug

14. Pharmacological characteristics involve
Acceptable
absorption
Potency
Duration of action
Selectivity for the
receptor or enzyme
Noncarcinogenicity
Nonteratogenicity
Nonmutagenicity

15. Most commonly used
classes of enhancers to
drug absorption from the
GIT
NSAIDs
SURFECTANTS
BILE SALTS
MEDIUM CHAIN FATTY ACIDS
MEDIUM CHAIN GLYCERIDES
ENAMINES
MIXED MICELLES
EDTA
PHENOTHIAZINES
LIPOSOMES
AZONE
FATTY ACID DERIVATIVE OF
CARNITINE AND PEPTIDES
SAPONINS
CONCANAVALIN A
PHOSPHATE AND PHOSPHONATE
DERIVATIVE
POLY ACRYLIC ACID
To increase bioavailability we need to increase solubility of the
drug if not the intrinsic solubility but the dependent ones and
further increasing the permeability across the physiological
membrane barrier by incorporating suitable enhancers in the
formulation of by preparing certain delivery systems

16. Biopharmaceutical support in
candidate drug selection
Dissolution,
solubility
affects
absorption
of the drug
Distribution
Degradation
and
metabolism
Models for
study
Computational
method
Partitioning
between oil
and water
Cell
cultures
Membrane
vesicles
Intestinal
rings or
sacs
Excised
segments
from
animals
using
suitable
chamber
In vitro and
in situ
intestinal
perfusions
In vivo
cannulated
or
fistulated
animals
and
In vivo
gavaged
animals

17. Early Drug Development and product
design
To provide clear direction and objectives for the project team
To gain bye in and input from all key functions at the start of development
To asses the feasibility of the project in commercial and technical terms
To identify any risks early and hence manage them
To avoid wasting valuable resources on developing a product that is not needed or wanted
To provide a good reference source for the development plan

18. Product design considerations
 Target product profile/minimum product profile
 Design specification and critical quality parameters
 Commercial and marketing considerations
 Technical issues and risk assessments
 Safety assessment considerations
 Environmental, health, and safety considerations
 Intellectual property considerations

19. Product optimization
Formulate
•Get specifications
•Propose tablet properties
•Choose fillers
•Choose disintegrants
•Choose binders
•Choose surfectants
•Choose glidants
•Choose lubricants
•Recommend formulation
•Evaluate formulation
•Compare against specifications
•Change excipients
•Optimize formulation

20. Post optimization
Scale up
Technology
transfer
Validation
and launch
Clinical trial
process
validation
Validation of
commercial
process
Preapproval
inspection
Postapproval
changes

24. Conclusion
These product optimization is done for solid
state only. For parenteral, ophthalmic,
inhalational and oral different formulation
excipients are taken into account.

25. Thank you