parenteral drug delivery system

1. PARENTERAL CONTROLLED DRUG
DELIVERY SYSTEM
Miss. SNEHAL K. DHOBALE
M-PHARMACY (2ND SEMISTER)
ROLL NO-02
PADM. Dr. D. Y. PATIL COLLEGE OF PHARMACY, AKURDI

2. INTRODUCTION
 Parenteral is the introduction of nutrition, a medication, or
other substance into the body via a route other than the mouth,
especially via infusion, injection or implantation.
 Controlled Release drug delivery systems aim to maintain
plasma concentration of drugs within the therapeutic window
for a longer period of time
 The Parenteral administration route is the most common and
efficient for delivery of active drug substances with poor bio-
availability and the drugs with a narrow therapeutic index
 Para: outside
 Enteron: intestine (i.e. beside the intestine)

3. OBJECTIVES of PARENTERAL
CONTROLLED DRUG DELIVERY
SYSTEM
1) Site-specific delivery
2) Reduced side effects
3) Increased bio-availability
4) Increased therapeutic effectiveness

4. Properties of ideal PCDDS
1.
• Simple to administer and remove
2.
• Inert
3.
• Biocompatible
4.
• Comfortable for the patient
5.
• Capable of achieving high drug loading
6.
• Readily processable

5. Advantages & Disadvantages of PCDDS
Advantages
• Improved patient
convenience and
compliance.
• Reduction in fluctuation in
steady-state levels.
• Increased safety margin of
high potency drugs.
• Maximum utilization of
drug.
• Reduction in health care
costs through improved
therapy, shorter treatment
period, less frequency of
dosing
Disadvantages
• Decreased systemic
availability
• Poor in vitro-in vivo
correlation
• Possibility of dose
dumping.
• Retrieval of drug is difficult
in case of toxicity,
poisoning or
hypersensitivity reactions.
• Reduced potential for
dosage adjustments.
• Higher cost of
formulations.

6. Routes of administration of PCDDS
1) Intramuscular
2) Subcutaneous
3) Intradermal
4) Intraarticular
5) Intraspinal
6) Intrathecal
7) Intracardiac
8) Intrasynovial
9) Intravaginal
10) Intraarterial

7. • Drug absorption is controlled by slow dissolution of
drug particle.
• Eg. Formation of salt or complexes with low
aqueous solubility, Suspension of Macrocrystals.
DISSOLUTION
CONTROLLED
DEPOT
• Binding of drug molecules to adsorbent [Al(OH)3]
• Eg. Vaccine preparations
ADSORPTION
TYPE DEPOT
• Encapsulating drug within permeation barrier
/dispersing drug particles in a diffusion matrix
• Eg. Naltrexone pamoate-releasing biodegradable
microcapsule, liposome, & Norethindrone-
releasing biodegradable beads.
ENCAPSULATION
TYPE DEPOT
• Esterifying drug to form bioconvertible Prodrug-
type ester & then into injection.
• Eg. Fluphenazine enanthate, nandrolone
decanoate in oleaginous solution.
ESTERIFICATION
TYPE DEPOT
Mechanism:On the basis of different mechanism,
depot formulation categorize into four types

8. DISSOLUTION TYPE DEPOT
FORMULATIONS
• Drug absorption is controlled by slow dissolution of drug
particles.
• Rate of dissolution is given by ;
where,
Sa – Surface area of drug particles
Ds – Diffusion coefficient of drug
Cs – Saturation solubility of drug
hd – Thickness of hydrodynamic diffusion
( Q
t )d
=
SaDsCs
hd

9. DISSOLUTION TYPE DEPOT
FORMULATIONS
Formation of salts or
Complexes with Low
solubility.E.g.,
Aqueous
suspensions of
benzathine penicillin
G.
Suspension of macro
crystals.
E.g., aqueous
suspension of
testosterone
isobutyrate for I.M.
administration.
Approaches
Release of drug
molecules is not of zero
order kinetics as
expected from the
theoretical model.
Surface area Sa of drug
particles diminishes with
time.
The saturation solubility
Cs of the drug at the
injection site cannot be
easily maintained.
Drawbacks

10. ADSORPTION-TYPE DEPOT
PREPARATION
• Formed by binding of drug molecules to adsorbents.
• Only unbound, free species of drug is available for
absorption.
• Equilibrium conc. of free, unbound drug species (C)f is
determined by the Langmuir relationship.
• E.g., - Vaccine preparations
1
a(C)b.m
(C)f
(C)b
= +
(C)f
(C)b,m

11. ENCAPSULATION-TYPE DEPOT
PREPARATIONS
• Prepared by encapsulating drug solids within a permeation
barrier or dispersing drug particles in a diffusion matrix.
• Membrane – biodegradable or bioabsorbable macromolecules
• Gelatin, Dextran, polylactate, lactide-glycolide copolymers,
phospholipids, and long chain fatty acids and glycerides.
• E.g., Naltrexone pamoate-releasing biodegradable
microcapsules.
• Release of drug molecules is controlled by
i. Rate of permeation across the permeation barrier
ii. The rate of biodegradation of the barrier macromolecules

12. ESTERIFICATION-TYPE DEPOT
PREPARATION
• Esterifying a drug to form a bioconvertible prodrug-type ester.
• Forms a reservoir at the site of injection.
• Rate of absorption is controlled by
1) Interfacial partitioning of drug esters from reservoir to tissue
fluid.
2) Rate of bioconversion of drug esters to regenerate active drug
molecules.
• E.g., Fluphenazine enanthate, nandrolone decanoate, and
testosterone 17B-cyprionate in oleaginous solution.

13. CLASSIFICATION OF PARENTERAL
CONTROLLED DRUG DELIVERY
SYSTEM
INJECTABLE DRUG
DELIVERY
IMPLANTABLE DRUG DELIVERY SYSTEM
1) In situ forming drug
delivery systems (ISFD)
i) Thermoplastic pastes
ii) In situ cross linked systems
iii) In situ polymer precipitation
iv) Thermally induced gelling system
v) In situ solidifying organogels.
2) Solutions
3) Microspheres
4) Liposomes
5) Suspension
6) Solid liquid nanoparticles
1) In-situ forming implant
i. Thermoplastic pastes
ii. In-situ polymer precipitation
2) Solid Implants
i. ALZET osmotic pump
ii. DUROS infusion implant

14. INJECTABLE DRUG DELIVERY: 1) In situ
forming drug delivery systems (ISFD)
1) THERMOPLASTIC PASTES
Semisolid polymers which injected as a melt and form a depot upon cooling to body
temperature.
2) IN SITU CROSS LINKED POLYMER SYSTEMS
Cross-linked polymer network can be found in situ by free radical reactions initiated by
heat (thermosets) /absorption of photon / ionic interactions between small cation &
polymer anions
3) IN SITU POLYMER PRECIPITATION
Water-insoluble and biodegradable polymer in biocompatible organic solvent.Phase
separation and precipitation of the polymer forming the depot at the site of injection
4) THERMALLY INDUCED GELLING SYSTEM
Gelation at body temperature when highly concentrated polymer solution
>15% w/w were injected
5) IN SITU SOLIDIFYING ORGANOGELS
Water insoluble amphiphilic lipids, which swell in water and forms various types of
lyotropic liquid crystals.

15. INJECTABLE DRUG DELIVERY:
2) Solutions
• HIGH VISCOSITY SOLUTIONS
• For comp. with mol. wt. more than 750
• For water sol. drugs
• Gelling agents or viscosity enhancers are used
• COMPLEX FORMULATIONS
• Drug forms dissociable complex with macromolecule
• Fixed amount of drug gets complexed
• Given by I.M. route
Aqueous
solutions
• Given by I.M. route.
• Process of drug availability consists of dissolution of drug
particles followed by partitioning of drug from oil solution to
aqueous medium.
• More prolong dug action as compared to oil solution and
aqueous suspension.
• E.g., Penicillin G procaine in vegetable oil
Oil
suspensi
ons

16. INJECTABLE DRUG DELIVERY:
3) Microspheres
 Each microsphere is basically a matrix of drug dispersed in a
polymer from which release occurs by first order process.
 Polymers used are biocompatible and biodegradable.
Polylactic acid, polylactide coglycolide etc.
 Drug release is controlled by dissolution degradation of matrix.
 Small matrices release drug at a faster rate.
 For controlled release of peptide/protein drugs such as LHRH
which have short half-lives.
 Magnetic microspheres are developed for promoting drug
targeting which are infused into an artery.
 Magnet is placed over the area to localize it in that region.

17. INJECTABLE DRUG DELIVERY:
4) Liposomes
 Spherule/vesicle of lipid bilayers enclosing an aqueous
compartment.
 Lipid most commonly used are phospholipids, sphingolipids,
glycolipids and sterols.
 Water soluble drugs are trapped in aqueous compartment.
 Lipophilic ones are incorporated in the lipid phase of liposomes.
 Can be given by I.M., S.C., for controlled rate release.
 Can be given by I.V. for targeted delivery.

18. INJECTABLE DRUG DELIVERY: 5)
Suspension
AQUEOUS SUSPENSIONS
• Given by I.M. or S.C. routes
• Conc. of solids should be 0.5
to 5 %
• Particle size should be < 10
μm
• Drug is continuosly dissolving
to replenish the lost.
• For oil soluble drugs
• Only crystalline and stable
polymorphic drugs are given
by this form
• Viscosity builders can be used.
• E.g., Crystalline zinc insulin
OIL SUSPENSIONS
• Given by I.M. route.
• Process of drug availability
consists of dissolution of drug
particles followed by
partitioning of drug from oil
solution to aqueous medium.
• More prolong dug action as
compared to oil solution and
aqueous suspension.
• E.g., Penicillin G procaine in
vegetable oil

19. INJECTABLE DRUG DELIVERY:
6) Solid liquid nanoparticles
 Nanoparticles are called as nanospheres or nanocapsules
depending upon the position of drugs
 Polymer used are biodegradable ones.
 Polyacrylic acid, polyglycolic acid
 For selective targeting therapy

20. IMPLANTABLE DRUG DELIVERY
SYSTEM
1) In-situ forming implant
i. Thermoplastic pastes
ii. In-situ polymer precipitation
2) Solid Implants
i. ALZET osmotic pump
ii. DUROS infusion implant

21. CLASSIFICATION OF IMPLANTABLE
DRUG DELIVERY SYSTEM
A) Controlled
drug release by
diffusion
1) Membrane
permeation-controlled
release system
2) Matrix diffusion-
controlled release system
3) Micro-reservoir
dissolution-controlled
release system
4) Membrane matrix
hybrid type-controlled
release system
B) Controlled
drug release by
activation
1) Osmotic pressure
activated eg.- Alzet pump
2) Vapour pressure activated eg.-
Infusaid pump
3) Magnetically activated
4) Phonophoresis
5) Hydrolysis activated eg.-
for control release of
levonorgestrel
(poly ortho esters used)
6) Hydration activated eg.-
Hydron implant
C) Controlled drug
delivery by
feedback regulated
mechnism
1) Bioerosion regulated
drug delivery system
2) Bioresponse activated
drug delivery system

22. A. Controlled drug release by diffusion
Approach Mechanism example
Membrane permeation-
controlled release
Drug encapsulated in
capsule / spherical
compartment
Norplant subdermal implant
Matrix diffusion-controlled
release
Homogenous dispersion of
drug in lipophilic/
hydrophilic polymer matrix
Compudose implant
Micro-reservoir dissolution-
controlled release
Drug in suspension in
aqueous solution of water
miscible polymer forms
dispersion of drug reservoir
in polymer matrix
Syncro mate implant
Membrane matrix hybrid
type-controlled release
Hybrid of polymer
membrane permeation
controlled DDS and
Polymer matrix diffusion
controlled DDS
Norplant II

23. 1) Polymer membrane permeation
controlled DDS
 Reservoir is solid drug or dispersion of solid drug in liquid or
solid medium.
 Drug enclosed in reservoir and reservoir is enclosed in rate
limiting polymeric membrane.
 Encapsulation of drug in reservoir can be done by
encapsulation, microencapsulation, extrusion, molding or any
other technique.
 E.g., Norplant Subdermal Implant
Polymeric membrane
nonporous
microporous
semipermeable

24. 2) Polymer Matrix diffusion controlled
DDS
 Drug is homogeneously dispersed throughout polymer matrix.
 Polymers used are :
 Lipophilic polymers
 Hydrophilipic polymers
 Porous
 Decreasing release with time
 E.g., Compudose implant

25. 3) Membrane-Matrix Hybrid type Drug
Delivery Device
 Hybrid of first two
 Minimizes the risk of dose dumping
 Drug reservoir is homogeneous dispersion of drug solids
throughout a polymer matrix, and is further encapsulated by
polymeric membrane
 E.g., Norplant II Subdermal Implant

26. 4) Microreservoir Partition Drug Delivery
Device
 Drug reservoir is a
suspension of drug crystals
in an aqueous solution of
polymer.
 Device is further coated with
layer of biocompatible
polymer.
 Polymer used for matrix :
water soluble polymers
 Polymer used for coating :
semipermeable polymer

27. B. Controlled drug release by activation
Approach Mechanism Examples
Osmotic pressure activated Drug reservoir solution or
semisolid placed within
semipermeable housing with
controlled water permeability
Alzet osmotic pump
Vapour pressure activated Drug reservoir is solution is
placed inside infusate chamber
Infusaid pump
Magnetically activated Magnetic wave triggering
mechanism is incorporated
into drug delivery device
Hydrolysis activated Solid drug is homogenously
dispersed throughout polymer
matrix of bioerodible or
biodegradable polymer
Levonorgestrel using
Poly ortho esters
biodegradable polymer
Hydration activated Solid drug is coated by
hydrophilic polymer
Hydron implant

28. 1) Osmotic pressure activated
 Osmotic pressure is
used as energy source
 Drug reservoir is either
a solution or semisolid
formulation
 Cellulosic outer
membrane
 Polyester internal
membrane

29. 2) Vapor pressure activated
 Vapor pressure is used as
the power source.
 Drug reservoir is a
solution formulation.
 Fluid which vaporizes at
body temperature is used
such as fluorocarbon.
E.g., Infusaid Pump for
Heparin.

30. 3) Magnetically activated
 Electromagnet is used as power source.
 Drug can be triggered to release at varying rates depending
upon the magnitude and the duration of electromagnetic
energy applied.
 A tiny donut shaped magnet at the centre of medicated
polymer matrix that contains a homogeneous dispersion of
drug
 It has low polymer permeability

31. C. Controlled drug delivery by feedback
regulated mechanism
Approach Mechanism
Bioerosion regulated Drug dispersed bioerodible
matrix fabricated with polymer
coated with immobilised urease
Bioresponse activated Drug enclosed in bioresponsive
polymer whose permeability is
controlled by concentration of
biochemical agent in tissue

32. 1) Bioerosion regulated
 Releases drug upon activation by hydration of device by tissue
fluid at the implantation site.
 Hydrohilic polymer is used for formulation which becomes
swollen upon hydration.
 Drug gets released by diffusing through the water saturated
pore channels in the swollen polymer matrix.
 E.g., Norgestomet releasing Hydron Implant

33. 2) Bioresponse activated
 Release drug upon hydrolysis of polymer base by tissue fluid
at implantation site.
 Polymer used is bioerodible or biodegradable polymer.
 Pellet or bead shaped implant.
 Rate of drug release is determined by rate of biodegradation,
polymer composition and mol. Wt., drug leading and drug
polymer interactions.
 Erosion rate is controlled by using a buffering agent.

34. RECENT DEVELOPMENTS:
CYCLODEXTRIN
 Lipophilic drug solubilisation for
parenteral use
 These compounds form inclusion
complexes with hydrophobic guest
molecule
 Modfied cyclodextrins such as
hydroxypropyl b-cyclodextrin and
sulphobutyl b-cyclodextrins are
regardedas safe for parentral use

35. RECENT DEVELOPMENTS:ADEPT
 Active tumour targeting
 It is an Antibody Directed
Enzyme Prodrug Therapy
 An antibody enzyme conjugate
is administered intravenously ,
localises in tumour tissue and
subsequently activates an
administered prodrug
predominantly within such
tumours

36. RECENT DEVELOPMENTS:POLYMER
DRUG CONJUGATES
 Passive tumour targeting
 These include soluble
polymeric prodrugs of
daunorudicin, doxorubicin,
cisplatin and 5- flurouracil
 These PDC accumulate
selectively within tumour
tissues

37. RECENT DEVELOPMENTS: Needle free
injections
 Decreased pain on injection
 Increased bioavailability of intradermal vaccines