1. Ocular Drug Absorption
Absorption routes
Corneal Absorption
Drug Installation
Dilution in tear fluid
Diffusion from mucin layer
Corneal Penetration
Transfer from cornea to Aqueous humor
Ocular Absorption
Non-Corneal Absorption
Involves penetration across Sclera & Conjunctiva e.g. Gentamicin, Prostaglandin F2, Timolol mealeate

2. Ocular Drug Availability Barriers
Pre-corneal Barriers
Drainage
Lacrimation
Tear dilution
Tear Turnover
Conjunctival absorption

3. Ocular Drug Availability Barriers
Post-corneal barriers
Enzymatic degradation
Absorption by ciliary body

4. Formulation Active Ingredients
Pilocarpine, carbachol, betaxolol, Echotiophate ect (Anti-glaucoma Drugs)
Atropine, Scopolamine, Cyclopentolate, tropicamide (Miotics)
Dexamethasone, Prednisolone, hydrocortisone, Medrysone (corticosteriods)

5. Particle Size Eyes are sensitive to particle size of 20 µm or more.
The desired particle size of a suspended drugs is 5 – 10 µm or less

6. ADDITIVES Preservatives
Multi dose formulation require preservation because when pressure of bottle is released, the suck back of unreleased drop or air may lead to contamination

7. ADDITIVES Benzalkonium Chloride Preservatives:
Combined with Di Sodium EDTA
Most effective & Rapid Acting
No degradation at hot storage temperature
Absorption to package components & surfactant
Not effective against P. aeruginose strain (resistant)

8. Preservatives Organic Mercural
More effective in neutral or alkaline pH
Weak and slow activity
Banned in several countries

9. Preservatives Chlorobutanol Relatively safe then mercurals
Slow activity
30% activity is loss when sterilized at 121 ͦC for 20 minutes at pH 5
Hydrolytic decomposition, produce HCl decrease pH
Permeate through polyolefin plastic containers

10. Preservatives Methyl & Propyl Paraben Effectively prevent mold growth
Low aqueous solubility
Bind to nonionic surfactants & large polymers
May cause burning sensation in eye
Permeate through polyolefin plastic containers

11. Preservatives Other preservatives used are; Polyaminopropyl biguanide
Phenyl ethyl alcohol
Chlorhexadine
Polyquat

12. Penetration enhancers
Azone (laurocaprum)
Very small concentration is required (0.1%)
Corneal absorption of hydrophilic drugs are increased by at least 20 folds e.g. Prednisolone & Bunolol.
Inhibit absorption of lipophilic drugs e.g. flurbiprofen
Other such agents are;
Hexamethylene lauramide, hexamethylene octamide, decylmethyl sulfoxide

13. Buffering Agents
Bicarbonate Phosphate Carbonate Citrate Borate in concentration range of 50 – 200 milimolar For targeted pH range of 7.4 ± 0.1 (buffer system chosen should have pka close to target pH to get maximum buffer capacity)

14. (concentration up to 0.3%)
Stabilizers
Sodium metabisulphate
Sodium bisulphate
Acetylcysteine
Ascorbic acid
Sodium thiosulphate
Disodium edetate
(concentration up to 0.3%)

15. Degree of ocular irritation
Surfactants
Polysorbate 80
Polysorbate 20
Tyloxapol
Polyoxyethylene
Poloxamers
(concentration 0.1 – 0.2 %)
Degree of ocular irritation
Nonionic
Cationic
Anionic

16. Viscosity Increasing Agents
Acrylicacid polymers (carbomers)
Methylcellulose
Hydroxypropylmethyl cellulose (HPMC)
Hoxyethyl cellulose (HEC)
Polyvinyl Acetate (PVA)
function:
Increase contact time
Increase bioavailability
Lubricating effect

17. Isotonicity adjusting agent
0.9% NaCl w/v
Mannitol

18. TYPICAL FORMULA 1% Prednisolone acetate Ophthalmic Suspension
Prednisolone Acetate (micronized) 1.0 %
Benzalkonium chloride %
Disodium edetate q.s.
Phosphate Buffer q.s.
HPMC q.s.
Polysorbate q.s.
Sodium Chloride q.s.
Sodium hydroxide q.s.
Purified Water q.s. 100 ml

19. Sterilization Stream sterilization (121 ͦͦC)
Gas sterilization (Ethylene oxide)
Ionization radiation (UV, Gama)
Filtration (0.22 µ filter)

20. Ocular Toxicity Draize test:
The procedure involves applying 0.5mL or 0.5g of a test substance to the eye of a restrained, conscious albino rates, and leaving it for four hours.
The animals are observed for up to 14 days, for signs of redness, swelling, discharge, ulceration, hemorrhaging, cloudiness, or blindness in the tested eye.

21. Packaging material
Low density polyethylene Polystyrene Polypropylene Type I Glass (highest hydrolytic resistance, transparent) For Ointment Collapsible tubes of tin or aluminum are used
suitable for cap making

22. Ointments
Sterile semi-sold preparations of homogenous appearance intended for application to conjunctives.
B.P

23. Base for Ointments;
Paraffin base, having melting point close to body temperature
non-irritant
Chemically inert
Anhydrous medium for delivery of moisture sensitive drugs.
For addition aqueous solutions Hydrous Wool Fat or aliphatic alcohol are added to the base to increase its emulsifying capacity.

24. GELS
Substantially dilute cross linked system which exhibits no flow when in steady state. Dispersion of molecules or particles within liquid in which the solid is the continuous phase and the liquid is the discontinuous phase.

25. Gelling agents Polyacrylic acid compound Hypromellose Carbomer
Gellar gum

26. Formulated Product Stability Studies
Finished product stability is tested according to International Conference on harmonization (ICH) guidelines i.e. Q1A (R2) Stability Testing of New Drug Substances and Products.