DDS Lecture 20 Content

Special Solutions and Drug Delivery Systems include

• ophathalmic drug delivery

• pharmacologic categories of ophthalmic drugs

• pharmaceutical requirements

• packaging ophthalmic solutions and suspensions

• proper admin of ophthalmic solutions and suspensions

• nasal preparations

• otic preparations

Ophthalmic drug delivery

• normal tear volume: 7-8 mcL

• nonblinked eye can accomodate about 30 mcL

• blinked eye can accommodate about 10 mcL

• administered quantities must be small

• drops vary in size, approx. 50 mcL

  • one drop per eye is enough

Common causes of inflamed eyes

• acute conjunctivitis

  • bacterial, viral, allergic, fungal, parasitic, chemical

• acute iritis

• acute glaucoma

• corneal trauma

Ophthalmic Drug categories

• Anesthetics

• Antibiotic and antimicrobials

• antifungals

• anti-inflammatory

• antivirals

• astringents

• beta-adnergic blocking agents

• miotics, glaucoma agents

• mydriatics, cycloplegics

• protectants/artificial tears

• vasoconstrictors and decongestants

Anesthetics

• topical anesthetics (tetracaine, cocaine, proparacaine)

• provide pain relief preoperatively, postoperatively, for ophthalmic trauma, and during ophthalmic exam

Antibiotic and antimicrobial agents

• systemic and local

• combat ophthalmic infection

• azithromycin, gentamicin sulfate, sodium sulfacetamide, ciprofloxacin hydrochloride, ofloxacin, polymyxin B-bacitracin, tobramycin

Antifungal

• used against fungal endophthalmitis and fungal keratitis

• amphotericin B, natamycin, flucytosine

Anti-inflammatories

• treat eye inflammation, as allergic conjunctivitis

• topical steroidal agents: fluorometholone, prednisolone, dexamethasone salts

• nonsteroidal: diclofenac, flurbiprofen, ketorolac, suprofen

Antivirals

• used against viral infections caused by herpes simplex virus

• trifluridine, ganciclovir, vidarabine

Astringents

Pharmaceutical Requirements for Ophthalmics

• Sterility and preservation

• isotonicity value

• buffering

• viscosity and thickening agents

• ocular bioavailability

• additional considerations

Ophthalmic Sterilization

• filtration (preferred)

• autoclaving

• dry heat

• gamma radiation

• ethylene oxide

Advantage of Filtration

• retention of all particulate matter (microbial, dust, fiber)

• removal of particles has substantial importance in the manufacture and use of ophthalmic solutions

Preservatives for ophthalmics

• must demonstrate stability

• chemical and physical compatibility with other formulation and packaging components

• very low concentrations of preservatives

• benzalkonium chloride (pref)

Isotonic solutions

• osmotic pressure similar to body fluid

• 0.9% sodium chloride or 1.9% boric acid

What contributes to the osmotic pressure of a solution?

All of an ophthalmic solution’s solutes, including the active and inactive ingredients, contribute to the osmotic pressure of a solution

Hypotonic solution

• solutions with LOWER osmotic pressure than body fluids or a 0.9% sodium chloride solution

• may induce HEMOLYSIS of red blood cells

• passage of water from site of an ophthalmic application through the tissues of the eye

Hypertonic solution

• solution with higher osmotic pressure than body fluids or 0.9% sodium chloride

• tendency to draw water from body tissues toward the solution in an effort to dilute and establish a concentration equilibrium

• can cause CRENATION (shrinking) of blood cells

• in eye, solution can draw water toward the site of the topical application

Osmotic pressure

• pressure difference between the solution and pure solvent resulted after adding solutes to one side

• pressure applied to a solution in order to nullify osmotic flow

• colligative property: solute particles in a solution directly influence osmotic pressure

• for non-electrolyte solute (sucrose), the concentration of solution will depend solely on number of molecules present

• for electrolyte solute, number of particles that it contributes to solution depends on concentration of molecules and degree of ionization

Other colligative properties

• vapor pressure

• boiling point

• freezing point

Comparison of what colligative property between solutions is most used for calculations of iso-osmotic solutions?

Freezing points

Buffering

• protects against changes in pH of the solution

• may be adjusted and buffered for:

  • greater comfort to eye

  • render formulation more stable

  • enhance aq solubility of drug

  • enhance the drug’s bioavailability (ex. favoring unionized molecular species)

  • maximize preservative efficacy

pH of normal tears

about 7.4

pH of tears in contact lens wearers

more acidic

The introduction of a medicated solution into the eye stimulates…

the flow of tears

attempts to neutralize any excess hydrogen or hydroxyl ions introduced with the solution

Most ophthalmic drugs are

weakly acidic

weak buffer capacity

The buffering action of tears normally…

neutralizes ophthalmic solution and prevents discomfort

The eye can tolerate a greater deviation from physiologic pH toward which direction (alkalinity/acidity)

alkalinity (less discomfort)

Viscosity

• property of liquids related to resistance to flow

Ocular bioavailabilitiy

• important in effectiveness of an applied medication

• physiologic factors that can affect ocular bioavailability:

  • protein binding

  • drug metabolism

  • lacrimal drainage

Can protein-bound drugs penetrate the corneal epithelium?

No, protein-bound drugs are incapable of penetrating the corneal epithelium because of the size of the protein-drug complex

Proteins in tears

albumin, globulins

usually 0.6%-2% of tears

The cornea is permeated most effectively by

lipophilic and hydrophilic drugs

Ophthalmic suspensions, gels and ointments mix with lacrimal fluids less/more readily than viscosity solutions

less

remain longer in cul-de-sac, enhancing drug activity

Antioxidants

• EDTA (ethylene diamine tetraacetic acid)

• sodium bisulfite

• sodium metabisulfite

• thiourea

Packaging Ophthalmic Solutions and Suspensions

• glass

• plastic

• 2-30 mL, depending upon the product

• can actually use a small syringe

• ex. plastic container with built-in dropper device

• ex. ophthalmic product packaging: liquids are in 5- and 15-mL droptainer dispensers =

• ophthalmic ointments are in tubes container 3.5 g of product

Ophthalmic quality control

• potency

• sterility

• appearance/clarity

• pH

• volume/weight

Proper admin of Ophthalmic solutions and suspensions

1. wash hands thoroughly

2. inspect for color and clarity

3. to instill drops, person should tilt head back and, with index finger of free hand, gently pull downward on lower eyelid of affected eye to form pocket or cup

4. while looking up, and without touching dropper to eye, prescribed number of drops should be instilled into formed pocket

5. lower eyelid should be released and the eye closed to allow to medication to spread over the eye

6. eye should be held closed, preferably for a full minute, without blinding, rubbing, or wiping

7. while eye is closed, gentle pressure should be applied just under the inner corner of the eye by the nose to compress the nasolacrimal duct to prevent drainage and enhance corneal contact time

8. any excess liquid may be wiped away with a tissue

Nasal preparations

• most preparations intended for intranasal use contain adrenergic agents and are employed for their decongestant activity on the nasal mucosa

• most preparations in solution form and administered as nose drops or sprays

  • few available as jellies

Types of nasal preparations

• decongestants (rhinitis, common cold, hay fever, sinusitis: usually <=1%)

• anti-infectives

• drops

• sprays

General Requirements for Nasal solutions

• pH 5.5-7.5

• mild buffer capacity

• tonicity

• nonviscous

• compatible

• preserved

General formula components for nasal aerosol solutions or suspensions

• Active ingredient: solubilized or suspended

• antioxidants

• preservatives

• buffers

• tonicity adjustment

• surfactants

• vehicle

Drugs administered nasally for systemic effects

• ocytocin

• desmopressin

• vitamin B12

• progesterone

• insulin

• calcitonin

• butorphanol

Types of Otic preparations

• cerument-removing solutions

• anti-infective, anti-inflammatory, and analgesic ear preparations

• otic suspensions

Can ear drops be used for the eye?

No! Otics are NOT required to be sterile

Vehicles for otic solutions

• propylene glycol

• polyethylene glycol (low MW)

• glycerin

• mineral oil

• olive oil

• lipid soluble to solubilize wax in ear! also viscous

Benzocaine otic preparations

• americaine otic

• local anesthetic for ear pain

Triethanolamine polypeptide oleate condensate

• cerumenex eardrops

• removes impacted earwax

Chloramphenicol otic

• chloromycetin otic

• anti-infective

Polymyxin B sulfate, neommycin sulfate, hydrocortisone otic

• cortisporin otic, pediotic suspension

• superficial bacterial infections

carbamide peroxide otic

• debrox drops

• earwax removal