PDD 12: Semi-Solid Dosage Forms – Dermatological Vehicles Flashcards
What are the 2 components of the dermal drug delivery system?
(both should be physically, chemically, and microbiologically stable)
- drug
- excipients – humectants, emollients, penetration enhancers, preservatives
Describe characteristics of physical stability of drugs and excipients. (5)
- viscosity and extrudability is maintained
- no loss of water or other volatile components
- homogenous phase distribution
- no change in particle size distribution of the dispersed phase
- release of drug unchanged
Describe characteristics of chemical stability of drugs and excipients. (3)
- visual appearance (colour) maintained
- no development of odour or loss of fragrance
- pH maintained
Describe characteristics of microbiological stability of drugs and excipients. (2)
- no growth
- no development of odour
What are the challenges associated with dermal drug delivery in pharmacy? (3)
- self-medication – numerous products available OTC, different formulations for the same drug
- non-compliance and overuse
- addition of drugs (ie. active ingredients) to existing products
What are humectants?
draw water from the dermis into the epidermis as opposed to drawing it from the atmosphere – acts to hold moisture in the striatum corneum
- ie. urea, glycerin, PEG, lactic acid, propylene glycol, sorbitol, retinol (vitamin A), pantothenol (vitamin B5)
- ie. application of 10% urea cream can double the amount of water in the striatum corneum
What are emollients?
provide an occlusive layer and trap insensible perspiration, and also mimic the effects of intercellular lipids, restoring suppleness of the skin
- ie. oils, lipids, waxes, fatty acids, greasy ointments
What are penetration enhancers?
cosolvents and surfactants
Penetration Enhancers
What are cosolvents?
influence intercellular lipids
- ie. ethanol, propylene glycol
Penetration Enhancers
What are surfactants?
lecithin (phosphatidylcholine and fatty acid diglycerides) may alter intercellular lipids
Penetration Enhancers
What is dimethyl sulfoxide (DMSO)?
very powerful solvent that penetrates skin readily – drugs dissolved in DMSO will also penetrate the skin
- theory: stratum corneum retains DMSO and drugs then dissolve in the DMSO, alters keratin conformation, distorts and swells stratum corneum
What are preservatives
creams and lotions containing oils and/or water require preservatives to prevent
microbial growth
- ie. methyl/propyl parabens, benzyl alcohol, chlorobutanol, chlorocresol, benzalkonium chloride
What are the 4 types of dermatological bases?
- oleagenous base
- absorption base
- emulsion base
- water soluble base
What is an oleagenous base (hydrocarbon base)?
oil
- used for their emollient effect (do not allow escape of moisture)
- water-free and can absorb very small amounts of water
- retained on skin for prolonged periods
- difficult to wash off with water
- ie. petrolatum (vaseline) – mix of semisolid hydrocarbons from petroleum
- ie. white petrolatum – decolourized petrolatum
Emulsions Recap
- since the outer phase of the O/W emulsion is water, we can wash it off with water – however, there are still oil droplets in the “wash-off”
- to make an emulsion thermodynamically stable, we normally use surfactants
- surfactant stabilizes the oil droplet – if we add more and more water, then we will dilute the surfactant (rinse it out of the droplet surface), and it cannot stabilize the droplet anymore
What is an absorption base?
oil to water in oil
- permit incorporation of water
- insoluble in water – greasy
- useful as emollients – not as good as hydrocarbon bases
- useful to incorporate aqueous solution of drugs
What are the 2 types of absorption bases?
- anhydrous but hydrophilic
- W/O emulsions
Absorption Bases
What are anhydrous but hydrophilic bases?
- incorporate water to form W/O emulsions
- contains emulsifier only
- ie. hydrophilic petrolatum, anhydrous lanolin
Absorption Bases
What are W/O emulsion bases?
- can absorb more water
- contains emulsifier and water
- ie. lanolin (hydrous), cold cream
Absorption Bases
What are some examples? (5)
- hydrophilic petrolatum
- aquabase
- simple ointment
- eucerin
- nivea
Absorption Bases
Hydrophilic Petrolatum
- components
- type of absorption base
- white wax, cholesterol, stearyl alcohol, white petrolatum
- forms W/O emulsion
Absorption Bases
Aquabase
- components
- type of absorption base
- petrolatum, mineral oil, mineral wax, lanolin alcohol, cholesterol
- forms W/O emulsion
Absorption Bases
Simple Ointment
- components
- type of absorption base
- wool fat, hard paraffin, cetostearyl alcohol, white soft paraffin
- forms W/O emulsion
Absorption Bases
Eucerin
- components
- type of absorption base
- water, mineral oil, ceresin, lanolin, alcohol, methylchloroisothiazolinone
- already a W/O emulsion
Absorption Bases
Nivea
- components
- type of absorption base
- paraffinum liquidum (mineral oil), PEG-150 (thickener, solvent, emulsifier, and surfactant), simethicone (synthetic silicone-based moisturizes, film former), parabens (preservative), BHT (antioxidant), natural and synthetic fragrances (might be contact allergens and sensitizers)
- already a W/O emulsion
What is an emulsion base (water removable base)?
oil in water (O/W)
- not soluble in water, but can be washed from skin
- often referred to as creams due to appearance
- may be diluted with water or aqueous solutions
- can absorb any discharge due to dermatological conditions
Emulsion Base (Water Removable Base)
What are some examples? (3)
- vanishing cream
- hydrophilic ointment
- glaxal base
How can we determine if an ointment is W/O or O/W? (3)
- conductivity test
- dye solubility test
- dilution test
What is a conductivity test?
more conductive if water, so the continuous (outer) phase is water, then high conductivity
What is the dye solubility?
add a water-soluble dye, will stain the emulsion if it is the outer phase (O/W), otherwise not
What is the dilution test?
only O/W emulsions can be diluted with water
- W/O need oil to dilut
What is a water soluble base?
water
- contains soluble components or may include gelled aqueous solutions
Water Soluble Bases
What is the major/only component?
polyethylene glycol (PEG)
- commonly used PEGs are PEG 1500, 1600, 4000, 6000
- range from soft to hard waxy materials
- get best results if PEGs with different MWs are blended
Water Soluble Bases
What is it idea to incorporate?
non-aqueous or solid substances
- aqueous solutions are not effectively incorporated – soften too much
- only up to 8% water uptake, then lose their desired physicochemical properties
Other Bases: Hydrogels
What are the 2 types?
- lubricating gels
- pluronic gels
Other Bases: Hydrogels
What are lubricating gels?
consists of methyl cellulose, carbopol, propylene glycol, methyl paraben, NaOH, water
Other Bases: Hydrogels
What are pluronic gels?
triblock copolymer (PEO-PPO-PEO)
- form thermo-reversible gels in water
- liquid at cold temperature
- semi-solid gel at warm temperature – form micelles in water – with increased temperature, the hydrated corona (ie. the outer layer of micelle) dehydrates resulting in aggregation of micelles into a 3D network
Other Bases: Penetration Enhancement Bases
What are they used for?
commonly used for topical application of NSAIDS
- ie. diclofenac
Other Bases: Penetration Enhancement Bases
What are the 2 types?
- plo gel
- phlojel
Other Bases: Penetration Enhancement Bases
What is plo gel?
pluronic lecithin organogel
- composed of pluronic gel, lecithin (solubilizer and penetration enhancer) and isopropyl palmitate (solubilizer and emollient)
Other Bases: Penetration Enhancement Bases
What is phlojel?
composed of pluronic, lecithin, isopropyl palmitate, preservatives, antioxidants, water
Other Bases: Liquid Preparations
What are the 3 types?
- solutions
- suspensions
- emulsions
Other Bases: Liquid Preparations
What are solutions?
contain mixtures of excipients such as propylene glycol, water, ethanol, glycerin, isopropyl alcohol, DMSO
- ie. betnovate scalp treatment – betamethasone valerate, carbomer, isopropyl alcohol, NaOH, water
- ie. pennsaid – diclofenac, glycerin, propylene glycol, ethanol, water, DMSO
Other Bases: Liquid Preparations
What are suspensions?
contain mixtures of wetting agents, flocculating agents, viscosity inducing agents, preservatives, cosolvents, water
Other Bases: Liquid Preparations
What are emulsions?
typically are oil in water (O/W) emulsions containing emulsifying agents, an oil phase, water, and preservatives
Oleaginous Base
- soluble in water
- water washable
- absorb water
- anhydrous/hydrous
- occlusive
- greasy
- example
- soluble in water: NO
- water washable: NO
- absorb water: NO
- anhydrous/hydrous: ANHYDROUS
- occlusive: YES
- greasy: YES
- ie. white petrolatum, white ointment
Absorption Forms W/O Emlusion Base
- soluble in water
- water washable
- absorb water
- anhydrous/hydrous
- occlusive
- greasy
- example
- soluble in water: NO
- water washable: NO
- absorb water: YES
- anhydrous/hydrous: ANHYDROUS
- occlusive: YES
- greasy: YES
- ie. hydrophilic petrolatum, aquabase, aquaphor, polysorb
W/O Emulsion Base
- soluble in water
- water washable
- absorb water
- anhydrous/hydrous
- occlusive
- greasy
- example
- soluble in water: NO
- water washable: NO
- absorb water: YES
- anhydrous/hydrous: HYDROUS
- occlusive: YES
- greasy: YES
- ie. nivea, lanolin (hydrous), eucerin, cold cream
O/W Emulsion Base
- soluble in water
- water washable
- absorb water
- anhydrous/hydrous
- occlusive
- greasy
- example
- soluble in water: NO
- water washable: YES
- absorb water: YES
- anhydrous/hydrous: HYDROUS
- occlusive: NO
- greasy: NO
- ie. glaxal base, hydrophilic ointment, dermabase, velvachol, unibase
Water Soluble Base
- soluble in water
- water washable
- absorb water
- anhydrous/hydrous
- occlusive
- greasy
- example
- soluble in water: YES
- water washable: YES
- absorb water: YES
- anhydrous/hydrous: HYDROUS/ANHYDROUS
- occlusive: NO
- greasy: NO
- ie. PEG ointment
Aqueous Gel Base
- soluble in water
- water washable
- absorb water
- anhydrous/hydrous
- occlusive
- greasy
- example
- soluble in water: YES
- water washable: YES
- absorb water: YES
- anhydrous/hydrous: HYDROUS
- occlusive: NO
- greasy: NO
- ie. carbomer gels, methocellulose gels, pluronic gels, gelatin gels, alginate gels
Why do we need to be cautious when diluting a commercially available topical product with a base?
could result in precipitation and/or degradation of the drug
- if the commercial product contains a cosolvent, addition of a base may dilute the cosolvent, resulting in reduced solubility of the drug in the formulation
- dilution with a different base may result in a change in pH or the addition of excess water which may lead to drug degradation
- addition of a base may result in anion-cation complexations and subsequent precipitation – often happens with preservatives (ie. sulphacetamide sodium and benzalkonium chloride)
What are the 2 things to consider when selecting a dermatological vehicle?
- optimization of drug delivery factors
- patient and skin disorder factors
Selecting a Dermatological Vehicle
Optimization of Drug Delivery Factors
- drug must have some solubility in the vehicle or drug dissolution will retard percutaneous absorption and may become rate limiting
- the drug must be stable in the vehicle (see previous slide)
- components of the vehicle may enhance percutaneous absorption (ie. permeation
enhancers and occlusive vehicles)
Selecting a Dermatological Vehicle
Patient and Skin Disorder Factors
- site of application – hairy, non-hairy, dry, oily, skin fold, thickness
- patient acceptance – what will the patient like to use
- type of wound – severity, protection, moist
What are the advantages and disadvantages of cream as a dermatological vehicle?
advantage:
- cosmetically elegant
disadvantage:
- less absorption
What are the advantages and disadvantages of lotion as a dermatological vehicle?
advantage:
- evaporates well
- good for large areas
- good for hairy areas
disadvantage:
- alcohol base will sting/irritate
What are the advantages and disadvantages of gel as a dermatological vehicle?
advantage:
- good for hairy areas
- good for oily skin
disadvantage:
- alcohol base will sting/irritate
What are the advantages and disadvantages of ointment as a dermatological vehicle?
advantage:
- excellent penetration
- emollient effect
- little or no irritation
disadvantage:
- cosmetically less acceptable
- thick greasy
