Occular Drug Delivery System

1. Prepared by:
Pawan Dhamala
Pharmacy
1

2. CONTENDS:
1. INTRODUCTION.
2. Composition of eye.
3. Anatomy of eye.
4. Mechanism of ocular absorption
5. Factor affecting intraocular
bioavailability.
6. Ideal characteristics of odds.
7. BARRIERS OF DRUG PERMEATION.
8. METHODS TO OVERCOME BARRIERS.

3.  A drug delivery system ideally should deliver a
specified amount of medication to site of action at an
appropriate time and date.
 Novel ocular drug delivery system are designed in
order to over come various drawbacks of
conventional medications and having improved
patient convenience and better therapeutic efficacy.
 Ocular administration of the drug is primarily
associated with need to treat ophthalmic diseases.
 Systemic action by using eye as a portal is generally
avoided in order to prevent the risk of eye damage
from high blood concentration of drug not intended
for eye.

4.  They are specialized dosage forms designed to be
instilled on to the external surface of the eye (topical),
administered inside (intraocular) or (periocular) to the eye
or used in conjugation with an opthalmic device.
 The drug can be instilled in the cull de sac cavity (the
space between eyelids and eyeballs) of eye.
 The ocular drug delivery must be able to sustain the
drug release and remain in the eye for prolonged period
of time.
 The preparation when instilled in the eye can be drain-
ed away due to tear flow and lacrimal nasal drainage.
 The most commonly used opthalmic dosage forms are—
solution, suspensions and ointments. Some of the newer
dosage forms are gels, gel forming solution, ocular inserts,
intravitreal injections and implants.

5.  Some of the major drugs used for this ocular drug
delivery systems are:
1. Miotics e.g. Pilocarpine Hcl
2. Mydriatics e.g Atropine
3. Cycloplegics e.g. Atropine
4. Anti-inflammatory e.g. corticosteroids
5. Anti-infectives e.g. (antibiotics, antivirals, antibacterial)
6. Anti-glucoma drugs e.g. pilocarpine Hcl
7. Diagnostic drugs e.g. sodium fluorescein
8. Anesthetics e.g. Tetracaine

8.  Non- corneal absorption:
 Penetration across sclera & conjunctiva into intra
ocular tissues.
 Non productive: because penetrated drug is
absorbed by general circulation.
 Corneal absorption:
 Outer epithelium: rate limiting barrier, with pore
size 60a, only access to small ionic and lipophilic
molecules.
 Trans cellular transport: transport between
corneal epithelium and stroma.

9. 1. Inflow & outflow of lacrimal fluids.
2. Efficient naso-lacrimal drainage.
3. Interaction of drug with proteins of
lacrimal fluid.
4. dilution with tears.
5. Corneal barriers.
6. Active ion transport at cornea.

10.  Good corneal penetration
 Prolong contact time with corneal
tissue
 Simplicity of instillation for the patient
 Non irritative and comfortable form
 Appropriate rheological properties
 Less drainage tendency
 Minimum protein binding

11. Barrier of drug permeation:

12. 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.

13.  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.
BIOCHEMICAL BARRIERS:

14. 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

15. METHODS TO OVERCOME
BARRIERS:
1. PHYSICAL METHODS.
2. CHEMICAL METHODS.
3. BIOCHEMICAL METHODS.

16. METHODS TO OVERCOME BARRIERS
1.PHYSICALMETHODS
 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.

17. 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.

18. 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.

19.  They are easily administered by the nurse
 They are easily administered by the patient
himself.
 They have the quick absorption and effect.
 less visual and systemic side effects.
 increased shelf life.
 better patient compliance.

20.  The very short time the solution
stays at the eye surface.
 Its poor bioavailability.
 The instability of the dissolved
drug.
 The necessity of using
preservative.

21.  N.K.Jain, Advances in Controlled & Novel Drug
Delivery, CBS Publication, & distributor, New
Delhi, pg No.219-223.
 Remington & Gennaro ; The Science & Practice
Of Pharmacy. Mack Publication Company. Easton,
Pennsylvania. Pg. No. 1563-1567.
 Web Sites:
www.vision-care-guide.com
www.google/images/eye/anatomy& physiology
REFERENCE:

22. Thank you