Formulation Science
Main steps of formulating a Drug Product
The role of Formulation Science in different stages of Drug Development
Trends and challenges in formulation development

1. Mohamad Haitham Ayad Pharmacist – MSc
THE ROLE AND THE ADDED VALUE OF
PROPER FORMULATION
DEVELOPMENT

2. M. H. Ayad 2
PRESENTATION OUTLINE
 Introduction to Formulation Science
 The role of Formulation Science in different
stages of Drug Development
 Trends and challenges in Formulation
Development
Drug Delivery Systems (DDS)
Biopharmaceutical Formulation
Outsourcing
 Conclusion – Q&A

3. FORMULATION SCIENCE
 Definition:
The science of transforming an Active
Pharmaceutical Ingredient (API) into a quality Drug
Product, in a specific dosage form, by developing an
appropriate Formula and Process
M. H. Ayad 3

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WHY TO FORMULATE A DRUG
SUBSTANCE (1)
 Basic requirement
Clinical need: Dosage Form adapted to the
indication→ Clinical efficiency
Patient needs: improve the test, add a color and
reduce the number of daily intake → Patient
compliance
Industrial needs: improve the flowability, density and
compressibility of API → Productivity
 Advanced requirement
Correct the poor drug-like properties of new
molecules identified mainly by HTS

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WHY TO FORMULATE A DRUG
SUBSTANCE (2)
 To be absorbed to the systemic circulation, the drug should
be soluble and permeable through the GI barrier
 The introduction of HTS allowed identifying more specific
molecules but bigger and more Lipophilic → Solubility
and/or Permeability issues

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BIOPHARMACEUTICAL CLASSIFICATION
SYSTEM (BCS)
 Development pipelines compared with top 200 US marketed drugs
Source: L. Benet – Bulletin Technique Gattefossé - 2006
Class I
High solubility
High permeability
~35% / 5%
Class II
Low solubility
High permeability
~30% / 70%
Class III
High solubility
Low permeability
~25% / 5%
Class IV
Low solubility
Low permeability
~10% / 20%

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THE ROLE OF FORMULATION SCIENCE IN
DIFFERENT STAGES OF DRUG
DEVELOPMENT PROCESS
Development Stage
Phase IIPreclinical Phase I
Hit-to-Lead/ Lead
Optimization
Assay
Dev/Screening
Phase III Commercialization
Drug Discovery Clinical Development
Life Cycle
Management
 Preformulation
 Formulation support for
Preclinical tests
 Evaluating the
“Developability” of clinical
candidates
 Formulation and Process
Development
 On time supply of clinical
trail material
 Reformulation
 Indication expansion
 Rx-to-OTC switch

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MAIN STEPS OF FORMULATION
DEVELOPMENT
 Preformulation
Characterization of API (Solubility, melting point,
density….)
 Formulation
Choosing the quantitative formula and its process
of fabrication
 Scale-up and process validation
Transferring the process from laboratory to
industrial scale

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TRENDS AND CHALLENGES
IN FORMULATION
DEVELOPMENT

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DRUG DELIVERY SYSTEM (DDS)
 Formulation or a device that enables the introduction of a therapeutic
substance in the body and improves its efficacy and safety by
controlling the rate, time, and place of release of drugs in the body*
*Source: Drug Delivery Systems - An Overview, Kewal K. Jain
 Example of DDS:
 Controlled Release (Matrix
tablet, Osmotic pumps)
 Solubility improving (Solid
dispersion, Nano-
technologies)
 Technologies for fast-
dissolving and taste-masking
pills (Orodispersible)

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DDS – BUSINESS OVERVIEW
 Growth of drug delivery market
 Development duration and cost
YEAR 2000 2006 2009 2016
DRUG
DELIVERY
MARKET ($bn)
26 60 101 199
DRUG DELIVERY
ENABLED PRODUCT
NEW DRUG
Time to approval 6.7 Years 12-15 Years
Clinical
Development and
approval success rate
25% 11%
Development cost 98 ($Million) 2200 ($Million)

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BIOPHARMACEUTICAL FORMULATION
 Biopharmaceuticals are medicinal products created by
Biotechnology method
 Accounted for only 12% Worldwide Pharmaceutical
sales in 2003 but steadily increasing market share and
expected to achieve 23 % in 2018*
 Half of the top 100 selling drugs are expected to be of
Biotechnology origin by 2018*
 Most Biopharmaceuticals are parenteral because of
the acidity of the stomach and poor intestinal
permeability
*Source: EvaluatePharma (29 May 2012)

13. BIOPHARMACEUTICAL DRUG DELIVERY
BEYOND INJECTION
 Oral route: Peptide tablet of Calcitonin
(Unigene Laboratories) includes an enteric
coating, organic acid and absorption enhancer
 Transdermal route: PassPort® (Altea - Nitto) batch with
applicator uses electrical pulses to create microchannels
through which Biopharmaceuticals can passes
 Nasal Route: few Biopharmaceuticals are
commercialized like Fortical® and Synarel®
 Pulmonary route: Promaxx® (Baxter) combine the
biopharmaceutical (Insulin) into a bioerodible protein
microsphere
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OUTSOURCING
 Allow access to quantities and specific technologies
which you do not have internally
 Improve productivity and flexibility of internal R&D by
leveraging external resources (knowledge, skills, FTE,
etc) and reduce the drug discovery & development life
cycle
 Reduce the cost of R&D programs and lower over-all
operating costs
40% of CMC activities are outsourced

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INDIA vs. CHINA
RIDING ON A TIGER OR A DRAGON
 In general, China is stronger in biology and is rapidly improving its
skills. It has been the only country in the developing world to
participate in the International Human Genome Project
 India has more complete services in CMC (Chemistry, Manufacturing
& Control), including formulation and analytical services, up to full
development for international filings. (it has the highest number of
approved FDA sites and ANDA outside of USA)
Reference: Frank Floether, On the Move: Pharmaceuticals R&D in Asia, 2009

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CONCLUSION
 The success of bringing a new medicine to the market is
the result of a complementary and equally important
contribution of scientists working in different scientific
fields.
 As Formulation Development is part of the process
of bringing every new drug to the market, the
quality of formulation contribution is very critical in
the success of new drugs.

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THE ROLE AND THE ADDED VALUE
OF PROPER FORMULATION
DEVELOPMENT
THANK YOU