Semisolid Dosage Forms Flashcards
What is in the he lipid bilayer in the stratum corneum?
Mainly ceramide, fatty acids, cholesterol, cholesterol esters and cholesterol sulfate
How does the structure and components of the stratum corneum relate to its barrier to drug absorption?
Stratum corneum consists of highly cross linked keratinocytes which are surrounded by an insoluble cornified cell envelope
Corneocytes are linked together by cormeodesmosomes. This provides support and stability for the stratum corneum.
Corneocytes have a unique oval structure, making them impermeable to solute.
What is ceramide?
The predominan lipid in the bilayer of the stratum corneum.
It has 9 different subclasses with hydrocarbon chains ranging from 14-36 carbons
What is the function of lipids in the stratum corneum?
To control and prevent transepithelial water loss.
What is natural moisturing factor?
NMF. This comprises 20-30% the dried weight of corneocytes.
It is water soluble and allows the skin to maintain hydrated
What is the main concept of transdermal and topical drug delivery?
Diffusion of the drug through various layers of the skin into systemic circulation.
What is topical (dermal) drug delivery?
Targeting of pathological sites within skin.
The disease is usually located within the skin e.g. Skin cancer, psoriasis, eczema
What are semisolids?
Formulations having viscosity and rigidity intermediate between that of a solid and liquid.
These are applied to the skin or mucous membrane for therapeutic, protective or cosmetic action
What is the semisolid dosage form mainly used for?
Localised effects,
However systemic absorption must not be overlooked. .e.g in pregnant women, some side effects may arise.
Semisolids can also be used for transdermal effects e.g. Progesterone cream used for postmenopausal hot flushes. It has poor systemic bioavailability
What are ointments?
Semisolid greasy preparations intended for external application or the skin or mucous membrane
These are Anhydrous with the active ingredient dissolved or dispersed in the base.
They can be medicated or non medicated
What are the common uses of ointments?
Acts as physical barrier to environment
Acts as emollient to soften skin and make it more pliable.
Carrier of medicament
What are the main classifications of ointment bases?
Hydrocarbon bases or oleaginous bases Fats and fixed oil bases Absorption bases Silicones Emulsifying bases Water soluble bases
What are the general property of ointment bases?
Anhydrous. Will not absorb water
Water resistant, not easily washed away
Forms greasy film on skin surface that inhibits moisture loss and improves skin hydration.
They also aid in the percutaneous absorption of drugs
What do hydrocarbon or oleaginous gases consist of?
Soft paraffin or a mixture of hard paraffin.
Water and aqueous ingredients may be incorporated into such gases in small amounts with difficulty.
What are the sources and forms of hydrocarbon bases?
Sources:
Vegetable oil-mineral oil
Animal fact-oleic oil
Petrolatum
Forms:
Liquid hydrocarbon-mineral oil
Semisolid hydrocarbon-Vaseline
Solid hydrocarbon-paraffin
What is petrolatum (Vaseline)?
A type of hydrocarbon base.
There are two forms:
1) petrolatum USP (yellow petrolatum or jelly petrolatum)
2) white petrolatum (decolourised petrolatum or white Vaseline)
These are a mixture of semisolid hydrocarbons with a MP between 38°C and 60°C
MP increases with increasing chain length
What are plastibases?
A series of hydrocarbons containing polyethylene
Forms structural matrix
It is soft, smooth, homogenous, neutral, odourless, non irritating and stable
Easy to spread and remove from the skin with good adhesion.
What are fats and fixed oils?
Non volatile oils, particularly of vegetable origin.
E.g. Mono and diglyceride mixtures of unsaturated and saturated fatty acids like sesame oil, almond oil.
These decompose upon exposure to air, light and high temeperatures,
Requires the addition of antioxidants like butylated hydroxytoluene, vitamin E etc.
What are the 7 main types of sesame oil?
Palmitic Palmitoleic Stearic Oleic Linoleic Linolenic Eicosenoic
How are silicones used?
They are nice corporates into barrier creams to protect the skin from water soluble irritations
E.g. Dimethicone, dimethyl polysiloxane
What are absorption (emulsifying bases) like?
Absorb water to form w/o emulsion while retaining their semisolid consistency
They are classified into two categories
What are the two categories that absoprtion/emulsifying bases are classified into?
1) Those that are water free and have ability to accommodate water resulting in w/o emulsion. (I.e. a hydrocarbon low HLB emulsifier + water results in w/o emulsion aka semisolid)
2) hydrocarbon base that has already absorbed small amounts of water and resulted in w/o emulsion. These may absorb more water and can result in 3x the weight of the original base. (Lanolin 0.25% water is composed mainly of long chain waxy esters)
What are emulsifying (water removeable bases?)
Oleaginous bases + high HLB surfactant
What are the three types of water removeable bases? What dictates these types?
Anionic (emulsifying ointment)
Cationic (cetrimide emulsifying ointment)
Non-ionic (cetomacrogol emulsifying ointment)
These depend on the type of surfactant incorporated into the oleaginous base
What are water soluble bases?
These do not not contain hydrocarbons or any other oleaginous components
They are a mixture of high and low MW polyethylene glycol (PEG)
These are non occlusive and can be easily washed from the skin surface
E.g. Macrogols ointment and PEG ointment
What is considered when choosing an appropriate base?
Desired release rate of drug
Desirability for transdermal or topical effect
Stability of drug in ion intent base
Effect of drug on consistency and other physical features of the base
Occlusive or washable nature
How are ointments prepared using the incorporation method?
Components of ointment are mixed together by various means until a uniform preparation has been achieved,
The ingredients are I mixed in a mortar and pestle or using a spatula and ointment slab.
The active ingredient can be added directly using a compatible levitating liquid like liquid paraffin in the case of petrolatum bases
Which rules should be followed (to ensure uniformity) in the incorporation method of ointment preparation?
Geometric dilution rules
When should the incorporation method be used?
When all ingredients can be triturated (no solid ingredients)
It is useful for altering the ointment e.g:
Diluting ointment base to reduce strength,
Adding liquid, adding powdered drug
Commonly used for dispensing small quantities
What are the limitations of the incorporation method?
It is very difficult to fix the product after initial formulation.
You can add more high/low viscosity component, keep triturating but in most cases you will probably have to start over.
What are the criteria for levitating agents used to prepare ointments?
Must be compatible with base (external phase)
Must not influence product viscosity
What are some common levigating agents used?
Mineral oil and glycerine
Some surfactants (polysorbate 80)
Coal tar
What is the fusion method for preparing ointments?
Ingredients are combined and melted together.
Components which are not melted can be added to the congealing mixture as it is cooled and stirred.
Heat labile substances and volatile constituents are added last when temperature is low enough to avoid decomposition
When is the fusion method used?
When you ingredients cannot be physically mixed easily. E.g. High viscosity ingredients or solids like beeswax, cetyl alcohol, paraffin, stearic acid, any fusible solid
What are limitations of the fusion method?
Ingredients cannot be overheated.
Lanolin and oleic acid can oxidise
Product should not discolour
Heat labile components can degrade.
Phases must be mixed at the same temperature
High melting ingredients can solidify
Phase separation can occur- need to reheat and stir vigorously
Often product has low viscosity-need to add high viscosity/MP ingredients like beeswax, paraffin, stearic acid.
Poor dispersion- need to reheat and add more surfactant
What are creams?
Semisolid emulsions for external applications in which the active ingredient if present is either dissolved or dispersed
Water containing absorption bases are often used,
What is an example of a cream which is a o/w emulsion?
Vanishing cream
What is an example of a cream which is a w/o emulsion?
Emollient and cleansing creams