Pharmaceutics II Final Exam: Topicals and Semisolid Formulations (Li)

3 key characteristics of mucosal membrane

-high permeability

-high sensitivity

-isotonic

3 advantages of semisolids

-stick to skin

-fluid enough to be applied with ease

-solid enough to stay in place

3 advantages of topical route

· Avoids GI tract and hepatic 1st pass metabolism

· Reduces systemic side effects (plasma conc of <10% compared to PO route)

· Allows elevated drug conc at site of application

drawbacks of topical route

-variations in the SC barrier

-rashes

-may be hard to use when using larger areas

-almost impossible to deliver accurate dosage when packaged in a tube

-higher dosage cannot be achieved for low permeability in SC

which 2 layers make up the epidermis

stratum corneum and stratum germinativum

where are capillaries and touch receptors located in the skin

in the dermis layer

what are the appendages of the skin

o Eccrine and apocrine sweat glands

o Hair follicles

o Nails

what are the 4 targets for topical drugs

1. skin surface treatment

2. stratum corneum

3. epidermis/dermis

4. skin glands

emollience

· re-moisturizing of the skin to restore pliability

o By occlusion (hydration) or lipid replacement

keratolysis

Dissolving/removing thickened stratum corneum

how do antipersperants work

stop sweating by precipitation of proteins, typically by multivalent cations; close off sweat glands

what do aluminum salts usually function as?

antipersperants

MOAs of deodorant

o interacting with odorous fatty acids liberated/produced by action of bacteria on lipids in sweat

o suppressing bacterial growth

o partly by decreasing pH

MOAs of antiperspirant

o closure of sweat ducts by protein precipitation to form a plug

o peritubular irritation that promotes increase inward pressure on tubule

what types of ingredients are astringents (antiperspirants)

o salts of cations aluminum, zinc, manganese, iron, or bismuth

o tannins or other related polyphenolic compounds

single phase ointments, what do they look like

they're translucent

dispersed system ointments, what do they look like?

opaque/ white because small droplets will scatter the light

what are the 4 types of ointment bases in order to most lipophilic to most hydrophilic

- oleaginous base

-absorption base

-water-removable base

-water-soluble base

oleaginous bases and aqueous components

only a small amount of aqueous component can be incorporated because there's nothing aqueous in the base

3 features of oleaginous bases (ointment with hydrocarbon)

· keep meds in prolonged contact with skin (occlusive)

· don’t dry out or change over time much

· greasy

what types of ingredients are used in oleaginous bases

mineral oil or silicone oil

can also use PEG

example of oleaginous base ointment

vaseline or neosporin

what is absorption base made of

oleaginous base + w/o surfactants

what type of emulsion can absorption bases form

w/o emulsion

3 features of absorption bases

· also useful as emollients

· hydrophilic in nature (sometimes greasy)

· occlusive (forming a protective layer on the surface of the skin and create a barrier to prevent moisture loss)

examples of absorption bases

aquaphor and eucerin

what type of emulsion is made with a water-removable base

o/w emulsion (cream)

features of water-removable bases

· Readily water washable

· Less occlusive than oleaginoius base

example of water-removable base

cetaphil

what is an important feature of creams

they do not stain

what is the oil phase of creams (water removable bases) usually composed of?

· The oil phase is typically composed of long chain alcohols, esters, or acids NOT mineral oil

examples of water removable base ointments

vanicream and panoxyl

examples of long chain alcohols and esters

o Isopropyl palmitate

o Ceteraryl alcohol

o Cetylalcohol

o Isopropyl myristate

o Stearyl alcohol

examples of fatty acids

o Oleic acid

o Palmitic acid

o Stearic acid

features of water soluble bases

-greaseless

- non-occlusive

-soft

-water washable

examples of water soluble bases

PEG and cellulose derivative

incorporation method

o Components are mixed until a uniform preparation is attained

o Can use mortar and pestle or a spatula

o Solids

o Liquids

fusion method

o All or some of the components are melted together and

o Components not melted are added as it cools

o Heat-labile substances and any volatile components are added last when the temperature is low

when to use fusion for preparing topicals

o When components don't mix well by incorporation

o Beeswax, paraffin, stearyl alcohol, and high MW PEGs

o For emulsion-based ointments, both melting and emulsification are involved

performance criteria for ointments

-shelf life usually 2 years at 25C

-qualitty reproducible batch to batch

which ointments should be sterile

only ophthalmic are required to be sterile

microbial tests for ointments should have an absence of what 2 bacteria

Staphylococcus aureus and pseudomonas aeruginosa

which topicals should be tested for yeast and mold

those applied to rectum, urethra, or vagina

packaging requirements for ointments

· Well-closed container to protect against contamination

· Store in a cool place to stop phase separation in heat

· Large mouth ointment jars

· Metal or plastic tubes

oxidation is common in what?

in vehicle components that are made with "natural" oils and waxes

stability considerations for ointments

-thermodynamically unstable

-oxidation

-loss of volatile components

-non-arrhenius temperature dependents

what do occlusive dressings do for drug delivery

they hydrate the stratum corneum and increase the delivery rate

ointments vs creams with absorption

creams are more easily absorbed

ointments are good for ___ skin

dry (because they're occlusive)

creams are good for ___ skin

oily

spreadability of ointments vs creams

ointments are thicker and greasier so they don't spread over large areas as well as creams

oil to water ratio of ointments vs creams

80% oil 20% water for ointments and more 50% oil 50% water for creams

gel definition

a liquid phase constrained in 3D (frequently polymeric) matrix with a strutcure from physical or chemical cross-linking

polymers usd to form gels

1. natural gums (pectin,agar)

2. semi-synthetic (methylcellulose, carboxymethylcellulose)

examples of gel medications

voltaren gel and bengay gel

paste consistency

usually stiffer, less greasy, more absorptive

20-50% insoluble solids

what to label lotions

shake well

lotion composition

low viscosity liquid emulsion

usually more than 50% volatile (water)

what is the benefit of low viscosity of lotions

o Easy application on hairy areas or large body surfaces

o Dry on skin quickly after application

what are the 3 routes of topical drug penetration

1. appendageal route

2. transcellular route

3. tortuous extracellular route

transcellular pathway

drug passes directly through phospholipid membranes and the cytplasm of the dead keratinocytes

shortest distance but significant resistance

intercellular route of drug penetration

drug fits through small spaces between the cells

this route is hard

diffusional path increases 20 fold and is very slow

mechanical functions of the skin

o Dermis provide the mechanical properties

o Elastic

o Wrinkles with age and becomes more rigid

o The horny layer is quite strong

protective functions of the skin

o Microbiological

o Chemical- the horny layer is impermeable to most chemicals

o Radiation: melanin

o Heat barrier and temperature regulation

hydration (occlusivity) ___ absorbption

increases