Lecture 15 - semi solid formulations Flashcards
Describe the anatomy of the soft skin
The skin is composed of three primary layers: the epidermis, dermis, and hypodermis.
The epidermis is the outermost layer, with the stratum corneum as its outermost sub-layer.
The dermis lies beneath the epidermis and contains sebaceous glands (oil glands), sweat glands, nerves, and blood vessels.
The hypodermis, also known as the subcutaneous layer, is the innermost layer that contains fat tissue and larger blood vessels.
what is the resistance model?
diffusion of the drug through the different layers of the skin
types of resistance the drug goes through in the skin
R1 = the vehicle resistance
R2= appendages resistance. This has very small fractional area
R3= stratum corneum resistance.
R4= viable tissue resistance. this has very small resistance compared to the stratum corneum
R = h/FDK
r is the chemical magnitude of barrier
h is the thickness of the resistor barrier
F is the fractional area of route
D is the drug diffusion coefficient through the resistor
K is the tissue capacity for the drug
what are strategies fro increasing drug penetration
Fick’s diffusion
* Increase Dsc – use lipophilic drug or prodrug, use penetration enhancer
* Increase Ksc/w – formulate lipophilic drug in an aqueous vehicle without competing lipophilic phase
* Increase ΔC – achieve saturated solution in aqueous diffusion layer and sufficient drug reservoir in the vehicle
what are penetration enhancers
They ideally should be pharmacologically inert, meaning they should not cause any drug-like effects themselves.
These enhancers work by interacting with intercellular proteins in the skin, which can disrupt the barrier function of the skin, or by enhancing the partitioning of the drug into the skin membrane, or both.
Types of penetration enhancers:
Water can have an occlusion effect,
Low molecular weight alcohols
Small aprotic solvents like DMSO
Fatty acids, specifically oleic acid,
Surfactants
Keratolytics, such as urea and salicylic acid, .
what are the pharmacokinetics of transdermal delivery
in vivo drug absorption involving passive percutaneous diffusion show a measurable lag time
lag time is related to membrane - h thickness and drug diffusion coefficient - D
lag time is shortest for trasnappendageal route and longest for trasnpeidermal route
T1 = h2 / 6D
hwhat are factors affecting percutaneous absorption ?
skin factors
skin health, skin hydration, occlusion, akin age, skin binding, regional variation, ethnicity and skin temperature
drug factors
drug concentration, partition coefficient, degree of ionisation, solubility, chemical structure
describe semi soldi preparations
semisolid preperations like creams, pastes, gels, poultices, medicated plasters, and patches are used for cutaneous application for local or transdermal delivery of drug through the skin.
they can be used for their emollient action or protectiveness of skin. they have a uniform appearance and are made of a base that is synthetic or natural and may have one or multiple phases. the compsition of the base can affect the drugs affectiveness and can be formualted as hydrophilic or hydrophobic. they may also have antioxidants, preservatives, emulsifiers, thickners, stabilisers and enahncers to improve performance. when intended for use os significantly damaged skin they are formulated as sterile to prevent infection
what are ointments
Ointments are single-phase bases where solids or liquids can be dispersed. They consist of a matrix former and a liquid component, similar to gels but without necessarily having two continuous phases. Drugs within ointments can either be dissolved or evenly dispersed throughout the base. Depending on their ingredients, ointments can be either hydrophobic or hydrophilic. Additionally, they can be formulated to be colored, colorless, or odorless, offering versatility in their appearance and application.
what are hydrocarbon bases
hydrocarbon bases are a picture of C30 – C50 hydrocarbons (acting as matrix formers) and C16 – C30 hydrocarbons, prepared through a co-melting process. The stiffness of the final product is influenced by the ratio of these hydrocarbons and the rate at which the mixture is cooled during manufacturing. As hydrocarbons are hydrophobic, they provide a pronounced occlusive effect, creating a strong barrier that prevents moisture loss from the skin.
what are other hydrophobic bases
Silicone and animal fat-based ointments are examples of hydrophobic bases that create a strong moisture barrier and act as excellent emollients. These types of ointments are suitable for dry lesions but are not recommended for weeping or exuding wounds due to their occlusive nature. They have a greasy texture and can be challenging to wash off. The bioavailability of drugs in these ointments may be limited by the low solubility of active ingredients in the lipophilic components, often referred to as high vehicle resistance. To enhance drug bioavailability, a co-solvent such as propylene glycol may be added.
what are water emulsifying ointments
Water-emulsifying ointments are specialized bases that utilize emulsifying agents to create creams when water is added. These bases may include ingredients like lanolin, wool alcohols, sorbitan esters, monoglycerides, fatty alcohols, sulfated fatty alcohols, polysorbates, and macrogol esters. They are particularly useful for treating exuding wounds asthey are emulsifying. Additionally, these ointments can incorporate hydrophilic drugs in aqueous solutions, enhancing their therapeutic capabilities for various skin conditions.
describe hydrophilic ointments
Hydrophilic ointments are water-miscible bases primarily composed of macrogols, also known as polyethylene glycols. These bases can contain varying amounts of water as a liquid component. Suitable for application on exuding wounds, hydrophilic ointments effectively incorporate hydrophilic drugs without significantly affecting their bioavailability, thanks to their low vehicle resistance.
describe what pastes are
Pastes are a type of ointment that contain a high concentration of insoluble solids, making up to 50% of their weight. These solids, which include substances like starch, talc, zinc oxide, and sulfur, contribute to pastes being stiffer and less greasy than typical ointments. Pastes exhibit shear thickening properties due to the high proportion of solids. They are effective in forming a protective barrier on the skin and can dry to an opaque film. This film offers sun protection and helps to reduce skin dehydration, making pastes useful for both protective and therapeutic purposes.
describe creams
“Creams are multiphase preparations consisting of a lipophilic phase and an aqueous phase.”
- Lipophilic creams: w/o emulsions
- Hydrophilic creams: o/w emulsions
- Creams are better accepted as they feel less greasy
- Plethora of cream bases available depending on the application, skin type, drug compound, disease state etc.
what are the 2 cream bases?
Fatty Acid Mixed Emulsifiers:
These are based on lamellar gel network phases, where acids are neutralized in situ using triethanolamine and less commonly with sodium or potassium hydroxide. The charged head groups of these molecules repel each other, creating a lamellar structure that can swell. These emulsifiers can be used to create creams without an oily phase, offering cosmetic benefits like leaving a pearly sheen after drying. They can also contain oil, with the fatty soaps serving as emulsifiers. However, these formations are very sensitive to mechanical disruption.
Self-emulsifying Glycerol Monoesters:
These consist of monoesters combined with ionic or non-ionic emulsifiers, known as “emulsifying waxes.” Their action is comparable to that of fatty alcohols, providing stable emulsification in cosmetic and pharmaceutical formulations.
