Pre Formulation Studies 1 2 3
Pre Formulation Studies 1 2 3
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• What is pre-formulation studies?
• Why do we perform pre-formulation
studies?
• What type of information is gathered from
such studies?
• Physical chemical properties of drugs and excipients
• Intrinsic and derived properties
• Potential interactions between a drug and the
excipients
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• Possibility of dosage form development
• Optimization of therapeutic agents
• Preliminary data on the stability of
drugs
• Suitable closures and containers
• Powder properties such true density,
apparent density, porosity, specific
surface, and surface area
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Rational for
Pre-formulation Studies
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• Approximately one out 5,000 to 10,000 chemical entities,
synthesized and investigated for its potential to treat a
disease, makes to the market.
• Therefore, new dug development is rather a cost
ineffective or a very expensive process.
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• A drug is synthesized and tested or screened for
pharmacological action;
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Prior to a chemical entity becomes a therapeutic agent and, pharmacists
and physicians begin to use that therapeutic agent, through a dosage form,
to treat a specific physiological or pathological abnormality or a disease, it
(the therapeutic agent) undergoes various kinds of investigations which
may take approximately 10 to 12 years and may cost approximately $ 1 to
3 billion.
"According to a
2014 study by the Tufts Center for the Study of Drug Development (TCSDD
)
, the cost of developing a new drug, from research and development (R&D)
to marketing approval, is approximately $2.9 billion. This includes actual
out-of-pocket costs averaging $1.4 billion, opportunity costs of nearly $1.2
billion, and the cost of post-approval studies amounting to $312 million" 7
Pre-formulation studies provide the scientists the
insight into the potential problems confronted in
the formulation of the dosage form of a drug.
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Additionally, pre-formulation studies may even
provide useful information to scientists, which
may determine the fate of that therapeutic agent
as to its suitability for the purpose of marketing.
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Sufficient quantity of a compound is synthesized
to perform:
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Goals of Pre-formulation Studies
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The goals of the program, therefore, are:
• To establish necessary physiochemical parameters of a
new drug substance.
• To determine the suitability of a drug for the desired
dosage form.
• To recommend changes or modification in the
compound, if necessary, to develop the desired dosage
form (Molecular optimization)
• To determine its kinetic rate profile (stability).
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• To establish its compatibility with common and routinely
used excipients.
• The study of drug-excipient interactions.
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Pre-formulation Research
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Bulk Characterization
• Crystallinity and polymorphism
• Hygroscopicity
• Particle or powder characterization (size and
size distribution, shape, surface characteristics,
true density etc.)
• Derived powder properties: Bulk density,
porosity, flow properties, bound and unbound
moisture content, etc. 15
Solubility Analysis
• Ionization constant – pKa
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Analytical Research & Development
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Analytical Research
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Analytical Development
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Molecular Optimization
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• Identification of pharmacologically active
compound
• Developing an optimum drug molecule from the
point of view of the development (formulation)
of a dosage form, administration of the dosage
form, drug solubility, drug stability, and
bioavailability.
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• Salts, pro-drugs, solvates, polymorphs, or even
new analogs may emerge as a result of this
molecular modification efforts.
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• Erythromycin and doxycycline are good examples.
• Erythromycin estolate is an example of a pro-drug with
improved pharmaceutical properties.
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• Erythromycin, a weak base, is water soluble, has a
very bitter taste, and its is very rapidly hydrolyzed
in gastric acid (t10%= 9 seconds) to yield the
degradation product.
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• To overcome this problem, a water insoluble
(estolate) salt was formed for suspension and
capsule dosage forms.
Erythromycin estolate
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