Paper No: 05 Product Development 1
Module No: 02 PREFORMULATION PART 1
Development Team
Prof. Farhan J Ahmad
Principal Investigator Jamia Hamdard, New Delhi
Dr. Vijaya Khader
Former Dean, Acharya N G Ranga Agricultural University
Dr. Gaurav Kumar Jain
Paper Coordinator Jamia Hamdard, New Delhi
Content Writer Dr. Gaurav Kumar Jain
Jamia Hamdard, New Delhi
Prof Roop K. Khar
Content Reviewer BSAIP, Faridabad
Prof. Dharmendra.C.Saxena
Dr. Vijaya Khader SLIET, Longowal
Dr. MC Varadaraj
1
Pharmaceutical Product Development 1
sciences PREFORMULATION PART 1
, Introduction
Prior to nomination into full development, a candidate drug should undergo a phase traditionally called
Preformulation. The word Preformulation is composed of two words pre and formulation i.e. Activities
done prior to formulation development. In simple definition Preformulation encompasses all studies
enacted on a new drug compound to produce meaningful information for subsequent formulation of a
biopharmaceutically suitable and stable drug dosage form.
To appreciate the importance of Preformulation in the overall process we must be aware of the process
of drug discovery and development. Drug molecules are rarely administered alone. They are
administered as dosage forms or formulations. In simple terms, the goal of drug discovery and
development is divided into two phases the first being “converting ideas into candidate drugs for
development”, and the other being “converting candidate drugs into products for registration and sale”.
In reality, these goals are extremely challenging and difficult to achieve because of the many significant
hurdles a pharmaceutical company has to overcome during the course of drug development. As an
example
Activity Requirements
Research Compound is novel and patentable; Fulfills unmet medical need;
Potent and selective
Safety Non-toxic; high margin of safety
Clinical Efficacious; tolerable
Regulatory Quality of data and documentation
Manufacturing Manufacturable; developed into a stable drug product; can be scaled up
Marketing Meet patient needs; competitive; high return on investment
The high risk of failure in drug discovery and development throughout the pharmaceutical industry
statistically shows that, on average, only 1 in 5,000 to 1 in 10,000 compounds screened in research will
reach the market. Of those that are nominated for development, the failure rate will vary from 1 in 5 to
2
Pharmaceutical Product Development 1
sciences PREFORMULATION PART 1
, 1 in 10. On top of that, there is a significant commercial risk from those that are marketed with only 3
out of 10 are likely to achieve a fair return on investment. The products which give poor return on
investment are often the result of poor candidate drug selection and/or poor product development, both
of which can avoided by careful Preformulation studies.
The scope of Preformulation studies will depend not only on the drug substance, equipment and expertise
available but also on the organizational preferences. Some companies like to conduct detailed
characterization studies, whilst others prefer to do the minimum amount of work required to progress
compounds as quickly as possible into development. Both of these approaches have their own pros and
cons. However, for the smooth progression of compounds through the Preformulation phase, a close
interaction between departments of Pharmaceutics, Medicinal Chemistry, Drug Substance Process
Development and Analytical Chemistry is essential.
Preformulation commences when a newly synthesized drug shows sufficient pharmacologic promise in
animal models to warrant evaluation in man. Preformulation starts with prenomination phase wherein
the studies must be conducted to select which compound to proceed with into development.
Prenomination studies provide a rationale for formulation design and confirms that there are no
significant barriers to the compound’s development. Although in vivo activity may be sufficient to
determine which of the candidates is selected, however, other factors such as physicochemical
characteristics of the compound(s), ease of scale-up for compound supply, availability of analytical
procedures and the nature of the anticipated dosage form should also be taken into consideration in the
decision process. As an example, for an oral solid dosage form, ideally, a water-soluble, non-
hygroscopic, stable and easily processed crystalline compound is preferred for development purposes;
however, other formulation types will have their own specific requirements. Notably, this is a critical
decision period that can profoundly affect the subsequent development of a candidate drug. A poor
decision at this point could mean a substantial amount of revisionary work, such as a change of salt or
polymorph being necessary, and a possible delay to the development of the drug to the market.
After nomination to full development, the increased quantity of candidate drug available will allow a
more complete physicochemical characterization of the chosen compound(s) to be carried out, with
3
Pharmaceutical Product Development 1
sciences PREFORMULATION PART 1
Module No: 02 PREFORMULATION PART 1
Development Team
Prof. Farhan J Ahmad
Principal Investigator Jamia Hamdard, New Delhi
Dr. Vijaya Khader
Former Dean, Acharya N G Ranga Agricultural University
Dr. Gaurav Kumar Jain
Paper Coordinator Jamia Hamdard, New Delhi
Content Writer Dr. Gaurav Kumar Jain
Jamia Hamdard, New Delhi
Prof Roop K. Khar
Content Reviewer BSAIP, Faridabad
Prof. Dharmendra.C.Saxena
Dr. Vijaya Khader SLIET, Longowal
Dr. MC Varadaraj
1
Pharmaceutical Product Development 1
sciences PREFORMULATION PART 1
, Introduction
Prior to nomination into full development, a candidate drug should undergo a phase traditionally called
Preformulation. The word Preformulation is composed of two words pre and formulation i.e. Activities
done prior to formulation development. In simple definition Preformulation encompasses all studies
enacted on a new drug compound to produce meaningful information for subsequent formulation of a
biopharmaceutically suitable and stable drug dosage form.
To appreciate the importance of Preformulation in the overall process we must be aware of the process
of drug discovery and development. Drug molecules are rarely administered alone. They are
administered as dosage forms or formulations. In simple terms, the goal of drug discovery and
development is divided into two phases the first being “converting ideas into candidate drugs for
development”, and the other being “converting candidate drugs into products for registration and sale”.
In reality, these goals are extremely challenging and difficult to achieve because of the many significant
hurdles a pharmaceutical company has to overcome during the course of drug development. As an
example
Activity Requirements
Research Compound is novel and patentable; Fulfills unmet medical need;
Potent and selective
Safety Non-toxic; high margin of safety
Clinical Efficacious; tolerable
Regulatory Quality of data and documentation
Manufacturing Manufacturable; developed into a stable drug product; can be scaled up
Marketing Meet patient needs; competitive; high return on investment
The high risk of failure in drug discovery and development throughout the pharmaceutical industry
statistically shows that, on average, only 1 in 5,000 to 1 in 10,000 compounds screened in research will
reach the market. Of those that are nominated for development, the failure rate will vary from 1 in 5 to
2
Pharmaceutical Product Development 1
sciences PREFORMULATION PART 1
, 1 in 10. On top of that, there is a significant commercial risk from those that are marketed with only 3
out of 10 are likely to achieve a fair return on investment. The products which give poor return on
investment are often the result of poor candidate drug selection and/or poor product development, both
of which can avoided by careful Preformulation studies.
The scope of Preformulation studies will depend not only on the drug substance, equipment and expertise
available but also on the organizational preferences. Some companies like to conduct detailed
characterization studies, whilst others prefer to do the minimum amount of work required to progress
compounds as quickly as possible into development. Both of these approaches have their own pros and
cons. However, for the smooth progression of compounds through the Preformulation phase, a close
interaction between departments of Pharmaceutics, Medicinal Chemistry, Drug Substance Process
Development and Analytical Chemistry is essential.
Preformulation commences when a newly synthesized drug shows sufficient pharmacologic promise in
animal models to warrant evaluation in man. Preformulation starts with prenomination phase wherein
the studies must be conducted to select which compound to proceed with into development.
Prenomination studies provide a rationale for formulation design and confirms that there are no
significant barriers to the compound’s development. Although in vivo activity may be sufficient to
determine which of the candidates is selected, however, other factors such as physicochemical
characteristics of the compound(s), ease of scale-up for compound supply, availability of analytical
procedures and the nature of the anticipated dosage form should also be taken into consideration in the
decision process. As an example, for an oral solid dosage form, ideally, a water-soluble, non-
hygroscopic, stable and easily processed crystalline compound is preferred for development purposes;
however, other formulation types will have their own specific requirements. Notably, this is a critical
decision period that can profoundly affect the subsequent development of a candidate drug. A poor
decision at this point could mean a substantial amount of revisionary work, such as a change of salt or
polymorph being necessary, and a possible delay to the development of the drug to the market.
After nomination to full development, the increased quantity of candidate drug available will allow a
more complete physicochemical characterization of the chosen compound(s) to be carried out, with
3
Pharmaceutical Product Development 1
sciences PREFORMULATION PART 1
