Transcript NOVEL Drug Delivery

Drug Delivery System
"A Challenge"
for
New Therapeutic Era
5th International Conference and Exhibition on
Pharmaceutics & Novel Drug Delivery Systems
March 16-18, 2015 Crowne Plaza, Dubai, UAE
Dr. B. B. Barik,
Professor, Dept. of Pharmaceutics
College of Pharmacy, Jazan University,
Kingdom of Saudi Arabia.
E-mail: [email protected]
NOVEL Drug Delivery
Challenges: Delivering the drug at the right place, at the
right concentration for the right period of time.
Goal: to deploy medications intact to specifically target
parts of the body.
Obstacles: large molecules, low solubility, instability in the
formulation, degradation in the biological system, rapid
clearance , toxicity, inability to cross biological barriers,
bioavailability & biodistribution etc.
Sophistication: The association of the drug with a carrier.
Advances: Micro- and nanotechnology
Why is Novel DDS needed
 Controlled drug delivery
 Targeted drug delivery
 Maximum efficacy with minimum side effects
 Optimize drug’s therapeutic effect, convenience & dose
 To enhance a product life- cycle
 Improve patient compliance
 Control over all healthcare cost
Need for new drug delivery systems
Controlled
release/
Targeted
delivery
Individualiz
ed therapy
Drug absorption,
distribution and
metabolism vary
among individuals
Various types of Drug delivery
Conventional/
Oral
Injection
based
Transdermal
Carrier based
Controlled/
Targeted DDS
Oral Drug delivery systems
Formulations range
from simple tablets to
newer modified
control release tablets
Involve use of various
polymers and
hydrogel based
formulations
Injection based Drug delivery system
• Provide fast systemic
effects bypassing firstpass metabolism
• Drugs can be administered
in
unconscious
or
comatose patients
• Drugs having short halflife can be infused
continuously
Transdermal Drug delivery system
• Adhesive patches containing the drug are
applied on the skin
• The drug crosses the skin surface by
diffusion by percutaneous absorption and
goes into systemic circulation
• Bypasses first-pass hepatic inactivation
Transderm-SCOP
(Scoplamine)
Used for motion sickness
Hydrogel transdermal patch:
Used in treatment of burns
Thin film drug delivery
Oral drug strips
to administer drugs
via absorption through
buccal or sublingual
route
• GI specific drugs
Hydrogels:
(a)hydrogel preparation
(b) After imbibition
Osmotic pressure controlled system
Inhalation/Pulmonary Drug delivery system
• Inspiration through the
nose or mouth
• Alveolar epithelium
offers good surface
area especially for lipid
-soluble drugs
• The drugs are also
excreted by this route
Inhalational drug delivery system
 Fastest growing drug delivery system
 Delicate
molecules allowing systemic administration
without degradation
 Offer
flexibility for multiple formulations
from nasal drop to suspension spray
 Good
ranging
for sight specific delivery of bio tech products
such as insulin and other hormones
Approaches for Controlled Drug Delivery:
- Reservoir Systems with a Rate Controlling Membrane
- Monolithic Systems
- Laminated Systems
- Chemical Systems
Approaches for Targeted Delivery:
- Local Targeted Delivery
- Differential Metabolism Approach
- Biological Recognition
- Bio-physical Approach
- Prodrugs
Types of polymers used for controlled release
Swelling controlled drug delivery system
Hydrogels are three dimensional networks of
hydrophilic polymers that are insoluble in water at a
physiological temperature and pH but swells.
Preparation of Hydrogels
Drug absorption barriers in the intestine
Mucosal absorption of protein-based pharmaceuticals is highly
inefficient as these large molecular weight compounds do not
efficiently cross the epithelial surfaces
Parameter for drug selection
Parameter :
Preferred value
Molecular weight/ size:
< 1000
Solubility:
> 0.1 µg/ml for pH 1 to pH 7.8
Pka Non ionized moiety:
> 0.1% at pH 1 to pH 7.8
Apparent partition coefficient:
High
Absorption mechanism:
Diffusion
General absorbability:
From all GI segments
Release:
Should not be influenced by pH and enzymes
Parameter
Elimination half life:
Total clearance:
Elimination rate constant:
Apparent vol of distribution (Vd):
larger
Absolute bioavailability:
Intrinsic absorption rate:
Therapeutic concentration Css av:
Toxic concentration:
Comment
Preferably between 0.5 and 8 h
Should not be dose dependent
Required for design
The larger Vd and MEC, the
will be the required dose size.
Should be 75% or more
Must be greater than release rate
The lower Css av and smaller
Vd, the loss among of drug
required
Apart the values of MTC and
MEC, safer the dosage form.
Also suitable for drugs with very
short half-life.
Carrier based drug delivery system
Targeted Drug Delivery
Monoclonal antibodies
 mAbs act directly when
binding to a cancer
specific antigen and
induce immunological
response to cancer cells
 mAbs was modified for
delivery of a toxin,
cytokine or other active
conjugates
monospecific antibodies that are the same because they are made
by identical immune cells that are all clones of a unique parent cell,
Monoclonal antibodies have monovalent affinity, in that they bind
to the same epitope.
Monoclonal antibodies & their targets
Nasal vaccines
 First site of contact with the inhaled allergen
 Influenza A & B
 Proteosoma-influenza
 Adenovirus
 Parainfluenza
 HIV
 Hep B
Liposomal Drug delivery
 Pre-clinical and clinical
liposomal packed drugs
exhibit reduced toxicities
with enhanced efficiency
 Due to altered
pharmacokinetics-drug
accumulation at disease
sites and reduced
distribution to sensitive
tissue-target delivery of
drugs
Liposomes are self-assembling closed colloidal structures
composed of lipid bilayers and have a spherical shape in
which an outer lipid bilayer surrounds a central aqueous
space. Syn from cholesterol
Application of liposomal drug delivery
 Liposomal doxorubicin- ALL, HIV associated Kaposi s sarcoma
 Liposomal amphotericin B – visceral leishmaniasis
 Liposomal PEG doxorubicin- met breast CA, ovarian ca, MM, AIDS





related Kaposi s sarcoma
L Vincritine—prolonged expression of neoplastic cells , increased
drug retention
L IL2 - RCC
L IL 7 – improves antibody titer, enhanced immunogenicity due to
prolonged release over 6 days
Liposomal gene transfer –CFTR gene to nasal epithelium of cystic
fibrosis patients – under phase 1 trial
To overcome the BBB- using thiamine transporter
Triggerable Liposomes
Nanoparticle based drug delivery
Using nanotechnology the drug can be targeted
to a precise location which would make the
drug much more effective & reduce the
chances of possible side-effects
• More specific drug targeting & delivery
• Reduction in toxicity while maintaining
therapeutic efficiency
• Nanocarriers, Nanoparticles, Nanotubule,
Nanoshell
Advantages of Nanoparticles:
Particle size and surface characteristics of Nanoparticles can be easily manipulated to
achieve both passive and active drug targeting after parenteral administration.
They control and sustain release of the drug during the transportation and at the
site of localization
Subsequent clearance of the drug so as to achieve increase in drug therapeutic
efficacy and reduction in side effects.
Drug Loading is relatively high and drugs can be incorporated into the systems
without chemical reaction.
Site-specific targeting can be achieved by attaching targeting ligands to surface of
particles.
The system can be used for various routes of administration including oral, nasal,
parenteral, intra-ocular etc.,
Nanoparticles for Drug Delivery
•
Metal-based nanoparticles-Au, Ag, Cd-Se, Zn-S etc
•
Lipid-based nanoparticles-Liposome & Neosome
•
Polymer-based nanoparticles-Dendrimer, Micelle
•
Biological nanoparticles-Bovine-albumin serum
•
Designing nanoparticles to be taken orally.
•
The development of particles that are nano scaled has
created great opportunities in the of improved drug
delivery systems.
Factors:
Size of Nanoparticles required.
 Inherent properties of the drug, e.g.: aqueous solubility
and stability.
 Surface characteristics such as charge and permeability.
 Degree of biodegradability, biocompatibility and toxicity.
 Drug release profile desired.
 Antigenicity of the final product.
Carbon Nanotubules
Used in treatment of Bronchial
asthma
ADR: Foreign body granuloma
and intestitial fibrosis
Gold Nanoparticles
Cancer chemotherapy
-free radical generation
Difference between Liposomes and Nanoparticles:
Liposomes
Nanoparticles
 Protecting drugs from degradation.
 Increase the stability of drugs.
 Less targeting to site of action.
 More targeting to site of
action.
 Reduction toxicity or side effects.
 Low encapsulation efficacy.
 Rapid leakage of water soluble
drug in the presence of blood
components and poor storage
stability.
 Increase the encapsulation
efficacy.
Minimize the leakage of water
soluble drug in the presence of
blood components.
Nanoerythrosomes
Nanoerythrosomes are resealed erythrocytes that can carry proteins,
enzymes & macromolecules.
They are used in the treatment of liver tumor, parasitic disease
& enzyme disease
(A) By the enhanced permeability and retention (EPR) effect, nanoparticles (NPs) can
be passively extravasated through leaky vascularization, allowing their accumulation
at the tumor region. In this case, drugs may be released in the extracellular matrix
and then diffuse through the tissue.
(B) Active targeting can enhance the therapeutic efficacy of drugs by the increased
accumulation and cellular uptake of NPs through receptor-mediated endocytosis.
CHALLENGES OF NANO DRUG DELIVERY
Small size & large surface area can lead to
particle aggregation .
Physical handling of nano particles is
difficult in liquid and dry forms.
Limited drug loading.
Toxic metabolites may form.
Although new delivery systems have a number of
therapeutic benefits, but they do have certain limitations
such as :
a) If systems fail, overdosing occurs due to doses dumping.
b) The large physical size of the dosage unit poses problems
in usage.
c) Often sub optimum bio-availability is observed.
d) Variability in drug levels is also observed.
A Research and Development work will continue to be an integral part
of developing novel drug delivery systems for ultimate commercial
exploitation in the coming years.
a) A number of problems for basic research which need to be
resolved at the molecular and cellular levels.
b) Reticulo-endothetial clearance and drug release into the
target cells.
c) Developmental work in terms of formulation of different drugs
for new therapeutic drugs should be an ongoing effort.
d) Polymer formulation to suit individual applications should
be the work of a developmental nature.
Gene therapy
•
•
•
•
•
Somatic
Germ line
Vectors
Viral and non viral
Non viral
– Dendrimers
– Sonoporation
– Magnetofection
– Electroporation
GENETIC TRANSFER SYSTEM
 Under evaluation & III Phase clinical trials for
Adenovirus & HIV
Nanoparticles provide massive advantages regarding drug
targeting,delivery with additional potential to combine
diagnosis and therapy
Anti-tumour therapy ,gene therapy ,AIDS
therapy,radiotherapy
Involved in delivery of virostatics,vaccines and as vesicles to
pass blood brain barrier
Future aspects
Dendrimer
Modified Buckyball
Dendrimer-highly branched They deliver radioactive atoms to
cancerous material.Eg:C-60 against CA
globular Biodegradable
colon Transfer of radiation is within the
synthetic molecule.
ball hence minimise strong radiation to
healthy tissue
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