T2 - Week 2 Flashcards
What are pastes?
High concentrations of finely powdered ingredients (25%) incorporated into ointment base or glycerol, or the lipophilic, greasy vehicle
What are the advantages of paste being stiff?
- Localizes drug delivery in case a corrosive ingredient needs to be applied to the skin
- Absorb exudates due to powder component (for open wounds)
- Effective sun barrier because it is less penetrating and form an unbroken relatively water impermeable film that is opaque
- Less greasy due the absorption of the fluid hydrocarbon fraction into particles
How are pastes prepared?
- Direct mixing or the use of heat to soften
- Levigation by incorporating solid into a congealed system
- Remainders of the base are added with continued levigation until solids are uniformly dispersed in the vehicle
What are the types of pastes?
- Fatty
- Non-greasy
How are fatty pastes different from non-greasy?
Fatty: (Lassar’s Plain Zinc Paste) prepared by zinc oxide and starch mixed with white ointment
Very firm and protects skin better by absorbing secretions
Non-greasy: (Bassorin Paste) Paste that contains the hydrophilic component of tragacanth gels in water
What are creams?
- Ointments which are made less greasy (because < 50% of hydrocarbons or waxes) by incorporation of >20% water
- Semisolid emulsion
- Uses emulsifying agent to disperse the aqueous phase in the oily
How do you differentiate creams from ointments?
- Softer and preferred due to easy removal from containers and good spreadability over absorption site
- Creams and ointments provide protective, emollient actions to surface or interior layers of the skin
- Creams can be used for cosmetics and medications
What are the classifications of creams?
- Oil in water (aqueous)
- Water in oil (oily)
What are the characteristics of o/w creams?
- Hydrophilic due to aqueous external phase
- Non-greasy and easily removed by water
- Good topical purpose and suited for oozing wounds by absorbing water
What are examples of hydrophilic creams?
- Vanishing creams
- Foundations
- Hand creams
- Shaving creams
What are the characteristics of w/o creams?
- Composed of small droplets of water dispersed in oily phase
- Difficult to handle and water wash
- Very effective skin moisturizing due to stratum corneum penetration
What are examples of lipophilic creams?
- Cold creams
- Emollient cream
What is the general procedure for making an emulsion?
- Oil-soluble ingredients are mixed by heating temperature to highest-melting ingredient
- Water soluble ingredients are dissolved in water by heating to same temperature as oily phase
- Combine oil and water phase
- Continue mixing (using lower shear) and cool system to room temperature
- Incorporate drug into cream base
How do you combine phases for an o/w emulsion?
Oil phase is added to water phase and mixed vigorously using high shear mixing to form a homogeneous dispersion of small oil droplets within the water phase
How do you combine phases for an w/o emulsion?
Water phase is added to the oil phase
How do you incorporate a cream base if drug is decomposed by heating?
- Drug is added to phase of higher solubility at the beginning of the process
- Drug then is added after emulsion is formed
What are gels?
Semisolid systems consisting of either suspensions made up of small inorganic particles in a liquid solvent or large organic molecules uniformly distributed throughout a liquid solvent
What are classifications of gels by gelling agents?
Inorganic and organic
What is an inorganic gel?
Consist of precipitates of inorganic salts or floccules of small particles of the inorganic salts as gelling agents creating a 2 phase system
What are examples of inorganic gels?
Magnesium hydroxide and Aluminum hydroxide
What is an organic gel?
Use a carbon-based hydrophilic polymer. They are single-phase systems
What are examples of organic gels?
Carbomer, tragacanth, or poloxamer in water system
What are the classifications of gels by solvent phase?
- Hyrdogels
- Organogels
What is the difference between hydrogels and organogels?
- Hydrogels contain water as the main continuous-phase solvent. They contain significant amounts of water but the inorganic salts gelling agents used remain water insoluble.
- Organogels may contain an organic liquid.
What are components of a gel?
- Gelling agents
- Liquid phase
- Drug substance
- Humectants
- Stabilizers
What is the purpose of gelling agents in gel?
Small inorganic particles or polymeric matrix which traps the liquid phase
What is the purpose of liquid phase in a gel?
Solvent or water (vehicle)
What is the purpose of the drug substance in gel?
Dissolved in liquid phase or suspended in the polymeric matrix
What is the purpose of humectants in gel?
Retain water so a skin doesn’t form
What is the purpose of stabilizers in gel?
Prevents microbial contamination
What are examples of natural polymers as gelling agents?
- Tragacanth
- Cellulose derivatives
- Alginates
- Pectin
- Gelatin
- Clays (Bentonite)
What are the characteristics of tragacanth?
- Concentrations between 2 - 5% produce different viscosities
- Prone to microbial contamination
- Tends to form lumps when added to water
How do we minimize lumps when water is added to tragacanth?
- Adding small quantities of tragacanth powder to water while mixing rapidly
- Using wetting agents such as ethanol, glycerol, or propylene glycol
What are the characteristics of cellulose derivatives as gelling agents?
- Neutral and stable gels
- Form clear gels with good film strength when dried on the skin
- Resist microbial attacks
What are examples of cellulose derivatives?
- Methylcellulose
- CMC
What are the characteristics of CMC?
- Produces gels of the medium viscosity grade in concentrations of 4% - 6%.
- Sensitive to pH: The viscosity of CMC gels decrease below pH 5 or above pH 10.
- Glycerin may be added to prevent drying. It is incompatible with ethanol.
What are examples of synthetic polymers as gelling agents?
- Carbomers
- Poloxamers
What are the characteristics of carbomers?
- Are high molecular weight, acrylic acid-based polymers; primarily used in aqueous systems.
- Used as gelling agents at concentrations of 0.5% to 2.0% in water.
- Also, thickening, suspending, and emulsifying in both oral and topical formulations.
- Many carbomers, with viscosity ranges from 0 to 80,000 cPs.
What factors effect the viscosity of carbomer gels?
- Their polymeric composition
- Addition of alcohol decreases their viscosity
- The presence of electrolytes and the pH
What are the characteristics of poloxamers?
- Are water soluble nonionic triblock copolymers
- Depending on the molecular weight of the building blocks and polar-to-nonpolar ratio
- Form thermo-reversible poloxamer hydrogels in concentrations 15% - 50%
- Aqueous solutions of poloxamers are stable in the presence of acids, alkalis & metal ions
- Gelling agents, solubilized, emulsifier, stabilizers, and wetting agents
What is a nonionic triblock copolymers?
2 polar and one non-polar blocks
What are the general procedures of making gels?
- Mix inactive ingredients in the solution base (room temp) occasionally adding heat while mixing
- Gelling agent is added to increase viscosity of the mixture and trap/suspend any solid particulate material
- Avoid introduction of bubbles by reducing the mixing shear as the viscosity increases
What are jellies?
Transparent or translucent non-greasy semisolid gels in which the structural coherent matrix contains a high portion of liquid, usually water
Describe the appearance of jellies?
- Some are transparent as water
- Others are turbid and may not be completely soluble
- May form aggregates that disperse light
What is the function of jellies?
- Lubricants for gloves, catheters, and rectal thermometers
- Preservatives prevent microbial contamination
How are topical dermatological semisolids are packaged?
- Jars
- Tubes
- Syringes
Describe jar packaging for semisolids?
Jars are clear or opaque glass or plastic
Describe tube packaging of semisolids?
- Made of aluminum or plastic
- Eliminates any interactions between the contents and the tube
- Aluminum tubes coated with epoxy resin, vinyl, or laquer
- Plastic tubes are made of HDPE or LDPE or a blend
How are ophthalmic, nasal, vaginal, rectal semisolid products packaged?
Tubes with applicator tips or syringes
What is the USP direction for packaging opthalmic ointments?
- Facilitate application of a narrow band ointment
- Must have an elongated narrow tips collapsible ointment tubes
How are rectal ointments and creams packaged?
Special perforated plastic tips for products to be administered into the anus
How are semisolid packaging material tested?
Jars and tubes must be compatible and stable at room temp and under accelerated temperatures
What are lip balms?
Formulations applied onto lips to prevent drying and protect against adverse environmental factors
What does medical lip balms contain?
- Antibiotics
- Local anesthesia
- Sunscreen
- Antiviral
What are the advantages of lip balms?
Don’t require the use of fingers to apply
What are the ingredients found in lip balms?
- Waxes
- Butters and oils
- Flavors/fragrances
- Preservatives
- Antioxidants
Why are waxes important for lip balms?
Give structure and allow the stick to be molded
Why are butters and oils important for lip balms?
Emollients/lubricants and softening agents
How are lip balms prepared?
- Mix the solid fat components by heating on hotplate until fusion
- Add the liquid oil phase preheated separately at around the same temperature of the wax mixture
- Transfer into final molded lip balm tube
What are the signs of an instable lip balm from inadequate preparation?
- Aeration
- Deformation
- Cracking
What are suppositories?
Dosage form of various weights, sizes, and shapes that is suitable for insertion into a body cavity, rectum, vagina, and urethra
What is the purpose for rectal suppositories?
To treat local and systemic conditions
What are some local treatments rectal suppositories provide?
- Constipation
- Hemorrhoids
- Fissures
- Inflammation
What are some systemic treatments rectal suppositories provide?
- Pain
- Fever
- Nausea
- Vomitting
- Migraines
- Allergies
- Sedation
What are the advantages of suppositories?
- Used to exert a local effect on the rectal mucosa or systemic effect to bypass metabolism by liver
- Drug that irritate GI tract can be administered this way
- Used for patients who are unconscious or vomiting or do not swallow
What are the disadvantages of suppositories?
- Unacceptable to certain patients
- Difficult to self-administer
- Unpredictable and variable systemic absorption
What are the contents of suppositories?
- Diluents
- Adsorbents
- Surface active agents
- Lubricants
- Antimicrobial preservatives
- Coloring agents
What are suppository bases?
Mixture vehicles in which drugs are either dissolved or dispersed in that either melt, soften, or dissolve when warmed to body temperature and release the drug they contain when in contact with epithelial membrane
What are the properties of an ideal suppository base?
- Nontoxic and nonirritating to mucous membrane
- Compatible with other drugs
- Should not interfere with the release and absorption of the drug from administration site
- Melts or dissolves in rectal fluids
- Stable on storage
What are the categories of suppository bases?
- Fatty or oleaginous bases
- Water-miscible or water-soluble bases
- Miscellaneous base
What are the properties of Fatty or oleaginous suppository bases?
- High molecular weight fatty acids for desired melting point and hardness
- Softens at 30ºC & melts at 34ºC; and yet maintain solid state at room temperature and below body temperature.
- Exhibits polymorphism
What is a widely used Fatty or oleaginous suppository base?
Theobroma oil (cocoa butter)
What is the purpose of hardening agents?
Used if melting point of the suppository base is lowered by any ingredients of the formulation
What is the preparation method of cocoa butter based suppositories?
Incorporating fine drug into molten state of the base and the resulting suspension is allowed to cool in suppository molds
How do we vary suppository melting points?
By substituting cocoa butter using veggie oil modified by esterification, hydrogenation, or fractionation
What are examples of water soluble suppository bases?
Glycero-gelatin Suppository Base
What are the properties of glycero-gelatin suppository bases?
- Used when prolonged localized action is desired
- Hygroscopic nature of gelatin slows softening and mixing of physiologic fluids
What is the purpose of slowing softening and mixing of a suppository base?
- Provide a more prolonged release
- Protection from atmospheric moisture to maintain their shape and consistency
What is the property of PEG suppository bases?
Combinations of PEGs with melting temperatures above body temperature are used as suppository bases
What are examples of water-dispersible bases?
PEGs alone or combinations with other vehicles
What are the characteristics of PEGs?
Don’t melt at body temperature but dissolve slowly in body fluids enabling slower release of drug, no refrigeration, and no leakage
What are examples of miscellaneous suppository bases?
- Mixtures of lipid and water soluble bases
- Hydrogel bases
What is the approximate drug release rate of oil-soluble drug with oily base?
Slow release, poor escaping tendency
What is the approximate drug release rate of water-soluble drug with oily base?
Rapid release
What is the approximate drug release rate of oil-soluble drug with water miscible base?
Moderate release rate
What is the approximate drug release rate of water miscible drug with water miscible base?
Moderate release based on diffusion, all water soluble
How are suppository molds calibrated?
By cocoa butter to make 1g, 2g, or 4g suppositories
What occurs when molds are filled volumetrically?
There will be density differences between suppository bases producing suppository weight differences
What happens if you alter the weight of suppositories?
Weight changes due to density changes require recalibration of the mold
How do you recalibrate a suppository mold?
- Empty suppositories are prepared from the base material alone
- The suppositories are weighed and their volume is determined by melting
- The density is computed for that particular base
How do you package cocoa butter suppositories?
Wrapped individually into partitioned boxes to prevent contact and adhesion
How do you package glycero-gelatin suppositories?
Packaged in well-closed screw-capped glass containers, preferably at a temperature < 35°C
How do you package light sensitive suppositories?
Wrapped in a metallic foil
How should suppositories be stored?
- Stored in a cool place but not frozen
- Cocoa butter: 2-8C
- Glycero: 20-25C
- PEGs: room temperature
- Suppositories are adversely affected by humidity
- High humidity → spongy
- Dry environment → brittle
What are the USP recommendations for stable suppositories?
- To observe excessive softening and evidence of oil stains on packaging materials.
- Excessive softening → major indication of instability
