Par-enteral drug delivery systems are the preparations that are given other than oral route. (Para-outside, enteric–intestine). ... The Par-enteral 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.

1. PARENTERAL CONTROLLED DRUG
DELIVERY SYSTEM
6/15/2020
By. Mr. Sachin Chandankar
Research Scholar
M. Pharmacy
(Pharmaceutics) & PGD-IPR

2. CONTENTS
 Introduction
 Objective
 Additives used in formulation
 Routes of administration
 Approaches for formulation
 Type of formulation
 Classification
 Approaches for formulations of Implants
 Infusion Devices
 References
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3. Objectives
 Site-specific delivery
 Reduced side effects
 Increased bio-availability
 Increased therapeutic effectiveness
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4. 6/15/2020

5. Advantages over conventional drug
delivery system
 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
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6. Disadvantages of controlled release
dosage forms
 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.
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7. Routes of administration
 Intravascular
 Intramuscular
 Subcutaneous
 Intradermal
 Intraarticular
 Intraspinal
 Intrathecal
 Intracardiac
 Intrasynovial
 Intravaginal
 Intraarterial
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8. CHARACTERISTICS
 Free from living microbes
 Free from microbial products such as pyrogens
 Should match the osmotic nature of the blood
 Free from chemical contaminants
 Matching specefic gravity
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9. ADDITIVES USED DURING FORMULATION
OF PARENTRALS
 Vehicles
 Stabilizers
 Buffering agents
 Tonicity factors
 Solubilizers
 Wetting, suspending, emulsifying agents
 Antimicrobial compounds
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10. APPROACHES FOR
FORMUALATION
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11. 116/15/2020
PARAMETERS MANIPULATED IN THE
DESIGN OF PARENTRAL CONTROLLED
FORMS
 Route of administration
 Vehicles
 Vaso-constriction
 Particle size
 Chemical modification of drug

12. Approaches
 Use of viscous, water-miscible vehicles, such as
an aqueous solution of gelatin or
polyvinylpyrrolidone.
 Utilization of water-immiscible vehicles, such as
vegetable oils, plus water-repelling agent, such
as aluminum monostearate.
 Formation of thixotropic suspensions.
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13.  Preparation of water-insoluble drug derivatives,
such as salts, complexes, and esters.
 Dispersion in polymeric microspheres or
microcapsules, such as lactide-glycolide
homopolymers or copolymers
 Co-administration of vasoconstrictors.
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14. TYPE OF FORMULATION
 Dissolution-controlled Depot formulations
 Adsorption-type Depot preparations
 Encapsulation-type Depot preparations
 Esterification-type Depot preparations
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15. 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
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( Q
t )d
=
SaDsCs
hd

16. Drawbacks
 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.
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17. Approaches
 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.
 Exception
 Penicillin G procaine suspension in gelled peanut oil for
I.M. injection.
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18. 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
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1
a(C)b.m
(C)f
(C)b
= +
(C)f
(C)b,m

19. 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.
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20. Encapsulation-type Depot
Preparations
 E.g., Naltrexone pamoate-releasing biodegradable
microcapsules.
 Release of drug molecules is controlled by
 Rate of permeation across the permeation barrier
 The rate of biodegradation of the barrier macromolecules.
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21. 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
 Interfacial partitioning of drug esters from reservoir
to tissue fluid.
 Rate of bioconversion of drug esters to regenerate
active drug molecules.
 E.g., Fluphenazine enanthate, nandrolone decanoate, and
testosterone 17B-cyprionate in oleaginous solution.
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22. CLASSIFICATION
INJECTABLES IMPLANTS INFUSION DEVICES
Solutions
Suspensions and
Emulsions
Microspheres and
Microcapsules
Nanoparticles and
Niosomes
Liposomes
. Resealed
Erythrocytes
Osmotic Pumps
Vapor Pressure
Powered Pumps
Intraspinal Infusion
Pumps
Intrathecal Infusion
Pumps
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23. Solutions
 Aqueous 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
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24. Solutions
 Oil solutions
 Drug release is controlled by controlling
partitioning of drug out of oil into surrounding into
aqueous medium
 For I.M. administration only
 No. of oils are limited
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25. Suspensions
 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
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26. Suspensions
 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
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27. Suspensions
 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
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28. Emulsions
 Can be given by I.M., S.C., or I.V. routes
 O/w systems are not used due to large interfacial
area and rapid partitioning.
 W/o emulsions are used for water soluble drugs.
 Multiple emulsions are used generally such as w/o/w
and o/w/o since an additional reservoir is presented
to the drug for partitioning which can effectively
retard its release rate.
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29. Emulsions
 Release of water soluble drugs can be retarded by
presenting it as oil suspension and vice versa.
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Aqueous phase
Oil phase
Water soluble drug
e.g., 5-Fluorouracil
Oil soluble drug
e.g., lipidol

30. Microsphere
 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.
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31. Microsphere
 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.
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32. Microcapsules
 Drug is centrally located within the polymeric shell.
 Release is controlled by dissolution, diffusion or
both.
 For potent drugs such as steroids, peptides and
antineoplastics.
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33. Nanoparticles and Niosomes
 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.
 Nanosomes are closed vesicles formed in aqueous
media from nonionic surfactants with or without the
presence of lipids.
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34. Liposomes
 Spherule/vesicle of lipid bilayers enclosing an
aqueous compartment.
 Lipid most commonly used are phospholipids,
sphingolipids, glycolipids and sterols.
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liposomes
MLV OLV ULV
GUVMUV LUV

35. Liposomes
 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.
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36. Liposomes
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37. Resealed Erythrocytes
 Biodegradable, biocompatible, nonimmunogenic.
 Can circulate intravascularly for days and allow large
amounts of drug to be carried.
 Drug loading in erythrocytes is easy.
 Damaged erythrocytes are removed by liver and
spleen.
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38. Ideal Characteristics
 Envionmentally stable
 Biostable
 Biocompatible
 Nontoxic and noncarcinogenic
 Nonirritant
 Removable
 Provide constant release
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39. Advantages and Disadvantages
 Advantages
 More effective and more prolonged action
 Small dose is sufficient
 Disadvantages
 Microsurgery is required
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40. Approaches to implantable drug delivery
CDD by diffusion Activation process Feedback regulated
Osmotic pressure
Vapour pressure
Magnetically activated
Phonophoresis
Hydration activated
Hydrolysis activated
Bioerosion
Bioresponsive
Polymer
membrane
Matrix
diffusion
Microreservoir
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41. 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.
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Polymeric
membrane
nonporous
microporous
semipermeable

42. Polymer membrane permeation
controlled DDS
 Encapsulation of drug in reservoir can be done by
encapsulation, microencapsulation, extrusion,
molding or any other technique.
 E.g., Norplant Subdermal Implant.
6/15/2020

43. 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
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44. 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
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45. 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
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46. Microreservoir Partition Drug
Delivery Device
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47. Controlled drug delivery by activation
process
 Osmotic pressure activated
 Vapor pressure activated
 Magnetically activated
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48. 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
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49. 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.
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50. Vapor pressure activated
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51. 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.
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52. Magnetically activated
 External surface is coated with pure polymer, such
as ethylene vinyl acetate copolymer or silicone
copolymer.
 The drug is activated to release at much higher rate
by applying the external magnetic field.
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53. Magnetically activated
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1mm
Magnet ring
Coated
Polymer
Magnet inside polymer matrix

54. Feedback Regulated DDS
 Hydration activated
 Hydrolysis activated
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55. Hydration activated
 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
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56. Hydrolysis 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.
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57. INFUSION DEVICES
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58. Infusion devices
 The implantable infusion pump (IIP) is a drug
delivery system that provides continuous infusion of
an agent at a constant and precise rate.
 The purpose of an IIP is to deliver therapeutic levels
of a drug directly to a target organ or compartment.
 It is frequently used to deliver chemotherapy directly
to the hepatic artery or superior vena cava.
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59. Intraspinal infusion device
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60. RECENT DEVELOPMENTS
LIPOSOMES
Passive tumour targeting
Vaccine adjuvants
Passive targeting to lung endothelium in gene delivery
Targeting to regional lymph nodes
Targeting to cell surface ligands in various organs/areas of
pathology
Sustained release depot at point of injection
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61. Niosomes
Passive tumour targeting
Vaccine adjuvants
Sustained release depot at point of injection
Nanoparticles
Passive tumour targeting
Vaccine adjuvants
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62. Microparticles:
Sustained release depot at point of injection.
Vaccine adjuvants
Implant system:
Localised depot systems for the treatment of infections and
cancers. Sustained drug release systemic therapies
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RECENT DEVELOPMENTS

63. 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
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64. EMULSION
 Lipophilic drug administration vehicles
 Targeting to cell surface antigens
 These are the dispersions of one liquid inside the other
liquid
 Droplet size of 100-200nm which results in high drug
liver uptake on I.V injection
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65. 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
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66. 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
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67. 6/15/2020
Needle free injections
Decreased pain on injection
Increased bioavailability of intradermal vaccines

68. 686/15/2020
 “Parenteral Drug Delivery and Delivery Systems”, in
“Controlled Drug Delivery System” by Y.W.Chein;
Marcel Decker Publications Vol. 50 pg – 381 -513.
 “Parenteral Drug Delivery”, in “Targeted and Controlled
Drug Delivery” by Vyas and Khar pg – 30-33.
 “Parenteral Products”, in “Controlled Drug Delivery” by
Robinson and Lee; Marcel Decker Publications, Vol. 29
pg – 433 – 450.
References

69.  “Parenterals” in “Sterile Dosage Forms and Delivery
Systems” by Ansel, pg 444-451, 488-489.
 “Parenteral Drug Delivery Systems” in “Encyclopedia of
Controlled Drug Delivery System” pg 752-753.
 “Controlled Release Medication” in “Biopharmaceutics
and Pharmacokinetics A Treatise” by D.M.Brahmankar,
Sunil B. Jaiswal; pg 357-365.
 http://www.pharmainfo.net
 www.pharmj.com/.../education/parenteral2.html
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70. Thank you!
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