This document discusses barriers to drug delivery and methods to overcome them. It outlines the main physiological barriers like the blood-brain barrier, intestinal epithelium, and skin. Biochemical barriers include metabolizing enzymes and efflux pumps. Chemical barriers relate to a drug's physicochemical properties like solubility and ionization. Methods to enhance delivery involve physical techniques like ultrasound and chemical approaches like absorption enhancers. New drug delivery systems using formulations with nanoparticles, liposomes, and prodrugs aim to improve transport across barriers and bioavailability of pharmaceutical agents.

1. BARRIERS ENCOUNTERED IN
DRUG DELIVERY
NATIONAL INSTITUTE OF
PHARMACEUTICAL EDUCATION
AND RESEARCH
1
PRACHI JOSHI M.S.PHARM
PHARMACEUTICS ISTSEM
I.D. NO. 310/14

2. CONTENTS
INTRODUCTION
BARRIERS
PHYSIOLOGICAL BARRIERS
BIOCHEMICAL BARRIERS
CHEMICAL AND PHYSICOCHEMICAL
BARRIERS
METHODS OF OVERCOMING BARRIERS
CONCLUSION
REFERENCES
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3. INTRODUCTION
 From many years researchers and scientists are
working a lot on the drug discovery.
 Many of the potent drugs have been yet discovered
but still the given drug dosen’t reach the site of action
especially the drugs given orally because of barriers
present in body and due to drug properties.
 And this problem also persist with biotechnological
products like peptides, proteins etc.
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4. BARRIERS
PHYSIOLOGICAL
BARRIER
BIOCHEMICAL
BARRIER
PHYSICO-
CHEMICAL
PROPERTIES OF
DRUG
CHEMICAL
BARRIER
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5. PHYSIOLOGICAL BARRIER
 Blood brain barrier: The blood-brain barrier (BBB) is a
membrane that controls the passage of substances from the
blood into the central nervous system.
 Intestinal epithelium: The intestinal epithelium is a single-
cell layer, largest and most important barrier against the
external environment.
 Blood ocular barrier: The blood-ocular barrier is a barrier
created by endothelium of capillaries of the retina and iris,
cilliary epithelium.
 Skin: The physical barrier is mainly located in the stratum
corneum and consists of protein-enriched cells and lipid-
enriched intercellular domains.
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6. BIOCHEMICAL BARRIERS
 Metabolizing enzymes: In the lumen of stomach, a mixture of
hydrochloric acid and proteolytic pepsins is the first metabolic
barrier and the enzymes of the upper small intestine act as
second barrier.
 Transporter and efflux pump: Substrate can be transported
through the brush border membrane in a carrier-mediated and
pH-dependent manner. P-glycoprotein (P-gp) is a known
MRP(multi resistance protein) that serves as an efflux pump.
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7. CHEMICAL BARRIERS
 Hydrogen bonding potential: A hydrogen bond is the
attractive force between the hydrogen attached to an
electronegative atom of one molecule and an electronegative
atom of a different molecule. Hydrogen bonding is a key
contributor to the specificity of intramolecular and
intermolecular interactions in biological systems.
PHYSICOCHEMICAL PROPERTIES
OF DRUG
 Physicochemical properties of drug are also important
determinants in the passage of drugs via the paracellular path.
The physicochemical properties such as solubility, ionization
lipophilicity, permeability, etc. are important for determination
of drug action.
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8. METHODS TO OVERCOME
BARRIERS
1.PHYSICAL METHODS
 In physical method some external stimuli are applied to open
the barrier it includes ultrasound, iontophoresis, stripping etc.
 Ultrasound, microwave or electromagnetic fields that can be
used to open the blood brain barrier.
 Microwave irradiation facilitated central effects of
domperidone by altering the permeability of blood brain
barrier and enhancing the entry of drug into the CNS.
 Stripping is a technique used to remove stratum corneum by
application of adhesive tape or cyanoacrylate Glue.
 Iontophoresis and electroporation require electrical forces for
drug delivery across stratum corneum.
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9. 2. CHEMICAL METHOD
 Chemical method involves the use of chemicals to increase the
permeability of the barrier.
 A large number of absorption enhancers have been studied,
such as fatty acids, bile salts, enamine derivatives of
phenylglycine, esters, ethers, salicylates.
 Mostly used blood brain barrier opening practice is via arterial
injection of hyperosmolar solution (e.g. mannitol, arabinose).
 Chemical enhancers for skin include the compounds that
interact with the lipid matrix of the stratum corneum to alter its
nanostructure and thereby increase permeability.
 The most common chemical enhancer is water, which leads to
hydration of the stratum corneum.
 Solvents, such as ethanol, methanol, chloroform and acetone,
as well as detergents increases the permeability of stratum
corneum.
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10. 3. BIOCHEMICAL METHOD
 Biochemical method involves the biological molecule as
permeability enhancer.
 A 45kDa biological molecule zonula occludens toxin (Zot), an
active tight junction modulator at the blood brain barrier.
 It also permits an enhanced transport of the therapeutic agents
doxorubicin and paclitaxel.
 Magainin, a naturally occurring pore-forming peptide increase
skin permeability by direct interaction with and disruption of
stratum corneum lipids.
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11. DRUG DELIVERY BY FORMULATIONS
 COLLODIAL DRUG CARRIERS: Colloidal drug carriers
include micelles, emulsions, liposomes and nanoparticles.
• BIODEGREDABLE NANOPARTICLES: Biodegradable
nanoparticles formulated from poly (D,L-lactide-co-glycolide)
(PLGA) are used for sustained and targeted delivery of
different agents including plasmid DNA, proteins and peptides
and low weight molecules.
• LIPOSOMES: Liposomes are small vesicles that are
composed of unilamellar or multilamellar phospholipids
bilayers surrounded by aqueous compartments.
 PRODRUG: The prodrug are used to overcome various
barriers which can hinder drug delivery, including solubility.
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12. CONCLUSION
 The absorption of an orally administered drug depends on
its passage through several barriers to deliver drug. The
drug can pass either between or through the cells, depending
on its physicochemical properties.
 Overcoming these barriers help in the development of
improved drug delivery systems to treat different diseases
conditions.
 Although many challenges exist in transporting the drug
from different barriers, that’s why pharmaceutical scientists
and medicinal chemists are overcoming them with new drug
delivery system that enhance drug delivery.
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13. REFERENCE
 Calcagno AM and Siahaan TJ. Physiological, Biochemical,
and Chemical Barriers to Oral Drug Delivery. Wang B,
Siahaan TJ, Soltero R. Drug Delivery Principles and
Application. John Wiley and Sons, Inc. Publications.16-24
 Valentino SJ, Nti-Addae KW. Prodrug strategies to overcome
poor water solubility. Advanced drug delivery
reviews.2007;59(7):677,679,687
 Chen Y, Liu L. Modern methods for delivery of drugs across
the blood–brain barrier. Advanced Drug Delivery
Reviews.2012;64:647-650
 Urtti A. Challenges and obstacles of ocular pharmacokinetics
and drug delivery. Advanced Drug Delivery
Reviews.2006;58(11):1133
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14. THANK YOU
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