This document discusses ocular drug delivery systems. It begins with an overview of eye anatomy and then introduces various ocular drug delivery formulations including solutions, suspensions, ointments, emulsions, and gels. It describes the advantages of controlled delivery systems for ocular drugs in increasing bioavailability and residence time. Various controlled delivery technologies are classified and evaluated, with examples like inserts, shields, and iontophoresis. Emerging areas like carbon nanotubes, pseudolatices, and vesicular systems are presented. The document concludes that controlled delivery can improve treatment effectiveness but that devices need further development for patient comfort.

1. Presented by:-
Sujit R. Patel,
Dept. of Pharmaceutics,
Maratha Mandal College Of Pharmacy,
Belgaum-590 010.

2. Contents:-
 Anatomy of eye
 Introduction
 Advantages
 Disadvantages
 Classification
 Evaluation of ocular drug delivery system
 Future trends
 Conclusion
February 11, 2013 Dept. Of Pharmaceutics 2

3. Anatomy of the Eye:-
February 11, 2013 Dept. Of Pharmaceutics 3

4. INTRODUCTION:-
Ophthalmic preparation
Applied topically to the cornea, or instilled in the
space between the eyeball and lower eyelid
Solution
• Dilutes with tear and wash away through lachrymal
apparatus
• Administer at frequent intervals
Suspension
• Longer contact time
• Irritation potential due to the particle size of drug
Ointment
• Longer contact time and greater storage stability
• Producing film over the eye and blurring vision
February 11, 2013 Dept. Of Pharmaceutics 4

5. Contd. . .
 Emulsions
• Prolonged release of drug from vehicle but blurred
vision, patient non compliance and oil entrapment
are the drawbacks.
 Gels
• Comfortable, less blurred vision but the drawbacks
are matted eyelids and no rate control on diffusion.
February 11, 2013 Dept. Of Pharmaceutics 5

6.  Controlled delivery system
– Release at a constant rate for a long time
– Enhanced corneal absorption
– Drug with not serious side effect or tolerate by the
patient
February 11, 2013 Dept. Of Pharmaceutics 6

7. ADVANTAGES:-
 Increase ocular residence, hence improving bioavailability.
 Possibility of providing a prolonged drug release and thus a
better efficacy.
 Increased shelf life with respect to aqueous solutions.
 Exclusion of preservatives, thus reducing the risk of
sensitivity reactions as compare to aqueous solutions.
February 11, 2013 Dept. Of Pharmaceutics 7

8. Contd...
 Possibility of targeting internal ocular tissue through non-
corneal routes.
 Reduction of systemic side effects and thus reduced adverse
effects in case of topical application.
 Reduction in the number of doses administration and thus
better patient compliance.
 Administration of an accurate dose in the eye, which is fully
retained at the administration site, thus a better therapy.
February 11, 2013 Dept. Of Pharmaceutics 8

9. DISADVANTAGES:-
It is Expensive.
Insertion technique is difficult & expulsion of shields may
occur not individually fit for each patient.
Shields are not fully transparent & thus reduce visual activity.
Occasional inadvertent loss.
Difficult to handle.
Foreign body sensation.
February 11, 2013 Dept. Of Pharmaceutics 9

10. CLASSIFICATION OF COTROLLED
RELEASE OCULAR DRUG DELIVERY
SYSTEMS:-
 Mucoadhesive/Bioadhesive dosage forms
 Ocular inserts
 Collagen shield
 Drug presoaked hydrogel type lens and pledges
 Ocular iontophoresis
 Polymeric solutions
February 11, 2013 Dept. Of Pharmaceutics 10

11. Contd…
Pseudolatices
Ocular penetration enhancers
Phase transition systems
Particulate system like, microspheres and
nanoparticles
Vesicular systems like liposomes, niosomes,
phamacosomes and discomes
Chemical delivery system for ocular drug
targeting
February 11, 2013 Dept. Of Pharmaceutics 11

12. EVALUATION OF OCULAR
DRUG DELIVERY SYSTEM
February 11, 2013 Dept. Of Pharmaceutics 12

13.  THICKNESS OF THE FILM :-
• Measured by Dial Caliper at different points and the
mean value is calculated.
 DRUG CONTENT UNIFORMITY :-
• The cast film cut at different places and tested for drug
as per monograph.
 UNIFORMITY OF WEIGHT :-
• Here, three patches are weighed.
February 11, 2013 Dept. Of Pharmaceutics 13

14.  PERCENTAGE MOISTURE ABSORPTION :-
• Here, ocular films are weighed and placed in a
dessicator containing 100 ml of saturated
solution of Aluminium Chloride and 79.5%
humidity was maintained.
• After three days the ocular films are reweighed
and the percentage moisture absorbed is
calculated using the formula –
Final weight – Initial weight x 100
% moisture absorbed = Initial weight
February 11, 2013 Dept. Of Pharmaceutics 14

15.  PERCENTAGE MOISTURE LOSS:-
• Ocular films are weighed and kept in a
dessicator containing anhydrous Calcium
Chloride.
• After three days, the films are reweighed and
the percentage moisture loss is calculated
using formula –
Initial weight – Final weight x 100
% moisture loss = Initial weight
February 11, 2013 Dept. Of Pharmaceutics 15

16. IN VITRO EVALUATION METHODS:-
 BOTTLE METHOD
In this, dosage forms are placed in the bottle
containing dissolution medium maintained at
specified temperature and pH.
The bottle is then shaken.
A sample of medium is taken out at appropriate
intervals and analyzed for drug content.
February 11, 2013 Dept. Of Pharmaceutics 16

17.  DIFFUSION METHOD
 Here ocular film is placed between the donor and
receptor compartment.
 Drug diffused from donor compartment to receptor
compartment containing buffer solution is
measured at various time intervals.
 MODIFIED ROTATING BASKET METHOD
 Dosage form is placed in a basket assembly
connected to a stirrer.
 The assembly is lowered into a jacketed beaker
containing buffer medium and temperature 37 °C.
 Samples are taken at appropriate time intervals and
analyzed for drug content.
February 11, 2013 Dept. Of Pharmaceutics 17

18. MODIFIED ROTATING PADDLE APPRATUS
Here, dosage form is placed in a diffusion cell
which is placed in the flask of rotating paddle
apparatus.
The buffer medium is placed in the flask and
paddle is rotated at 50 rpm.
The entire unit is maintained at 37 °C.
Aliquots of sample are removed at appropriate
time intervals and analyzed for drug content.
February 11, 2013 Dept. Of Pharmaceutics 18

19. IN VIVO DRUG RELEASE RATE STUDY:-
 Here, the dosage form is applied to one eye of
animals and the other eye serves as control.
 Then the dosage form is removed carefully at
regular time interval and are analyzed for drug
content.
 The drug remaining is subtracted from the initial
drug content, which will give the amount of drug
absorbed in the eye of animal at particular time.
 After one week of washed period, the
experiment was repeated for two times as before.
19

20. ACCELERATED STBILITY STUDIES:-
 These are carried out to predict the breakdown
that may occur over prolonged periods of
storage at normal shelf condition.
 Here, the dosage form is kept at elevated
temperature or humidity or intensity of light, or
oxygen.
 Then after regular intervals of time sample is
taken and analyzed for drug content.
 From these results, graphical data treatment is
plotted and shelf life and expiry date are
determined.
February 11, 2013 Dept. Of Pharmaceutics 20

21. FUTURE TRENDS
February 11, 2013 Dept. Of Pharmaceutics 21

22. February 11, 2013 Dept. Of Pharmaceutics 22

23. Carbon nanotube:-
Carbon nanotubes are made up of graphite.
Its name is derived from its size, since the
diameter of a nanotube is in the order of a few
nanometers (approximately 1/50,000th of the
width of a human hair), while they can be up to
several millimeters in length.
February 11, 2013 Dept. Of Pharmaceutics 23

24. 3D structure of Carbon nanotube
February 11, 2013 Dept. Of Pharmaceutics 24

25. February 11, 2013 Dept. Of Pharmaceutics 25

26. February 11, 2013 Dept. Of Pharmaceutics 26

27. Pseudolatices:-
• Organic solution of polymers is dispersed in an aqueous phase to form O/W
emulsion
• The pseudolatex-based ocular formulations of Pilocarpine were prepared
using different combinations of Eudragit RS 100 and Polyvinyl Pyrrolidone
(PVP)for prolonged and controlled release of the drug.
• Water is removed partially to an extent that residual water is removed
sufficient enough to keep polymeric phase discrete & dispersed
• On application leave an intact noninvasive continuous polymer film which
reserves drugs
• Drug released slowly over prolonged period of time , better ocular
bioavailability patient compliance
27

28. Microspheres & Nanoparticles:-
• The drugs are bound to small particles which are then
dispensed in aqueous vehicles
• Nanoparticles of polybutylcyanoacrylate have been
used for human being as a drug carrier
• Pilocarpine nitrate loaded egg albumin microspheres
were prepared by thermal denaturation process in the
size range of 1-12 μm.
28

29. Ocular Iontophoresis:-
 It is the process in which the direct current drives ions into cells or
tissues
 Types:-
I. Trans-corneal
II. Trans- scleral
 Antibiotics, Antifungal(e.g. Natamycin), Anesthetics(e.g. Benoxinate)
and Adrenergic(e.g. Timolol) are delivered by this method
29

30. February 11, 2013 Dept. Of Pharmaceutics 30

31. February 11, 2013 Dept. Of Pharmaceutics 31

32. Vesicular System:-
• Liposomes : Phospholipid-lipid vesicles
• Niosomes : Vesicles based on some non-ionic surfactants like dialkyl
polyoxyethylene ethers
• Phamacosomes : Pharmacosomes are amphiphilic phospholipid
complexes of drugs bearing active hydrogen that bind to phospholipids.
Pharmacosomes impart better biopharmaceutical properties to the drug,
resulting in improved bioavailability. Pharmacosomes have been prepared
for various non-steroidal anti-inflammatory drugs, proteins, cardiovascular
and antineoplastic drugs. Developing the pharmacosomes of the drugs has
been found to improve the absorption and minimize the gastrointestinal
toxicity.
• Discosomes : Systems formed by addition of specific amount of surfactant
to vesicular dispersions consisting of mixed vesicular and micelle regions
32

33. February 11, 2013 Dept. Of Pharmaceutics 33

34. Continuous delivery system based
upon the osmotic property:-
Implantable mini-pump such as Alzet is the
example of such system.
Such system is placed beneath the skin of
the scalp.
To deliver the drug to the eye, the pump is
connected to the upper fornix by means of
polyethylene tubing.
February 11, 2013 Dept. Of Pharmaceutics 34

35. Contd. . .
Delivery of diethyl carbamazine in ocular
onchocerciasis
February 11, 2013 Dept. Of Pharmaceutics 35

36. CONCLUSION:-
February 11, 2013 Dept. Of Pharmaceutics 36

37.  Controlled ocular drug delivery systems increase the
efficiency of the drug by reducing its wastage and by
enhancing absorption by increasing contact time of
drug to the absorbing surface.
 They improve patient compliance by reducing the
frequency of dosing.
 They reduces the dose and thereby reduces the
adverse effects of the drug.
February 11, 2013 Dept. Of Pharmaceutics 37

38. Contd. . .
 Although controlled release devices could be more
useful in the management of many ophthalmic
conditions, they are not very much popular because
such devices have to be put in place and taken out
from under the eyelid periodically.
 Moreover, the devices can move around in the
precorneal space resulting in discomfort and visual
disturbances.
February 11, 2013 Dept. Of Pharmaceutics 38

39. References :-
1. Controlled drug delivery – Concepts and Advances, by S.P. Vyas
and Roop K. Khar.
2. Ansel’s Pharmaceutical dosage forms and drug delivery systems,
by Loyd V. Allen, Nicholas G. Popovich and Howard c. Ansel.
3. Advances in Controlled and Novel drug delivery, edited by N.K.
Jain.
4. Textbook of Industrial Pharmacy, edited by Shobharani R.
Hiremath.
5. Novel drug delivery systems, by Y.W. Chein, published by
Marcel Dekker, volume 50.
6. http://google.co.in Crystalsert Crystalens Delivery System - YouTube.flv
7. http://youtube.com
EndoSerter MDEA Finalist 2012 - YouTube.flv
February 11, 2013 Dept. Of Pharmaceutics 39

40. Important Questions:-
 20 Marks
1) What are the causes of poor drug availability from conventional
ophthalmic preparations? Explain design, mechanism and adv of
ocuserts? [2005]
2) Give an account of ocular absorption, Give examples of controlled
release products for ocular route?[2002]
3)
a) Explain different methods for formulating ocular controlled drug
delivery systems?
b) Explain different methods for formulating ocular controlled drug
delivery systems?[2001]
February 11, 2013 Dept. Of Pharmaceutics 40

41. 10 Marks
1)Bring out the specific advantages & disadvantages ocuserts
systems for ocular drug delivery? sketch a neat blow up diagram of
ocusert diagram of “ocusert”?[2004]
2)Explain the formulation of ocuserts?[2006]
3)Explain the drug release pattern of ophthalmic inserts ?[2006]
4)Giving the disadvantages of ophthalmic formulations .write a note
on ocusert?[2007]
5)How do you design and manufacture ocuserts?[2008]
February 11, 2013 Dept. Of Pharmaceutics 41

42. o u
Y
n k
h a
T
February 11, 2013 Dept. Of Pharmaceutics 42