Full lecture is available in youtube
Part1: https://youtu.be/-8v5VmM-kVg
Part2: https://youtu.be/TdrEUEDAcbU
The Lecture includes:
Introduction to Novel Drug Delivery Systems
What is Drug?
Drug Discovery and Drug Development
Challenges in Drug Discovery & Drug Development
Novel Drug Delivery Systems
Conventional vs Novel Drug Delivery Systems
Various Novel Drug Delivery Systems
NDDS Course contents are available at https://theabhi.in/pharma/ndds
4. Abhijit Sir
TheAbhi.in
Drug & Formulation
A drug is any substance that causes a change in an organism's
physiology or psychology when consumed
In pharmacology, a drug is a chemical substance, which
administered to a living organism, produces a biological effect.
A Drug is a chemical substance used to treat, cure, prevent, or
diagnose a disease or to promote well-being.
01 Drug
5. Abhijit Sir
TheAbhi.in
Aspirin, Penicillin, Morphine
Methoxamine, Meperidine
Atropine bromide, Penicillin substrates
Natural Derivatives
Natural
Synthetic
Drug & Formulation
01 Drug
6. Abhijit Sir
TheAbhi.in
No Side effects
Effective ADME
Non-Toxic
Safe
High Efficacy
No Adverse Reaction
Drug & Formulation
01 Quality of a Good Drug
7. Abhijit Sir
TheAbhi.in
Drug & Formulation
01 Drug Delivery System
Drug delivery is the method or process of
administering a pharmaceutical compound to
achieve a therapeutic effect in humans or animals.
Drug delivery system is often used to refer to the
way dosage form releases the drug and delivers it
to the target organ, tissue, cell or even cellular
organelle.
10. Abhijit Sir
TheAbhi.in
Drug & Formulation
01 Dosage forms
Dosage forms are pharmaceutical drug products in the form in which they are marketed for use, with a
specific mixture of active ingredients and inactive components, in a particular configuration, and apportioned
into a particular dose.
Dosage Form Route of administration
• Oral
• Tablets
• Capsules
• Solutions
• Syrups
• Elixirs
• Suspensions
• Magmas
• Gels
• Powders
• Sublingual
• Tablets
• Troches and Lozenges
• Parenteral
• Solutions
• Suspensions
• Conjunctival
• Contact lens inserts
• Ointments
11. Abhijit Sir
TheAbhi.in
Drug & Formulation
01 Difference between dosage form
and drug delivery
Dosage form and Drug delivery system can be used
interchangeably, dosage form is often used to refer to the physical
appearance of drug like tablets, capsules, syrups, ointment and
creams whereas the drug delivery system is often used to refer to the
way dosage form releases the drug and delivers it to the target
organ, tissue, cell or even cellular organelle
For example, OROS system of nifedipine (Procardia tablet by
Pfizer): Dosage form is tablet but OROS system is the drug delivery
system where the drug is released through laser drilled orifice in the
semipermeable membrane either by the action of osmotic effect of
KCL pushing layer or effervescent pushing layer.
Drug Delivery
system
17. Abhijit Sir
TheAbhi.in
Steps involved in Drug Discovery and
Drug Development
Discovery of New
Drug Molecule
Pre Clinical
Studies
Early Formulation
Development
Clinical Studies
New Drug
Application
Industry Scale
Production
pharmacovigilance
Marketing
18. Abhijit Sir
TheAbhi.in
Drug discovery y
Drug Development
Drug Regulatory Affairs
Discovery of New
Drug Molecule
Pre Clinical
Studies
Early Formulation
Development
Clinical Studies
New Drug
Application
pharmacovigilance
Industry Scale
Production
Marketing
Discovery of New
Drug Molecule
28. Abhijit Sir
TheAbhi.in
Challenges in Drug Discovery
03 Challenge No# 7
Toxicity
Toxicity
30% of lead candidates
fail due to Toxicity.
Toxicity related to human organs, long term
genomic toxicity or Toxicity
Environmental Toxicity is a Major Challenge
1
2
3
29. Abhijit Sir
TheAbhi.in
Challenges in Drug Discovery
03
A 2014 global review of pharmaceuticals
in the environment, commissioned by
Germany’s environment ministry, found
that of the 713 pharmaceuticals tested
for, 631 were found above their detection
limits.
Environmental Impact
Challenge No# 8
36. Abhijit Sir
TheAbhi.in
Challenges in Drug Delivery
04
Class of therapeutic Challenge Example
Small molecules
Controlling PK parameters (in particular,
half-life, biodistribution, exposure and
maximum concentration)
Osmotically controlled-release oral-delivery system of methylphenidate HCl (Concerta) to
overcome the tolerance of the drug by controlling its PKs215
Improving solubility
Ritonavir (Norvir), a protease inhibitor for HIV treatment, thiazole-modified for improved
metabolic stability and aqueous solubility13
Improving permeability
Benazepril (Lotensin), an alkyl ester prodrug to mask ionizable groups and increase
lipophilicity216
Target development
Ezetimibe (Zetia), a selective cholesterol-absorption inhibitor discovered through library
screening217
Reducing off-target toxicity
Naloxegol (Movantik), a PEGylated naloxone derivative to prevent crossing of the blood–
brain barrier218
Proteins and peptides
Improving physicochemical stability
Desmopressin (DDAVP), an analogue of vasopressin with non-natural amino-acid
substitution for improved half-life and stability219
Controlling PK parameters (in particular,
half-life and biodistribution)
Leuprolide acetate for depot suspension (Lupron Depot), a sustained-release
microsphere formulation of luteinizing hormone-releasing hormone, providing extended
half-life51
Non-invasive administration
Insulin human inhalation powder (Afrezza), an inhaled insulin product consisting of
microparticles formulated with fumaryl diketopiperazine to achieve suitable
characteristics for inhaled delivery220
Bypassing biological barriers
Semaglutide (Rybelsus), an oral GLP-1 agonist formulated with SNAC for improved
absorption in the stomach46
Reducing immunogenicity
Pegademase bovine (Adagen), a PEGylated protein therapy with extended half-life and
reduced immunogenicity221
Improving target selectivity
Belatacept (Nulojix), a fusion protein with amino acid substitutions for improved
selectivity to CD86 and CD80 (ref. 222
)
37. Abhijit Sir
TheAbhi.in
Challenges in Drug Delivery
04
Class of therapeutic Challenge Example
Antibodies
Controlling PK parameters (in particular,
half-life and biodistribution)
Certolizumab pegol (Cimza), the first FDA-approved PEGylated antibody fragment, it
extends half-life and increases solubility223
Improving physicochemical stability
Blinatumomab (Blincyto), a lyophilized antibody with trehalose for improved stability of
the antibody structure in the formulation224
Non-invasive administration
Trastuzumab and hyaluronidase-oysk (Herceptin Hylecta), a subcutaneous depot with
hyaluronidases for the sustained release of Herceptin225
Bypassing biological barriers Trastuzumab and hyaluronidase-oysk225
Reducing immunogenicity
Panitumumab (Vectibix), the first FDA-approved fully human antibody, it reduces
immunogenicity and prevents the generation of anti-antibodies226
Achieving high-dose requirements
Tocilizumab (Actemra), a subcutaneous formulation with excipient, it delivers a high
concentration of antibody (180 mg ml−1
)227
Nucleic acids
Controlling PK parameters (in particular,
half-life and biodistribution)
Patisiran (Onpattro), the first FDA-approved siRNA-based therapy, the lipid nanoparticle
improves trafficking to the liver and its uptake by target cells198
Improving physicochemical stability
Fomivirsen (Vitravene), the first FDA-approved antisense oligonucleotide, incorporates a
phosphorothioate backbone modification for improved stability against nucleases228
Bypassing the target-cell membrane
Givosiran (Givlaari), a GalNAc–siRNA conjugate for improved uptake in liver
hepatocytes229
Accessing the cytosol or nucleus
following uptake
Patisiran (Onpattro), ionizable cationic lipids mediate endosomal escape following
endocytosis198
Reducing immunogenicity
Nusinersen (Spinraza), the first FDA-approved therapy for spinal muscular atrophy, the
2′-O-methoxyethyl phosphorothioate modification reduces immunogenicity and improves
stability230
Preventing off-target gene editing
CRISPR-CCR5-modified CD34+
cells for HIV-1 (NCT03164135); the CD34+
cells are
edited ex vivo, and whole-genome sequencing performed after editing and after
engraftment detects off-target effects231
38. Abhijit Sir
TheAbhi.in
Challenges in Drug Delivery
04
Class of therapeutic Challenge Example
Live-cell therapies
Controlling unpredictable PK parameters
Preclinical alginate-based biopolymer implants for the controlled release of CAR T cells
directly at the site of action204
In vivo persistence and viability
SIG-001, factor-VIII-secreting genetically engineered cells in an antifibrotic matrix
(NCT04541628); it enables long-term cell persistence at the site of action203
Reducing immunogenicity
Fludarabine conditioning chemotherapy for CAR T cells (NCT01865617); conditioning
chemotherapy reduces the immune rejection of infused cells232
Maintaining therapeutic-cell phenotype
Sipuleucel-T (Provenge), the first FDA-approved cell-based (dendritic cell)
immunotherapy, induces and maintains a therapeutic phenotype through ex vivo antigen
presentation105
Targeting to disease location
Matrix-induced autologous chondrocyte implantation for the maintenance of
chondrocytes at the site of action233
, the first FDA-approved cellularized-scaffold product
Manufacturing and scale-up
Tisagenlecleucel (Kymriah), the first FDA-approved CAR T-cell therapy, established the
manufacturing process for genetically engineered autologous cell therapies234
39. Abhijit Sir
TheAbhi.in
Challenges in Drug Delivery
04
Poor
Solubility
Poor
Permeability
Poor
Bioavailability
Poor Drug
Absorption
Inadequate
Distribution
Deposition of
Drug in Adipose
Tissue
Stability of
the Drug