The document discusses novel drug delivery systems. It begins with an overview of conventional drug delivery routes and their limitations. It then outlines the need for and goals of newer drug delivery modalities, which aim to control drug absorption, distribution, metabolism, and elimination. Several novel delivery routes are described in detail, including oral, sublingual, inhalation, transdermal, intranasal, and targeted delivery. Polymer-based delivery systems such as microspheres, nanoparticles, and intelligent delivery are also discussed. The document concludes by noting that advanced delivery technologies are playing an increasingly important role in improving drug safety, efficacy, and patient experience.

1. Novel Drug delivery
systems
Dr PRASHEETA V PRAVIRAJ
1ST YEAR MD PHARMACOLOGY
RANGARAYA MEDICAL COLLEGE

2. CONTENTS
 Conventional routes of drug delivery
 Need and Goals of newer modalities
 Oral and sublingual route of drug delivery
 Transdermal routes of drug delivery
 Inhalational routes of drug delivery
 Polymer based delivery systems

3. •Depot system
• Newer Delivery techniques
•Targeted drug delivery
•Prodrugs
•Gene Therapy
•Conclusions
•References

4. CONVENTIONAL ROUTES OF DRUG DELIVERY
OVERVIEW

5. NEED FOR NEWER MODALITIES
Controlled release
Individualized
therapy
Targeting

6. GOALS OF NEW MODALITIES
Is to alter the following four pharmacokinetic
properties:
 Absorption of drug
 Distribution of drug
 Metabolism of drug
 Elimination of drug

7. ORAL ROUTE OF DRUG DELIVERY
 Advantages
 Disadvantages
SUSTAINED /EXTENDED RELEASE FORMULATION
 Prolonged plasma drug conc.
 Excipients
 Coating
 Osmotic pump capsules
SPANSULES
Newer advancements – drug released in colon
lower levels of protease activity.(azoreductases)

8. SUBLINGUAL ROUTES
 No first pass metabolism
 Faster absorption
 Can be spit out
 Eg : Sublingual immunotherapy
 Warfarin Ketamine
 Fentanyl Methadone
 Nifedipine Diazepam
 Buprenorphine Domperidone
 Fentanyl sprays

9. INHALATIONAL ROUTES OF DRUG DELIVERY
POTENTIAL ADVANTAGES:
 Rapid delivery of drug
 Instantaneous absorption
 No first pass hepatic loss
 Action at desired site
 Non invasive
 Large alveolar surface/thin tissue lining
 Limited number of proteolytic enzymes

10.  PARTICLE SIZE –single most factor determining the
site of aerosol deposition
 Other factors
 Examples – asthma , insulin
 Common drugs – beta 2 agonists, corticosteroids, mast
cell inhibitors
 Under trial-Insulin,glucagon,antitrypsin
o>10mi oropharnynx
o5-10mi trachea, bronchi
o1-5mi lower airways
o<0.5mi act as gas and exhaled
oInertial impaction appropriate inhalation
oGravitational sedimentation technique
oBrownian motion

11. 1.METERED DOSE INHALERS
• Description
•Aerosol cloud
•Particle size
45mi
0.5-5.5mi
Lower airways
Disadvantges
•BREATH ACTUATED MDI’S
CFC-10”
HFA-6”
Inspiratory pressure baffle
opens dose expelled
No spacer device
Minimal hand-lung
coordination
•Ban on CFC- pressing
demand for newer modalities

12. 1.Spacer devices
- oropharyngeal deposition
- lung delivery
Types-Simple
-Valve holding chamber: opens during inhalation
>allows evaporation prior to inhalation
>no hand-lung coordination required
>minimal oropharyngeal deposition
2.Dry powder inhaler
-micronized powder
-flow dependent
3.Nebulizers
-Jet nebulisers
-Ultrasonic nebulisers

15. INTRANASAL ROUTES
Needle free
Patient friendly route
No biohazardous waste
Absorption rapid
No first pass metabolism
Dosage formulation
Normal physiology disruption should be
avoided
Eg : Insulin ( Exubera & afrezza )
Vitamin B12 (CALOMIST)

16. TRANSDERMAL DRUG DELIVERY SYSTEM
 Stratum corneum - lipophilic drugs
 No first pass metabolism
 Drugs delivered: NTG, estrogen(HRT),
 clonidine, fentanyl , nicotine , for motion sicknessss
,testosterone , methylphenidate
 Types
Passive TDDS
Active TDDS
 Unilamellar /Multilamellar

17. •Iontophoresis
•Electroporation
•Sonophoresis
•Laser ablation
•Radiofrequency thermal/heat
ACTIVE TDDS

18. Depot technology
 Introduction
 Medication mixed with polymers engineered to
biodegrade at desired rate
 Solution then injected into patient either s.c/i.m with
a fine gauge needle
 Injected solution solidifies and becomes implant that
acts as depot and releases drug over days / months
 Eg : DEPOPROVERA
 TESTOVIRON
 ANATENSOL

19. POLYMER BASED DELIVERY SYSTEM
Three general mechanisms via which polymer based drug
delivery can be achieved:
 Diffusion
 Chemical reaction
 Solvent activation
DIFFUSION
 -reservoir/matrix
 -molecular size approx 300daltons
 -microcapsule system
 Eg : Norplant
GnRH analogue

20. CHEMICAL REACTION
 -covalent bonds connect drug to the polymer
 -cleaved by endogenous enzymes
 -pegylation : water soluble : inc. half life
 -Eg : PEG Intron , PEG Grafeel
 -Bulk erosion
-Surface Erosion Hydrophobic
monomer connected by
anhydride bonds
 -Eg : Carmustine wafer
(GLIADEL)

21. SOLVENT ACTIVATION
 Swelling / Osmosis
 Eg : Extended release Nifedipine
Drug+osmotically active agent +membrane
coating(permeable to water but not drug)+laser drilled
hole
 Concerta:Methylphenidate - ADHD

22. POLYMER RELEASE MECHANISMS

23. INTELLIGENT DELIVERY
 Magnetic beads system
-along with 2yr supply of insulin embedded in polymer
matrix
-requires oscillating magnetic field externally
-alternating expansion and contraction of drug carrying
pores
 Ultrasound based system
-similar to magnetic bead system; cavitation
 Environmental stimuli
-sense temp.,pH,molecular structures
-Hydrogel :water+polymer
- pulsatile delivery

24.  Electric current system
electrolysis of water at polymer surface
decrease in local pH
H2 bonds disrupted
degradation of polymer
transient release of large dose
 Silicon microchips
-1000 tiny drug reservoirs ; covered with gold film
-small external voltage
-electrochemical reaction drug release

25. COMPUTERISED MINIATURE PUMPS
 Programmed to release drugs at a definite rate
 Continuous – Insulin
 Pulsatile – GnRH
 Patient controlled analgesia
pump
 Biosensor technology –
neurosciences(glutamate)

26. CARRIER SYSTEMS
 LIPOSOMAL
Microscopic vesicles – lipid bilayers
High drug carrying capacity
Stealth liposomes - pegylated liposomes , prolonged
circulation time , large doses , protection from immune
system
Eg: lip. Amphotericin
lip. Cyclosporin-
lip. Tretinon
lip. Doxorubicin
lip. Anthralin

27.  NANOPARTICLES
- 10-1000nm colloidal system
- Eg: Paclitaxel bound to albumin is
microemulsified into nanoparticles (ABRAXANE)
• increases solubility
• no hypersensitivity- no premedication
• less myelosuppresion
• but increased peripheral neuropathy
• Increased bioavailability

28. MICROSPHERES
 Polyanhydride microspheres adhere to the
intestinal mucosa and penetrate intestinal epithelium
.
 The complex drug molecule carried within them are
released slowly .
 Eg: Benzyl peroxide cream{already in use}

29. IMPLANTS
 Norplant
- levonorgesterol
- 6 capsules of sialistic rods
- placed subdermal inner aspect of upperarm within
one week of menstruation onset
- 5 years
 Gliadel wafer implant
-carmustine : 8 small polymer drug wafers
- GBM : following surgery placed in the cavity
- slowly erodes over
1 month

30. TARGETED DRUG DELIVERY
 Larger and more effective doses delivered
specifically to the tissue of interest.
 Anatomic placement of polymer based drug
delivery
1. Carmustine
wafer delivery
2. Estring

31. 1. Drug-eluting stents
2. Ocuserts

32. VITRASERTPROGESTASERT

33. 1. Intravesical drug delivery
2. Intraurethral delivery

34. Targeted drug delivery
PASSIVE ACTIVE
TARGETING TARGETING
Exploits vascular difference
between target tissue and other
tissue
Higher moleculer mass polymer
drug complexes accumulate in
some tumor tissues due to high
permeablity of capillary beds.
Eg: Doxorubicin conjugated to a
water soluble ,non-immunogenic ,
polymer through a peptide linker
inside the tumor.
Polymer drug conjugate linked to
a molecule that is recognized
specifically by cell surface receptors
in tissue of interest.
Eg: A human IgM antibody
directed against a tumor-associated
antigen can be used to target a
polymer–doxorubicin complex to
malignant tissues. Linked to the
polymer with an acid-labile bond,
the doxorubicin is selectively
released in the acidic environment
of the tumor .

35. MONOCLONAL ANTIBODIES
 Antibodies produced by a single clone and directed
against a single epitope
 Hybridoma technology
 Types
 Nomenclature : “mab”- suffix
 Letter “mab”- represents the source eg: “o” , “xi” , “zu” .
 Letter before that : represents therapeutic use eg: “tu” ,
“vi” , “ci”
 No prefix – immunomodulator
1. Murine MAb’s
2. Chimeric MAb’s
3. Humanised MAb’s

36. Hybridoma technology

37. Monoclonal eg
Monoclonal antibodies Indication
Alemtuzumab Chronic lymphocytic leukemia
Bevacizumab Brain , breast , colon , kidney , lung cancer
Cetuximab Colon cancer , head and neck cancer
Rituximab CLL , NHL
Transtuzumab Breast , Stomach cancer
Muromunab CD 3 Prevent transplant rejection
Edrecolomab Colorectal cancer
Abciximab Prevent platelet aggregation

38. PRODRUGS
 This is inactive form of a drug which gets
metabolised to an active drug in the body .
Prodrug Use
Levodopa Parkinsonism
Esters of penicillin Infection
Talampicillin Antibiotic for infection

39. Gene therapy
 Introduction of functional genetic material into
target cells to replace or supplement defective genes
or to modify target cells so as to achieve therapeutic
goals .
 Can impart new function to the cell
 Short term expression of introduced gene
 Eg: ADA deficiency treatment- SCID (Autosomal
recessive inheritance)


40. CONCLUSION
 Despite many obstacles , advanced drug delivery
technologies play an increasingly valuable role in
making the pharmacologic management of disease safer,
more effective , and more agreeable to patients.
 Targeted delivery has crossed its infancy period and
now touching heights of growth , still a lot of
developments have to come .
 Future scopes : "Nanomachines that could move through
the body troubleshooting and repairing tiny brain or
cardiovascular lesions lie in the future" (Morrow et al,
2007).

41. Reference
 Joshua D Moss , Robert S Langer ; Fundamental
Principles of Pharmacology; Drug delivery modalities ,
Chapter 64 ,Pg 917-923
 Joseph .T. Dipiro ,Et.al ;Pharmacotherapy- a
pathophysiologic approach , 7th edition , chapter 28
pg 472-474
 H.L. Sharma and K.K .Sharma Principles of
pharmacology , 2nd edition , chapter 3,4 Pg 7-15
 Gaurav Tiwari Et.al ;Drug delivery – An updated
review ; International journal of Pharmaceutical 2012
Jan-March .

42.  http://search.proquest.com/docview/219189423/B8C3F56BB2C34609P
Q/7?accountid=46224 Berkowitz, Angelia Colwell; Goddard, Diane M
. Journal of Neuroscience Nursing 41.2 (Apr 2009)Novel Drug
Delivery Systems: Future Directions: 115-20.
 Learn.Genetics ; University of Utah :ADA deficiency treatment

43. 10/20/2012 43
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