Drug design and delivery

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 Lesson objectives

 Understand the problems of drug delivery and

some simple solutions

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 Success criteria

 Give advantages and disadvantages of oral

and injections
 Explain how hydrogels and liposomes work
and their advantages and disadvantages

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Keywords

 Injection
 Inhalation
 Liposomes
 hydrogels

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 Drug Delivery

 Drug delivery is the method or process of

administering pharmaceutical compound to
achieve a therapeutic effect in humans or
animals.

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 Common methodS of drug
delivery
 Oral -mouth
 Inhalation-nose
 Topical-skin
 Rectal-rectum

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 Drug Delivery
 Many medications such as peptide and protein,
antibody, vaccine and gene based drugs, in general
may not be administered using these routes because
they might be susceptible to enzymatic degradation or
can not be absorbed into the systemic circulation
efficiently due to molecular size and charge issues to
be therapeutically effective.

 Proteins and peptides are administered through

injection

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Research

 Group 1 –Oral
 Group 2-injection
 Group 3-hydrogels
 Group 4-liposomes

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 Why do we need NDDS?
 The conventional dosage forms provide drug release
immediately and it causes fluctuation of drug level in
blood depending upon dosage form.

 Therefore to maintain the drug concentration within

therapeutically effective range need novel drug
delivery system.

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 Novel Drug Delivery System
 NDDS is advanced drug delivery system which
improves drug potency, control drug release to
give a sustained therapeutic effect, provide
greater safety, finally it is to target a drug
specifically to a desired tissue.

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 Novel Drug Delivery System
 NDDS is a system for delivery of drug other than
conventional drug delivery system.

 NDDS is a combination of advance technique and

new dosage forms which are far better than
conventional dosage forms.

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 Hydrogels
Three dimensional structures of hydrophilic
polymers having chemical and physical cross
links provide a network structure to hydrogels.
These are insoluble due to network structure and
provide desirable protection of liable drugs,
proteins and peptides).

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 Advantages of hydrogels
 Optimum dose at the right time and right location.

 Efficient use of expensive drugs, excipients and

reduction in production cost.

 Beneficial to patients, better therapy, improved

comfort and standard of living.

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 Advantages of hydrogels
 Decreased dosing frequency.
 Reduced rate of rise of drug concentration in
blood.
 Sustained and consistent blood level within the
therapeutic window.
 Enhanced bioavailability.
 To achieve a targeted drug release.
 Reduced side effects.
 Improved patient compliance.
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 What are Liposomes?

 Lipsomes are vesicular structures

consisting of hydrated bilalyers which
form spontaneously when phospholipids
are dispersed in water.
 Concentric bilayer vesicles in which
aqueous volume is entirely enclosed by a
lipid bilayer made of phospholipids.
 What are Liposomes?

 Phospholipid Bilayers are the core structure of liposome and cell membran

formations.

 `

Liposome Cell Membrane

Liposome structure
Hydrophilic heads

Aq. cavity
Lipophilic
tails
 Advantages of liposomes...
• Liposomes are biocompatible, completely biodegradable,
non-toxic, flexible and non-immunogenic for systemic and
non-systemic administrations.
• Improved solubility of insoluble drugs
• Improved Stability (Protects drug)
• Improved PK (Changes the absorbance and biodistribution)
• Increased efficacy and therapeutic index
• Reduced toxicity and side effects
• Site specific delivery (Directly to site).
• Controlled drug release: Prolong time -increase duration of
action and decrease administration
• Altered liposome surface with ligand (antibodies,
enzymes, protein A, sugars).
DISADVANTAGES
  OF LIPOSOME
• their rapid clearance from circulation due to uptake, by the
reticulo endothelial system(RES), primarily in the liver.
• Short half-life.
• Fewer stability
• Low solubility.
• Low encapsulation efficiency
• Leakage and fusion of encapsulated drug / molecules.
• Production cost is high.
Exam style questions
A number of drugs, such as insulin for diabetics,
are delivered by injection rather than by mouth
(oral delivery). Suggest two reasons why this migh
be necessary.

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Circle two bonds, each in a different functional
group, that could be hydrolysed in the digestive
ystem

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 One way of protecting drug molecules that are
taken by mouth is to enclose them in liposomes.
These are artificially created spheres made from
phospholipids which have an ionic phosphate
‘head’ and two hydrocarbon ‘tails’.

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 State in which area of the liposome, A, B or C,
each of the following types of drug would be
carried.
 a hydrophilic drug .........................
 a hydrophobic drug .......................
 (ii) For the remaining position, A, B or C, explain
why this would not be a suitable area for carrying
a drug

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 One way of carrying drugs in the bloodstream is to
attach them by a chemical bond to a polymer. One
such polymer is polyethylene glycol or PEG.
 HO – (CH2 – CH2 – O)n – H
 (i) Where would a drug be attached to a molecule of
PEG? ............................................................................
...................................................... (ii) Suggest why a
liposome can carry more drug molecules than a
molecule of
PEG. .............................................................................
.....................................................

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 Better-targeted delivery of drugs allows smaller
amounts to be used, which brings significant
advantages. Suggest two advantages of using
smaller drug
doses. ....................................................................
................................................................

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Which one of the following compounds would not be
suitable to be taken orally?

On the structure of your chose circle all the functional

groups that might be broken down by acid.
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By considering the nature of the functional groups
in A, B and C, explain why these drugs can be
carried at position R in the liposome

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 Another method of protecting drug molecules is
to ‘trap’ them inside gold nano-cages. When they
reach the site where they are needed, such as a
tumour, the drug is released by exposing the site
to infra-red radiation. (i) Suggest the size of the
nano-cages in
metres. ..................................................................
...........................................................................

 Suggest why infra-red, rather than higher
frequency radiation is used.

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Drugs can be delivered in a number of ways. The method chosen
depends both on the nature of the drug, and the problem it is being
used to treat.

(a) Many common drugs are taken by mouth in forms similar to

those shown. P Q digestible gel casing
(i) Some drugs are available in solution. How would the speed of
action of this form compare with P and Q? Explain your answer.
...

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(ii) Explain which of the two forms, P or Q,
would act the most rapidly when taken by
mouth.
(iii) Some drugs are broken down before they
can be absorbed by the intestine. Suggest how
the design of Q prevents this...
(b) After an abdominal operation drugs are often
delivered by means of a ‘drip’ inserted into a
blood vessel in the patient’s arm. Explain why
this is more effective than taking painkillers by
mouth.

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 Oseltamivir is an antiviral drug that slows the spread of
the infl uenza (fl u) virus.

 A) Circle two bonds, each in a different functional

group, that could be easily hydrolysed in the body.

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 b) Oseltamivir is a chiral drug. This drug is
usually taken as a single optical isomer rather
than as a mixture of isomers. Suggest one benefi t
of taking a drug in this way.
 c)Oseltamivir is a competitive inhibitor of an
enzyme produced by the fl u virus. Explain the
meaning of the term competitive inhibitor and
state how its action could be overcome

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 Methoxetamine is a derivative of the pharmaceutical
drug, ketamine.

 (i) What is the molecular formula of

methoxetamine?
 On the diagram above, circle any chiral centres that
are present in methoxetamine.
 (iii) Name two functional groups in methoxetamine,
in addition to the aryl group

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In the table, complete the structure of each of the compounds
formed when methoxetamine is reacted with the following
reagents. State the type of reaction in each case.

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