Otic Drug Delivery (3/27/26) - Pharmaceutics II

What structures make up the External Outer Ear?

Pinna (Auricle)

External Auditory Meatus (Ear Canal)

Tympanic Membrane (Eardrum)

What structures make up the Air-Filled Middle Ear?

Ossicles (Ear Bone); includes Malleus, Incus, and Stapes

Eustachian Tube

What is the function of the Eustachian Tube?

Where is it located in the ear?

Connects the middle ear to the throat (Pharynx) and helps equalize air pressure

Located in the Air-Filled Middle Ear

What structures make up the Fluid-Filled Inner Ear?

Sensory Organs of Hearing (Cochlea) and Balance (Semicircular Canals)

Hair Cells, Perilymph, and Endolymph in the Cochlea

Vestibule

What is the function of the Vestibule?

Where is it located in the ear?

Connects the Cochlea and Semicircular Canals to help detect head position and motion

Located in the Fluid-Filled Inner Ear

What is Cerumen?

Where is it produced?

What is its main function?

Ear Wax

Produced in the Ear Canal

Main function is to lubricate the ear canal and entrap dust + foreign materials

What is the Organ of Corti?

Where is it located?

What is its main function?

Primary sensory organ for hearing

Located in the Cochlea of the Inner Ear

Function is to convert sound vibrations into nerve impulses that the brain interprets as sound

What is the Vestibular System?

Where is it located?

What is its main function?

System in the Inner Ear responsible for Balance and Spatial Orientation

Located in the part of the Inner Ear responsible for Balance, Posture, and Spatial Orientation

Function is to detect head movements and send signals to the brain to coordinate body position and eye movement

What are the Semicircular Canals?

Where are they located?

What are their main functions?

Three loop-like structures in the Inner Ear that are part of the Vestibular Systemc

Located in the Inner Ear

Function is to detect Rotational (angular) movements of the head and help maintain balance and spatial orientation

Where are Inner and Outer Hair Cells located?

Located in the Organ of Corti (within the Cochlea of the Inner Ear)

What is the Hearing Mechanism of the Organ of Corti?

1. Sound waves enter ear canal, striking the Tympanic Membrane and causing vibrations

2. Vibrations are amplified by the Ossicles

3. Stapes transmits vibrations to Cochlea via Oval Window

4. Hair Cells in Cochlea detect vibrations and generate Nerve impulses

5. Auditory nerve carries impulses to the Brain (Auditory Cortex in Temporal Lobe) for sound interpretation

What is the Balance Mechanism of the Organ of Corti?

1. Semicircular Canals detect head movements and send signals to the brain

2. Vestibule (Utricle and Saccule) senses gravity and linear motion

3. Brain integrates this information to maintain posture and balance

What are the four major diseases of the human ear?

1. Hearing Loss

2. Autoimmune Ear Disorder (AIED)

3. Meniere's Disease

4. Tinnitus

What is Hearing Loss?

Major disease of the ear caused by damage to the Inner Ear or the Nerve that connects the ear to the brain

What is Autoimmune Ear Disorder (AIED)?

Major, rare disease of the ear that occurs when the body's immune system attacks cells in the Inner Ear after mistaking them for a Virus or Bacteria

What is Meniere's Disease?

What are some examples of symptoms associated with Meniere's?

Major disorder of the ear that is caused by fluid buildup in the chambers of the Inner Ear

Symptoms include:

- Vertigo

- Nausea

- Vomiting

- Loss of Hearing

- Ringing in the Ears

- Headache

- Loss of Balance

- Sweating

Which part of the ear does Acute External Otitis (Swimmer's Ear) affect?

Otitis Media?

Hearing Loss, AIED, Meniere's Disease, and Tinnitus?

Acute External Otitis (Swimmer's Ear) --> Outer Ear

Otitis Media --> Middle Ear

HL, AIED, Meniere's, Tinnitus --> Inner Ear

What are the four main Vestibular and Semicircular Canals Disorders?

Describe each of them.

1. VERTIGO - sensation of spinning

2. VESTIBULAR NEURITIS - inflammation of the vestibular nerve causing dizziness

3. MENIERE'S DISEASE - inner ear disorder with Vertigo, Hearing Loss, and Tinnitus

4. LABRYNTHITIS - inflammation of the Inner Ear affecting both hearing and balance

What is considered the most convenient method of drug administration for parts of the ear?

Oral and Parenteral Routes

What are the main limitations to Systemic Drug Delivery via Otic drug delivery?

Blood-Perilymph Barrier (BPB)

Blood-Cochlear Barrier (BCB)

Undesired Side Effects

How does the bioavailability of drugs for Systemic Drug Delivery compare with Local Drug Delivery when utilizing Otic administration?

Systemic <<< Local

Systemic has LIMITED bioavailability

Which type of drug delivery is the first-line approach when treating diseases of the human ear?

What types of drugs benefit from utilizing this type of drug delivery?

LOCAL drug delivery

Beneficial for drugs that:

- Have a narrow therapeutic window

- Significant first-pass metabolism

- Serious side effects

What are some advantages to Local Drug Delivery to treat diseases of the ear?

Ability to bypass BPB / BCB

Higher drug concentration is present at the local site

Reduced side effects

What are the three possible types of Local delivery systems when treating diseases of the ear?

1. TOPICAL Drug Delivery

2. INTRATYMPANIC / TRANSTYMPANIC Drug Administration

3. INTRACOCHLEAR Drug Administration

What is the Topical Drug Delivery method of Otic administration?

What are some common examples of drugs administered via this delivery method?

Direct administration of the drug into the ear canal

Examples of topical otic medications include ANTIBIOTICS and ANTIFUNGALS in the form of DROPS or GELS

What is the Intracochlear (IC) Drug Delivery method of Otic administration?

What are some common examples of drugs administered via this delivery method?

Drug delivery bypasses the middle ear and allows drugs to reach the intended sites directly

Examples of IC administration include COCHLEAR IMPLANTS and OSMOTIC MINI-PUMPS

What is the main advantage to the Intracochlear (IC) Drug Delivery method?

Main disadvantage?

Can achieve better bioavailability than other delivery methods

Invasive

What is the Transtympanic Drug Delivery method of Otic administration?

What are some common examples of drugs administered via this delivery method?

Broader term that refers to any method of delivering medication through the Tympanic Membrane; includes direct injection in the Tympanic Cavity

Examples of Transtympanic administration include INJECTIONS (INTRATYMPANIC) or SUSTAINED-RELEASE SYSTEMS (TYMPANOSTOMY TUBES / IMPLANTS)

What is the Intratympanic Drug Delivery method of Otic administration?

Involves injecting the drug into the Middle Ear Cavity near to the Oval Window / Round Window, allowing the drug to diffuse through the Round Window Membrane into the Inner Ear

Compare INTRAtympanic and TRANStympanic Drug Delivery for these characteristics:

- Method

- Target

- Delivery Methods

INTRAtympanic:

- METHOD: direct injection into Middle Ear

- TARGET: Inner Ear (Cochlea and Vestibule) via round window absorption

- DELIVERY METHODS: Single or Multiple injections

TRANStympanic:

- METHOD: any drug delivery method that goes through the Tympanic Membrane

- TARGET: Middle or Inner Ear (dependent on method)

- DELIVERY METHODS: Injections and Implants

What are examples of Pharmaceutical Dosage Forms and Devices for INTRAtympanic Administration to the Ear?

Solutions and Suspensions

Hydrogels

Nanomedicines

Medical Devices

What are examples of Pharmaceutical Dosage Forms and Devices for INTRAcochlear Administration to the Ear?

Solutions

Medical Devices

Implant Coating

What are examples of Pharmaceutical Dosage Forms and Devices for SYSTEMIC Administration to the Ear?

Oral Dosage Forms

Injectable Solutions

Nanomedicines

What are some Barriers and Limitations of INTRAtympanic Administration to the Ear?

Round and Oval Windows

Bone of the Otic Capsule

Clearance through the Eustachian Tube

What are some Barriers and Limitations of INTRAcochlear Administration to the Ear?

No anatomical barriers

HIGHLY Invasive

What are some Barriers and Limitations of Systemic Administration to the Ear?

Blood-Cochlear Barrier (BCB)

Bone of the Otic Capsule

Low Local Vascularization

Side Effects

What are the two main routes of administration for Systemic Drug Delivery to the Ear?

Advantages?

Disadvantages?

Routes include ORAL and IV

Advantages:

- Self-Administration

Disadvantages:

- Blood-Cochlear Barrier (BCB)

- Side Effects

What are the four main routes of administration for Local Drug Delivery to the Ear?

Advantages?

Disadvantages?

Routes include TOPICAL, TRANSTYMPANIC, INTRATYMPANIC, and INTRACOCHLEAR

Advantages:

- (T) Self-Administration, Noninvasive

- (TT) Noninvasive

- (IT) Easy Access, Less Surgical Trauma

- (IC) Increased Bioavailability

Disadvantages:

- (TT) Lower Bioavailability

- (IT) Invasive

- (IC) Highly Invasive

What are Otic Ointments?

Give an example.

Semisolid preparations that are applied to the exterior of the ear

Example: Otomax - powerful first-line, broad spectrum topical medication administered twice a day for 7 days to treat Otitis Externa in dogs

What are Otic Suspensions?

Give an example.

Suspensions that can be used when a long duration of drug effect is desired or when the drug is NOT soluble in the vehicles

Example: Posatex - indicated for the treatment of Otitis Externa in dogs; strong yet gentle solution for severe cases

What are Otic Irrigating Solutions?

Give an example.

Solutions uses to remove earwax, purulent discharges of infection, and foreign bodies from the ear canal

Example: Saline Solution

What are the eight main excipients used in Otic Preparations?

1. Solvents / Vehicles

2. Viscosity Enhancers

3. Preservatives

4. Buffers / pH Adjusters

5. Antioxidants

6. Surfactants (Emulsifiers and Wetting Agents)

7. Penetration Enhancers

8. Osmotic Agents (Humectants and Moisturizers)

What are some common Solvents / Vehicles used in Otic Preparations?

What do each of them do?

GLYCERIN - increases viscosity and improves drug solubility

PROPYLENE GLYCOL - enhances drug solubility and penetration

MINERAL OIL - used in oily-based otic formulations

POLYETHYLENE GLYCOL (PEG) - used in water-miscible formulations

ETHANOL or ISOPROPYL ALCOHOL - used as a solvent and antiseptic

What are some common Viscosity Enhancers used in Otic Preparations?

What do each of them do?

CARBOXYMETHYLCELLULOSE (CMC) - increases viscosity and helps in prolonged drug retention

HYDROXYPROPYL METHYLCELLULOSE (HPMC) - improves the residence time of the drug

POLYVINYL ALCOHOL (PVA) - provides viscosity and film-forming properties

What are some common Preservatives used in Otic Preparations?

What do each of them do?

BENZALKONIUM CHLORIDE - broad-spectrum antimicrobial agent

CHLOROBUTANOL - antimicrobial preservative commonly used in otic solutions

PARABENS (METHYL- AND PROPYL-) - prevents microbial contamination

What are some common BUFFERS / pH ADJUSTERS used in Otic Preparations?

What do each of them do?

all maintain pH stability

CITRIC ACID + SODIUM CITRATE

ACETIC ACID

PHOSPHATES (NaPO4, MONO- AND DIBASIC POTASSIUM PHOSPHATE)

What are some common Antioxidants used in Otic Preparations?

What do each of them do?

SODIUM METABISULFITE - prevents oxidation of APIs

ASCORBIC ACID - protects against oxidative degradation

EDETATE DISODIUM (EDTA) - chelating agent that enhances stability

What are some common Surfactants (Emulsifiers and Wetting Agents) used in Otic Preparations?

What do each of them do?

POLYSORBATES (TWEEN 80, TWEEN 20) - improve solubility of hydrophobic drugs

SODIUM LAURYL SULFATE (SLS) - wetting agent in some formulations

What are some common Penetration Enhancers used in Otic Preparations?

What do each of them do?

DIMETHYL SULFOXIDE (DMSO) - enhances drug penetration through the ear canal

OLEIC ACID - helps improve drug absorption

What are some common Osmotic Agents (Humectants and Moisturizers) used in Otic Preparations?

What do each of them do?

GLYCERIN - helps in preventing excessive drying of the ear canal

SORBITOL - maintains osmotic balance and improves drug stability

Why is viscosity an important factor for Otic formulations?

Helps keep the medication in the ear canal

Why is it important for us to include Surfactant in an Otic preparation?

Helps the medication spread out and also helps aid in breaking up earwax to allow for easier removal of any foreign material

What is the function of Carbamide Peroxide and Hydrogen Peroxide with Otic formulations?

Contribute a mechanical "bubbling" action that softens and breaks up dried Cerumen; also have anti-infective properties

What is the primary vehicle of most Otic ointments?

Petrolatum

Give an example of an Otic Solution, with its API and vehicle.

Example Otic Solution:

- Benzocaine 200mg, API

- Glycerin qs 15 mL, Vehicle

Given the formulation record for Ciprofloxacin and Hydrocortisone Otic Solution:

- What are the four ingredients included in this formulation and their therapeutic activities?

CIPROFLOXACIN HCL - Antibacterial

HYDROCORTISONE - Glucocorticoid, Anti-Inflammatory

GLYCERIN - Antimicrobial Preservative (>20%), Emollient, Humectant (<30%)

PROPYLENE GLYCOL - Humectant (15%), Inhibitor of Mold Growth (15-30%), Solubilization Agent (10-25%)

Given the formulation record for Ciprofloxacin and Hydrocortisone Otic Solution:

- What is the strength of the Solution?

0.3% Ciprofloxacin

0.5% Hydrocortisone

Given the formulation record for Ciprofloxacin and Hydrocortisone Otic Solution:

- What was the date of Last Review / Revision?

- Who completed the Last Review / Revision?

08/01/2012

Completed by Robert Shrewsbury

Given the formulation record for Ciprofloxacin and Hydrocortisone Otic Solution:

- What was the quantity used of each ingredient included in making the solution?

CIPROFLOXACIN HCL - 0.36 g

HYDROCORTISONE - 0.5%

GLYCERIN - 60 mL

PROPYLENE GLYCOL - qs 120 mL

Given the formulation record for Ciprofloxacin and Hydrocortisone Otic Solution:

- What descriptions are given for each ingredient included in making the solution?

CIPROFLOXACIN HCL - light yellow crystalline powder

HYDROCORTISONE - white to creamy-white odorless powder

GLYCERIN - viscous, clear, colorless, odorless, hygroscopic liquid

PROPYLENE GLYCOL - viscous, clear, colorless, odorless, tasteless, hygroscopic liquid

Given the formulation record for Ciprofloxacin and Hydrocortisone Otic Solution:

- What are the solubilities for each ingredient included in making the solution?

CIPROFLOXACIN HCL - soluble in water (1g / 25mL)

HYDROCORTISONE - insoluble in water (0.028%) and glycerin; propylene glycol 12.7mg/mL

GLYCERIN - sp. gr. is 1.25g/mL; miscible with water and alcohol

PROPYLENE GLYCOL - miscible with water, glycerin, and alcohol; sp. gr. is 1.038g/mL