Microemulsions
• Large, swollen micelles containing the internal
phase stabilized by surfactants
• Optically transparent
• ~100A (10nm) to 1000A (100nm)
• Surfactants HLB range 15-18
o Polysorbate 60, polysorbate 80 (Tween
60,80)
• Rapid, efficient oral absorption of drugs; big
surface area; increased drug diffusion
• Target cytotoxic drugs to cancer cells
• Difficult to formulate and make stable
Opthalmic
• Know parts of the eye
• Tear(lacrimal fluid) volume: 7 ul
o Cul-de-sac: 30ul w/out blinking, 10ul after
o Aqueous, clear, pH~7.4
o Protein: 0.6-2.0% albumins and globulins,
enzymes, organic compounds, glucose,
salts
• Opthalmic dispenser drop: 50-75 ul (50 ul
excess)
• Topical administration: 10ul
• <10% drug is absorbed
• Precorneal liquid film: lipid, tear, mucus
• Cornea: 0.5-1mm thick; corneal absorption is
the major ophthalmic absorption route (most
eff. For drugs with both lipophilic and
hydrophilic prop.)
o Corneal epith: lipophilic (eff. Bacterial
barrier)
o Stroma: hydrophilic
o Corneal endothelium: less lipophilic than
epith.
• Sterilize drugs by autoclave or filtration
• Preservatives for multiple dose prep:
o Chlorobutanol: 0.5%
o Benzethonium Cl & benzalkonium Cl: 0.01%
o Thimersol: 0.01%
o Phenylmercuric nitrate 0.004%
o Tonicity “comfort zone” 0.5-2.0% NaCl (we
tolerate hypertonic soln better)
o Isotonic: 0.9%NaCl; 1.9% boric acid
o Can also use dextrose, glycerin,
propylene glycol to adjust
• Desirable pH range 6-8 (tear=7.4). buffer
capacity should be enough to maintain stability
but still allow tear to reverse the soln to
physiological pH
• Viscosity: 15-25 cps; thickening agents
methylcellulose, hydroxypropyl
methylcellulose, polyvinyl alcohol
• Particle size for susp: <10 um
• Ointment: white pet/liquid pet (mineral oil)
based; PEG/mineral oil based
• Ocusert® cont. release of pilocarpine (5mg)
20-40ug.hr for 4-7 days. Zero order release
• Lacrisert® hydroxypropyl cellulose: 5mg rod
shaped water soluble form severe dry eye
syndrome
• Contact lenses:
o Cleaning soln: contain nonionic or
amphoteric surfactants
o Wetting soln: lubricate and dec. surface
tension
o Soaking and storage soln: hydrate in aseptic
environment
o Preservatives in all products
Otic
• Know parts of the ear
• Ear canal: 1 in in length; point down in adults
o Can hold 0.85 ml (~17 drops)
• Cerumen=earwax=lubricates, protects, cleans
• OTC meds:
o Excessive earwax treatment (Not in water)
 Hydrogen peroxide, mineral oil, vegetable
oil
 Debrox®: 6.5% carbamide per., Sodium
lauroyl sarcosinate, glycerin, propylene
glycol
 Murine®: 6.5% carbamide per.,
Polysorbate 20, glycerin, ethanol
o Water clogged ears
 95% isopropyl alc & 5% anh. Glycerin
(Swim-Ear®, Auro-Dri®
• Adults: UP AND BACK
• Children < 3: DOWN AND BACK
Pulmonary
• Clearance: cough, sneeze, mucociliary action
~24 hr
• Absorption: ~70m2, 300 million alveoli
• Preferably permeable to unionized drugs
• Particle size: <6um for resp. bronchioles;
<2um for alv. Ducts and alveoli
• Impact in upper airways (particles >5um)
*slower breathing avoids this
• Gravitational sedimentation for small airways
and alveoli (particles 0.5-3um) *Stoke’s
Eq.*hold breath
• Brownian diffusion for small particles (<0.5um);
[high][low] (diff. @ stagnant air @ lower
airways) *hold breath
• Aerosol Pressurized container: uses CFCs &
HFAs in aluminum, plastic-coated glass, or tin-
plated steel container
• MDI: uses metering valve to deliver 25-100ul
of liquid (soln, dispersion, powder) *shake well
o Use a spacer to reduce initial droplet
velocity, efficient propellant evaporation, do
not need inh/actuation coordination
• DPI: generate turbulent air flow to de-
aggragate and disperse
 o Spinhaler: unit dose device with drug in • Antioxidants: butylated hydroxytoluene
hard gelatin capsules • Solubilization agents/cosolvents: glycol
o Diskhaler: multidose device with drug in foil derivatives
blister • Buffers
o Diskus/Accuhaler: multidose with drug • Tonicity contributors
preloaded in inhaler *Advair • Viscosity-increasing agents: methylcellulose
o Turbohaler: multidose device with drug • Humectants: prevent drying, min. irritation;
preloaded in inhaler glycerol
• Formulation for DPIs: powder size <5um; • Absorption enhancers
carrier particle (Lactose) 30-60um • Single-dose applicator(swab): coat nostrils
• Nebulizer: for aerosol w/ large volume • Butorphanol Tartrate (Stadol MS®): migraine
o Jet: compressed air, continuously operated and post operative pain 1-2mL (spray)
o Ultrasonic: droplets gen. by high ultrasonic • Vitamin B12 (Cyanocobalamin, Nasocobal®)
vibration piezoelectric crystal, dist by (spray,gel)
inhalation or air flow • Salmon calcitonin (Miacalcin®) post-
o Sterile, isotonic, neutral (pH 5-8) solns; menopausal osteoporosis (metered nasal spray)
water for vehicle, co-solvents (ethanol, prop • Flumist®: influenza vaccine, LAIV, intranasal,
glycol), stabilizers, antiox, preservatives
approved 2003, age 5-49, store -15*C
• Metaproterenol sulfate: bronchodilator, beta- • Narfaralin acetate: Synarel, endometriosis
adrenergic agonist (micronized powder)
• Nicotine: Nicotrol NS, smoke cessation
• Beclomethasone: corticosteroid(aerosol.nasal
• Nasal decongestant soln
spray)
o Adrenergic agents (ephedrine HCl,
• Advair: fluticasone(steroid), salmeterol(B-adr) phenyeph)
lactos o Preservatives
• Exubera: pulmonary human insulin powder o pH 5.5-6.5
(rapid) o isotonic
Nasal • Inhalants: drugs with high vapor pressure.
• Nasal cavity ~20mL, SA~200cm2 (conchae) Inhaler-device, inhalations-drug or drug solution
• Mucosal membraneepith. Cellsblood vessels o Propylhexedrine (Benzedrex): adrenergic
• Mucous: water, ions, glycoproteins, enzymes, (vasoconstrictor), temp relieves nasal
Ig. Gel layer and soln layer pH 5.5-6.5 congestion
o Amyl nitrate-need Rx, vasodilator to treat
• Cilia on epith. L=10um d=0.1um; beating at
angina pain, store 2-8*C, extremely
10Hz
flammable
• Physical barrier (for drug abs): mucociliary
clearance towards nasopharynx (20min/cycle)
• Enzymatic barrier: nasal metabolism (cyt
P450, CYP450) *sneezing is another barrier
• Molecule size limit for abs=1000 Dalton
• Topical and systemic, fast abs, rapid onset,
avoid 1st pass, close to brainpotential for
delivery to CNS
• Dosage forms: required to be sterile OR
preserved
• Powder: good stability, (>4um~10um) need to
control size and use metered delivery device,
may be irritating
• Ointment/gel: inc contact time, reduce leakage,
mask taste, soothe & emollient effects, dosing
is inaccurate (except using precise dosing
device)
• Drops: simple, cheap, multi-dose, volume
inaccurate
• Nasal spray: (squeeze bottle) spray liq. By
partially atomized jet
• Nasal spray: (metered dose pump) deliver soln,
susp, emul in a predetermined vol b/t 25-200ul
• Excipients:
• Antimicrobial preservatives: benzalkonium cl