Transcript Introduction

Introduction
Mohammad Mahareeq
Introduction
Definitions
• Technology: The application of science to industrial or
economical objectives
• Drug: Any substance or mixture of substances manufactured,
sold or represented for use in:
i. Diagnosis, treatment, mitigation or prevention of a disease,
a disorder, an abnormal physical state or the symptoms
thereof in humans or animals
ii. Restoring, correcting or modifying organic functions in
humans or animals
Introduction
• Active pharmaceutical ingredient (API): Any substance or
mixture of substances intended to be used in the manufacture
of a pharmaceutical dosage form and that, when so used,
becomes an active ingredient of that pharmaceutical dosage
form.
• Bulk product: Any product that has completed all processing
stages up to, but not including, final packaging.
Introduction
• Pharmaceutical product: Any material or product intended
for human or veterinary use presented in its finished dosage
form.
• Finished product: A finished dosage form that has undergone
all stages of manufacture, including packaging in its final
container and labelling.
• intermediate product: Partly processed product that must
undergo further manufacturing steps before it becomes a bulk
product.
• Pharmaceutical Development: The road from API to a
finished product in its primary packaging material, including
production methods and all necessary documentation
Introduction
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Materials + machines (equipment)
Men (personnel)
Methods (procedures)
Management
Documentation
• Product constituents:
i. Active pharm. Substance
ii. Intermediates
iii. Excipients
Product
Large – scale prod.
Consistent
Approved quantity
Introduction
• Raw materials:
 APIs
 Inactive materials
1. APIs
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Produced through certain chemical processes:
 Nitration
 Sulfonation
 Halogenation
 Friedel-crafts
 Acylation
 Esterification
 Hydrolysis
 Amination
 Diazo
 Oxidation
 Reduction
 Photochemistry
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Using certain unit operations:
Heating/Cooling
Mixing
Drying
Crystallization
Distillation
Precipitation
Filtration
Extraction
Milling = Particle size Reduction
Introduction
 Sources of APIs:
 Natural products and Extracts (e.g. carbohydrates, glycosides,
lipids, proteins, alkaloids, volatile oils, plants exudates (resins,
oleoresins, gum resins, balsams), enzymes, prostaglandins,
hormones, vitamins, antibiotics……etc )
 Synthetic products: Total synthesis
 Semi- synthetic products: partial synthesis
 Nature of APIs:
 Organic
 Inorganic
 Names of APIs:
 Chemical: Systemic name, IUPAC name, Trivial name
 Generic name: nonproprietary name, USAN,…..etc
Introduction
2. Excipients: non active materials added to formulations for
different purposes:
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Purpose
pH control
Preservative
Antioxidant
Solvent
Surfactant
Ointment base
Flavour
Example
Citric acid, NaCO3
Na Benzoate, Phenol
Ascorbic acid, Na Bisulfite
Alcohol, Water
Cetyl alcohol
Petrolatum, PEG
Peppermint oil, Menthol
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Drug products dosage forms:
Solids: tablets, capsules, powders, granules
Liquid: solutions, syrups, elixirs, suspensions, emulsions
Semi-solids: cream, ointment, gel, emulgel, paste, suppository
Specialty: gases, aerosols, transdermal patches, inhalation
sprays
Routes of administration
Route
Dosage form
oral
Tab., caps., solutions, susp., powders, emulsions,
gels, lozenges
Topical
Oint., cream, pastes, lotions, gels, solutions
Parenteral
Injections (iv, sc, im, ip, it (intrathecal), ia
(intraarterial)…..
Transdermal
Oint., creams, lotions, patches, infusion pumps
Intraocular/nasal/aurel
Solutions, suspensions
Pulmonary
aerosols
Rectal
Solutions, oint., suppositories
Vaginal
Solutions, oint., supp., gels, foams
Urethral
Solutions, supp.
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Needs for dosage forms:
Provide safe and accurate delivery of given dosage
Protect drug from environmental degradation
Protect drug from GI degradation
Conceal bitter, salty taste, offensive odour
Allow for administration of poorly soluble drugs
Provide rate- controlled action
Allow for administration by desired route
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Drugs are seldom administered alone
Given as formulation
Contain additional ingredients (i.e. excipients)
Objectives of dosage form design: To achieve a predictable
therapeutic response to drug included in a formulation.
• In formulation we must consider physical, chemical, and
biological properties of all components
Drug Product Development (DPD)
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Different DPD approaches are generally used to produce:
New drug products- NCE, 3 Phases, (NDA). Brand Product
Product Line Extension: New Dosage Form, New Strength
Generic drug products- "one" phase (ANDA)
NCE = New Chemical Entity
NDA = New Drug Application
ANDA = Abbreviated New Drug Application
NCE – Phases of Product Development
Preclinical
Testing
Phase I
Years
3.5
1
Test
population
Laboratory &
animal studies
20-80 healthy
volunteers
100-300 patient
volunteers
1000-3000
patient
volunteers
Purpose
Assess safety &
biological
activity
Determine
safety and
dosage
Evaluate
effectiveness,
look for side
effects
*
Verify
effectiveness,
monitor adverse
reactions from
long-term use
Success rate
5000 compounds
evaluated
5 enter
trials
*: Drug Formulation
Phase II
Phase III
2
FDA
Review
Phase IV
3 2.5
Review
process/
Approval
1
approved
Addition
al Post
marketin
g testing
Drug Product Development (DPD)
• Activities and information required to develop drug
product:
 Preformulation: the investigation of all chemical and
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physical properties of the drug substance (API) in question,
which are considered important in the formulation of a stable,
effective and safe dosage forms.
Formulation: to find the balance between API, Excipients,
manufacturing processes and delivery form in a highly
regulated environment.
Final Drug Product: Considerations to be taken
 ( colour, shape, size, taste, flavor, viscosity, skin feel, and physical
appearance of the dosage form)
 Size and shape of the package container
 Production equipment
 Country in which to market the drug