ophthalmic dosage forms

ophthalmic dosage forms

• dosage forms used in the treatment of eye diseases

• must be sterile, particle free (some exceptions), isotonic and free from pyrogens/endotoxins

• prepared using aseptic techniques

  • procedures used to maintain the sterility of the product

ophthalmic preparations

• specialized dosage forms designed to be administered on to:

  • the external surface of the eye (topical)

  • inserted (intraocular) or

  • adjacent (periocular) to the eye in conjunction with an ophthalmic device

• intraocular & periocular preparations restricted to therapeutic applications or surgical adjuncts

  • due to dangers associated with their administration, or repetitive administration

ophthalmic preparations cont

CONT

• topical therapeutic ophthalmic dosage forms

  • solutions

  • suspensions and ointments

  • gels and ocular inserts

• injections and implants developed in intraocular drug delivery

• -there is good blood supply in the back of the eye (absorption can take place back there)

similarity to parenteral dosage forms

ophthalmic preparations are similar to parenteral dosage forms in their requirements for:

• sterility

• osmotic pressure (tonicity)

• preservation

• tissue compatibility

• avoidance of pyrogens

  • pyrogens: fever causing metabolic bi-products of bacteria

    • if there are bacteria, the bacterial cell wall (one of the components LPS (lipopolysaccharide); fragments of the cell wall), if in parenteral products above a certain level, will cause fever

• particulate matter and suitable packaging

physiological factors affecting ophthalmic bioavailability

• normal fluid volume capacity of the eye is ~ 30 µL

• normal commercial eyedropper dispenses 50-75 µL

• about half of delivered dose is lost via overflow

• in humans the normal turnover of tear fluids in the eye is every 2-3 minutes

  • accounts for loss of drugs delivered ophthalmically

• ideally, higher contact time with the eyes favors higher bioavailability

what are the four formulation factors?

1. sterility

2. pH

3. viscosity

4. contact time

formulation factors

1. sterility

must be sterile to protect the eyes from infection

formulation factors

2. pH

• pH 7.4 is ideal but the outer surface of the eye can tolerate a pH range of 6.5 - 8.5

  • less than 6.5 will cause burning sensation

  • more then 8.will cause pain

• extreme pH causes irritation to the eye

formulation factors

3. viscosity

to increase the retention of the drug in the eye

• viscosity increases the thickness of the solution

  • if viscosity is high, there is less flow of the fluid

  • loss due to spillage/loss due to lacrimal duct will decrease with increase viscosity

formulation factors

4. contact time

increased contact time achieved by increasing the viscosity of the formulation

what are the five types of ophthalmic dosage forms?

1. solutions

2. gel-forming solutions

3. suspensions

4. ointments

5. drug-impregnanted inserts

types of ophthalmic dosage forms

1. solutions

• most commonly administered ocular dosage form

• washes off easily from the eye, hence less contact with the eye

• types: simple solutions, powders for reconstitution

types of ophthalmic dosage forms

2. gel-forming solutions (anti-thixotropy)

• increased contact with the eye

types of ophthalmic dosage forms

3. suspensions

• particle size must be less than 10 µm

• particles should not aggregate into larger particles

• polymorphism (due to storage temp, change in pH)

types of ophthalmic dosage forms

4. ointments

(thicker in comparison to regular liquids and suspensions)

• do not wash off easily hence longer duration of action

• relatively slower onset time and longer time for peak absorption

  • why?

    • ointments are thicker (viscous formulation) and have high solid contents

      • drug will need to be released from ointment and then have to partition into the fluids of the eyes which will then be absorbed into the eyes

        • that release from the ointment is slower onset time

    • they are typically oily in nature

• -ointments will typically block your vision so apply it during the nighttime

types of ophthalmic dosage forms

5. drug-impregnated inserts

• provide drug release for extended period of time

• ocusert - glaucoma therapy

  • release of pilo carpine at a fixed rate

    • attach a small patch to the eye (can last for about a week)

  • eliminates need for frequent doses

  • placed in the cul-de-sac of the eye