Parenteral drug delivery

1. PARENTERAL CONTROLLED –
RELEASE SYSTEMS
Presented by
Dasara Thanmayi

2. Classification of parenteral controlled release
systems
• Injectablets :
• Solutions
• Corse dispersion
a) emulsions
I ) simple emulsion
ii) multiple emulsion
b)suspensions
• Colloidal dispersion
a) liposomes
b) Niosomes
c)polymeric micelles
d)nano particles
 Micro particles
a)microspheres
b) microcapsules
 Resealed erythrocytes
• Implants
a) In-situ forming implants
b) solid implants
• Infusion devices
a) Osmotic pumps
b) Vapour pressure powered pumps
c) Battery powdered pumps

3. Microspheres
• Microspheres are characteristically free flowing powders
consisting of proteins or synthetic polymers which are bio
degradable in nature and ideally having a particle size less
than 200 micro meters

4. General methods of preparation microspheres
• The general methods of preparation and its choice are
equivocally determined but some formulation and
technology related factors as mentioned below
• The particle required
• The protein should not be adversely affected by the
process
• Reproducibility of release profile and method
• No stability problem.
• There should be non toxic product associated with the
final product

5. Polymerization technique
• This technique is used for conventional used for
preparation of microspheres
• normal phase method
• Interfacial polymerization
• Interfacial polymerization:
• Invokes reaction of monomers at interfaces between two
immiscible liquid phase to form a film of polymer that
essentially envelopes the dispersed phase

6. Methods of preparation of emulsion
Single emulsion
• sonication
•
heat
denaturation
centrifugation
Double emulsion
•Aq .solution / suspension
polymer
Dispresed in oil phase
Micro spheres in
organic phase
Micro spheres in
organic phase
Micro spheres
Aq .phase+
drug
polymer
Organic
phase
Free
emulsion
Multiple
emulsion
microspheres
A
a
sonication
addtion of
aqueous
phase
Solvent
evaporation

7. Normal phase polymerization
BULK
Suspension (bead / pearl
polymerization)
monomers
Polymer block
microspheres
Monomer bioactive
material initiator
Droplets
Microspheres
Dispersed in
water
polymerization

8. Phase separation and coacervation
• Specially designed for preparation of reservoir type of the
system also used for matrix type devices.
• Simple coacervation ; occurs in presence of only one macro
molecule eg : water/ gelatin. Induced by
• Non solvent addition
• Temperature change
• Incompatible polymer addition

9. Complex coacervation
• Two /more macromolecules of opposite charges
• Eg ; solution of positively charged gelatin with negatively
charged gum arabica
Aq/ organic solution of polymer
Drug dispersion in polymer solution
Drug in polymer rich globules
Microspheres in aq .phase
microspheres

10. Solvent extraction
• Polymer and drug must be soluble in organic
solvent
Drug + polymer in organic solvent
Aqueous phase
Extraction with water miscible
organic solvent
Microspheres in aqueous phase

11. characterization
• Particle size :particle size is determined 2-D microscopic
evaluation with a^1/3”ccd camera image accessory
• Determination of percentage yield :
•
total weight of micro spheres
total weight of raw material
Determination of drug loading: the drug loading is determined by
uv- visible spectrophotometer
m acutual
= weighed quantity of powdered micro spheres
100% yield =
Drug
loading
%
*100

12. • Incorporation efficiency of micro spheres:
• m actual
• m theoretical
• M actual is the actual drug content in weighed quantity of
powder of micro spheres
• M theoretical is the theoretical amount of drug in microspheres
calculated from the quantity added in the fabrication process
• Determination of solubility: take excess quantity of micro sphere
in 50 ml of water in a screw capped glass vials
• The solution was filled through the watt men filter paper no;1
and drug concentration was determined at a particular lamada
max value of drug
• Dissolution studies of micro spheres : dissolution of micro
Incorporation efficiency % =

13. Applications
• Micro encapsulated products currently on the markets such as
aspirin, theophylline and its derivatives , vitamins, potassium ,
chloride , progesteron ,and contraceptive harmone
combinations.
• Micro encapsulated kcl is used to prevent gastro intenstinal
complications associated with potassium chloride.
• Micro spheres have also found potential application as injection
or inhalation products.
• Other applications :
• Micro spheres are also extensively used as diagnostic agents for
example temprature sensitive micro encapsules for thermo
graphical detection of tumours.

14. parenteral suspensions
• Introduction : Parenteral suspension are dispersed
,heterogeneous system containing insoluble drugs
particles which when are to be resuspended in either
aqueous phase or oil vehicles before administrating to a
patient.
• They administered by either subcutaneous or intra
muscular route .
• For example procaine penicillin G.

15. Preparation of parenteral suspension
 Two basic methods used for preparation of suspension
are:
 Aseptically combining sterile powder and vehicle
Previously sterilized
& milled active
ingredients
Sterile
receiving
vessel
Vehicle& excipients
Sterilizing filter
(i.,e 0.22 micron)
Mixed/ milled
Final suspension
Aseptically disperse
active ingredients
Aseptic filling

16. In situ crystal formation by combining sterile solutions
Active ingredient in
solution ( organic
solvent )
Sterilizing filter (i.e,
0.22 micron)
Counter
solvent
Sterilizing filter
(i.e, 0.22 micron
Vehicle and
necessary excipients
Sterilizing filter
(i.e, 0.22 micron
Remove
organic solvent
Mill/mix

17. Characterization of parenteral suspension
• Physical evaluation :
• Syringeability
• Injectablity
• Resuspendibility
• Sedimentation volume
• Freeze thaw
• Crystal growth
• Particle size measurement
• viscosity

18. Applications
• Intratumoral administration of suspension
• Intravenous administration of suspension
• Micro particulate drug carrier administration
as intravenous suspension
• Delivery of drugs used in infections and viral disease
• Controlled release applications

19. Parenteral emulsion
• Introduction : an emulsion is a dispersion of a liquid
as globules in another liquid that is immiscible with
the first .
• Out of 2 liquids one is oil and the other is water
• Broadly emulsions are of 2 types
• simple emulsiom
a)o/w type
b) w/o type
• multiple emulsion
a) w/o/w emulsion
b) o/w/o emulsion

20. Preparation of simple parenteral emulsion
The emulsifier , an osmotic
agent and any preservatives
are usually dissolved or
dispressed in aqueous phase
The phospholipids ,anti oxidants and
lipophilic drugs to be incroprated
are usualiy dissolved or dipressed
Both the phases are then heated to
70-80 °c with agitation
The coarse emulsion is then formed
by vigorous stirring or mixing
Final P of formulation is adjusted
H

21. • Homogenization and particle size reduction :
It can be done by
• Ultra sonic homogenizers
• Micro fluidizer
• Collodial mills
• Filtration: membrane filtration is used for final filtration
to remove larger particles
• Sterilization : it is archived by autoclaving for large
volume parenterals (100-1000) injectable fat emulsions

22. Preparation of multiple emulsion
Primary emulsification
• water + drug
Secondary emulsification
Oil phase + primary
emulsifier
Primary emulsion
Primary
emulsion
rpm 5000
External aqueous
phase
Secondary
phase

23. Evaluation of parenteral emulsions
• Droplet Size:- optical microscope, atomic force microscope
electron microscope
• Zeta Potential:- zeta potential value of +_ 25mv has been
suggested to produce a stable emulsion
• Viscocity:- it should be optimum
• Ph:- it decreases during the sterilization of storage
• InVitro release:- diffusion cell method
• centrifugal ultra filtration
• Sterility test –membrane filtration
• direct inoculation
• pyrogen test-lal test
• rabbit test

24. Applications of parenteral emulsion
• Enhancement of solubility or stability: several de novo
emulsions formulations of pencolmedin
• For this emulsion solubility or stability is enhanced by
decreasing particle size i.e., 500nm to 250nm
• Physical compatibility : rhodamine B , into tnp plastics
was studied and found to be decreased by the addtion of
albumin , egg phospholipids , and parentral fat emulsions
• Lipid emulsion for sustained –released drug delivary :
• soya bean oil using egg phosphatides and using some
emulsifers an emulsion was prepared.
• Which prolongs the duration of action of barbiturates the
oil drop lets apparently serve as a depot from which the
drug was released either to blood or cell membrane

25. references
• Rajesh m. patel ; parental suspensions : an
over view international journal of current
pharmacueutical research vol 2 ,issue 3,2010.
• w.w.wSlideshare.net
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