Dosage Forms Final-Pharmacy

Suppositories

True, as well as the rectum and urethra.

False, suppositories are a solid dosage form.

False, vaginal is larger.

1. administering drugs to infants and small children.

2. severely debilitated patients

3. those who cannot take medications orally

True

False,
•Acidic pH of stomach or
enzymes destroy drug
•Drugs irritating stomach
•Drugs destroyed by first
liver passage

•Un-comfort
•Variation of absorption
•Irritation for mucous caused
by some drugs or bases

1. Hemorrhoid (astringent, local anesthetic, vasoconstrictor, anti-pruritic (pruritic=itchy), antiseptic)
2. Fungal infection
3. Bacterial infection
4. Chronic inflammation
5. Constipation (Glycerin)

True

Main Blood Circulation
1. Inferior haemorrhoidal vein (HV)
2. Middle HV.
3. Superior (upper) HV.

anti-emitic (emitic=vomitting), transquilizer,
vasodilator,
analgesic=painkiller,
hypnotic,
antipyretic,
anti-asthmatic

False, dosing curve for suppositories is smoother and more consistent.

1. Lipid solubility
2. Particle size
3. Suppository vehicle

True

The base should also:
1. dissolve or disintegrate in the presence of mucous secretions
2. Melt at body temperature
3. Be stable during storage

True, these physical properties are oleaginous (fatty) bases and water soluble or miscible bases

False, there are actually 3 components:

1. active ingredient
2. suppository base
3. ADDITIVES

False, GI irritation is a type of systemic action. Some examples of local action are anti-inflammation, anti-fungal, anti-bacterial, and astringent.

1. plasticizers (propylene glycol)
2. antioxidant
3. dispersant (surfactant)
4. absorbance enhancer

False, cocoa butter is oil-soluble.

True

True

False, although it does melt at body temperature, Cocoabutter is a polymorphic compound and if
overheated will convert to a metastable structure that melts in the 25°to30°C(77°to86°F) range.

False, the beta form is used and melts between 34-36oC.

The other forms are
2. beta crystal (mp 27 C)
3. alpha crystal* (mp 22 °C)
4. gamma crystal* (mp 18 °C)

Synthetic Triglycerides
•consist of hydrogenated vegetable
oils.
•do not exhibit polymorphism
•more expensive.

Synthetic triglycerides.

•triglycerides derived from palm, palm kernel and coconut oils
•stable with a low irritation profile
•needs no special storage conditions
•exhibits excellent mold release characteristics
•solid with a melting point of 35-37°C

Water, btw PEG=polyethylene glycol

False, 70% glycerin, 20% gelatin, and 10% water

may exert an osmotic effect and a defecation reflex, more useful for vaginal suppositories

should be packaged in a tight container, as they are hygroscopic

False, glycerinated gelatin are translucent.

False, store in glass because PEG reacts with polystyrene.

silver salts, tannic acid,
aminopyrine, quinine, aspirin, benzocaine, and
sulfonamides

1. chemically stable
2. miscible with water and mucous secretions
3. can be formulated by molding or compression

True.

True, also a water soluble drug shows rapid release in a oil soluble base.

True, as well as individually wrapped.

• Rolled (Hand-Shaped) Suppositories
–cocoa butter base
• Compression-Molded (Fused)
Suppositories
–no heat, mold under pressure
• Fusion or Melt Molding

True

Experimentally determine by double casting.

1. local/systemic effects
2. protection
3. hydration

1. semi-solid dosage forms are complex.
2. skin is not homogenous
3. skin is 16% of body weight

1. protective barrier by epidermis
2. homeostasis (temp+water) by epidermis
3.sensory
4. secretory (vit D production)
5. excretory (via sweat glands)

Keratinocytes

False

Stratum Corneum

True, is translucent. It is also more common is thick skin.

Stratum Spinosum, also has langerhan cells

Stratum Basale/Germinativum

True

True

epidermal, D3

Growth, division, repair, secretion

connective

basal, reticular

True

False, these structures are located in the dermis.

hydodermis

Adipose

sweat and sebaceous glands
hair follicles
nails
nerves and nerve receptors

(1) Manipulate the barrier
(2) Direct drugs to viable skin tissues
(3) Skin treatment for systemic
conditions

Antipruritic
Antihistamine

Demulcents: can alleviate irritation of mucous membranes

Rubefacients: increase skin temperature by increasing
circulation at the surface

Caustics: destroy skin at the applied site (warts,keratoses, hyperplastic tissue)

Keratolytics: cause peeling of skin, useful in thetreatment of eczema, acne, etc.

Very slow, Not all topical agents must permeate the skin to act, but for those that must permeate the
skin, the most common routes are
transepidermal and transappendageal .

True, False

corneum

mineral oils, glycerin, PEG, alcohol

base
medicinal agent (not always)
preservative

True, the non-medicated is an emollient, lubricant, or a vehicle for the preparation or medicated ointments.

• Hydrocarbon bases (=oleaginous)
• Absorption bases
• Emulsion bases - water-in-oil type
• Emulsion bases - oil-in-water type
• Water-miscible bases

False, will transport through a non-occlusive ointment. Occlusive ointments are hydrocarbons.

petrolatum, white petrolatum, yellow ointment (petrolatum+yellow wax)

True, an example of a single phase is hydrophillic petrolatum, and an example of a 2 phase is lanolin

• Insoluble in water
• Not water washable
• Anhydrous
• Can absorb water
• Emollient
• Occlusive
• Greasy

False, it can also absorb alcohol to a lesser extent.

cholesterol, both contain alcohol, white wax, and petrolatum

• Insoluble in water
• Water washable
• Will absorb water
• Contains water
• Emollient
• Non - Occlusive

• Water soluble
• Water washable
• Will absorb water
• Non - Occlusive
• Non - Greasy

hydrophillic petrolatum
aquaphor

hydrophillic ointment

PEG, also glyceryl monostearate, cellulose derivatives, and carbopol 934

1. desired release rate
2. desirability topical or percutaneous drug absorption
3. desirability of occlusion
4. stability of drug in vehicle
5. affect of drug on other features of ointment
6. patient factor-dry or weeping skin

True, incorporation involves mixing (ointment mill+levigating powder)

10% or 3g excess

True, levigation uses geometric dilution and levigating agent to wet powder

gritty feel and poor uniformity

*Must be compatible with base
– External phase of 2-phase systems
*Mustn’t unduly influence product viscosity
-Mineral oil & glycerin (Main agents)
- - Propylene glycol PEG 400, cottonseed oil, caster oil
– Surfactants , e.g. polysorbate 80 (Tween 80)
– Not all surfactants are compatible

False,
-Very difficult to fix once have problems
-Add more high/low viscosity component
-Keep triturating
-Start over

False, it is the other way around.
hard in soft

– Solids that cant’ be easily triturated

– DON'T OVER HEAT!

True, most ingredients in ointments will liquefy at 70oC.

• …the aqueous phase tends to cool faster than the oil phase
and may cause premature solidification of some ingredients.
• use the lowest temperature possible and keep the time of
heating as short as possible.
• This will minimize the quantity of water lost through
evaporation.
• Melt the ingredient with the highest melting point first
• Reduce the heat to melt the ingredient with the next
lowest melting point
• Continue this process until all ingredients have been added

False, this can change the product's consistency or make it STIFFER

False, the last step is the not the protocol, you add them when the product is cool to the touch. This could be the last step.

• Final product weight
• Visual appearance
• Color
• Odor
• Viscosity
• Homogenity/phase separation

False, they should be stored at room temperature, away from children, and away from heath and direct sunlight. IE, a high shelf in the bedroom.

False, no preservative is needed if no water is present.

• Chemical antimicrobial preservatives: phydroxybenzoates,
phenols, benzoic acid,sorbic acid, quaternary ammonium salts, organic mercury compounds, formaldehyde

True

After application: water evaporates, leaving a THIN residue film of stearic acid

• Usually the internal phase ranges from 15 - 40% w/w.
• They can absorb varying amounts of water.
• Under optimal conditions, the drug concentrates without crystallizing out

• The high concentration in the drug film can be good for drug delivery
• The thin film is not continuous and not oleaginous, so it will be less occlusive than oily ointments.
• Since they are less occlusive, o/w creams will generally be less protective and less emollient than the oily ointments.
Most acceptable topical dosage form!

Larger proportion of solid material and stiffer than ointments.

Pro: stable, in sold form
Con: hygroscopic, absorbs water from environment

1. promote drying
2. can reduce friction
-talc is more lubricating, no water absorption
-zinc oxide in middle
-corn starch is less lubrication with water absorption

solution: aqueous vehicle
tincture: alcoholic vehicle

True

tinctures

Plaster

Collodion, ie. liquid bandage.

False, it actually takes a long time to dissolve. Provides an occlusive protective coating to skin.

epithelial

Acidic, pH~4-5

Lactobacilli

• The avoidance of hepatic first-pass metabolism.
• A reduction in the incidence and severity of gastrointestinal
side effects.
• A reduction in hepatic side effects of steroids used in
hormone replacement therapy or contraception.
• It overcomes the inconvenience caused by pain, tissue damage and probable infection by other parenteral routes.
• The self-insertion and removal of the dosage form is possible.
• Large surface area
• Rich blood supply: ensures rapid absorption.
• Alternative when oral route is unfeasible.

• Limited to potent molecules
• Adverse effects (locally irritating or sensitizing drugs)
• Hormone dependent changes (cyclical changes in the
reproductive system)

True

--Contain antiinfective/hormonal substance, prepared by
compression, ovioid shape, plastic inserter.
--Bioadhesive vaginal tablets: Controlled release of drugs
having both local and systemic effects

1. can be used for a year
2. inhibits sperm survival locally
3. no estrogen, hormonal action only at uterus

True, ie Cervidil

•Rectal ointments to incorporate drugs (local anesthetics, analgesics, anti-inflammatory agents)
•Topical treatment (hemorrhoids), special rectal insertion and delivery tips

Rectal

rectum and lower intestine

water, baking soda
(sodium bicarbonate)

Inner, middle, outer ear

Pinna (auricle), and the external auditory canal

ossicles and eustachian tube.

True,
– Receptors that make
hearing and balance
possible
– Two sac-like structures,
called the vestibule
– Three semicircular canals

otitis media and otitis externa

• Otitis media
– An infection of the middle ear that is common in young
children
– Occurs when fluid builds up in the middle ear
– Usually accompanied by ear pain, fever, and difficulty hearing
• If untreated, otitis media can cause scarring of the tympanic membrane and a permanent loss of hearing
• If the infection is bacterial, antibiotics are usually given to treat it

True,

• Otitis externa
– Common in people who swim frequently or get the insides of their ears wet during showering or bathing
– Commonly referred to as “swimmer’s ear”
– An infection of the lining of the external auditory canal
• The ear becomes very painful to the touch
• Antibiotic ear drops are usually needed to treat the infection

Sterile, local

Disease of the inner ear
• It causes:
– Dizziness (vertigo)
– Ringing in the ear (tinnitus)
– Temporary hearing loss
– A feeling of pressure or fullness in the ear
• There is usually no cure for this disorder
• A person with Ménière’s disease may need to take more time
when getting up from a sitting or lying position, to prevent an
attack from occurring

True,
– Conductive hearing loss
• Occurs when something prevents sound waves from reaching the
receptors in the cochlea
– Sensorineural hearing loss
• Occurs when the receptors are unable to receive stimuli or transmit
nerve impulses
• There are many other causes of sensorineural

Cerumen

True, also warm for wax removal.

Analgesic

1. Warm bottle in hand
2. Lie on side and tilt head so ear is up
3. Pull ear lobe away from neck
4. Squeeze drops
5. Keep head tilted for 5 minutes
6. Straighten head and wipe excess liquid
7. Cap bottle

Water, do not swim and be careful in bath

-Pull ear lobe out and down and have them lie on their side for 2 minutes (not 5).

Oral, topical, intranasal, vaginal, rectal

1. Small inorganic discrete particles (2-phase system)
2. Large organic particles (1-phase)

1. clear or turbid (cloudy)
2. clarity and sparkle
3. water washable and greaseless

• …useful as liquid formulations in oral,
topical, intranasally, vaginal, and rectal
administration.
• Cooling effect
• moisturize

Bacterial/mold growth

Imbibition

Swelling

Gel exudes fluid causing shrinkage and water comes out of the pores.

Thixotropy

Xerogel

True

True,
• acrylic acid based polymers
• gel viscosity is pH dependent
• form acidic aqueous solutions (pH ~ 3),
thicken at a higher pH (5-6) (NaOH, KOH)
• a maximum of electrolytes (3%) can be added before a rubbery mass form
• Addition of alcohol: viscosity decreases
• Used for: oral suspensions, topical gels

True, except for CMC, the viscosity is maintained over a wide range of pHs

Carboxymethyl Cellulose (CMC)
• Soluble in water at all temperatures
• Sensitive to pH, viscosity decr.< pH5
• Stable between pH 7-9
• 30 producers make over 300 types of CMC
• Anhydroglucose polymer with 100 to 3,500
units (Degree of polymerization = DP)
• CMC has broad food usage (salad dressings, ice cream)

True, it is fat insoluble.

True

• Food uses:
– Stabilizer for flavor emulsions
– Encapsulated flavors
– Water binding
– Inhibit sugar crystallization

• Viscosity varies with grade
• Acid stable at pH 4-8
• Less common
• High cost

protein, collagen

• Mixture of low-molecular weight
polyethylene and 95% mineral oil.
• Mineral oil is immobilized by in the network of entangled insoluble polyethylene chains
• Gel can be heated up to 60°C (140°F) without substantial loss of viscosity

True

True

• Gelling agent
• Water
• Cosolvents
• Preservatives
• Stabilizers

• If gelling agent is added to the dispersing
medium: agent tends to “clump”
– Fix: sieve the agent onto the surface of the
medium as medium is stirring
• Some gelling agents require neutralizer to creategel
• Most gelling agents require 24 – 48hrs to completely hydrate and reach max. viscosity

• Appearance
• Uniformity
• Weight / Volume
• Viscosity
• Clarity
• pH

False, they can be stored at room temp or refrigerated in a tight container.

1. shape
2. size
3. surface properties
4. patient position: on back (supine) increase risk
5. no water increase risk
6. Disease-diabetes, chronic alcoholism, esophagitis

1 hour

Slowly,
Lozenge: prepared and formulated like candy (zinc + cough drops)
Troche: compressed into a hard disc (Mycelex troche)

True, because chewing takes place

mannitol

Effervescent, gives of CO2 to mask taste

True

1. easier to take and swallow, no need for water
2. possible faster onset of action by often not true

Faster onset bc of faster disintegration/dissolution
Not always true bc drug dissolution can be rate limiting and drug particles can be coated to mask taste

1. Lyophilization (free-drying)
2. Direct compression with special disintegrants
3. Molding

False, product is sponge-like and tablet is brittle

Tablets must be well protected because effervescent excipients are hygroscopic and don't open until ready to use.

lining of check and between teeth and gums

ventral surface of tongue and floor of mouth

local and systemic

Because it is coated with mucous, but a squamous epithelium

True, it is good for systemic delivery

False, they are not keratinized. The oral mucosa is keratinized.

Buccal

Sublingual

Neutral, pH=7

It can dissolve drug and it can wash it away.

False, there are variations, ie. a pool of saliva under the tongue

1. Avoidance of GI acid degradation, GI enzymatic degradation, and hepatic first pass effect
-drainage is to jugular vein
2. Can achieve rapid onset of action and high blood levels (ie SL NTG 1-3 min)
3. Can also be used for prolonged action (can be several hours for buccal)

1. Relatively low permeability for most drugs because skin-like barrier properties (small lipophillic are best absorbed)
2. The drug can be washed away by saliva, eating, and drinking
3. Sometimes bioavailability is unpredictable due to mucosal variation

True, drug dissolves in sublingual pool of saliva...must be quickly absorbed before being washed away

True, lower permeability and relatively easy to keep dosage form in place

False, they should be bland and non-irritating so as to not stimulate saliva flow.

Sublingual
1. Tablet: dissolves rapidly with little residue
2. Spray: long-shelf life ie Nitroglycerin
Buccal
1. Chewing gum
2. Lozenge
3. Lollipop
4. Mucoadhesive tablets
5. Orally disintegrating tablets

lightly,

some examples: Isosorbide dinitrate and Nitroglycerin

Reduces volatility and explosive risk

Prepared by forcing a moistened blend of drug and excipients into a mold, followed by forcing the wet mass out of the mold and allowing to dry

True

Lactose: Reduces volatility and explosive risk
Polyethylene glycol: lowers vapor pressure

1. Powder mix is moistened in 60% v/v alcohol
2. Moistened mass pressed into mold plates
3. Wet tablets forced out
4. Tablets usually dried under ambient conditions to limit NTG evaporation

Glass, 6 months

1. Good hepatic first pass
2. Good buccal absorption

Cation, nicotine is exchanged with saliva cations. Chewing is critical.

pH to 8.5, basic pH increases the nonionized form.

True

Commit, nicotine is released by cation exchange as the lozenge dissolves.

Fentanyl citrate, it has a high hepatic and intestinal first pass and it is also very lipophillic

15 minutes

False, it has rapid absorption in mouth, followed by prolonged absorption via GI

It is unlikely to be swallowed and can be easily removed if side effects occur

To keep in place, designed to slowly disintegrate/dissolve

Cellulose derivatives

1. Striant (testosterone buccal system)
a. testosterone-high hepatic first pass
b. stays until removed (~12 hrs)

2. Nitrogard (nitroglycerin)

False, not all.

Ex. Zelapar (selegiline hcl) for Parkinson's disease
-prepared by lyophilization
-placed ON tongue where is rapidly dissolves buccaly...avoid liquid 5 min before and after

Avoid eating, drinking, chewing, smoking, and talking

DO NOT DISTURB

local

True

1. Outermost: conjunctiva/sclera and the cornea
2. Middle: Uveal tract (choroid, ciliary body, and iris)
3. Innermost: retina

Vitreous humor aka anterior and posterior SEGMENT (not chamber)

IRIS

True

Conjuctiva: thin, transparent, vascularized mucous membrane that extends from the edge of the cornea, across a portion of the sclera, then extends to the internal sac of the eyelids to form the conjuctival sacs

2. Lacrimal gland: gland responsible for tear production and removal of foreign materials through puncta

3. Puncta: small openings to the lacrimal canaliculi

4. Nasolacrimal apparatus: the drainage system for lacrimal fluid.

Tears drain through the canaliculi to the lacrimal sac then to the nasal cavity via the lacrimal duct. Tear drainage occurs by gravity and through an active process employing a pumping mechanism like the blink of an eye. Tear drainage from the nasal cavity, they are moved toward the nasopharynx.

Cornea

Tear

Three
1. Mucoid layer: involved in adhesion of the aqueous tear fluid to keep the cornea wettable
2. Tear Fluid: Aqueous solution of inorganic electrolytes, glucose, and proteins including enzymes and immunoglobulins
3. Lipid film: a layer of wax and cholesterol esters adsorbed to the tear fluid to reduce evaporation of the tear fluid

passive diffusion

False, its from outer to inner

True

Squamous, increase

epithelium, it is primarily a lipophilic barrier (lipophilic drugs permeate well) and the drugs ionization state can be important because (unionized drugs are more lipophilic and permeate better)

True, esterases, peptidases, and proteases

Collagen

Stroma is mostly water, which is a barrier for lipophilic drugs

Single

False, it is much more permeable than the epithelium

o/w, because of the diverse barriers.

True

False, better absorption through damaged epithelium

20 to 60 minutes

True

True, from 25-56 microliters (avg 39)

1. Spillage
-can accomidate 30 microliters without spillage
-blinking increases spillage and facilitates removal by nasolacrimal apparatus (leads to 10 micoliters residual volume)

2. Removal by nasolacrimal drainage
-gravity and blinking forces fluid through puncta

3. Enzymatic degradation

4. Conjunctival permeation followed by systemic absorption

1. Penetration into deeper intraocular tissues
-Greatest concentrations are usually achieved within the aqueous humor in the anterior region of the eye. The concentration within the anterior chamber with be less than the applied product by 2 orders of magnitude
-The amount reaching the posterior region is insignificant. Dont usually treat this area.

2. Binding to proteins
-some lipophilic drugs can bind to melanin in the iris in dark irides, can reduce the drug effect or act as a depot

3. Elimination: Drugs can enter the systemic circulation from within the eye via:
-aqueous humor turnover thru canal Schlemm
-uveal blood vessels

True, can also bind to melanin in the iris.

True

1. Through the tissues encountered following nasolacrimal drainage
-significant fraction can be absorbed through the nasal cavity
-as well as lacrimal sac, nasopharynx, cheeks, GI tract

2. Through blood vessels in the conjunctiva
-conjunctiva is more permeable than the cornea and covers a larger surface area to facilitate drug absorption
-conj. is highly vascularized, most that permeates is absorbed systemically
-from within the eye

Sterility
pH
Osmolarity
Viscosity

Pseudomonas aeruginosa

Benzalkonium chloride (BAC) 0.01% or less, can damage the corneal epithelium if concentration is too high, can act as a penetration enhancer

True

1. Polyquad-does not penetrate the cornea well, an alternative to BAC
2. Thimerosal-an organic mercurial, hypersensitivity is a problem
3. Oxidants (PURITE)

basic, pH~7-7.4

Causes irritation, reflex tears, and blinking, which SPEEDS up drug elimination

True, very limited buffer capacity.

Both strong acids and strong bases

True

NaCl, Mannitol, and dextrose

Pros:
1. Increased retention time/reduced drainage/increased bioavailability
2. lubricating effect

Cons:
1. Can irritate
2. May cause crust formation and transient blurring

glycerin, cellulose derivatives, polyvinyl alcohol, PEGs

True

Heat or Membrane filtration (0.2 micron filter)

False, because you will remove the drug particles. so must add the sterilized solid to the sterilized solution

1. Used for poorly water-soluble drugs to improve stability
2. Mix with tears less rapidly, stay in cul-de-sac longer

a. antioxidant, look at fites as a clue

b. chelator (binds metals)

Besides its ability to limit oxidation by chelating metals, EDTA increases the activity of BAC against p. aerugnosa

c. surfactant

Used as wetting agent for suspensions and can facilitate spreading of the drops b/c they reduce surface tension

sterilized

Ointments and gels

Prolonged contact time.

Ointments can be cleared as slowly as 0.5% per minute.

Carbomer or gum gel former

Can cause blurred vision and matting of the eyelid

1. Ointment base is usually white petrolatum, with or without mineral oil to reduce viscosity
2. Sterilize the ointment base by heat, then filter while molten
3. Used following surgery
4. The standard tube is 3.5g

1. Wash hands
2. Shake for 10 sec (if suspension)
3. Remove cap, hold container between thumb and middle finger with index finger on the bottom of vial
4. lie down or tilt head back
5. Gently pull downward under affected eye to form pouch
6. Look up and place one drop in the conjunctival sac
7. Gently release eyelid and keep eye closed for 30 seconds
8. With eye closed, apply pressure against the inner corner of the eye for at least 30 seconds
9. Do not rub, wipe, or squeeze eye
10. Replace cap

Second drop will wash out first drop

True, with 5 min interval.

False, other way around with a 10 min interval.

BAC can bind to contacts.

30 days after opening or at sign of contamination

1. Wash hands
2. Hold tube between thumb and forefinger of opposite hand
3. Tilt head back
4. Pull eye down
5. Place 1/4-1/2 inch ribbon of medication with a sweeping motion into conjunctival sac. Close eye for 1-2 minutes and roll eye ball in all directions
6. Wipe off excess
7. Replace cap

True, blurred vision