PRE-FORMULATION STUDIES
is the foundation of developing robust formulation
it can be defined as a phase of research & development process for an investigation of physical and
chemical properties of new drug substance alone or in combination w/ other excipients in order to
development of safe and effective dosage form
Phase w/c is initiated once the new molecule is seeded in a broader way, it deals w/ studies of physical,
chemical, analytical and pharm'l properties related to molecule and provides idea about suitable modification
in molecule to show a better performance
group of studies that focus on the physicochemical properties of a new drug candidate that could affect the
drug performance and the development of a dosage form
this could provide important information for formulation design or support the need for molecular
modification every drug has intrinsic chemical; and physical properties w/c has been consider before
is the stage of development during w/c the physicochemical properties of the drug substance are
characterized, and established knowledge of the relevant physicochemical and biopharmaceutical
properties determines the appropriate formulation and delivery method for pre-clinical and phase 1 studies
Objectives of Preformulation Studies
1. to generate useful data needed in developing stable and safe dosage forms that can be manufactured on a
commercial scale.
2. to provide in-depth knowledge and understanding of the physical characteristics of a candidate drug
molecule prior to dosage form development.
3. to generate useful information on how to design a drug delivery system w/ good bioavailability.
Goals of Preformulation Studies
1. to establish the physicochemical parameters of a candidate drug molecule.
2. to determine the kinetic rate profile of drug substances.
3. to establish the compatibility of a candidate drug molecule w/ common excipients.
Classes of Preformulation Studies
Preformulation studies can be classified into:
A. Fundamental Preformulation Studies
These studies are specific to candidate drug molecules and it include solubility analysis (e.g. ionization
constant, partition coefficient, solubilization, thermal effect, common ion effect, dissolution etc.), solid state
properties, e.g. polymorphism, solvated forms and amorphous form), stability analysis (e a solution-state
stability and solid-state stability) and permeability studies
these studies are dependent on the chemical structure of the candidate drug molecule
B. Derived Preformulation Studies
these studies include characterization of particle properties (e.g particle size and particle size and particle
size), bulk density, powder flow properties, compaction behaviour etc.
they are carried out on the intended dosage form
before embarking on preformulation studies, scientists must consider
1. the available physicochemical data including chemical structure, difft salts, potency relative to the
competitive prods and the dosage form etc.
2. anticipated dose and the proposed route of drug administration
3. supply situation and development schedule
4. availability indicating assay
Evaluated Parameters in Preformulation Studies
A. Physical characteristics
1) organoleptic properties of the candidate drug molecule e.g. color, odor and taste
2) bulk characterization e.g. particle size and surface area, powder flow properties, density, compressibility,
crystallinity, polymorphism and hygroscopicity
3) solubility analysis e.g. ionization constant/drug pKa, partition coefficient, solubilization, thermal effect,
common ion effect (ksp) and dissolution
4) stability analysis e.g. solution-state stability testing, solid-state stability testing and drug-excipient
compatibility studies
B. Chemical characteristics
1. Hydrolysis
2. Oxidation
3. Photostability
4. Racemization
5. Polymerization
6. Isomerization
The main components of Preformulation Studies are:
1) development of a suitable spectroscopic assay method for determining concentration and purity
2) determination of solubility and dissolution rates of parent compound and salts in water and other solvents
3) chemical stability of parent compound and salts in solution and solid state
4) determination of pKa and pH dependence of solubility and I chemical stability
5) determination of lipophilicity (oil: water partition coefficient, expressed as KD
6) determination of particle morphology, melting point and suitability for milling
7) characterizations of importance for the dosage forms of choice, e.g bulk density, powder flow, angle of
repose and compression properties
