SUSAN BABU

SEMESTER VI
 The Federal Food, Drug and Cosmetic Act(FDCA)
by FDA, defines the term “drug” to include “articles
intended for use in the diagnosis, cure, mitigation,
treatment, or prevention of disease in man or other
animals.”

 A drug is not effective unless it is present at its site

of action for an adequate period of time.
ROUTE ADVANTAGES DISADVANTAGES
Intravenous injection 100% bioavailability Discomfort to patient,
requires health care
provider, risk of overdose
or toxicity, risk of infection
Intravenous infusion 100% bioavailability, Requires hospitalization,
continuous control risk of infection
over plasma levels
Subcutaneous & Usually high Discomfort to patient
intramuscular bioavailability
injection
Oral Convenient, self- Drug degradation before
administered absorption, limited
absorption of many drugs
Topical Local delivery, self- Limited to agents that are
administered locally active
Intrathecal injection Direct delivery to Limited drug penetration
brain into brain tissue, high risk
Controlled release Long term release Requires surgical
implants procedure
 Delivery of drug at a predetermined rate(locally or
systemically) for a specified period of time.
 Regulate both duration and spatial localization of
therapeutic agents

 Rate of release of drug depends on characteristics of

device(physical & chemical properties of polymer)
1. Temporal controlled- deliver the drug over an
extended duration or at a specific time. Highly
beneficial for drugs that are rapidly metabolized
and eliminated from the body after administration.

2. Distribution controlled- aim to target the

release of the drug to the precise site of activity
within the body.
 RESERVOIR
AND MATRIX
TRANSDERMAL

TYPES

HYDROGELS DEGRADABLE
 Reduction in frequency of drug administration
 Improved patient compliance
 Reduction in drug level fluctuation in blood
 Reduction in total drug usage
 Reduction in drug toxicity
 Stabilization of medical condition
 Improvement in bioavailability of some drugs
because of spatial control
 Economic to health care providers & the patient
 Delay in onset of drug action

 Cost per unit dose is higher compared to

conventional doses

 Not all drugs can be used

 Requirement of surgery
 • Active agents + binders
SUSTAINED • Alter agent’s rate of
RELEASE dissolution/adsorption
• By drug formulation

• Duration/rate of release
is controlled
CONTROLLED • By altering polymer
DELIVERY properties
• Zero order release
 Non-
Biodegradable Water-soluble
biodegradable
• Silicone • Polyesters • Naturally
elastomers • Poly(ortho occurring
• Poly[ethylene- esters) polymers
co-(vinyl • Polyanhydrides • Acrylates and
acetate)] • Poly(amino acrylamides
• Polyurethanes acids) • Poly(ethylene
glycol)
 Non-biodegradable
 Excellent biocompatibility, with only a limited
inflammatory response following implantation.

 Prepared by hydrolysis of alkylsilicon or arylsilicon

halides
 In 1962 Folkman and Long discovered its use in
controlled drug delivery
 Silicone tubing SILASTIC® is used
for controlled delivery of contraceptive
hormone levonorgestrel.

 Provide reliable contraception for

5 years after implantation.

 Silicone can also be formulated

into a matrix with dispersed drug.
 EVAc, ELVAX®, DuPont Corp.
 Exceptionally good biocompatibility

 Mostly 40% vinyl acetate

 Matrices with EVAc and proteins made by solvent
evaporation or compression moulding
 Solvent is methylene chloride
 Used for making variety of drug delivery devices
 It was used to deliver pilocarpine to the surface of
eye for glaucoma treatment

 Used in progestasert intra-uterine device for

delivery of contraceptive hormones to female
reproductive tract.
 Polylactide, polyglycolide and copolymers of
lactide/glycolide(PLGA).
 PLA degrade slower than PGA.

 They break down to naturally occurring metabolites

 Degradation requires only water
 Even though PLGA is extensively used, increased local
acidity due to the degradation can lead to irritation at
the site of the polymer employment.
 Poly(L(+)-lactic acid) – delivery of contraceptive
steroids

 Nano particles of PLGA encapsulated with taxol

and surface modified with PEG showed greater
tumor growth inhibition

 Nano particles of PLGA encapsulated with

Paclitaxel by interfacial deposition method showed
improved antitumoral efficacy as compared to free
drug.
DRUG/POLYMER TRADE NAME INDICATION
Estradiol/Poly[ethylen Estraderm®, Ciba Estrogen replacement
e-co-(vinyl acetate)] Pharmaceutical Co. therapy
BCNU/Poly[carboxyph Gliadel®, Rhone- Recurrent
enoxy-propane-co- Poulene Rorer glioblastoma
(sebacic acid)] multiforme
Leuprolide Lupron Depot®, Endometriosis
acetate/Poly(DL- Takeda chemical
lactide-co-glycolide) industries
Levonorgestrel/ Norplant®, Wyeth- Implantable
Silicone elastomer Ayerst laboratories contraceptive
Nitroglycerin/poly[ethyl Transderm-Nitro®, Prevention of angina
ene-co-(vinyl acetate)] Summit
pharmaceuticals
Pilocarpine/poly[ethyle Ocusert®, Alza Corp. Glaucoma therapy
ne-co-(vinyl acetate)]

Ref: Drug delivery- engineering principles for drug therapy by W. Mark Saltzman
 Recent development.
 Bioactive ceramics like calcium phosphates, glass,
layered double hydroxides, iron oxides etc
 They are biodegradable and biocompatible as
well.
 Multifunctional -substitute bone tissue
-promote surface reactivity
-act as drug delivery systems

 Drugs incorporated- antibiotics, anticancer drugs,

anti-inflammatories, bone growth factors, proteins
and hormones and genes.
 Drug delivery- engineering principles for drug therapy by W.
Mark Saltzman
 Synthetic biodegradable polymer scaffolds by Anthony Atala
and David Mooney
 Biomimetic, bioresponsive and bioactive materials by Matteo
Santin and Gary J. Phillips
 Debjit Bhowmick et al , the Pharma Innovation, controlled
release drug delivery systems
 Polymeric Systems for Controlled Drug Release Kathryn E.
Uhrich et al.
 Biodegradable polymeric nanoparticles based drug delivery
systems Avnesh Kumari et al.