Pharmaceutics Ii Exam 3 Review Sheet

Microemulsions • Large, swollen micelles containing the internal phase stabilized by surfactants • Optically transparent • ~100A (10nm) to 1000A (100nm)

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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

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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

Otic • Know parts of the ear

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<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

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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

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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 tinplated 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 deaggragate and disperse

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o Spinhaler: unit dose device with drug in hard gelatin capsules o Diskhaler: multidose device with drug in foil blister o Diskus/Accuhaler: multidose with drug preloaded in inhaler *Advair o Turbohaler: multidose device with drug preloaded in inhaler • Formulation for DPIs: powder size <5um; carrier particle (Lactose) 30-60um • Nebulizer: for aerosol w/ large volume o Jet: compressed air, continuously operated o Ultrasonic: droplets gen. by high ultrasonic vibration piezoelectric crystal, dist by inhalation or air flow o Sterile, isotonic, neutral (pH 5-8) solns; water for vehicle, co-solvents (ethanol, prop glycol), stabilizers, antiox, preservatives • Metaproterenol sulfate: bronchodilator, betaadrenergic agonist (micronized powder) • Beclomethasone: corticosteroid(aerosol.nasal spray) • Advair: fluticasone(steroid), salmeterol(B-adr) lactos • Exubera: pulmonary human insulin powder (rapid) Nasal • Nasal cavity ~20mL, SA~200cm2 (conchae)

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Mucosal membraneepith. Cellsblood vessels Mucous: water, ions, glycoproteins, enzymes, Ig. Gel layer and soln layer pH 5.5-6.5 Cilia on epith. L=10um d=0.1um; beating at 10Hz 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

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Antioxidants: butylated hydroxytoluene Solubilization agents/cosolvents: glycol derivatives Buffers Tonicity contributors Viscosity-increasing agents: methylcellulose Humectants: prevent drying, min. irritation; glycerol Absorption enhancers Single-dose applicator(swab): coat nostrils Butorphanol Tartrate (Stadol MS®): migraine and post operative pain 1-2mL (spray) Vitamin B12 (Cyanocobalamin, Nasocobal®) (spray,gel) Salmon calcitonin (Miacalcin®) postmenopausal osteoporosis (metered nasal spray) Flumist®: influenza vaccine, LAIV, intranasal, approved 2003, age 5-49, store -15*C Narfaralin acetate: Synarel, endometriosis Nicotine: Nicotrol NS, smoke cessation Nasal decongestant soln o Adrenergic agents (ephedrine HCl, phenyeph) o Preservatives o pH 5.5-6.5 o isotonic Inhalants: drugs with high vapor pressure. Inhaler-device, inhalations-drug or drug solution o Propylhexedrine (Benzedrex): adrenergic (vasoconstrictor), temp relieves nasal congestion o Amyl nitrate-need Rx, vasodilator to treat angina pain, store 2-8*C, extremely flammable