Ceutics 2 Exam 1

Ointment, cream, gel, suppositories, drug process

Suggestion for topical product usage in pregnant or nursing mothers

Apply only to desired area to avoid systemic effects

Breast milk and fetal circulation draw in ____

Basic drugs

Topical product drug target

Skin

Transdermal product drug target

Systemic circulation

Ointment definition

Semisolid preparations applied to skin or mucous membranes

What ingredient prevents moisture escape in ointments

Oleaginous base

Oleaginous base characteristics

Effective as occlusive dressings, remain on skin for a long time because they are non-immiscible

Types of ointments

Medicated and non-medicated (physical effects)

Emollients

Softening, maintain moisture

Protective barriers

Anti-dehydrant

Types of bases in ointments

Hydrophilic and hydrophobic

Semisolid bases in order from hardest to easiest to remove

Oleaginous base → absorption base → water-removable base → water-soluble base

Oleaginous base examples

Petrolatum, white petrolatum, yellow ointment, white ointment, mineral oil

Petroleum

Purified mixture of semisolid hydrocarbons obtained from petrolatum

White petroleum

Purified mixture of semisolid hydrocarbons obtained from hydrocarbons and decolorized

Mineral oil

Liquid petroleum
Levigating agent when powdered substances are to be incorporated into hydrocarbon bases

Con of oleaginous base

Ruins clothes

Absorption bases

Allows for absorption of fluids outside of the skin
Draws out inflammatory exudate to allow healing to start
Not easily washed from the skin with water because of high lipophilic content

Absorption base examples

Hydrophilic petroleum, anhydrous lanolin, lanolin, cold cream

Hydrophilic petroleum composition

30g cholesterol + 30g stearyl alcohol + 80g white wax + 860g white petroleum = 1000g

Lanolin

Purified wax-like substance from sheep wool
Not very hydrophilic

Emulsifiable base

Water in oil emulsions
Permit incorporation of aqueous solutions

Emulsified base

Water in oil emulsions
Allows for additional aqueous solutions to be added

Cholesterol

Nonionic, mixture of cholesterol and its esters can serve as an emulsifying agent (lipophilic)

Water-removable bases

Oil in water emulsions resembling creams
Easily washed from skin
Can be diluted with water or aqueous solutions

Water removable bases can absorb ___

Serous discharge

Are water removable bases 100% water soluble

No because it still has lipophilic characteristics in the internal phase

Water removable base composition

0.25g methylparaben + 0.15g propylparaben + 10g sodium lauryl sulfate + 250g stearyl alcohol + 250g white petroleum + 120g propylene glycol + 370g purified water = 1000g

Water soluble bases

Do not contain any oleaginous components, greaseless
Used for incorporation of solids in preparation

Water soluble base composition

400g Polyethylene glycol 3350 + 600g polyethylene glycol 400 = 1000g

Factors to consider when choosing base

Action desired, physical and chemical properties of drug, bioavailability, and stability of the active ingredient and product

Base selection factors

Release rate, desirability of drug absorption and occlusion from the skin, solubility in ointment base, effect of the drug on the consistency or other features of the ointment base, desire for a base that is easily removed by washing with water

If lipophilic ointments release drugs slower, what happens to the duration of action?

Longer duration of action

Ointments generally applied to ___

Dry scaly skin (psoriasis)

Creams applied to ___

Weeping or oozing surfaces, allows passage of exudate

Lotions applied to ____

Intertriginous areas (folds) or where friction may occur

Incorporation/levigation

Components are physically mixed until a uniform preparation is obtained

Fusion

All or some components are melted together and cooled with constant mixing until congealed

Potential problems with fusion

Heating can destabilize active molecules; monitor temperature to not destroy ointment

Cream definition

Semisolid dosage forms containing one or more drug substances dissolved or dispersed in a suitable base
w/o, o/w, wwb

T/F: Creams have the potential to contain oleaginous and water base

True

Cream uses

Primarily topical skin products, can be for rectal or vaginal use

Pros of creams

Ease in spread and removal

Vanishing cream

Oil in water, high water content, humectant, formation of a thin film after water evaporation

Excessive use of vanishing cream can cause

Drying of the skin due to humectant pulling water from the stratum corneum

Vanishing cream composition

18g stearic acid + 2g mineral oil, light + 0.5g lanolin + 2g arlacel 80 (span 80) +0.7g potassium hydroxide + 3.7g sorbital solution 70% + 100g purified water qs ad

Cold cream composition

125g Cetyl esters wax + 120g white wax + 560g mineral oil + 5g sodium borate + 190mL purified water = 1000mL

Rosewater ointment composition

125g cetyl esters was + 120g white wax + 560g almond oil + 5g sodium borate + 25 mL stronger rose water + 165 mL purified water + 0.2 mL rose oil = 1000g

W/o type emulsion bases

Eucerin, polysorb hydrate, nivea cream

Gel definition

Semisolid systems consisting of either suspensions made up of small inorganic particles or large organic molecules interpenetrated by a liquid
AKA Jellies

Single phase system

Macromolecules uniformly distributed with no boundaries between dispersed macromolecules and liquid

Two-phase system

Gel mass consisting of floccules of small distinct particles, can separate phases

T/F: two-phase systems do not require mixing

False, they require frequent mixing

Magmas definition

In a two-phase system, if the particle size of the dispersed phase is relatively large, the gel mass, is sometimes referred to as a magma

Thixotrope

Thickening upon standing, requires shaking before use to reliquefy gel and enable pouring

Magmas are known to ___

Precipitate

What is added to topical gel, cream, or ointment vehicle for transdermal preparations

Penetration enhancers

Penetration enhancers

DMSO, EtOH, PG, glycerin, PEG, urea, SDS poloxamers, terpenes, pluronic lecithin organogel

Pluronic lecithin organogel

Aids in rapid penetration of active drugs through the skin

T/F: penetration enhancers have intrinsic activity on their own

False, they do not alter the active ingredient

Why would you apply salicylic acid to a thick callous on your heel

Acid eats away at the thick callous

Pastes definition

Semisolid dosage forms that contain one or more substance intended for topical application
Can sometimes be used for transdermal application

Pastes preparation

Same as ointments or by heating

Pros of pastes

Stiffness allows it to remain in place after application for more direct release, effectively employed to absorb serous secretions

Cons of pastes

Incompatible with hairy parts of the body

Plasters definition

Solid or semisolid adhesive masses spread on a backing of paper, fabric, moleskin, or plastic
Applied for long term contact at the site

Unmedicated plasters

Provide support and protections (ex: casts)

Effects of ointments on the skin

Surface, stratum corneum, and epidermal effects

Drug in a medicated ointment should ___ and be ___ in the skin for a while

Penetrate; retained

Limiting barrier for rate and degree of penetration

Normal, unbroken skin

What penetrates faster, lipophilic or hydrophilic ingredients

Lipophilic because they can cross the lipid membrane

Number one variable of absorption

Thickness or stratum corneum

Stratum spinosum

Where inflammatory exudate comes from

Skin surface aspects

Film of emulsified mixture containing sebum, sweat, desquamated epidermal cells
Composition depends on amount of sebum sweat

Entry ways for drug molecules

Hair follicles and sweat gland ducts; only a minor factor in drug absorption

Stratum corneum aspects

Keratinized SC behaves as semipermeable artificial membrane and drugs pass by diffusion

For topical products, the therapeutically effective drug concentration in the skin is ___

Not known; treatment is based on qualitative measures and clinical efficacy varies between patients

Application of topical products

Thin layer and gentle pressure on clean and dry skin

Should a bandage be used to cover topical products all the time?

No, only use a bandage when specified

T/f: allergic responses to topical products are common

True

What can occur is you expand the surface area of application when using topical products?

Toxicity

Non-dermatologic topical applications

Eye, ear, nose, and vagina

Ophthalmic ointment entry routes

Cornea most common, conjunctiva and sclera are alternative routes

Suppositories definition

Solid bodies of various weights and shapes, adapted for introduction into the rectal, vaginal, or urethral orifice of the human body

Suppository composition

Drug + suppository base

After administration of suppositories, the base should

Melt or dissolve. This increases surface area of drug and coating, which can contribute to systemic absorption

Types of suppositiories

Rectal, vaginal, and urethral

T/F: suppositories have both local and systemic effects

True

Three major hemorrhoidal veins

Superior, middle, and inferior

What do the three major hemorrhoidal veins feed into

Inferior mesenteric vein, leading up to the inferior vena cava

Which hemorrhoidal veins bypass the liver

Middle and inferior

The middle and inferior hemorrhoidal veins are prone to ___

Damage and varicosity

Ideal suppository base

Firm for insertion at room temperature, melt/dissolve/disperse at 37C, nonirritating, stable during manufacture and storage, chemically compatible with drug, and is retained in the body orifice after melting

Oleaginous suppository bases

Cocoa butter and cocoa butter substitutes which melt

Cocoa butter

Mixture of stearin, palmitin, olein, laurin, linolein, and traces of other glycerides
Melting point 30-35C
Freely soluble in ether or chloroform form

T/F: cocoa butter is not used intravaginally

True; it is not used intravaginally because it is insoluble in water and not absorbed, causing irritation
May be used in the urethra because more common washout but still not as preferred

Cons of cocoa butter

Lower melting point after incorporation with drug and has multiple crystal forms

Cocoa butter substitutes

Witepsol and wecobee (long chain fatty acids)

Water soluble bases

Polyethylene glycol base, glycerinated gelatin, surfactant suppository base
Slower to mix and soften (liquefy) with physiological fluids → slower release

Glycerinated gelatin composition

10g purified water and drug + 70g glycerin + 20g gelatin