Pharmaceutics Flashcards

Question

What is aerosolisation?

Answer 1

- prior to inhalation, DPI formulation has no potential to be deposited in the lungs - forced inspiratory action provides the energy for fluidisation + entrainment of formulation and de-aggregation of drug

Answer 2

fine particle fraction = % reaching lungs dependent on: - inhaler device - patient expiratory flow - powder formulation

Answer 3

resistance /= de-aggregation but is a side effect internal resistance of device affects speed of airflow through device higher resistance devices generally perform well at lower flow rates

Answer 4

- van der Waals - electrostatic - capillary

Answer 5

- finite attractive forces between all atoms - sum of attractions between molecules that are temporarily dipolar - short range forces - dominant at low humidity in absence of electrostatic forces

Answer 6

- condensation of water vapour between contigous bodies - forms a liquid bridge - magnitude of forces directly related to relative humidity and hydrophobicity

Answer 7

- caused by frictional contact between dissimilar material - long range force - attractive or repulsive

Answer 8

- particle sizes - particle shape - surface roughness - surface chemistry - humidity

Answer 9

- carrier-based systems - agglomerated powder systems

Answer 10

- blending the drug with carrier

Answer 11

- allows accurate metering of small quantities of potent drug - improves handling and processing - FPF can be controlled

Answer 12

- for high dose drugs, when carrier isn't possible - free-flowing macroscopic agglomerates can be produced via cohesive bond formations - efficient de-aggregation of agglomerates can be produced via cohesive bond formation

Answer 13

- propellant free - some have no excipients - breath actuated - can deliver large doses - drug is in dry solid form

Answer 14

- powder de-aggregation dependent on patients ability to inhale - more inhalation = more de-aggregation of particles - exposure to ambient condtions can reduce stability - less efficient delivery

Answer 15

- require specific technique - can't do very large doses - need to stop oxygen to administer - can't use DPIs when ventilated

Answer 16

- drug is contained in sterile aqueous solution - uses an external enjoy source to aerosolise - areosol is then inhaled tidally

Answer 17

- generates aerosol using compressed air which is expelled past the end of a capillary tube - shear force of air creates droplets - baffle traps oversized droplets

Answer 18

- cheap - small particle size

Answer 19

- variable performance - portability - lower output/doses take time

Answer 20

- performance is more reproducible - small particle size - small + quiet - lower aerosol inertia

Answer 21

- expensive - poor for suspensions - gets hot

Answer 22

- emerging class of portable inhalers - drug dissolved in a non-volatile liquid - volumetric dosing - aerosolised in a single breath actuation - aerosol emitted as sloww moving cloud

Answer 23

- drug solution is forced through a micro-nozzle as patient inhales - medication stored as a solution - avoids problems of moisture absorption and powder aggregation - use of solution ensures metered doses

Answer 24

- Large absorption area, rich in subcutaneous blood vessels - Rapid drug absorption and fast action - Not only for local therapy but also systemic delivery - Avoids first-pass metabolism - Easy to administer

Answer 25

Turbinates warm and humidify air as it passes through nasal cavity Turbinates can swell and contract (allowing/ stopping air form passing through) In most people one turbinate will swell while other contracts (air through one nostril above the other)- alternates in ‘nasal cycle’ Help detect pathogenicity of inhaled particles Problems can impair quality of life (e.g., over-swelling or excess mucus)

Answer 26

- Breathe: part of the respiratory system - Smell: millions of receptors in the nasal epithelium. Warning system but relates to memory and emotions - Identity: shape and age - Keep debris out: nasal epithelium, mucus and sneezing - Condition air: warms and moistens air (turbinates)

Answer 27

- Pseudo-stratified epithelium with cilia - Goblet cells produce mucus - Mucus traps dirt/ particulates and cilia move (wavelike) to push them out of nose >1,000,000 times more viscous than water

Answer 28

- Mucus layer: mostly water, some salts, lipids and proteins (e.g. mucins) - Mucins are high molecular weight and released by the secretory vesicles (goblet cells) - Traps particulates but may also bind to drugs (electrostatically/ hydrogen bonding) - Affects how drug behaves (absorption/ prevent diffusion/ cause degradation)

Answer 29

- Drug deposition: where the drug is deposited in the nasal cavity - Mucosal absorption: how the drug is absorbed across the mucosa - Mucocilliary clearance: the movement of the mucus layer to the nasopharynx

Answer 30

Mucus clears every 10-20 mins (towards nasopharynx) Drug on ciliated regions (posterior of nasal cavity): cleared immediately Drug on non-ciliated regions (anterior of nasal cavity): move slowly Larger particles (at nasopharynx): swallowed and lost

Answer 31

pH - 5.5-6.5 isotonic

Answer 32

Ointments/ creams - Long retention time - Mainly for nasal bacterial infections - Limited types on market Aerosols - Mainly to deliver solid particles Drops/ sprays - Widely used - Sprays: even distribution and can control dose. Avoids postnasal dripping or anterior leakage

Answer 33

For breakthrough pain in adults already receiving background opioid therapy for chronic cancer pain Single dose (50-200 micrograms fentanyl per dose) Absorbed very rapidly through the nasal mucosa.

Answer 34

No needle (good for young children and adolescents) Live attenuated virus Small dose into each nostril (0.1mL) Rapid clearance and inefficient uptake American Association for Pediatrics: No longer recommends. Reduces chance of getting virus by only 3% compared to no intervention

Answer 35

Nicotine replacement therapy Each spray: 0.5 mg of nicotine (per nostril), about half of which is absorbed Rapid absorption compared to other delivery methods

Answer 36

Olfactory bulb: Avoids systemic clearance and first pass metabolism. Effectively no BBB. Intracellular or extracellular path Strategy for tackling migraines in adults Extracellular (generally faster but has ‘slow’ and ‘fast’ routes). Great for hydrophilic drugs, proteins and peptides Drug interacts with nerve endings of olfactory receptor neurons and trigeminal neurons Residence time of drug important for effective absorption!

Answer 37

- Drug permeability: permeation enhancers, controlled delivery system, colloidal drug carriers - Mucocilliary clearance: mucoadhesives (increasing viscosity, adding polymers, using gel formulations) - Enzymatic degradation: protective coatings (nanocarriers) but do they reduce efficiency? - Toxicity: improved formulations - Small volume: increasing concentration could lead to toxicity therefore optimization needed

Answer 38

Drug permeability (i) the transient opening of tight junction between adjacent cells for improved paracellular diffusion (ii) perturbation of lipid bilayer integrity and increased membrane fluidity promoting transcellular permeation of drugs

Answer 39

External ear: from pinna to TM Middle ear: air-filled cavity with temporal bone of skull around it. Eustachian tube connects to inner ear Inner ear: cochlear (auditory organ) and vestibular system (organ of balance) TM not the same thickness in all! (80-100µm; surface area 64.3mm2)

Answer 40

Acute and chronic otitis media Ménière's disease (vertigo) Sensorineural hearing loss Tinnitus

Answer 41

Outer layer: stratified squamous keratinised epithelium Middle layer: collagen-rich layer Inner layer: cuboidal mucosal epithelium Impenetrable to most things except small, mainly lipophilic molecules Perforation: middle ear infection hearing loss

Answer 42

Cerumen: sebum, skin cells, sweat and dirt Function: protective coating and traps particulates (moving them away from the TM via hair in the auditory canal) Acidic: not conducive to bacterial growth

Answer 43

Impaction: narrow auditory canal, overproduction of cerumen or cotton-tipped applicators Impaction: can lead to tinnitus, vertigo, pain or ear feeling ‘full’ Live insects could cause further issues, inflammation (otitis externa) and infants placing small items into ear

Answer 44

Types: acute/ chronic (wet/dry) Acute and wet: heal quickly (usually a few weeks if using topical therapies)

Answer 45

Epidermis closes first (because of the cell migratory behaviour). Begins almost immediately with flooding of cells and growth factors Fibrous layer reconstruction (fibroplasia, collagen synthesis, wound contraction, neovascularisation) Maturation is last phase with long-term remodeling and reorganisation (stronger collagen fibres to restore as much tensile strength as possible)

Answer 46

Chronic: needs surgery (myringoplasty/ tympanoplasty using grafts) Problem: perforated eardrum (TM) Current: autologous graft inserted from behind the ear (‘patch’ may need further surgery) PhonoGraft: biomaterial initially provides structure but also stimulates self-healing Inserted though ear canal (less invasive)

Answer 47

3 auditory ossicles. Transmit sound from air to fluid-filled part by amplifying vibrations from TM) Eustachian tube/ auditory tube: drugs administered in middle ear can be cleared Mostly round window (approx. 70µm thick) used to deliver drugs after injection through TM

Answer 48

Cochlear: auditory organ Vestibular systems: balance Contains hair cells: sensory receptors for hearing and balance Mechanoreceptors with cilia at different heights (different frequencies) Movement generates nerve impulse which is transmitted to the brain After drugs travel through the round window, distribution depends on inner ear fluids and more barriers! Difficult to get to and small

Answer 49

Routinely to treat: otitis externa, otitis media, ear wax removal (drops/ sprays) Small volume as most will be lost out of ear passage Outer ear not fully formed at birth (changes in physiology with age) External auditory canal straighter and narrower in infants Not much difference in formulations

Answer 50

Noninvasive: diffusion to middle ear Invasive: injection/device crossing TM Invasive: drug delivery system on RW allowing diffusion of drugs to inner ear (or other processes such as endocytosis). No stratum corneum in RW compared to TM

Answer 51

Drug production methods resemble those for transdermal drugs (e.g., hydrogels and nanoparticles) Chemical permeation enhancers: enhance flux across barriers Difficult to predict what will happen to drugs after they cross the barrier

Answer 52

Direct administration into ear canal Antibiotics, antifungal drugs, gels and foams (with/ without cotton wool plugs) High concentration locally than systemic (can easily mix drug treatments) Rapid and good patient compliance (good for paediatric patients) Ototoxicity with high concentration

Answer 53

Adverse reaction to drugs affecting inner ear or auditory nerve via cell degeneration Affects cochlear or vestibular system or both Over 600 drugs classified as ototoxic: some antibiotics (e.g., aminoglycoside or macrolide), some chemotherapeutic agents, loop diuretics, antimalarials Tinnitus to permanent hearing loss, vertigo and dizziness

Answer 54

Drugs need to stay on TM for while to be effective (difficult with children) Hydrogel: liquid solid/gel (e.g., Poloxamer 407) Provides prolonged release Need to think about mechanical properties of the hydrogel (degradation? stiffness?)

Answer 55

E.g., surfactants (limonene, sodium dodecyl sulfate) Increase flux across barriers (not provided by hydrogel system) Same principles as drugs across skin Could combine CPEs and hydrogels?

Answer 56

<1µm diameter therefore able to cross barriers Can be used in combination with lipid softeners and surfactants Some method of deposition (microshotgun using water and dispersed using magnets)

Answer 57

Clearance via Eustachian tube can be avoided Otiprio (a poloxamer) in chinchillas cure for otitis media in 18h! Hyaluronic acid is shear thinning (gels after injection): Keyzilen (acute inner ear tinnitus) and Sonsuvi (sudden hearing loss) in Phase 3 trials

Answer 58

Surface modification of nanoparticles can enhance penetration properties pH-sensitive nanoparticles: pH of inflamed tissues 0.2–0.6 units lower than normal Magnetic nanoparticles for inner ear drug delivery

Answer 59

Ultrasound induced microbubbles to drive drugs through the round window into inner ear 2.8-fold increase in biotin delivery (guinea pigs)

Answer 60

Mainly tested in animal models to control low diffusion rates Programmable and implantable delivery devices Precision control of drug release (10-100 nL min-1)

Answer 61

emulsions, microemulsions and creams - oral suspensions - topical dosage forms (e.g., lotions) - injections (IM and SC depot) - aerosols (nasal and inhalation)

Answer 62

For 2 spherical particles of radius “a” at a distance apart “H” Total potential energy of interaction, Vtotal = VA + VR VA = attractive potential energy; VR = electrostatic repulsive energy Attractive forces from van der Waals interactions, VA α -1/H VR decays exponentially with distance: VR α exp(-κH)

Answer 63

1. At short inter-particle distances, attractive forces predominate (primary minimum) and particles tend to agglomerate 2. As inter-particle distance increases (i.e., sufficient energy added to separate particles) repulsive forces predominate, and particles remain in suspension (maximum) 3. If inter-particle distance increased further, repulsive force decreases, and particles are weakly attracted (secondary minimum)

Answer 64

A: Low electrolyte concentration → total energy curve has large primary maximum but no 2ndary minimum. B: Moderate electrolyte concentration → a 2ndary minimum and permits stable suspension to form: flocculation occurs in the 2ndary minimum and modest primary maximum sufficient to prevent coagulation in primary minimum. C: High electrolyte concentration → no primary maximum or 2ndary minimum.

Answer 65

Prevent rigid cohesion by forming loose aggregates Held together with comparatively weak interparticulate forces Lattice type structure - resists complete settling, reduces caking, aids re-dispersion Effect of electrolyte depends on valence of counterion - greater the valence, greater its effect on VR In flocculated systems, repulsive barriers have been reduced and particles form loosely bonded structures (flocs) in 2ndary minimum particles settle as flocculates not individual particles Sediment is not closely packed and caking does not occur Suspension formulation aims for partial or controlled flocculation

Answer 66

In deflocculated systems, particles are not associated However, pressure on individual particles → their close packing at bottom of container 2ndary energy barriers overcome and particles forced together in primary minimum Irreversibly bound into ‘cake’ Cake avoided with a flocculating agent in formulation Caking not prevented by reducing particle size or increasing viscosity

Answer 67

Flocculation controlled w/ non-ionic polymers to increase aq. phase viscosity * Hinders particle movement, may form adsorbed layers on particles too → steric stabilisation and/or inter-particle bridging * Exs: naturally gums (e.g., tragacanth), cellulose polymers (e.g., sodium carboxymethylcellulose) * Ideal suspending agent for controlled flocculation: - is easily and uniformly incorporated in formulation - readily dissolves/disperses in water w/o need of special techniques - ensures formation of loosely-packed system that does not cake - does not affect dissolution rate or absorption rate of drug - is inert, non-toxic and free from incompatibilities

Answer 68

Hydrophile Lipophile Balance A way of measuring a substances solubility within water or oil Expressed on arbitrary scale from 1 to 20 High HLB => hydrophilic surfactant Low HLB => oil-soluble surfactants (w/o emulsifiers)

Answer 69

ME = Thermodynamically stable, homogenous, transparent, isotropic, low-viscosity colloidal mixtures of oil, water and surfactant

Answer 70

Systems with constant velocity of zero shear stress

Answer 71

Non-Newtonian behavior is generally exhibited by liquid and solid heterogeneous dispersions. Examples: colloidal solutions, emulsions, liquid suspensions, and ointments

Answer 72

Plastic flow curves do not pass through the origin Instead, they intersect shearing stress axis at the yield value. Flow does not begin until a shearing stress corresponding to the yield value is exceeded. At stresses below yield value, the substance acts as an elastic material. Substances that exhibit a yield value are classified as solids, whereas substances that begin to flow at the smallest shearing stress and show no yield value are defined as liquids. Plastic flow is associated with presence of flocculated particles in concentrated suspensions, a continuous structure is set up throughout the system. The more flocculated the suspension, the higher is the yield value. A plastic system resembles a Newtonian system at shear stresses above the yield value.

Answer 73

Pseudoplastic flow is typically exhibited by polymers in solution. The rheogram for a pseudoplastic material begins at origin, therefore, there is no yield value Viscosity of a pseudoplastic material cannot be expressed by any single value. The viscosity of a pseudoplastic substance decreases with increasing rate of shear. Apparent viscosity at any shear rate = slope of tangent to curve at specified point. As shearing stress increases, normally disarranged molecules begin to align their long axes in direction of flow. This orientation reduces internal resistance of material and allows a greater rate of shear at each successive shearing stress.

Answer 74

Certain suspensions with a high percentage of dispersed solids exhibit an increase in resistance to flowbwith increasing rates of shear. Dilatant flow is the opposite of pseudoplastic systems. Dilatant materials are often termed “shear-thickening systems.” When stress is removed, a dilatant system returns to its original state of fluidity. Substances with dilatant flow properties are invariably suspensions containing a high concentration of small, deflocculated particles. However, such flocculated particulate systems are expected to have plastic flow characteristics. At rest, particles are closely packed with minimal interparticle volume Thus, a dilatant suspension can be poured from a bottle because under these conditions it is reasonably fluid. As shear stress is increased, the bulk of the system expands or dilates; hence the term dilatant.

Answer 75

Material has a lower consistency at any one rate of shear on down-curve than it had on up-curve. Indicates a breakdown of structure that does not reform immediately when stress is removed or reduced. This is known as thixotropy, defined as “an isothermal and comparatively slow recovery, on standing of a material, of a consistency lost through shearing.” As defined in this way, thixotropy can be applied only to shear-thinning systems. Thixotropy means ‘to change by touch’. Thixotropy describes a material which exhibits a reversible time-dependent decrease in apparent viscosity.

Answer 76

Rheogram = plot of shear rate as a function of shear stress. Rheologic properties of a given material are most completely described by its unique rheogram. Simplest rheogram is the linear behaviour shown by Newtonian systems. Plasticity = simplest non-Newtonian behavior; curve is linear only beyond its yield value. If the curve is nonlinear for all shear rates tested, then system is non-Newtonian and either pseudoplastic (shear thinning) or dilatant (shear thickening). If the curve shows hysteresis, then system is thixotropic.

Answer 77

Utilised in the application of creams and lotions Viscosity decreases upon shearing. Subsequently, a slow increase. These features can be manipulated to provide better application experience of topical products.

Answer 78

For non-Newtonian systems, essential that viscometer operates at a variety of shear rates to produce a complete rheogram. For example, multipoint evaluation of pseudoplastic materials allows assessment of viscosity of a suspending agent at rest (negligible shear rate), while being agitated, poured from a bottle, or applied to the skin (moderately high shear rate). Four common types of viscometer: capillary – Newtonian materials only falling-sphere – Newtonian materials only cup-and-bob – for both Newtonian and non-Newtonian systems cone-and-plate – for both Newtonian and non-Newtonian systems

Answer 79

Stratum corneum Epidermis Dermis

Answer 80

- Modulate barrier function - Treat disease states in the epidermis and dermis (i.e., dermatology) - Alleviate local pain/inflammation in subcutaneous tissues - Elicit systemic pharmacological effect

Answer 81

- Absorption of drugs from the skin surface into the body drug penetrates into the skin - Drug cannot be removed by washing - Drug is taken up by microcirculation, enters systemic circulation, or is carried to deeper tissues beneath the skin Percutaneous absorption depends on: - Physicochemical properties of the drug - Interactions of drug with vehicle or delivery system and with the skin - Condition of the skin

Answer 82

In vitro - Methodology and data analysis - Permeability coefficient, % dose absorbed In silico - Permeability coefficient - Maximum flux calculation In vivo - Pharmacodynamic measurement {vasoconstriction assay} - Stratum corneum tape-stripping {dermatopharmacokinetics} - Microdialysis

Answer 83

- Interaction of vehicle with skin (enhancement effects?) - Interaction between drug and vehicle - No "rules" for matching a formulation to a particular drug - What happens to formulation, and components thereof, when it is massaged into skin?

Answer 84

Formulations selected by type of emulsion, lipid content and occlusivity For chronic skin disease, hydrocarbon-based formulations preferred for their occlusive and protective properties Water free formulations (PEG-gels, oleogels, fatty ointments) best for psoriasis, chronic eczema, mycosis. Emulsion gel - Hydrogel containing a dispersed lipid phase Suspension gels = suspensions of water-insoluble drugs in hydrogels Gels are not favoured for psoriasis and eczema. appropriate for anti-allergics, repellents, anti-inflammatories and for acne or rosacea. Creams (emulsions) = disperse systems; majority of aqueous formulations w/o emulsions blend easily with SC lipids, improving bioavailability of lipid-soluble drugs and moisturizing skin via slight occlusive effect. o/w emulsions more cosmetically appealing (less sticky and greasy) as lipids therein are finely dispersed. w/o lotion: hydrophobic, semi-liquid w/o cream: hydrophobic, semi-solid Typically used to treat psoriasis, chronic eczema, mycosis o/w lotion: hydrophilic, semi-liquid o/w cream: hydrophilic, semi-solid Typically used to treat acne and acute and sub-acute eczema

Answer 85

PEG-gel: polar, 1-phase, semi-solid system, based on polyethylene glycols. Lipogel: polar, 1-phase, semi-solid system, principally based on triglyceride derivatives. Oleogel: polar, 1-phase, semi-solid system comprising triglycerides +/or hydrocarbon/silicon oils + inorganic filler. Fatty ointment: Apolar, 1-phase, semi-solid system, based on hydrocarbon materials, e.g., vaseline, mineral oil.

Answer 86

Hydrogel: semi-solid system, typically comprising large organic molecules (e.g., cellulose derivatives, polyacrylic acid and esters) inter-penetrated by water. Emugel: 2-phase system, consisting of large organic molecules inter-penetrated by water and small fraction of emulsified lipids.

Answer 87

w/o lotion: hydrophobic, semi-liquid, 2-phase system, comprising water and a continuous lipid phase, e.g., triglycerides, waxes, + w/o emulsifiers. w/o cream: hydrophobic, semi-solid, 2-phase system, comprising water and a continuous lipid phase (as above), + w/o emulsifiers.

Answer 88

o/w lotion: hydrophilic, semi-liquid, 2-phase system, comprising lipids, e.g., triglycerides, waxes, and a continuous aqueous phase + o/w emulsifiers. o/w cream: hydrophilic, semi-solid, 2-phase system, comprising lipids (as above) and a continuous aqueous phase + o/w emulsifiers.

Answer 89

- Structural matrix of formulation may change due to rubbing or loss of volatile excipient(s) - Rubbing may cause emulsifying effects - Evaporation may produce a desired cooling effect - Evaporation also desirable for repellent/fragrance formulations

Answer 90

Gel formulations to treat local muscle and joint pain and inflammation. Significant non-steroidal anti-inflammatory drug (NSAIDs) market. Results in significantly lower systemic exposure (and avoids any major drug-related side-effects, such as GI disturbance).

Answer 91

Any defect or damage in the skin caused by: Physical, chemical or thermal factors Damage caused by an infectious disease

Answer 92

- Incisions - Lacerations - Abrasion - Punctures - Penetrations - Avulsion

Answer 93

- Contusion - Hematoma - Crashing

Answer 94

- Inflammatory phase - Proliferative phase - Remodelling phase

Answer 95

Hydrogel dressing Hydrocolloids Gauze impregnated Gauze non-impregnated Composite dressings Wound fillers Alginate dressings Foam dressings

Answer 96

Tape Elastic bandage Transparent film dressings Gauze dressing Carbon dressing

Answer 97

For clean, healthy wounds with minimal granulation bed For wounds with no need for debridement, granulation and contraction Best to use at early stages of wound repair for shallow wounds Increases wound contraction but delays epithelialization

Answer 98

- Contains a solid polymer matrix with propylene glycol. - Dependent on wound conditions, it has the ability to absorb wound exudates while maintaining an excellent moisture balance. Donates moisture Permits autolytic debridement (removal of dead or infection tissue) Increases collagenase activity in burns (promoting debridement) Promotes granulation & epithelialization Promotes contraction

Answer 99

Early to mid-repair phase of healing Can also reduce pain in wounds. Encourages also angiogenesis in acute wounds Indication: Wounds with the need for granulation Minimal to moderate exudates Advanced wound contraction Decupital ulcers (pressure ulcers, bed sores), burns, cavity wounds Action: Occlusive to semi-occlusive Highly absorbent Promotes moist wound healing Promotes autolysis to debride wounds that are sloughy and necrotic. Promotes granulation (may cause hypergranulation) Adhesiveness may reduce contraction

Answer 100

Non-adherent dressing Can absorb large amounts of exudates several times their own weight & accumulate the exudate at the back of dressing Can also be used as secondary dressing Indication: Inflammatory or repair phase of healing Deep wounds with mild to moderate exudates Decubital ulcers Can be used at any stage of healing Best used after granulation, to encourage epithelialization and contraction.

Answer 101

Natural polymers from Brown algae Composed of either mannuronic or guluronic acid complexes. Good gel-forming and film-forming properties Calcium alginate is mainly used in the formation of wound dressing. Calcium alginate is widely used as hemostatic agent (encourages the clotting cascade within a bleeding wound) Indication: Burns, shearing/avulsion injuries, cavity wounds Also encourages wound healing Best early repair phase of wound healing (after gross contamination & necrotic tissue has been removed) Best for moderate to highly exuding wounds Highly absorptive, encourages epithelialization Promotes autolytic debridement and granulation

Answer 102

Semi-permeable dressings Play important role both as primary & secondary dressings. Comfortable dressings Resistant to shear and tear Can prevent bacterial colonisation but do not absorb exudate. Vapour permeable Allow fluid to evaporate while keeping the wound moist

Answer 103

Natural polymers source: animal, microbial & vegetal Usually are of protein (e.g. fibrinogen, thrombin, collagen, gelatin and albumin) or polysaccharide ( chitosan, chitin, polyN-acetyl glucosamine and cellulose) nature. Suitable substitutes of the ECM and original cellular environment of the native skin. Advantages: Biocompatibility, biodegradability and hydrophilicity Limitations: Batch to batch variability, large heterogeneity, prone to high biodegradability Successful use of chitosan, collagen and gelatine for wound dressing fabrications.

Answer 104

One of the most commonly used natural polymer with a key role in wound dressing The most abundant protein in the body, major component of skin and musculoskeletal tissues. Promotes healing by allowing attachment and migration. Is composed of 3 polypeptide chains with triple helical domains. Is one of primary initiators of the coagulation process. Its high thrombogenicity has led to its application as a hemostatic agent. Frequently used in formulation of different solid wound dressings for blood clotting. Causes blood clotting through a pathway similar to physiological haemostasis. Dry collagen material are prepared which physically adsorb blood by trapping blood cells and effectively adhere them to the wound site, providing mechanical strength. Collagen powder is effective in blood loss reduction in the patients undergoing cardiac operations.

Answer 105

The principal structural component of the exoskeleton of invertebrates Chitin can be converted into soluble derivatives, such as chitosan, carboxymethyl chitin & glycochitin. Chitin-based biopolymers are versatile materials processed into fibers, sponges, membranes, beads and hydrogels. Chitosan is prepared from deactelytaion of chitin by enzymatic or alkaline hydrolysis.

Answer 106

One of the most abundantly found natural polymers suitable tor use in wound dressings. Properties: Bioactive in slightly acidic media, depolymerises to release b-1-4-linked-D-glucosamine which initiates fibroblast proliferation and aids collagen deposition during the wound healing. At the same time it has hemostatic properties. - Is also involved in the rapid mobilization of platelet and red blood cells to the injured site during the healing process. - Also helps in vasoconstriction and activates blood clotting factors, responsible for blood clotting. In addition to aiding the healing process it is: biodegradable, biocompatible, non-toxic, bioadhesive, bioactive, non-antigenic and also antimicrobial against a wide range of pathgenic organisms. It possesses good film-forming properties and is used as hemostatic agent in different forms such as gels, films & scaffolds.

Answer 107

Synthesized & modified in a controlled manner (constant and homogenous physical and chemical properties and stability). Disadvantage: Biologically inert, so do not offer a therapeutic advantage as seen with natural polymers. Commonly used synthetic polymers for wound dressings Advantageous in healing process: Non-toxic, biocompatible, non-immunogenic, hydrophilic and flexible. PEO & PEG: Can be used to further incorporate mediators such as growth factors to assist the healing process.

Answer 108

Gels are viscoelastic solid-like materials comprised of an elastic cross-linked network and a solvent, which is the major component. The solid-like appearance of a gel is a result of the entrapment and adhesion of the liquid in the large surface area of a solid 3D matrix. The formation of the solid matrix is a result of cross-linking of the polymeric strands of macromolecules by physical or chemical forces.

Answer 109

Large increase in viscosity above gel point Appearance of rubber-like elasticity Gel retains shape under low stress, but deforms at higher stress

Answer 110

Hydrogels retain significant amount of water ( up to 100x their dry weight in H2O) - but remain water-insoluble - used in topical drug delivery, wound healing - soft contact lenses - Implant coating

Answer 111

= irreversible systems 3-D network formed by covalent bonds between macromolecules Formed by polymerization of monomers of water soluble polymers in presence of x-linker

Answer 112

= heat-reversible Held together by intermolecular bonds (e.g., H-bonds) Gel on cooling below T = gel point

Answer 113

If water-soluble polymer chains are covalently x-linked into a 3D structure gel forms when dry material interacts with water. Polymer swells but cannot dissolve due to x-links. Applications include fabrication of expanding implants; Similar polymer used to fabricate soft contact lenses

Answer 114

Gels of a low molecular mass compound are usually prepared by heating the gelator in an appropriate solvent and cooling the resulting isotropic supersaturated solution to room temperature. When the hot solution is cooled, the molecules start to condense and 3 situations are possible (1) A highly ordered aggregation giving rise to crystals i.e., crystallization. (2) A random aggregation resulting in an amorphous precipitate. (3) An aggregation process intermediate between these two, yielding a gel

Answer 115

(1) Supramolecular organogels used in cosmetics formulations. (2) Biomedical applications: Media for tissue engineering

Answer 116

At very low amphiphile concentration, the molecules will be dispersed randomly without any ordering. At slightly higher concentration, amphiphilic molecules will assemble into micelles or vesicles. This is done with the hydrophobic tail of the amphiphile inside the micelle core. At higher concentration, the assemblies will become ordered into a roughly hexagonal lattice. At still higher concentration, a lamellar phase ‘neat soap phase’ may form, wherein extended sheets of amphiphiles are separated by thin layers of water.

Answer 117

- Liposomes are vesicular structures based on lipid bilayers encapsulating an aqueous core. - The lipid molecules are usually phospholipids - Such moieties spontaneously orientate in water to give the most thermodynamically stable conformation, in which the hydrophilic head-group faces out into the aqueous environment and the lipid chains orientate inwards avoiding the water phase. - This gives rise to bilayer structures. - Liposomes can serve as carriers for both water-soluble and lipid-soluble drugs. - The rigidity and permeability of the bilayer strongly depend on the type and quality of lipids used. - The alkyl-chain length and degree of unsaturation play a major role. - The presence of cholesterol also tends to rigidify the bilayers. - Such systems are more stable and can retain the entrapped drug for relatively longer periods

Answer 118

Lipid composition Storage condition - Light - Oxygen - Temperature Stabilizers - Cholesterol - Alpha-tocopherol - Inert atmosphere

Answer 119

- bio-compatible/biodegradable. - biologically inert; weakly immunogenic ; Low intrinsic toxicity. - substantially alters tissue distribution of carrier-associated agents

Answer 120

- Conventional liposomes, which are neutral or negatively charged, are generally used for passive targeting to the cells of the MPS (mononuclear phagocyte systems). - Sterically stabilised liposomes with hydrophilic coatings used to obtain prolonged circulation times. - Immunoliposomes, either conventional or sterically stabilized, are used for active-targeting purposes. - Cationic liposomes, positively charged, are used for the delivery of genetic material.

Answer 121

- Liposomes that are typically composed of only phospholipids (neutral or negative) and/or cholesterol. - Protect encapsulated molecules from degradation - Can passively target tissues or organs that have a discontinuous endothelium On intravenous administration, are rapidly taken up by the phagocytic cells of the MPS localizing predominantly in the liver and spleen, and removed from blood circulation Used when targeting to the MPS is the therapeutical goal:

Answer 122

Made by attaching the hydrophilic polymer, polyethylene glycol to the liposomes bilayers. The highly hydrated PEG group create a steric barrier against interactions with molecular and cellular components in the biological environment.

Answer 123

Immunoliposomes have specific antibodies or antibody fragments on their surface to enhance target site binding. The primary focus of their use has been in the targeted delivery of anticancer agents. Long-circulating immunoliposomes can also be prepared. The antibody can be coupled directly to the liposomal surface, however the PEG chains may provide steric hindrance to antigen binding.

Answer 124

The cationic lipid components of the liposomes interact with, and neutralize, negatively charged DNA, thereby condensing the DNA into a more compact structure. Depending on the preparation method used, the complex may not be a simple aggregate, but an intricate structure in which the condensed DNA is surrounded by a lipid bilayer.

Answer 125

Most liposome formulations are very well-tolerated Cationic liposomes may activate complements and induce adverse effects via IV route. PEGylated liposomes may induce a transient reaction upon injection in a subset of patients.

Answer 126

- Solid colloidal particles ranging in size from 1-1000nm - Consist of macromolecular materials - Can be used as drug carriers in which the active drug is adsorbed or attached’

Answer 127

- Increased drug penetration and stability - Too small to be detected by immune system - Deliver the drug in the target organ using lower doses so as to reduce side effects

Answer 128

- Lipid bilayer structures made of phospholipids (and cholesterol) - Hydrophilic drugs are entrapped in the aqueous layer of the liposomes, while hydrophobic drugs are incorporated in the lipid bilayers

Answer 129

- Biocompatibility, low toxicity - Targeted delivery of drugs to the site of action

Answer 130

- Limited penetrating ability - Chemically and physically unstable

Answer 131

- Ultra-deformable liposomes, composed of phospholipids and additional surfactant /emulsifier - Edge activators: Destabilize the lipid bilayers of the stratum corneum and increase in deformability by lowering interfacial tension of lipid bilayers

Answer 132

By squeezing themselves along the intracellular sealing lipid of the SC, the drug penetrating ability increases. Localized at higher concentration

Answer 133

Edge activators must be highly pure to avoid skin irritation & toxicity

Answer 134

Soft lipid vesicles composed of phospholipids, water and ethanol in relatively high concentrations (up to 45% W/W).

Answer 135

- More effective transdermal delivery than classical liposomes - They are smaller and have higher entrapment efficiency - Interferes with lipid bilayers of the SC due to fluidizing effect of alcohol - Shows better skin permeation and stability than classical liposomes - Alcohol also enhances the deformability of the vesicles

Answer 136

- Skin irritation due to high concentration of alcohol

Answer 137

- Ethosomes developed by adding another type of alcohol to the classical ethosomes. The most commonly used alcohols in binary ethosomes are propylene glycol (PG) and isopropyl alcohol (IPA).

Answer 138

- Transethosomes are the new generation of ethosomal systems - Contains the basic components of classical ethosomes and an additional compound, such as a penetration enhancer or an surfactant in their formula. - Developed in an attempt to combine the advantages of classical ethosomes and transfersomes in one formula to produce transethosomes.

Answer 139

- NSAID COX-2 inhibitor - Prevent skin cancer development and increase the effectiveness of anticancer drug - Ex vivo permeation studies through excised human skin - All formulations improved the drug penetrating ability with respect to an aqueous suspension - Larger amount of CXB penetrated into the excised human skin when transfersomes and ethosomes were used

Answer 140

1st generation of LNs Increased adhesiveness to surfaces Controlled occlusion effect Increased skin hydration

Answer 141

- Homogenous matrix model (release form) - Drug-enriched shell model (fast compound delivery) - Drug-enriched shell core (slow controlled release)

Answer 142

- decreased loading capacity - expulsion of drug during storage

Answer 143

2nd generation of lipid nanoparticles Overcome the limits of SLN Different matrix structure

Answer 144

- Imperfect type (blend of different solids + liquids) - amorphous type (lipid solid matrix) - multiple type (drug solubility in liquid lipids higher than in solids)

Answer 145

- Low toxicity - Small particle size - Increase skin hydration -> occlusive effect - Enhance the stability of liable compounds - Physical sunscreen on their own - Reduce skin irritation

Answer 146

Bilayered structures made of non-ionic surfactant and cholesterol

Answer 147

- Able to entrap wide range of chemicals (both hydrophilic and hydrophobic) - Less toxic than carriers with ionic surfactant

Answer 148

- Limited shelf-life - Time-consuming & specialised required for the preparation process

Answer 149

Isotropic dispersed systems of 2 immiscible liquids: o/w or w/o nanoemulsions

Answer 150

- Both hydrophilic and hydrophobic drugs can be applied - Solubilisation/extraction of SC lipids, thereby decreasing resistance for drug transport - Greater and extended cellular penetration - Raised efficacy due to increasing surface-to-volume ratios - Non-toxic and non-irritant - Kinetically stable

Answer 151

Stability problems

Answer 152

- Sclera - Iris - Cornea - Pupil - Lens - Cilliary body + muscle - Conjunctiva

Answer 153

- Retina - Optic nerve - Macula - Retinal blood supply - Vitreous body

Answer 154

Dry eye Blepharitis: inflamed eyelids. Eyelid cleansing treatments Conjunctivitis Uveitis: inflamed uvea tract. Steroid treatment or surgery Keratoconus (KCN): gradual thinning of cornea (contact lenses/ corneal cross-linking or keratoplasty)

Answer 155

Portion of lens hardens and becomes cloudy Annoying to painful (with a range of blurred vision and sensitivity to glare in between) Causes: age, eye injury, previous surgery, certain medications No known treatments other than surgery Surgery: replacement of lens with a plastic lens (usually monofocal) 1: phacoemulsification: ultrasound tip to break down cataract 2: removal of debris 3: lens implantation into capsule

Answer 156

Age-related macular degeneration (AMD): degeneration of central part of retina (macula) causing loss of focus. Irreversible. No cure but can manage symptoms (e.g., reducing abnormal vessel growth) Central Serous Retinopathy (CSR): disorder of the outer blood-retinal barrier. Fluid build-up under retina. Laser-based therapies

Answer 157

Primary open angle glaucoma: slow build-up of fluid caused by blockages Acute angle closure glaucoma: sudden fluid build-up caused by blockages Secondary glaucoma: existing underlying eye condition (e.g., uveitis)

Answer 158

Palpebral conjunctiva: inner surface of upper and lower eyelids Bulbar conjunctiva: surface of the globe Fonix (forniceal): region connecting palpebral and bulbar areas

Answer 159

Epithelium: lipid-rich epithelium next to conjunctiva. 1 week turnover for cells Stroma: thickest layer composed of collagen matrix and keratinocytes. Collagen fibril bundle spacing contributes to cornea being clear Endothelium: single cell layer also lipid-rich to maintain hydration as it faces the inner part of eye

Answer 160

Tears: distribute nutrient across surface of eye, maintain hydration and remove debris Blinking: 15-20 blinks per min (clearing approx. 1 µL/min) Composition: water, lipids, lysozyme, lipocalin, glucose, and sodium pH 7.4 (good buffering properties which could affect drug formulations) Isotonic with blood (0.9% w/v NaCl; important to note for ocular formulations)

Answer 161

Sterility Chemically stable: preservatives as most eyedrops are multidose pH ideal: buffering potential of lacrimal fluid vs stability of formulation Viscosity match: (a) easily filtered during manufacture, (b) easily sterilised (by filtration), and (c) compatible w/ other excipients (e.g., preservatives) Salt match: affects solubility but high concentration causes irritation Comfort/ no irritation: stinging/ irritation caused by formulation which affects tear production/ clearance Low MW and small particle size: <10 µm Amphipathic: cornea structure is lipid-aqueous-lipid

Answer 162

Mixture of semisolid and solid hydrocarbon (paraffin) with a melting point of ocular physiological temperature (34°C) Helps to sustain drug release and improves bioavailability Viscosity of formulation an issue Greasiness/blurred vision caused by thicker formulation (better overnight) Prolonged exposure and repeated blinking can lead to irritation/ inflammation Systemic complications with chronic administration

Answer 163

Periocular: around the eyeball (but within the orbit) Transscleral pathway; systemic circulation through the choroid; or through the tear film, cornea, aqueous humor, and the vitreous humor Still various barriers to contend with Drainage an issue in some strategies

Answer 164

Intravitreal: into vitreous (direct administration) Distribution is non-uniform Particle size matters (small easily distributed, large not so much) Chemistry and MW of formulation matters (vitreous component interaction)

Answer 165

Fluocinolone acetonide (corticosteroid) implant for Chronic Diabetic Macular Oedema (DMO) Reduce VEGF (a protein that increases vascular permeability and causes oedema) Intravitreal injection 3.5mm implant sits in vitreous fluid and can release drug for up to 36 months

Answer 166

Treatment for chronic diabetic macular oedema (DMO) and neovascular (wet) age- related macular degeneration (AMD) 1 mL contains 10 mg ranibizumab Intravitreal injection Reduces abnormal blood vessel growth (anti-VEGF)

Answer 167

For inflammation following surgery (e.g., cataract) or persistent itching associated with allergic conjunctivitis Active ingredient: dexamethasone Hydrogel-based implant acts as a plug into tear duct Degrades over time

Answer 168

Typically, under 100 nm Research for both anterior segment and posterior segment Advantages: decrease irritation, improve dispersion and improve tissue compatibility Nanomicelles: most common. Surfactant or polymer-based but generally amphiphilic Liposomes: lipid-based vesicles with a phospholipid bilayer and an aqueous core Dendrimers: branched/ star-shaped. End of branches can carry cargo (drugs) Nanoparticles: generally, protein/ lipid/ another natural matrix component-based. Drug-loaded spheres (throughout) or capsules (inside)

Pharmaceutics Flashcards

(193 cards)