DOSAGE EXAM 3

Sterilization

destruction of living organisms and their spores or their complete removal from the preparation

method determined by nature of preparation and ingredients

Steam Sterilization

conducted in autoclave

bacterial cells are killed easily (active), but not spores (dead)

moist heat denatures + coagulates microbial proteins, causing microorganisms to die

maximum steam temp at atmospheric pressure = ~212F

usual method of choice if product can withstand

effective for sterilizing bulk solutions, glassware, surgical dressings/instruments

not useful for oils, fats, and oleaginous preparations bc steam cannot penetrate oil

Dry Heat Sterilization

carried out in ovens and may be heated by gas or electricity

bacterical death due to dehydration of microbial cell followed by oxidation

less effective in killing microorganism than moist heat; not as effective as steam

higher temp + longer duration required

only smaller items (dery heat cannot reach inside)

method of choice when dry apparatus/containers are required

Sterilization by Filtration

physical removal of microorganisms by adsorption on the filter membrane or sieving mechanism

used for heat-sensitive solutions

physically removes bacteria by passing fluids through filters with pores so small that the bacteria gets arrested; does not remove bacteria

ability to sterilize thermo-labile materials

relatively inexpensive equipment

Gas Sterilization

for heat/ moisture sensitive materials

sterilization by exposure to ethylene oxide or propylene oxide gas

highly flammable when mixed with air:. hence mixed with inert gas such as CO2, or fluorinated hydrocarbon

requires 4-16 hours of exposure

used to sterilize medical + surgical supplies due to its penetrating power

Sterilization by Ionizing Radiation

sterilization via exposure to ionizing radiation (UV lamp, ionization, beta rays, gamma rays, X-rays)

application: solutions, bandages, baby bottle nipples (heat sensitive items)

cold sterilization

disadvantages: highly specialized equipment + trained personnel are required

Pyrogens

fever-producing metabolic products from outer cell wall of gram negative bacteria (bacterial endotoxin)

thermostable and water soluble; cannot be removed via heat or filtration

removed by oxidation and separated from water by distillation

Pyrogen Testing — Rabbit Test

conducted in healthy rabbits

producted injected into ear vein → if no rabbit shows rise in temp = no pyrogens present

if individual rabbit shows rise in temp → continue testing with 5 other rabbits

Pyrogen Testing — Limulus Amebocyte Lysate (LAL) test

Limulus Polyphemus (horseshoe crab blood cells) contains enzyme that coagulates in presence of low levels of lipopolysaccharides → cloudy = pyrogens present

more sensitive than rabbit test, can test in small test tube

valid only for bacterual endotoxin, vancomycin may interfere (cause false positive)

Topical Dosage Forms

applied to skin or mucous membrane (eye, external ear, nasal mucosa, buccal mucosa, rectal lining, vaginal lining, urethral lining)

Dermatologicals

applied to skin and scalp

Factors of Drug Absorption Into/Across the Skin Layers

1) the physiochemical properties of the drug (lipid solubility + ability to cross the skin)

2) physiochemical properties of the vehicle (oily drugs like oily bases; allows drug to release slower)

3) interaction of vehicle with skin (vehicle can disrupt skin structure temp → faster absorbance)

Drug Absorption Rules

more skin area applied → more absorbance

higher skin hydration → higher skin absorbance

more rubbing force → better absorbtion

more contact time -→ better absorbtion

large area, well-hydrated, strong rubbing force, long contact time = optimal absorption

Semi-solid Dosage Forms

intended for topical use usually in skin, eye, nose, vagina, rectum

mainly intended for local effect

systemic absorption should be taken into account for pregnant women/nursing mothers

Ointments

semisolid preparations intended for external application to skin/ mucous membrane

may be medicated or non-medicated (nm provide protective + lubricating effects; can just mix API to make medicated)

formulation = drug + ointment base

soften/ melt at body temp + spread easily

works best for dry, scaly skin

Ointment Base — Oleaginous/Hydrocarbon Base

protect skin against escape of moisture; occlusive/ emolient

remain on skin for longer period of time (as effective as occlusive dressings)

greasy + difficult to wash off

wide melting points

good compatibility

common bases: petrolam, white petrolam, yellow ointment, white ointment

Ointment Base — Absorption Bases

can absorb significant amounts of water or aq. solutions without major changes in consistency

two types: emulsifiable or emulsion bases

may be used as emolients but are not as occlusive as oleaginous bases

not easily removed from skin with water bc external phase = oleaginous

useful as pharmaceutical adjuncts for small volumes into hydorcarbon bases

Ointment Base — Absorption Bases; Emulsifiable Bases

do not contain water but become w/o emulsion upon incorporation of water

base absorps water and becomes w/o

e.g. hydrophillic petrolam; cholesterol, steryl alcohol, white wax, white petrolam)

Ointment Base — Absorption Bases; Emulsion Bases

W/O emulsions to begin with that allow incorporation of additional water; can absorb more water without changing consistency

e.g. Lanolin USP (purified wax-like substance obtained from wool of sheep)

Ointment Base — Water Removable (Washable Bases)

O/W emulsions; creams

easily removed from skin

can absorb faor amounts of aqueous solutions

can be diluted (not dissolved) with water/ aqueous solutions

not/less greasy/ occlusive

e.g. hydrophillic ointment

Water Removable/Washable Formulation

Sodium Lauryl Sulfate = surfactant

Stearyl Alcohol + white petrolam = oil phase

Parabens = preservatives

Ointment Base — Water Soluble (Greaseless) Bases

no oleaginous base at all; completely water washable

mostly used for incorporation of solid substances

cannot accomodate for mixture of aqueous solutions → will become too soft/watery; more cream-like consistency

e.g. PEG ointment

MW < 600 = clear + colorless

MW > 1000 = wax-like material

600 < MW < 1000 = semi-solids

Ointment Preparation

based on nature of ingredients

two types: incorporation or fusion

Ointment Preparation — Incorporation of Drug

drug is incorporated into the small quantities of an ointment base

occurs via geometric dilution

incorporated with spatula or mortar and pestle (small scale)

made into a fine powder when wet (levigated) with small amount of vehicle or miscible component of formulation to form a concentrate

levigating agents = mineral oil or PEG

concentrate is mixed with remainder of bases

large scale manufacturing = unguator; stainless steel tank w counter sweep agitation + built-in homogenizer, ointment roller mill

mixed until uniform preparation is attained

Ointment Preparation — Incorporation of Liquid

small quantity of aqueous solution may be incorporated in oleaginous bases

if an aqueous solution is to be added to an oleaginous base, the solution is mixed with a small amount of hydrophillic base first and then oleaginous base

up to certain limit, water-soluble substances can be mixed with water-soluble bases

Levigation

process of grinding insoluble substance to a fine powder, while wet

Geometric Dilution (Incorporation Ointment Preparation)

ideal method to make powdered drug into ointment

equal amounts of drug are added to mixture of drug and excipient to make total amount

Ointment Preparation — Fusion

ointmentd having emulsion bases involve both melting and emulsion (simple mixing won’t work)

oleaginous components and water soluble components are melted separatelt then WSC is added to OC then it is stirred and cooled until congealed

Creams

semisolid emulsion that have creamy appearance due to reflection of light

used for weeping/oozing surfaces

medication(s) may be dispersed in either w/o or o