solutions suspensions o intments intraocular injection

1. Ophthalmic Preparations
• Solutions
• Suspensions.
• Ointments
• Intraocular injection.
Anatomy of the eye

2. Ophthalmic preparations
should be sterile unlike
otic or nasal
Not necessary to
be isotonic,
Explain?

3. Advantages
• Ensures that the required site.
• Low incidence of side effects.
• Administered easy by the patient.

4. Disadvantages
• Low retention time; absorption of 1% of the original dose.
• Loss of the majority of dose by tears; two drops is 30 µL and the tears
volume is 7 µL- 30 µL.
• Patient inconvenience; pain, irritation and blurring of vision.
• Being sterile requires special facility for manufacturing.

5. Formulation of Aqueous Ocular Dosage Form
 Drug salt.
Physical properties of the dispersed phase of the therapeutic
substance.
pH
Chemical stability
Absorption across the cornea
Vehicle
Viscosity
Preservative
Antioxidant
Surface active agent.

6.  Choice of the drug salt
• Solubility
- Pain and irritation ( stinging)
- Adrenaline bitartarate pH 3-4 moderate stinging
- Adrenaline borate pH 5.5 – 7.5 mild stinging
- Adrenaline hydrochloride pH 2.5 – 4.5 neutralized Reduced stingin
• Salt producing discomfort will result in lacrimation anfd hence the wash
effect.

7.  Physical Properties of dispersed agent
• Particle Size:
- large particles causes irritation
• 95% of the dispersed particles should have average particle
diameter less than 10 µm.

8.  pH
• Ideally should be 7.4 and this the tears pH.
• This to enhance stability, acceptability and absorption.

9.  Chemical Stability
• Effect of pH and temperature on the stability of pilocarpine
Temp pH Half-life
121 6.8 34 min
121 5 24 hrs
25 6.8 66 days
25 5 Several years

10.  Drug Absorption Through the Cornea
• Co-existance of the drug in ionized and non-ionized to achieve
effective absorption due to the different nature of the corneal layers.
Layer Nature Drug form
Epithellium Lipid rich Non-ionized
Stroma Aqueous Ionized
endothellium Lipid rich Non-ionized

11.  Vehicle
•Purified water Not WFI is commonly used. USP

12.  Viscosity
• Viscosity modifier is required to:
1- control the drop unit from the container.
2- to control the residence time of the solution within the precorneal.
• 55 mP/s above which no increase in the contact time.
• Formulation should be less than 30 mP/s
• Increasing the viscosity will enhance the physical stability of the
suspension.

13. • The viscosity modifier should have the following properties:
- Easily filtered through 0.8 micron filter
- Easily sterilized by filtration or heat.
- Compatible with the components.
Examples of viscosity modifiers:
- HPMC 0.45 – 1% w/w
- Poly vinyl alcohol 0.25 – 3% w/w
- Polyacrylic acid.

14.  Preservative because it is multi-dose container
• Benzalkonium chloride 0.01% w/v. to enhance its activity agaist
pseudomonas aurignosa we added EDTA 0.1%.
• Organic mercurial compounds 0.001-0.002% w/v but of limited use.
• Organic alcohols: chlorobutanol ( 0.5% w/v)and phenylethylalcohol
0.25 – 0.5% w/v.
Cationic preservative

15. Antioxidants: to optimize the stability of therapeutic agent
that degrade by oxidation as sod.metabisulphite 0.3%
• Surfactants: Non-ionic sufactants are generally used.

16. Manufacture of Aqueous ophthalmic
Formulations
+ Similar to parenteral preparations.
• Cleanroom conditions followed by sterilization by autoclaving.
• Clean or aseptic conditions followed by aseptic sterilization by filtration
0.22 micron.
• Production under aseptic condition; dispersion of sterile therapeutic
agent into sterile vehicle and excipients and packing under aseptic
conditions suitable for suspension.

17. Ophthalmic Ointments
• Dispersion of therapeutic agent into prepared ointment base
in the same way as general ointments but required to be
sterile.
• Have a disadvantage that it causes greasiness and blurring of
vision but it can be used during night time.

18. Ointment Bases for Ocular Administration
1- Hydrocarbon bases:
mixture of paraffins ( yellow soft paraffin, white soft paraffin)
2- Non-emulsified absorption bases:
liquid and yellow soft paraffins and emulsifying agent.
lanolin derivatives; aqueous solution can be incorporated.
3- water soluble bases/ aqueous gels; polyethylene glycol, polyacrylic acid
gels

19. Other excipients
• Non-aqueous antioxidants
butylated hydroxyl toluene, butylated hydroxyanisole.

20. Manufacture of Ophthalmic Ointment
• Same as ointments but required to be sterile .
• Manufactured and packed under aseptic conditions.
• Sterile therapeutic agent added to sterile base>
• Filling in container under aseptic conditions.

21. Nasal Formulations
• Aqueous based system
• Rapid absorption
• Avoid first pass metabolism

22. • Control of pH: 5.5 – 6.5
• Tonicity : Inclusion of NaCl
• Choice of vehicle: Purified water, non-aqueous vehicles are not used.
Glycerol can be added as co-solvent and humectant.
• Viscosity modifier: to enhance administration and retention of drops
on the nasal mucosa.
methylcellulose, hydroxyethylcellulose, polyacrylic acid.
• Preservative: chlorobutanol 0.5%, Parabens 0.2% benzalkonium
chloride 0.003 -0.02% w/v.
• Antioxidants: Sod.metabisulphite, Sod.sulphite.
• Manufacture: similar to non-sterile liquid preparations.

23. Otic Formulations
• May be aqueous or non-aqueous.
• Vehicles: depends on the solubility of the active substance.
- Aqueous vehicle as purified water.
- Non-aqueous as mineral oils as paraffin oil, vegetable oils as archis oil.
- Non-aqueous but miscible with water as glycerol.
Preservative, antioxidants and viscosity modifier can
be added.