parenteral solid dosage forms

topical, transdermal, and mucosal

stratum corneum characteristics (outermost layer)

barrier (dead cells) to permeation (lipid barrier)

permeation b/t dead cells through lipid

hydration state relative to ease of permeation

living epidermis (viable epidermis)

skin color, living cells w/o capillaries (nutrition source via diffusion)

dermis

pain/thermal, capillaries (drugs here acheive systemic action)

skin function

protective barrier

topical drug delivery

local barrier effects, glands, deep tissues

transdermal drug delivery

systemic effects, helps with short systemic half-life drugs

topical drug delivery local barrier effects example(s)

1. surface effects (deordorant, lip balm)

2. stratum corneum effects (emolliency, keratolysis/horny tiss removal)

topical drug delivery skin’s glands effects example

acne, antiperspirants

topical drug delivery deep tiss effects example

skin cancer, NSAIDs, local anesthetics

ointment types

hydrocarbon bases, silicone bases, absorption bases, water soluble bases

hydrocarbon base example (ointment)

petrolatum, polyethylene in mineral water (hydrophobic)

silicone base example (ointment)

polydimethylsiloxane oil

absorption base example (ointment)

contain W/O emulsifiers

water soluble base example (ointment)

polyethylene glycol (hydrophilic)

types of skin formulations

pastes, creams, gel, rigid foams

transdermal drug delivery diagram

…

transdermal drug delivery characteristics

impenetrable, permeation correlates w drug MW/Kow, useful for low dose drugs and high skin permeability

scopolamine and nitroglycerin transdermal patches

membrane-modulated

short half-life

nitroglycerin (deponit) transdermal patches

adhesive dispersion (ex: rivastigmine)

nitroglycerin (nitrodur) transdermal patches

matrix dispersion

list of transdermal patch active ingredients

clonidine, .. oestradial ,N, fentanyl, lidocaine, epi, nicotine, nitroglycerin, norenthindrone, oxy, scopolamine, testosterone

transdermal contraceptive

combination, matrix-type transdermal system

factors affecting skin permeability

hydration, stratum corneum drug solubility, excipients, pH

penetration enhancements

iontophoresis, electroporation, ultrasound, prodrugs, chemicals

enhancers examples

ionic surfactants, ascorbate/dithiothreitol, azone, DMSO

azone enhancer

nonpolar liquid, fluidize intracell stratum corneum lipid

DMSO enhancer

dipolar solvent, interact w lipid polar heads in aq region of stratum corneum

microneedle types

dissolving, separable, hydrogel, hollow

patches

applied in areas without body hair, frequency largely depends

transdermal patch errors

preparation, removal, application, monitoring, storage/disposal

mucoadhesion purpose

prolong mucosal residence time, enable controlled release systems, enhance absorption, immobilize dosage form at site of action

mucoadhesion mechanisms

electrostatic (cationic polymer and anionic sialic acid), hydrogen bonding, covalent (disulfide between mucin and polymer)

mucus characteristics relevant to mucoadhesion

goblet cell secretion, diffusion barrier and lubricant, variable thickness, mucin negatively charged (sialic acid), cystein-rich domains (disulfide), high water content (glycoproteins)

desirable drug properties for mucosal delivery

lipophilic, small MW (enhancers for larger/hydrophilic molecules), stability against enzymes

sublingual vs buccal

more permeable, rapid onset, short-term emergencies, affected by saliva

less permable, slow onset, less influenced by saliva, sustained delivery

proper way of applying buccal drug

1. place flat side of tablet on fingertip

2. apply round side to upper gum

3. hold placement for 30s

4. let dissolve

5. alternate application sides each dose