PHARMACEUTICAL INDUSTRY

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PHARMACEUTICAL INDUSTRY
Drug Discovery - natural sources,
synthesis/modification
biological properties - pharmacology,
pharmacokinetics
Preclinical Studies
preformulation - chem/phys properties -
analytical assays

• Formulation
• development of dosage form
• large-scale manufacturing

Clinical Trials
Approval for Distribution
Post-Marketing Surveillance
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Definitions

• drug - Any substance or mixture of substances
  manufactured, sold or represented for use in
• a) the diagnosis, treatment, mitigation or
  prevention of a disease, a disorder, an abnormal
  physical state or the symptoms thereof in humans
  or animals
• b) restoring, correcting or modifying organic
  functions in humans or animals
• c) disinfection in premises in which food is
  manufactured, prepared or kept
• pharmaceutics - the area of study concerned with
  the formulation, manufacture, stability, and
  effectiveness of dosage forms
• pharmacology - the science of the properties of
  drugs and their effects on the body
• pharmacokinetics - the study of the kinetics of
  absorption, distribution, metabolism, and
  excretion of drugs and their corresponding
  pharmacologic response in animals/man
• clinic - a facility or area where ambulatory
  patients are seen for special study and treatment

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Introduction

• Drugs seldom administered alone
• contain additional ingredients called excipients
• Need for dosage forms
• provide safe and accurate delivery
• protect drug from environmental and in vivo
  degradation
• provide rate-controlled action
• conceal bitter/salty taste, offensive odor
• allow for administration by the desired route
• Objective of dosage form design
• achieve a predictable therapeutic response to a
  drug included in a formulation which is capable
  of large scale manufacture with reproducible
  product quality

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Excipients
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Routes of Administration

• Considering only systemic delivery, wherein the
  objective is to get the drug into the blood
  stream. There are essentially two classes of
  delivery approaches
• enteral
• oral (peroral), rectal, buccal and sublingual
• parenteral
• injection (s.c., i.v., i.m.)
• transdermal
• nasal
• pulmonary

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Bioavailability

• extent of absorption and the rate at which an
  administered dose reaches systemic circulation in
  its active form

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Absorption

• Affected by
• 1. Physiological factors
• route of administration
• drug distribution
• 2. Drug chemical physical properties
• dissolution rate (solids)
• hydrophilicity/hydrophobicity

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Oral
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Oral Absorption
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Oral

• gastric emptying
• volume of gastric contents determines drug
• time dosage form/drug spends in stomach
  influences absorption
• liquids emptied faster than solids
• acids slow gastric emptying
• natural triglycerides inhibit gastric motility
• eating influences transit

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Drug Absorption

• oral administration plasma concentration time
  profile

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Therapeutic Window

• therapeutic response is dependent on drug
  achieving an adequate plasma concentration (Cp)

Cp
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Oral

• advantages
• patient compliance
• cheap compared to other routes
• transit time is consistent among individuals
• disadvantages
• hepatic first-pass effect
• possible enzymatic degradation/acid degradation
• effect too slow for emergencies
• presence of food retards absorption
• short window of time for absorption

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Rectal

• Rectal route
• lined with one or more layers of epithelial cells
• luminal side covered with mucus layer
• contains a small amount (1-3 ml) of fluid
• fluid has low buffering capacity
• abundantly vascularized
• drug absorption primarily by passive diffusion
• avoids some first pass clearance

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Buccal and Sublingual

• Avoids exposure to GIT.

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Parenteral

• i.v.

plasma concn
time after administration
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Parenteral

• i.m. and s.c.
• not all drugs fully absorbed
• tissue more acidic than most tissues
• blood flow is important
• good supply of capillaries
• drug absorption function of diffusion rate

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Transdermal

• rate limiting step is diffusion through stratum
  corneum

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Transdermal
Factors affecting absorption
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Transdermal

• Limitations
• drug must be potent
• drug must be effective when delivered slowly over
  a long period of time
• benefits over existing methods?
• Drug qualifications
• narrow therapeutic window
• subject to extensive first-pass degradation
• taken many times/day
• unpleasant side-effects

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Transdermally Delivered Drugs
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Nasal
advantageous for drugs poorly absorbed orally for
some peptides and small molecules,
bioavailability comparable to injections drugs
lypressin, desmopressin, vitamin B-12,
progesterone, insulin, calcitonin, propanolol
external naris
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Pulmonary

• - large contact surface (surface area gt 30 m2 )
• - extensive blood supply (2000 km of capillaries)
• - thin membrane separating air from blood

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Conventional Dosage Forms