Lecture 22: Ointments Flashcards
What is an ointment?
- A semi-solid dosage form usually anhydrous with a hydrophobic oily base
- Intended for external application to the skin or mucous membrane
How are ointments occlusive?
- Increases skin hydration by minimising transepidermal water loss
- Also enhances drug penetration
What are the 3 types of ointments?
- Hydrophobic (oleaginous) ointment
- Water emulsifying ointment
- Hydrophilic (greasless) ointment
What are the characteristics for hydrocarbon bases for hydrophobic ointments and name an example?
- Occlusive - emollient effect
- Non water washable
- Greasy
- E.g. Petrolatum (paraffin)
What are the characteristics for absorption bases for water emulsifying (W/O) ointments and name an example?
- Form W/O emulsions with skin secretions (water comes from skin)
- W/O emulsifier
- Emollient effect
- E.g. Lanolin and derivatives
What are the characteristics for water removable bases for water removable bases and name an example?
- Form O/W emulsions with skin secretions
- O/W emulsifier
- Water washable
- Cetostearyl alcohol, cetomacrogol
What are characteristics for water soluble bases for hydrophilic ointments and name an example?
- Water-washable
- Non-greasy
- Macrogols (polyethylene glycols = PEG)
What are the 2 basic components of an ointment?
- Drug
- Ointment base
What 3 things can an ointment also contain and what are their purposes?
- Solvent: Dissolve components, miscible (forming mixture when added together) w/ ointment base
- Antioxidant: Prevent oxidative degradation (reacidification)
- Emulsifying agent: For water emulsifying ointments
Why are preservatives not generally required in ointments?
- As no water content
What is the purpose of betnovate ointement?
- Relief of inflammatory and pruitic manifestations of steroid responsive dermatoses (skin conditions that respond well to treatment with corticosteroids)
What is the purpose of white soft paraffin and liquid paraffin in Betnovate?
- Ointment base
- Ointment base
What is Fucidin ointment used for and what is the purpose of all-rac-a-tocopherol and butylhydroxytoluene in Fucidin ointment?
- Treatment of skin infections caused by bacteria
- Vitamin E antioxidant : for all-rac-a-tocopherol
- Butylhydroxytoluene = antioxidant
What is the purpose of cetyl alcohol in Fucidin ointment?
- More emulsifier but can be ointment base (water-removable emulsifier
What is Rancidification and what does it happen to?
- Oxidative chain reaction mediated by free radicals, changing organoleptic properties due to chemical decomposition
- Oxygen containing fats and oils derived from animals or plants
How do antioxidants work?
- Deplete free radicals by sacrificing itself, thus terminating oxidative chain reactions
- Needs to be soluble in ointment base
How do you incorporate a drug into an ointment?
- Dissolve directly into ointment base
- Dissolve drug in suitable solvent, then incorporate solution into ointment base
- Levigate solid drug into ointment base to disperse evenly with geometric dilution
What is levigation?
- (reduce (a substance) to a fine powder or smooth paste)
- Crushing particles in presence of a fluid (levigation fluid) to reduce particle size as it being incorporated into ointment
What are the 2 types of penetration enhancers?
- Physical and chemical
Do chemical penetration enhancers (CPE) need auxilliary equipement?
- No its its included as an excipient in the formulation
Do physical penetration enhancers need auxilliary equipement and name examples?
- Yes
- Examples: microneedles, iontophoresis, electroporation, laser ablation, sonopheresis, thermal ablation
How do chemical penetration enhancers increase permeability?
- increasing Drug partitioning and diffusivity (amount of drug absorbed per unit area per unit time)
What does the lipid-protein- partitioning theory propose?
- Proposes that the skin has lipophilic and hydrophilic domains
How does CPEs work by using lipid partitioning theory?
-Lipid: Disrupting stratum corneum lipids (lipohilic domain) increasing diffusivity for lipophilic drugs
- Protein: Altering SC proteins (hydrophilic domain) increasing diffusivity for hydrophilic drugs
- Partitioning: Enhancing drug partitioning from formulation into skin, increasing partitioning
- Partition into the lipid matrix of the stratum corneum, Diffuse through this lipid-rich pathway, Exit into deeper layers (viable epidermis/dermis).
What are ideal properties for penetration enhancers?
- Chemically inert and non-toxic
- Transient, reversible and selective penetration enhancement effect
What type of molecules act as strong penetration enhancers and what do they resemble in relation to skin?
- Amiphilic compounds that have a polar head group and long hydrocarbon tail
- They resemble Stratum corneum lipids
How do amphiphilic compounds work as chemical penetration enhancers?
- Insert into SC extracellular lipids to loosen packing
What are examples of amphiphilic compounds as penetration enhancers?
- Surfactants
- Fatty alcohols
- Fatty acids
- Phospholipids
What type of amphiphilic compounds are most effective as chemical penetration enhancers?
- Unsaturated (double bond) and cis hydrocarbon tail are more effective
Why are cis isomers more effective than unsaturated (trans)?
- The cis has a kink which forces open a gap in the SC lipid structure which allows small molecules to pass through
Polar CPE and non-polar CPE are more effective on what type of drug?
- Hydrophilic: polar
- Lipophilic: non-polar
Name some examples of penetration enhancers?
- Water
- Alcohols: ethanol, isopropanalol, propylene glycol, isopropyl myristate
- Fatty acids: Oleic acid, linoleic acid, lauric acid
- Surfactants
- Phospholipids
- Urea
- Sulfoxides
