opthalmic diseases and available dosage form

1. OPTHALMIC DOSAGE
FORM
PRESENTED BY
VARSHA AWASARKAR

2. Ophthalmic preparations
DEFINATION:
“Ophthalmic preparation is sterile product that is intended
to be applied to the eyelids or placed in the space
between the eyelids and the eyeball.”
They are specialized dosage forms designed to be
instilled onto the external surface of the eye (topical),
administered inside (intraocular) or adjacent (periocular)
to the eye or used in conjunction with an ophthalmic
device.
A drug delivery to circumvent ailments of the eye.
A challenge to formulator is to avoid a protective barrier
of the eye.
• Need of a successful design.

3. OCULAR ANATOMY AND
PHYSIOLOGY
Fig. Anatomy and Physiology of the Eye

4. BARRIERS IN OCULAR
ABSORPTION
It includes-
• Solution drainage
• Cornea as rate limiting barrier
• Lachrymation
• Anatomy of cornea
• Tear dilution 1. Outer-Epithelium (lipophilic)
2. Middle-Stroma (hydrophilic), Conjunctival
absorption
3. Inner-Endothelium (lipophilic )
Precorneal constraints Corneal constraints

5. Drugs used in the eye
• Miotics e.g. pilocarpine Hcl
• Mydriatics e.g. Atropine
• Cycloplegics e.g. atropine
• Anti-inflammatory e.g. corticosteroids
• Anti-infectives (antibiotics, antivirals and antibacterials)
• Anti-glucoma drugs e.g. pilocarpine Hcl
• Surgical adjuncts e.g. irrigating solutions
• Diagnostic drugs e.g. sodiumfluorescein
• Anesthetics e.g. tetracaine

6. Sterility

7. Corneal absorption

8. Figure. Some of the routes of administration in the eye.

9. Cont…….

10. CLASSIFICATION OF OCULAR
DRUG DELIVERY SYSTEMS:

11. B. Manufacturing Techniques:
Aqueous ophthalmic solutions:

12. Aqueous suspensions

13. Ophthalmic ointment

14. Gels
• Ophthalmic gels are composed of mucoadhesive polymers that
provide localized delivery of an active ingredient to the eye. Such
polymers have a property known as bioadhesion meaning
attachment of a drug carrier to a specific biological tissue.
• These polymers are able to extend the contact time of the drug with
the biological tissues and thereby improve ocular bioavailability. The
choice of the polymer plays a critical role in the release kinetics of
the drug(s) from the dosage form. Several bioadhesive polymers are
available with varying degree of mucoadhesive performance.
• Some examples are carboxymethylcellulose, carbopol,
polycarbophil, and sodium alginate.

15. Emulsions
• Topical ophthalmic emulsions generally are prepared by
dissolving or dispersing the active ingredient(s) into an
oil phase, adding suitable emulsifying and suspending
agents and mixing with water vigorously to form a
uniform oil-in-water emulsion.
• Each phase is typically sterilized prior to or during
charging into the mixing vessel.
• High-shear homogenation may be employed to reduce
oil droplet size to sub-micron size which may improve
the physical stability of the oil micelles so they do not
coalesce.

16. Cont…
• The resulting dosage form should contain small
oil droplets, uniformly suspended.
• To prevent flocculation, creaming and
coalescence of the emulsions, manufacturers
commonly add surfactants to increase the
kinetic stability of the emulsion so that the
emulsion does not change significantly with
time.

17. Strips
• Ophthalmic strips are made of
filter paper and are individually
packed to ensure sterility until
the time of use.
• They can be used in the
measurement of tear production
in dry eye conditions.
• E.g. fluorescein sodium used
as a diagnostic strips to
visualize defects or aberrations
in the corneal epithelium by
staining the areas of cellular
loss.

18. Injections
• While injections are considered
a dosage form for nomenclature
purposes, they are not treated
as a dosage form in this paper.
• Instead, refer to the appropriate
physical form, such as,
suspension, etc., for general
information.

19. OCUSERTS
Ocular inserts are defined as preparations with a solid or semisolid
consistency, whose size and shape are especially designed for
ophthalmic application (i.e., rods or shields). These inserts are placed in
the lower fornix and, less frequently, in the upper fornix or on the cornea.
They are usually composed of a polymeric vehicle containing the drug
and are mainly used for topical therapy.
The mechanism of controlled drug release into the eye is as follows:
A. Diffusion, B. Osmosis, C. Bio-erosion

20. OCUFIT SROCUFIT SR

21. ADVANTAGES:
Low dose.
Control release.
Patient compliance.
DISADVANTAGES:
Costly
Retain in eye for 7 days.
Periodic check.
Replacement of contaiminated unit with fresh one.
Challenging to position into eye

22. CONTACT LENS
• Contact lenses can be a way of
providing extended release of
drugs into the eye.
• Conventional hydrogel soft
contact lenses have the ability to
absorb some drugs and release
them into the postlens lachrymal
fluid, minimizing clearance and
sorption through the conjunctiva.
• Their ability to be a drug reservoir
strongly depends on the water
content and thickness of the lens,
the molecular weight of the drug,
the concentration of the drug
loading solution and the time the
lens remains in it.

23. • The ability of contact lens to load drugs and to
control their release is in general inadequate and
the following approaches, based on modifications
of the polymer network, are under evaluation:
(1) Covalent binding of the drug to the lens network via labile bonds;
(2) Inclusion of the drug in colloidal structures that are dispersed in the
lens and are responsible for controlling drug release;
(3) Functionalization of the network with chemical groups that work as
ion-exchange resins; and
(4) Creation in the lens structure of imprinted pockets that memorize the
spatial features and bonding preferences of the drug and provide the
lens with a high affinity and selectivity for a given drug.

24. IMPLANTS
• Implants have been widely employed
to extend the release of drugs in ocular
fluids and tissues particularly in the
posterior segment. Implants can be
broadly classified into two categories
based on their degradation properties:
(1) biodegradable and
(2) nonbiodegradable
• With implants, the delivery rate could
be modulated by varying polymer
composition.
• Implants can be solids, semisolids or
particulate-based delivery systems.

25. DRUG RELEASE KINETICS
 The mathematical models are used to evaluate the kinetics and
mechanism of drug release from the tablets.
 The model that best fits the release data is selected based on
the correlation coefficient (r) value in various models.
 The model that gives high ‘r’ value is considered as the best
fit of the release data.

26. Mathematical models
1)Zero order release model
2)First order release model
3)Hixson-crowell release model
4)Higuchi release model
5)Korsmeyer – peppas release model

27. ZERO ORDER RELEASE EQUATION
• The equation for zero order release is
Qt = Q0+ K0t
where
Q0= initial amount of drug
Qt = cumulative amount of drug release at time “t”
K0 = zero order release constant
t = time in hours
• It describes the systems where the drug release rate is
independent of its concentration of the dissolved substance.

28. • A graph is plotted between the time taken on x-axis and the
cumulative percentage of drug release on y-axis and it gives a
straight line.

29. FIRST ORDER RELEASE EQUATION
• The first order release equation is
Log Qt = Log Q0+ Kt /2.303
where
Q0= initial amount of drug
Qt = cumulative amount of drug release at time “t”
K = first order release constant
t = time in hours
• Here, the drug release rate depends on its concentration

30. • A graph is plotted between the time taken on x-axis and the
log cumulative percentage of drug remaining to be released on
y-axis and it gives a straight line.

31. HIXSON - CROWELL RELEASE
EQUATION
• The Hixson - Crowell release equation is
Where
Q0 = Initial amount of drug
Qt = Cumulative amount of drug release at time “t”
KHC = Hixson crowell release constant
t = Time in hours.
• It describes the drug releases by dissolution and with the
changes in surface area and diameter of the particles or tablets

32. • A linear plot of the cube root of the initial concentration
minus the cube root of percent remaining versus time in
hours for the dissolution data in accordance with the Hixson-
crowell equation.

33. HIGUCHI RELEASE EQUATION
• The Higuchi release equation is
Q=KHt1/2
where
Q = cumulative amount of drug release at time “t”
KH= Higuchi constant
t = time in hours
• The Higuchi equation suggests that the drug release by
diffusion.
• A graph is plotted between the square root of time taken on x-
axis and the cummulative percentage of drug release on y-axis
and it gives a straight line.

35. KORSMEYER-PEPPAS EQUATION
• Korsmeyer – peppas equation is
F = (Mt /M ) = Kmtn
Where
F = Fraction of drug released at time ‘t’
Mt = Amount of drug released at time ‘t’
M = Total amount of drug in dosage form
Km = Kinetic constant
n = Diffusion or release exponent
t = Time in hours

36. • ‘n’ is estimated from linear regression of log ( Mt/M ) versus
log t
• If n = 0.45 indicates fickian diffusion
• 0.45<n<0.89 indicates anomalous diffusion or non-fickian
diffusion.
• If n = 0.89 and above indicates case-2 relaxation or super case
transport-2.
• Anomalous diffusion or non-fickian diffusion refers to
combination of both diffusion and erosion controlled rate
release.
• Case-2 relaxation or super case transport-2 refers to the
erosion of the polymeric chain.

37. • A graph is plotted between the log time taken on x-axis and
the log cummulative percentage of drug release on y-axis and
it gives a straight line.