2202 CSV Flashcards

Question

how do dry powder inhalers work? Give some advantages and disadvantages.

Answer 1

- fine particles +/- an inert carrier eg lactose Advantages - less patient coordination needed, breath holding not needed and no propellant required Disadvantages - requires moderate to high inspiratory flow, some units are single dose, difficult to deliver high doses

Answer 2

- Compressed gas or an ultrasonic device is used to convert a liquid into a fine mist - Drug is breathed in through a facemask or mouthpiece via a connecting tube - Two types: jet nebuliser + ultrasonic nebuliser

Answer 3

• Multi-dose, propellant-free, liquid inhaler • Higher fraction of fine particles than pMDIs and DPIs • Aerosol spray exits slowly and for a longer duration than pMDIs • Higher lung / lower oropharyngeal deposition • Lower doses without lowering efficacy

Answer 4

• Drug dissolved in liquefied propellant-based formulations • The propellant is a gaseous compound which pushes the product out of the container and produces a spray Advantages = convenient, difficult to contaminate, portable Disadvantages = patient coordination is vital, difficult to deliver high doses

Answer 5

1. Absorption into the bloodstream 2. Local inactivation = accomplished through macrophage injection 3. Lymphatic clearance = absorbed into lung tissue + cleared through lymphatic drainage 4. mucociliary transport = occurs if the drug is deposited on the airway surface and then swallowed

Answer 6

1. Pressurised metered-dose inhalers (pMDIs) • With holding chamber (spacer) 2. Nebulisers • Jet • Ultrasonic 3. Dry powder inhalers (DPIs) 4. Soft mist inhalers

Answer 7

- they don’t contribute to climate change - They have good safety - they are chemically stable; non-inflammable dose monitoring required when patients where switching from CFC to HFA as they had different lung distribution (HFA particles where smaller therefore could get deeper into the lungs) they where them matched mcg to mcg to CFC by changing (lowering) the amount of drug in the chamber

Answer 8

- Improved efficacy, e.g. increased bioavailability from aqueous solutions - Easier handling, e.g. easier dose measurement, reduced viscosity of aqueous systems - Reduced side effects, e.g. intramuscular parenteral suspensions are painful, non-precipitation of drugs from intravenous parenteral formulations - Marketing (aesthetics)

Answer 9

- Formulation of poorly water-soluble drugs in aqueous environments may be enhanced by the use of surface-active agent(s) at concentrations above their critical micelle concentration (cmc). - The surfactant acts as a ‘bridge’ between aqueous and non- aqueous environments and the drug may be solubilised by being held within the micelle or the outer, more hydrophilic long-chain structures (palisade layer). - Solubilising surfactants have a greater hydrophilic character (HLB>16) compared, e.g. to emulsifying surfactants. Examples include polyoxyethylene sorbitan mono-oleate (Tween 80) and monolaurate (Tween 20), polyoxyethylene lauryl ether (Brij 35).

Answer 10

1. polar solutes (drugs) 2. Non-polar solutes (drugs) 3. semi-polar solutes (drugs)

Answer 11

- surfactants - co solvents - complexation - modification of solid state - chemical modification - synthesis of enhanced solubility derivatives

Answer 12

- that there will be less tham complete mixing and the drug will have a finite solubility in water. - the greater the difference the lower the drug will be soluble in aqueous solvent

Answer 13

• Drug insoluble in the delivery vehicle • Mask bitter taste of the drug • Peadiatric medicines • Increase drug stability • Patient unable to swallow solid dosage form

Answer 14

• Physical stability – sedimentation and compaction • Bulky formulation – in comparison solid dosage forms • 500 ml & 1000 ml bottles not uncommon • Uniform and accurate doses cannot be achieved unless formulation is well shaken just before use

Answer 15

1. colloidal - 1 nm to 1 μm • Tyndall effect – light scattering 2. coarse - 1 to 100 μm • More liable to settling ou

Answer 16

Aqueous solutions that increase the viscosity of the formulation Used in deflocculated systems

Answer 17

used in flocculated systems Some insoluble solids easily wetted by water and will disperse readily throughout the aq. phase with minimal agitation

Answer 18

• Sedimentation of particles or floccules as a result of gravitational forces in the liquid • Flocculated suspensions – flocs form and increase sedimentation rate • Form loose porous sediment • Deflocculated suspension – individual particles begin to sediment • Form dense cakes

Answer 19

Heterogeneous mixture in which insoluble solid particles are dispersed evenly in a liquid medium

Answer 20

1. convection drying 2. conduction drying 3. Spray drying 4. Freeze drying

Answer 21

- Wet solid on direct contact with hot surface, hence heat transfer occurs via conduction - Most important example - vacuum oven

Answer 22

• Drying takes place via latent heat of evaporation provided via a hot air stream • May be fixed bed - air passes over static powder mass •tray drying • May also be dynamic - powder is in motion •fluid bed drying

Answer 23

• Hot air stream through powder bed gives buoyancy to particles • Particles form a fluidised suspension in air • Water loss takes place from individual particles

Answer 24

• Method used to produce dried product (from aqueous solutions or suspensions in vials) • Particularly important because it involves the use of low temperatures • Results in porous solid • Widely used for the preparation of proteins

Answer 25

• Method used to produce dried product from aqueous solutions or suspensions • Solution atomised (liquid converted to small droplets) and sprayed into stream of hot air • Results in free -flowing powder sample

Answer 26

• Water of crystallisation (e.g. hydrates) • ‘Free’ water - water essentially present as a liquid • ‘Bound’ water - hydrogen bonded to the substrate

Answer 27

• Inappropriate choice of drying conditions can lead to rapid water loss from surface of material which forms a hard dry crust (caking) • This caked material then prevents further water loss from deeper in the bed while the now dry crust becomes hot

Answer 28

- Sample loses water from surface of bed and saturates air immediately above surface . - Water replaced immediately, hence water is effectively being lost from a free liquid surface - Rate will therefore be constant, as it is limited by rate of vapour removal from above bed - Controlled largely by rate at which water vapour can be removed

Answer 29

removal of some or all of a solvent from a system - Pharmaceutical importance: • chemical stability • processing and handling • toxicity • dosing

Answer 30

• Rate of vaporisation not sufficient to • saturate air above surface • Drying rate determined by rate of transfer to surface. • As drying proceeds, this becomes increasingly difficult hence rate decreases with time • Rate of transfer determined by diffusion, suction potential of porous materials and capillary force

Answer 31

• In first falling rate period, water is still being lost from surface. • In second falling rate period, water loss is from within bed itself, i.e. no more free water • As solid becomes dryer thermal conductivity also decreases, • may need to increase bed temperature (an issue for thermolabile materials) • In practice, first and second falling rate periods seen in continuity

Answer 32

• High concentration of drug on apical side of cell • Low concentration inside the cell • Molecule diffuses into cell and out the other side into intercellular area and the blood - many lipophilic drugs and neutral molecules

Answer 33

• Transcellular route by passive diffusion • Transcellular route via active transport • Transcellular route via facilitated diffusion • Paracellular route (tight junctions)

Answer 34

- limited absorption for drugs - absorbs water - absorbs lipids - gut microbiome will metabolise many nutrients and drugs

Answer 35

- absorbs nutrients, salts + drug molecules.

Answer 36

- mechanical digestion of food = peristalsis - mixes the food with gastric juices = chyme - this facilitates the absorption of nutrients

Answer 37

- parietal cells (kills bacteria / aids breakdown) - peptic cells (breaks down protein) - mucosal cells (protects the stomach from auto digestion)

Answer 38

• Bile salts are produced in the liver stored in the gallbladder • They are released in the duodenum in the presence of food, where they act as surfactants and emulsifiers • Most of the quantity of bile salts is reabsorbed (mainly in the ileum) and stored back in the gallbladder to be reused

Answer 39

Study of the physical and chemical properties of drugs, their route of administration, and how these affect the rate and extent of absorption

Answer 40

• Reduction in the amount of drug enteringvthe systemic circulation • Oral dose needs to be higher when a drugvundergoes extensive first-pass metabolism • This effect limits bioavailabilit

Answer 41

hepatic portal vein, taking drug compounds to the liver where they undergo 1st pass metabolism

Answer 42

• The drug is covered with a slowly dissolving coating • The liquid surrounding the unit dissolves the coating • Rate-limiting dissolution step • Solid drug is exposed to the liquid and dissolves

Answer 43

• Drug is dispersed as solid particles within a matrix formed of a water-insoluble polymer (e.g., poly(vinyl chloride) or in a matrix forming a gel in contact with water • Release from a matrix system involves: 1. Drug particles located at the surface will be dissolved and released rapidly 2. Drug particles at increasing distances from the surface will be dissolved and released by diffusion in liquid- filled pores of the matrix or in the gel to the exterior of the release unit

Answer 44

Release of drug from a reservoir system involves: - Partition of the drug dissolved inside the release unit to the solid membrane - Transport by diffusion of the drug within the membrane - Drug will partition to the solution surrounding the release unit

Answer 45

Absorption through the gap between neighbouring cells – tight junctio

Answer 46

- Molecule “piggybacks” into the cell using a system designed for natural substrates e.g. amino acids, vitamins - Molecules are moving against a concentration gradient - Therefore this process requires energy

Answer 47

• A form of passive transport • No energy is required • Uses carrier proteins • Requires a concentration gradient • Structurally selective • Competition of different drugs for binding sites • Saturation on apical side if not enough carrier

Answer 48

Vol 1/2 =0.5 monnographs for medicinal and pharmaceutical substances. Vol 3 = monographs for formulated products Vol 4 = infrared reference spectra Vol 5 = veterinary

Answer 49

Provide publicly available and legally enforceable quality control standards for common drugs

Answer 50

EP has no monographs on individual formulated products, whereas the BP does!

Answer 51

European pharmacopeia doesn’t contain any formulated drug monographs and is updated every few years, whereas the British Pharmacopoeia contains formulated drug monographs and is updated every year

Answer 52

• Stratum corneum barrier integrity compromised by disease. • Raised skin temperature (increased rate of drug diffusion). • Occlusion of skin (by formulation or applied dressing) - increases water content of stratum corneum by reducing transepidermal water loss, opening out tightly packed structure and decreasing resistance to diffusing drug. • Chemical manipulation of barrier (penetration enhancement). • Maximising drug concentration in solution in applied surface film (formulation)

Answer 53

- increasing the barrier (suncreams / barrier creams) - reducing the barrier efficiently (transdermal delivery) - treating a barrier damaged by skin disease or infection (antibiotics, steriods) - restoring the physical characteristics of a barier adversely affected by the environment (emollient / moisturuser)

Answer 54

1. stratum germinativum = resting upon the basal lamina. Cells undergo mitosis - replacement of shed epidermis 2. Stratum spinosum = as prickles or spines extending from the surface of the cell. No mitosis but metabolically active. Spines link via intercellular bridges - improved structural rigidity and resistance to abrasion 3. Stratum granulosum = granular cells with granules of keratatohyalin, a precursor of keratin 4. Stratum lucidum = not always present/observed. Cells are elongated, translucent, lacking cytoplasmic organelles. 4.

Answer 55

- outermost layer of the skin (in contact to environment) - Stratified epithelium, consisting of five distinct layers.

Answer 56

when you apply a product to the skin with the intent for it to be systemically absorbed, for a whole body delivery. Whereas, topical is application to the skin with the effect of a local outcome, ie no systemic absorption = local effect

Answer 57

Approximately 2m2 and 1/3 the blood

Answer 58

Type 1 (high resistance, least reactive, high cost) to type 4 (low resistance, most reactive lower cost_

Answer 59

1. compliance aid - blister packs, help patients remember to take their medication 2. Specialised packing for specific populations - eg arthritis friendly caps for easy opening 3. Portability - slim packing to fit in pocket 4. Dosage control - eg metred dose inhaler / insulin pens

Answer 60

- clear labelling is important for patients - key information needed eg dosing and warnings - marketing and brand recognition

Answer 61

- preservation against microbiological contamination (sterile packaging + air tight seals) - particularly important in injection (IV)

Answer 62

- temperature control (increased temp increases rate of reactions) - moisture control (hydrolysis + supports growth of microorganisms + dilution of product) - light (photodegradation - especially UV light) - atmospheric gases (mainly carbon dioxide + oxygen (oxidation reactions))

Answer 63

primary packaging - vials, ampoules, bottles, jars - widely used for liquids, semi solids and solids

Answer 64

Advantage: - easy to mould - cheap - easy to sterilise - impermeable to gas and moisture disadvantages: - fragile (easily broken) - heavy (transport costs)

Answer 65

1. soda glass (mostly silica - 72%) - reduced temperature needed to produce - improved mechanical strength and chemical durability - adds some amount of alkali to the water solutions (disadvantage) 2. Amber glass - similar to soda glass but iron oxide added - this gives colour which provides block to UV light absorption 3. Borosilicate - overcomes defects of soda glass by decreasing alkali - boric acid is very temperature resistant - very expensive to make (disadvantage)

Answer 66

Resistance to the release of soluble mineral substances into water under prescribed conditions of contact

Answer 67

collection of different components which surround the pharmaceutical product from the time of its production to its use.

Answer 68

- the packaging materials that are directly in contact with the product eg blister packs / strip foil packaging - it should not interact physically or chemically with the product

Answer 69

- pack component with no physical contact - usually made by paper or card - useful to contain information and labelling

Answer 70

- further packaging that surrounds the secondary packaging - useful for logistics and supply chain management

Answer 71

1. Protection and containment 2. Preservation 3. Presentation and information 4. Compliance

Answer 72

MHRA, underpinned by the human medicines regulations 2012

Answer 73

• Can withstand repeated thermal cycles to soften/melt/mould • Formed by techniques including injection moulding, blow moulding, extrusion, lamination • Usually resistant to breakage • Cheap to produce and therefore used more often than thermosets

Answer 74

• Foil for blister packs • Excellent barrier properties and can totally exclude moisture, oxygen/other gases, microorganisms, and light • This can help to maintain degradable products in peak condition for long periods • The manufacturing processes mean that the foil is sterile when formed • Other advantages: • Can be printed on • Flexibl

Answer 75

Leaching of DEHP from PVC bags (plasticising agent) - Plasticised PVC is used for IV and blood bags and infusion tubing, enteral and parenteral nutrition feeding bags, and tubing used in cardiopulmonary bypass devices - DEHP has been detected in liquids stored in plasticised PVC - DEHP has shown a wide range of toxic effects on the male neonate reproductive system development, as well as on lungs, heart and kidneys, and it has been classified as possibly carcinogenic by The International Agency for Research on Cancer

Answer 76

- Plasticised PVC: The addition of a plasticise Disadvantages • Lowers strength • Lowers melting point • Decreases barrier properties • Leaching of DEHP associated with health concerns • Not easily recyclable Uses • Widely used for tubing, infusion bags and other similar medical devices

Answer 77

- properties are relates to high and low density forms - this is the most common and economical packaging plastic 1. Increased density: • Greater rigidity • Higher distortion and melting temperatures • Lower gas and vapour permeability • Increased tendency to crack 2. Low density • LDPE is used for flexible packs e.g. bags, dropper bottles

Answer 78

• Similar to PE, except every fourth H is replaced by a methyl (CH3) group • Suitable for rigid packs • Good resistance to most chemicals, except organic solvents • Similar barrier properties to HDPE • Better resistance to higher temperatures than HDPE, therefore more suitable for steam sterilisation • More brittle at lower temperatures than PE

Answer 79

• Gas molecules can diffuse through plastics • Different plastics have different gas permeabilities, with lower density plastics showing greater gas permeability • The addition of fillers (inert clays or fibres) can reduce permeability by lengthening the route of diffusion

Answer 80

• Used to produce air-tight closures for bottles, cap liners, and bulbs for dropper assemblies • Used in multi-dose vials and disposable syringes • Natural rubber, and neoprene and butyl/nitrile rubber (synthetic rubbers) are most common • Problems have been observed when rubber is in contact with parenteral solutions

Answer 81

often where glass has disadvantages, plastics have the opposite advantages 1. Advantages • Good mechanical properties, even in thin-walled containers • Less brittle than glass • Relatively lightweight = reduced transport costs • Readily mouldable into various geometries • Suitable for containers and closures 2. Disadvantages • Majority will not withstand significant heat without distortion • Permeable to water vapour and atmospheric gases • May interact with certain chemicals in a manner that alters material properties • May absorb substances from solution • May release substances into solution • e.g. unpolymerised monomers or residues used in their processing

Answer 82

• Rapid adsorption of the API onto the plastic surface, followed by partitioning into the plastic • Adsorption is an extremely rapid process whereas the rate of absorption is thought to be much slower • Rate determining step is therefore the diffusion of API into the plastic matrix • The loss of API from solutions stored in infusion bags is driven principally by the ability of the drug to diffuse into the plastic • Net effect: Loss of drug into packaging = loss of potency of product - drug adsorption onto plastic surface = fast - diffusion across plastic = slower (rate limiting step) = Lower concentration of API in solution therefore suboptimal dose

Answer 83

- they have a single processing window, and cannot be reshaped after curing - they are harder and tougher than thermoplastics - mostly used for rigid screw caps as cost limits their use example is plastic used for plug sockets

Answer 84

• Clear/colourless • Good chemical resistance • Good barrier to moisture/gases • Low impact resistance • Use is diverse: bottles and blister packs

Answer 85

1. Surface area of the material available for absorption 2. Initial concentration of the API in solution 3. Diffusivity of the API into the PVC plastic 4. Partition coefficient (P) of API between the aqueous solution and the plastic material 5. The pH of the solution, which influences API ionisation

Answer 86

- thermosetting - thermoplastic

Answer 87

• Drug can be adsorbed onto or absorbed into the packaging material • This can compromise its barrier properties and/or reduce product potency

Answer 88

• Compounds that can be extracted from a packaging material under extreme conditions • e.g. exposure to solvent or elevated temperature

Answer 89

• Compounds that can leach passively into the drug product formulation from the packaging material as a result of contact under normal conditions

Answer 90

Coni-Snap® • Tapered rim to aid closure • Air vents allow air to escape • Six dimples to provide pre-lock • Closely-matched locking rings Dbcaps® • Larger diameter, shorter length • The cap covers most of the body; impossible to hold the body and open without crushing it • Provides increased security of the contents

Answer 91

measurement of gel rigidity (used to characterise the grade of gelatin) Defined as: The load/weight in grams required to push a plunger with a set bottom diameter (12.7 mm) a set distance (4 mm) into a 6.67% w/w gelatin gel that is prepared in water and allowed to mature at 10 °C for 16-18 h” high bloom strength = harder material and more viscous in solution

Answer 92

1. dependent - • e.g. the auger system - Dosing systems that use the capsule body directly to measure the powder weight 2. Independent - e.g. the dosator system - Powder is measured independently of the body - Weight uniformity is not dependent on filling the body completely - Capsules can be part filled

Answer 93

1. Gelatin band sealing • A dilute solution of gelatin and colour pigment is applied to the centre of the capsule to hermetically seal it; this prevents leakage, contains odour, and reduces oxygen permeation 2. Hydroalcoholic solvent seal • 50:50 water/ethanol mixture is sprayed onto the joint between the cap and the body; excess is removed by suction • Capillary action draws the fluid into the joint and the presence of water softens the gelatin • Gentle heating (45°C) fuses the two layers fuse together, forming a sea

Answer 94

1. hard capsules - two piece system consisting of a cap and body - locking device - most common 2. Soft capsules - one piece system eg docusate

Answer 95

- some tablets are very difficult to make as they can change polymorphic form after being compressed. - patient preference (easier to swallow) - suitable for drugs that need additional protection - combination therapies and biphasic release - masks taste and odour

Answer 96

• Non-toxic & widely used in foodstuffs • Readily soluble in biological fluids at body temperature • Good film former (strong & flexible) • Concentrated (40%, w/w) aqueous solutions of gelatin are mobile liquids above 45 °C • This is extremely important during manufacture • Undergoes a solution-to-gel transition when cooled down

Answer 97

Particles with the same size have less tendency to separate in capsules where they could be spun or moved around.

Answer 98

1. Improved drug absorption: Reduction in variability for poorly soluble drugs 2. Patient compliance: Easy to swallow, taste-free 3. Safety of potent and cytotoxic drugs: Avoids dust, better operator safety 4. Oils and low melting point drugs: Overcomes problems that these drugs have as tablets 5. Dose uniformity for potent drugs: Liquid flow has higher precision than powder flow Liquids have better homogeneity than powder or granule mixtures 6. Product stability: protected from water and oxygen

Answer 99

• Dyes are defined as intensely coloured organic substances that impart colour to a substrate by selective absorption of light • Dyes are used in their water soluble form

Answer 100

Mode of action: Interferes with cell membrane function, nucleic acid synthesis, and enzyme activity

Answer 101

• Work by scattering light due to a high refractive index • Titanium dioxide is used extensively as an opacifying agent • Protects from light and conceals the capsule content

Answer 102

• Includes a capsule that is coated with a semipermeable membrane • Allows water in but doesn’t allow drug out • The capsule contains a layer of osmotically active agent (push layer) and the drug formulation(s) layer(s) • Following ingestion, water is drawn into the push layer • This expands gradually, pushing drug out of the capsule • This system releases drug over a prolonged time, maintaining a more stable drug concentration in the blood

Answer 103

• Pigments are defined as coloured particulate organic or inorganic solids which are usually insoluble in the substrate • They alter appearance by selective absorption and/or scattering of ligh

Answer 104

• Includes an insoluble capsule body and a swellable/degradable plug, typically made of a hydrophilic polymer or lipid • The lag time is controlled by the plug, which is pushed away by swelling or erosion, allowing a pulse of drug release from the insoluble capsule

Answer 105

Mode of action: Antioxidant to prevent oxidative spoilage and is toxic to bacteria and fungi

Answer 106

1. Piston filling • Volumetric dosing device • Prevention of leakage • Semi-solids are filled in the liquid state, where possible, either by heating for thermosoftening mixtures) or by stirring (for thixotropic mixtures) • After filling, these revert to the solid state 2. The effect of viscosity • The viscosity of the fluid affects the variability of the fill volume • Low viscosity: loss of liquid due to splashing from capsule during filling • High viscosity: difficult to pump and problems in transfer from nozzle to capsule body

Answer 107

• Powder flow problems avoided • Avoidance of airborne particles • Improved fill weight accuracy • Convenient for formulations with a low melting point (e.g. oils) • Can improve solubility and absorption • Low dose/high potency drugs

Answer 108

1. thermosoftening mixtures - filled in the molten state, when they can be pumped and filled , and subsequently solidify 2. Thixotropic mixtures - Thin upon shearing by mixing (low viscosity) - Form hard masses upon standing when shearing ceases (high viscosity) - Filled as fluids and semisolid during storage 3. Pastes

Answer 109

1. Water-miscible liquids Some PEGs/poloxamers • Vehicle dissolves/disperses readily in the GI fluids, liberating the drug either as a solution or fine dispersion • Depending upon aqueous solubility, this can aid rapid absorption 2. Water-immiscible liquids Lipophilic liquids, castor, olive, & sunflower oil • Release is followed by dispersion in the GI fluids • Drug may be present as an emulsion, fine suspension, or nano-emulsion • Well formulated systems to improve drug solubility will ensure that the drug does not precipitate in GI fluids

Answer 110

The equilibrium moisture content refers to the amount of moisture that the capsule material will hold when it is in balance with the surrounding environmen. Moisture content too high: Capsule shell softens Moisture content too low: Capsule shell becomes brittle and can fracture Hygroscopicity is the ability of a substance to absorb moisture from its surroundings High levels of hygroscopic excipients must be avoided

Answer 111

• Temperature: Controls heat available for capsule seal formation • Timing: The timing of the dosing unit quantifies liquid fill matrix into the softgel • Pressure: The pressure exerted between the two rotary dies controls the softgel shape and final cut from the gel ribbon

Answer 112

1. swelling - The disintegrants are hydrophilic non-soluble polymers with affinity to water. During uptake of water the polymer will swell to a degree depending on particle size, degree of cross-linking etc. 2. Wicking - effect of drawing water into a tablet 3. Recovery of energy of elastic deformation from compaction of the tablet - During tableting, particles may undergo elastic deformation but become interlocked before they can relax. As water penetrates the tablet matrix, these particles can relax and regain at least partially their original shape, thus forcing other particles away 4. Repulsion (mainly for starch) - particels in water diapers in such a way that they repel each other 5. Heat of wetting - The energy released during interaction with water heats up air entrapped in the tablet, which then expands 6. Interruption of bonding forces - During tabletting the particles interlock forming new bonds. These are interrupted when water is present thus releasing the particles

Answer 113

- inert (except foe their intended characteristics) - be physiologically harmless - have comparable physical and chemical characteristics between batches - comply with certain microbiological standards depending on the administration route.

Answer 114

1. The traditional disintegrants • Native starches • Alginic acid • Ion exchange resins 2. The superdisintegrants • Sodium starch glycolate • Croscarmellose sodium • Crospovidone

Answer 115

• Disintegrant: Any solid, pharmaceutically acceptable material included in the formulation that acts to cause the tablet matrix to break up when the tablet comes into contact with aqueous media.

Answer 116

- they are employed to increase the mass of tablet, making manufacture more reliable and reproducible. - they must have good compression properties and be inexpensive

Answer 117

- Overmixing may impact disintegration and dissolution. - Mixing of disintegrant with lubricant should be avoided as it leads to formation of film on the surface of disintegrate reducing wettability. - Efficacy is increased if particle size is reduced

Answer 118

protect the drug from the acidic environment in the stomach - enteric coating = gastro resistant

Answer 119

conventional compressed tablets - designed to provide rapid disintigration multiple compressed tablets - Prepared by subjecting the fill material to more than a single compression - Each layer may contain a different medicinal agent, separate for reasons of chemical or physical incompatibility, staged drug release or simply for the unique appearance of the layered table

Answer 120

because it is a effervescence reaction - instead of a disintegrate, we need to use a carbonate salt eg citric acid and sodium bicarbonate.

Answer 121

See photo from 24th January for answers

Answer 122

3. Coating composition - plasticisers (added to coating to modify the physical properties of the polymer) - colourants (water soluble pigments) - solvent (to dissolve, disperse and convey the polymers and other additives)

Answer 123

2. Coating process - coating equipment - parameters of coating process - spray application systems - automation coating process

Answer 124

1. Tablet properties - tablet hardness (not less than 80N) - tablet friability (aim for 0.1%) - tablet core shape (as close to sphere as possible) - tablet porosity (increases force of attraction between coating) - Ingredients (do they interact with the coating)

Answer 125

- protection from light / moisture - protection from GI - taste masking - appearance masking - release profile

Answer 126

Q value (%) = (mass of active substance released at given timepoint / total mass of active substance) x 100

Answer 127

- it is the assessment of the time taken for solid dosage forms to break down into smaller particles or granules It is important as: • Disintegration is an important pre-requisite to dissolution • It is vital for release of active ingredients • Quality control of disintegration is important to ensure tablets will break down in a predictable and timely manner • Ensures dosage forms will break down at the appropriate site within the body, e.g., gastro-resistant tablets

Answer 128

• A measurement of the rate and extent at which the active substance is release from a solid dosage form into solution

Answer 129

Friability is a measure of the physical resistance of the tablet to abrasion and breakage during production, packaging, transport, and handling before usage it is important: ensure tablets are durable enough to withstand the rigours of manufacturing, packaging, and handling without crumbling or breaking apar

Answer 130

• The force required to break the tablet (tablet breaking force) - why is it important? - An extremely hard tablet could indicate excessive bonding potential between active ingredients and excipients, which can prevent proper dissolution of the tablet needed for an accurate dosage - A softer tablet could be a result of weak bonding and may lead to premature disintegration when ingested by the patient - Patient acceptability and compliance

Answer 131

• The test for uniformity of content is based on the assay of the individual contents of active substance(s) • It is determined for a number of single-dose units to determine whether the individual contents are within limits set with reference to the average content of the sample - it is important as it is critical to know how much of the active substance is in each dosage unit

Answer 132

- it is ensuring each dosage form is consistent in weight - it is important that we do this as uniformity off mass is linked to the dosage the patients receive

Answer 133

➡ Solubility = choice of salt in the formulation, ➡ Osmolarity = products may be tolerated over a fairly wide range of tonicity. ➡ Vehicle Viscosity = increase in vehicle viscosity = the residence time in the eye ➡ Stabilisers = drugs that are prone to degradation need these ➡ Antimicrobial Preservatives = for sterility

Answer 134

๏ Eye ointments are sterile semi-solid preparations intended for application to the conjunctiva. ๏ Increased contact time & better bioavailability compared to solutions. ๏ Night-time application, ๏ Poor patients compliance - often cause blurred vision.

Answer 135

<10% (typically 1%)

Answer 136

advantage - high solution concentration can be achieved - good dose uniformity and better bioavailability - easy to manufacture disadvantage - rapidly drained from the eye (makes you blink more)

Answer 137

Advantage - ease of administration, - improved patient compliance

Answer 138

1. hard lens 2. Semi hard 3. Soft lens 4. Soft continuous wear lens

Answer 139

- conjunctiva = microvilli layer - cornea = tight junctions - sclera - tear production/blinking - protein binding

Answer 140

For most topically applied drugs, 1. Passive diffusion along the concentration gradient, either transcellularly or paracellularly, is the main permeation mechanism across the cornea. 2. Carrier-mediated active transport mechanism is also indicated. LIPOPHILIC DRUGS TEND TO FAVOUR THE TRANSCELLULAR ROUTE HYDROPHILIC DRUGS TEND TO FAVOUR THE PARACELLULAR ROUTE - therefore drugs that have both lipophilic and hydrophilic properties tend to permeate most effectively - logP = 2/3 fot corneal permeation

Answer 141

- Topical administration - Systemic (parenteral) administration - Oral administration - Periocular & intravitreal administration

Answer 142

- unionised form usually permeates the lipid membranes more easily than the ionised form - corneal epithelium is negatively charged - charged cationic drugs permeate more easily through the cornea than anionic drugs do - molecular size <500 daltons

Answer 143

Aqueous or oily suspension eye-drop formulations may be considered for drugs that are poorly water soluble, or because of poor aqueous drug stability Prolong the residence time of drug particles in the eye, allowing time for dissolution in the tears and an increase in ocular bioavailability

Answer 144

as the g/ml (2.5/100) is much higher than the solubility of of ampicillin means we have a suspension. Therefore, the amount of ampicillin in solution is always constant. And because the OH- is buffered (remained constant) therefore it is a pseudo 0 order reaction

Answer 145

as the solution is buffered, this means that the concentration of OH- is kept constant, hence the only thing that is “changing” is the ampicillin. Hence it is pseudo 1st order

Answer 146

Apparent Therefore pseudo order reaction = apparent order reaction

Answer 147

Chemically speaking, the equation is first order with respect to sucrose, H20 and H30+. So we add these up to get a reaction rate of 3. This can be considered psuedo first order because the sucrose is dissolved in H20, hence the H20 can always be in excess. Also because we have equal amounts of H30+ on each side then we can essentially forget about it. Hence, the reaction is pseudo with respect to sucrose

Answer 148

- specific acid catalysis = straight line with slope of -1 - specific base catalysis = straight line with slope of +1

Answer 149

- formulate it at close to neutral pH

Answer 150

design drug assay, changing ph values over range, measure drug concentraion at time points, get log K and plot log K vs Ph. If its -1 it is acid specific and +1 is base specific.

Answer 151

when the rate law for the degradation of a drug contains a term involving either [H+] or [OH-], the reaction is subject to acid-base catalysis.

Answer 152

k = kH[H+] + kOH[OH-] + k0 Where k is the apparent 1st order rate constant, kH is the specific acid rate constant and KOH is the specific base rate constant, k0 represents the rate constant for the pH independent reaction, ie catalysis by the solvent (usually water)

Answer 153

Basic units are the curie and the becquerel

Answer 154

roentgen: a unit for measuring the amount of gamma radiation rad: a unit for measuring the absorbed energy from radiation rem: a unit for measuring biological damage from radiation

Answer 155

this is often a secondary process that occurs after initial decay of B emissions, each isotope emits y rays of a distinct energy. This can be measured for identification of the isotope. - they will get back to the ground state by emitting energy, which will release a package of energy as discrete photon energy

Answer 156

1. electron formed by B- decay 2. positron formed by B+ decay - these are the most commonly used radioisotopes in biochemistry - emitted in a range of energies form a given isotope (energy is characteristic of an isotope) - The anti neutrino is an almost massless particle that carries away some of the energy from the decay process - These particles can travel 15 to 1600 cm in air - They can be stopped by low atomic number materials, such as plastics - Particles emitted from tritium sources have insufficient energy to penetrate outer dead layer of skin

Answer 157

1. Emitted particle is a nucleus of helium eg 2 neutrons and 2 protons It is: • heavy • slow moving • densely ionising • causes considerable biological damage • unsuitable for tracer work • travels a few cm in air and can be stopped by paper

Answer 158

1. Radioactivity - - results from spontaneous nuclear disintegration arises from unstable isotopes. 2. Nuclear stability - depends on the ratio of neutrons to protons - gives rise to spontaneous decay with emission of particles.

Answer 159

= ((observed cpm - background cpm) / actual dpm) x 100

Answer 160

The gray describes amount of energy transferred by radiation to an object An absorbed dose of 1 gray is equal to the absorption of 1 joule of radiation energy by 1 kilogram of matter.

Answer 161

The sievert is the correct unit to use when you wish to monitor the biological danger of radiation the difference between the rem and the sievert is a proportionality factor: 100 rem equal 1 sievert.

Answer 162

Spontaneous disintegration is a first-order process.

Answer 163

99mTc-methylene diphosphonate (MDP) Bone Scan • Detects lesions long before skeletal x-ray • Fast blood clearance • High skeletal affinity

Answer 164

the RP emits gamma radiation: - Detected by a gamma camera or SPECT (single-photon emission computed tomography) - Important that the energy of the decaying gamma ray photon is within the specific energy window of the camera (generally 100-250 keV) - Gamma decay energies outside of this range may produce low-quality images

Answer 165

• Positron decay results in the emission of two 511 keV gamma ray photons 180oC apart • Detected by a PET camera • PET scanners contain a circular array of detectors designed to specifically detect the 511 keV photons emitted in opposite directions

Answer 166

• Water-soluble radiopharmaceuticals are excluded from normal brain due to intact BBB • To screen patients for the presence of primary tumours • To detect cerebral metastases • To evaluate patients with cerebrovascular disease • To detect intracranial injury • To study patients with intracranial disease

Answer 167

• To image solitary or multiple thyroid nodules • To assess thyroid size and function • Aid in the management of thyroid cancer • Typically radioactive iodine- based (usually oral 123I NaI)

Answer 168

• Active transport • Simple diffusion • Capillary blockade • Phagocytosis

Answer 169

• Minimum half-life • Mode of decay • Cost and availability • Physical properties • Organ/tissue specificity

Answer 170

2-[18F]fluoro-2-deoxyglucose (FDG) • Rapidly distributes to all organs of the body • PET images yield apparent data on glucose utilisation and hence metabolic activity o Distinguish viable, but functionally impaired, ischemic myocardium from nonviable (infarcted) myocardium o Indicated for neurological and psychiatric disorders, especially associated with foci of epileptic seizures o Can also differentiate benign from malignant tissue

Answer 171

Should be: • Long enough to carry out the desired chemistry to synthesise the radiopharmaceutical • Long enough to accumulate in the target tissue while clearing non-target organs - it must minimise radiation dose to the patient - it must range from 2 mins to several days

Answer 172

Primarily directed against cancerous tissues utilising “the concept of tissue radiosensitivity” i.e. rapidly dividing cells are more radiosensitive

Answer 173

- myocardial ischemia = TI chroride / TI isonitriles - myocardial necrosis = In antimyosin / Tc glucarate - myocardial inflammation = ln leukocytes

Answer 174

1. antigens added to bloodstream (vaccine) 2. Antigen presenting cells capture / ingest antigen, displaying pieces of it on its surface 3. These activate T helper cells, which trigger killer T cells and B cells 4. These cells then target the antigen 5. Therefore if the antigen is presented again then there is memory killer T cells and memory b cells

Answer 175

1. Conjugate vaccines • Made using the polysaccharides, or sugars, that form the outer coating of many bacteria 2. Toxoid vaccines • Made using inactivated version of bacteria releasing toxins 3. Recombinant protein vaccines • made using bacterial or yeast cells to manufacture the vaccine

Answer 176

- whole pathogen vaccines (• Live attenuated (weakned ) / • Inactivated) - sub unit vaccines - nucleic acid vaccines - viral vectores vaccines

Answer 177

• Obtained from live pathogenic organisms • Pathogenic organisms are treated to become attenuated (or weakened) – lose capacity to induce full-blown disease but retain immunogenicity • Pathogenic organism is attenuated by introducing it into a species in which it does not replicate well or forcing it to replicate repeatedly in tissue culture • Activates T-killer cells

Answer 178

• Unlike other vaccines, these vaccines do not supply the protein antigen to the body • Provide the genetic material (DNA or RNA) of specific antigens to develop immunity • Nucleic Acid Vaccines include: DNA and RNA Vaccines eg covid vaccine was RNA

Answer 179

• One or more antigenic fragments of the pathogen (e.g. proteins, polysaccharides, capsid) are used to stimulate the immune response • Antigens may be obtained through recombinant protein expression, production in yeast cells or bacteria or extraction from infected cells • Generally require addition of an adjuvant

Answer 180

• A vaccine is a biological preparation • Typically contains weakened or inactive parts of a particular disease-causing pathogen

Answer 181

• Like nucleic acid vaccines, these vaccines do not supply the protein antigen to the body • Provide the genetic material (DNA or RNA) of the antigen to host cells using a safe virus • In turn, the cells produce the antigen which stimulates an immune response • Viral vectored vaccines include: Replicating and non-replicating vaccines

Answer 182

• Refers to indirect protection of a community of people from a disease by immunising a critical proportion of that population

Answer 183

innate: • First line of defense • Responds quickly to invaders adaptive: • It has been ‘educated’ • Second line of defense • Slower response

Answer 184

• Term that describes how contagious/transmissible an infection disease is • R0 = Basic Reproduction Number • Average number of secondary cases arising from a primary infection case in an entirely susceptible population How many people does one infected person averagely infect?

Answer 185

Sterile water

Answer 186

• Identify the correct site for IM injection • Stretch the skin at the site • Insert the needle at a 90° angle • Depress the plunger • Gently remove the needle • Apply light pressure if bleeding occurs

Answer 187

- antigen - adjuvants - preservatives - stabiliser - surfactants - residuals - diluent

Answer 188

1. Phase 1 - Tested on a small number of healthy volunteers - assesses safety - determines the right dosage 2. Phase 2 - Tested on several hundred volunteers - Volunteers in this phase have the same characteristics (age, sex) as the people for whom the vaccine is intended. - assesses safety - determines correct dosage - confirms vaccine generates an immune response 3. Phase 3 - Tested on thousands of volunteers - determines efficiency of vaccine - assesses safety in large group

Answer 189

describes the recommended cold temperature conditions for a vaccine according to the manufacture during transport and storage until the point of administration • Vaccines must be kept in the cold chain from the manufacturer to some of the most remote places on earth • Vaccines are highly susceptible to environmental factors

Answer 190

- Improves the immune response to the vaccine - Examples of adjuvants: Aluminium salts (like aluminium phosphate, aluminium hydroxide or potassium aluminium sulphate)

Answer 191

- Active component or contains ‘blueprint’ to make the active component - Generates immune response

Answer 192

- Dilute a vaccine to the correct concentration immediately prior to use

Answer 193

- Prevent the vaccine from becoming contaminated once the vial has been opened - Not all vaccines contain preservatives (not needed)

Answer 194

- Tiny amounts of various substances used during manufacturing or production of vaccines

Answer 195

- Prevent chemical reactions from occurring within the vaccine - Keep the vaccine components from sticking to the vaccine vial

Answer 196

- Keep all the ingredients in the vaccine blended together - Prevent settling and clumping of elements that are in the liquid form of the vaccine

Answer 197

• Injected into the deltoid muscle in the upper arm (2 fingers down) • If insufficient muscle mass in the area of the deltoid or a particular reason the deltoid muscle is otherwise unsuitable, vaccine should be injected into the vastus lateralis muscle in the anterolateral aspect of the thigh

Answer 198

grade a = the local zone for high risk operations. These conditions are provided by laminar air flow: providing a homogeneous air speed of 0.45m/s +- 20% at the working station. grade b = this provides the background environment for grade A zone items needing aseptic preparation and filling grade c/d = areas graded C and D are used for performing less critical tasks that are carried out during less critical stages in the manufacturing process.

Answer 199

(most popular) - start with an unrealistic bioburden, find out a D value form this (usually spores of thermophile) - then complete for a total of 12 D values, which will kill all ‘normal bacteria”

Answer 200

- sterility is an absolute concept (either sterile or not) - it is The likelihood of a product being sterile (free from microorganisms) can be expressed in terms of the probability of a microorganism surviving the treatment process. - this gives rise to the concept of Sterility Assurance Level (SAL)

Answer 201

- (N0) initial level of contamination (the bioburden) - k - the rate of kill, which is dependent on the temperature and the thermal resistance of the organism

Answer 202

- Stage 1 –PROCESS DESIGN: The commercial process is defined during this stage based on knowledge gained through development and scale-up activities. - Stage 2 – PRCESS QUALIFICATION: During this stage, the process design is confirmed as being capable of reproducible commercial manufacturing. - Stage 3 –CONTINUED PROCESS VERIFICATION: Ongoing assurance is gained during routine production that the process remains in a state of control.

Answer 203

• Stage 1 – Process Design: The commercial process is defined during this stage based on knowledge gained through development and scale-up activities. • Stage 2 – Process Qualification: During this stage, the process design is confirmed as being capable of reproducible commercial manufacturing. • Stage 3 – Continued Process Verification: Ongoing assurance is gained during routine production that the process remains in a state of control.

Answer 204

- personell - process - environment

Answer 205

- knowledge of the lethality of the chosen sterilization process (D value)

Answer 206

• Lethality of the process • Effects of changing sterilization conditions

Answer 207

when a gas at its phase boundary temperature interacts with a colder object, it undergoes phase transition (think of a kettle gaseous water hits cold air around it and recondneses = steam)

Answer 208

this is hidden heat - we don’t see a temperature increase despite adding heat (eg water @100C - can keep using a bunsen burner but temp won’t rise)

Answer 209

Parametric release is a system of release that gives the assurance that the product is of the intended quality based on information collected during the manufacturing process. - based on evidence of successful validation of the manufacturing process

Answer 210

process validation is defined as the collection and evaluation of data, from the process design stage throughout production, which establishes scientific evidence that a process is capable of consistently delivering quality products. Process validation is a requirement of current Good Manufacturing Practices

Answer 211

is the amount of heat that, when added or removed from a substance, causes a change in its temperature but does not cause a phase change (eg raising water from 40C to 60C)

Answer 212

time (mins) taken to reduce the population size by 90%

Answer 213

the degree of assurance with which the process in question renders the population of items sterile

Answer 214

increase in temperature required to reduce the D value for an organism by 90% reduction

Answer 215

time required to kill a population of the target microorganism at a given temperature

Answer 216

Parametric release can only be applied to products terminally sterilised in their final containers

Answer 217

- F is defined as the equivalent time at temperature (T) is delivered to a container or unit of product for the purpose of sterilization. - Permits comparison of lethal effects of heating at any temperature to prescribed conditions (121oC)

Answer 218

- cutting methods - compression methods - impact methods - combination impact and attrition

Answer 219

• Sample forced to pass through a very small gap at high pressures (500-2500 bar) • Impact and attrition lead to micro/nanonisation • The sample can recirculate to the homogenisation chamber

Answer 220

• Small beads (0.1 – 5 mm) are the milling media • Impact and attrition lead to micro/nanonisation • The sample recirculates to the milling chamber

Answer 221

• Consists of a series of knives attached to a horizontal rotor • Knives act against a series of stationary knives attached to the mill casing. • Size reduction occurs by fracture of particles between the two sets of knives, which have a clearance of a few millimetres. • A screen is fitted in the base of the mill casing; thus it is self-classifying.

Answer 222

• Consists of a series of knives attached to a horizontal rotor • Size reduction occurs by fracture of particles between the two sets of knives, which have a clearance of a few millimetres.

Answer 223

steps involved are: • Mixing of excipients and drug (planetary bowl/rotating drum/high- speed) • Compression of powders into tablet

Answer 224

• Involves production and subsequent compression of granules into final dosage form • No solvent is required • Two principle methods 1. Slugging - double compression technique, mix drugs, form large tablet, mill, compress 2. Roller Compaction - mix drugs, compress powder between two rollers, mill the ribbon produced, compress into tablets

Answer 225

particles interact to form aggregates Two primary stages involved: - Particle-particle interactions facilitated by formation of liquid bridges - Particle-particle interactions facilitated by formation of solid bridges.

Answer 226

1. Electrostatic forces - Play a role in initial cohesive interactions but not so in granule strength. 2. Van der Waals interactions - major role and increase in magnitude as particle distance decreases 3. Melting of components - Granules exposed to high shear rates that may result in partial melting. Upon cooling (solidification) increased interactions between adjacent particles occur

Answer 227

- Increased dissolution rate - Increased saturation concentration - Enhanced bioadhesion

Answer 228

• Blending & Oscillating Granulator • High Speed Mixer/Granulator • Fluidised Bed Granulatior • Extrusion Granulator

Answer 229

• Improved Drug Dissolution • Uniformity of Dosage Forms • Enhanced Mixing and Homogenization • Tailoring Drug Release Profiles • Micro and Nanosizing • Reduced Agglomeration

Answer 230

powders need to have the same particle size, this is done via milling

Answer 231

• It allows the manipulation of physical properties of active pharmaceutical ingredients (APIs), and excipients. • By reducing particle size, milling enhances the dissolution rate, bioavailability, and overall performance of drugs in various dosage forms. • The primary objective is to reduce the size

Answer 232

helps the powder stick together during compression

Answer 233

ensures that when the powder is compressed into a tablet it doesn’t stick within the metal die

Answer 234

individual steps or processes involved in the manufacturing of pharmaceutical products.

Answer 235

Negative mixing occurs in a two-phase system where the phases differ in density and will separate unless continuously agitated. Example: Oil and water.

Answer 236

Neutral mixing occurs when neither mixing nor separation of the system occurs unless it is acted upon by a system of forces

Answer 237

Positive mixing applies to systems that given time, would spontaneously and completely mix. Example: Two gases or miscible liquids.

Answer 238

bringing particles together - Melt agglomeration obtained through addition of a solid binder that melts during the granulation processing (50-80°C) - Mechanism similar to granulation with liquid addition - No need for drying

Answer 239

- Small volume Parenterals (SVP) (100ml or less) - Large volume Parenterals (LVP) (up to 500ml)

Answer 240

- Local effects can be achieved where desirable – anesthesiology - Formulations can permit prolonged drug release profiles  Depot injections  Long-acting steroids  Long-acting penicillins by deep IM injection - Provides a means of correcting serious disturbances of fluid and electrolytes - When food cannot be swallowed or taken orally, total parenteral nutrition can be tailored to meet the individuals exact nutritional needs

Answer 241

- Clear, colourless and odourless (pH 5 - 7) - Purity specifications limit - Cl-, Ca2+, SO42-, NH3, CO2, heavy metals and oxidisible substances total amount of dissolved solids < 10 ppm - Must be used within 24h unless sterilised, sealed in ampoules or containers

Answer 242

- Requires aseptic technique - Skill of administration required - Pain on administration - Rapid development of allergic reactions in sensitive individuals - Difficult to reverse effects of drugs given parenterally, even immediately after administration - Inherent requirements (sterility, freedom from particulate matter & pyrogens, stability) requires understanding from all personnel who manufacture or administer the formulation

Answer 243

- Sterile - Non-pyrogenic - Free of Particulate Matter - Packaged as single dose containers

Answer 244

- Intrathecal, intracisternal and peridural (epidural) use (CSF injection) - Intracardiac or intraocular injections - Injections in which a single dose is greater than 15mL, unless the BP monograph specifically allows the presence of a preservative

Answer 245

When a non-volatile solute is dissolved in a solvent certain properties of the resultant solution are largely independent of the nature of the solute and are determined by the concentration of the solute. Most important one for pharmaceutical pot is osmotic pressure

Answer 246

- in a hypertonic solution (osmotic pressure greater than blood serum), water will pass out of the cell - the cell shrinks and the cell wall appears crenulated

Answer 247

- In a hypotonic solution (osmotic pressure less than blood serum), water will pass into the cell until equilibrium is established - the cell swells rapidly and bursts

Answer 248

Antimicrobial preservative agents serve to maintain sterility of the product during shelf life and use

Answer 249

a substance that induces fever - they are derived mainly from gram negative bacteria

Answer 250

- Solution where the osmotic pressure is the same as the blood serum - This is what all parenteral systems need to be

Answer 251

- drug injected into superficial layer of skin - absorption is slow - generally reserved for diagnostic tests - small volumes around 0.1 - 0.2mL

Answer 252

- Volume circa 2 mL (up to 5 mL gluteal administration) - Typical sites include the shoulder (deltoid), thigh and buttock (gluteal medials) - Very suitable for aqueous and oily solutions and suspensions which are irritant by the SC route - More rapid absorption than SC - can be modified by formulation type (oily liquid, suspension etc.)

Answer 253

- Large or small volumes (up to 500mL) can be administered to the veins for rapid effect - Formulations relatively simple - active drug, other ingredients (TPN components, preservatives etc.) and a solvent system (preferably aqueous) - Results are rapid and predictable but potentially dangerous (no retreat following administration) - Irritant drugs rapidly diluted in blood - Number & location of vein = accessibility

Answer 254

Simply the minimum pressure needed to prevent osmosis. - The force per unit area, or pressure, required to prevent the passage of water through a selectively permeable membrane and into a solution of greater concentration is equivalent to the osmotic pressure of the solution

Answer 255

- Drug injected into loose subcutaneous tissue beneath skin - Volume circa 1 mL - Usually administered in the upper arm or thigh - Popular route of administration (e.g. insulin) - More rapid onset of action than intradermal

Answer 256

enteral = administered via the gut Parenteral = administered by bypassing the gut

Answer 257

suspension = dispersion of drug in one continuous phase Emulsion = disperse systems in which one immiscible liquid is dispersed in the other

Answer 258

the effects are mainly due to - effect on the properties of the solid or liquid, e.g. molecular cohesion - effect of the substituent on its interaction with water molecules ie whether its hydrophobic or hydrophilic - hydrophobic will have better solubility

Answer 259

- acidic drugs are less soluble in acidic solution (over abundance of protons) - basic drugs are more soluble in acidic solutions (as it gains a proton) - For amphoteric drugs, it is observed that the zwitterion has the lowest solubility

Answer 260

• The relative low solubility of the para compound is due to the greater stability of its crystalline state • In the ortho state, intramolecular hydrogen bonding in aqueous solutions may occur, therefore decreasing the interaction of the OH group with water

Answer 261

• Modified starches • Glucopyranose units form a ring : 6 unit ring : 7 unit ring : 8 unit ring • The ring is cylindrical with a hydrophilic outer surface and a hydrophobic interior • Appropriately sized lipophilic molecules may be housed in the central portion

Answer 262

1. Vehicle = act as a solvent or carrier 2. Preservative = control microbial growth eg parabens 3. Sweetening agents = add flavour eg sucrose 4. Viscosity = optimise pour ability eg modification of conc of sugar or hydrophilic polymers 5. Flavours = salt, bitter, sweet, sour 6. Colours = provide colour

Answer 263

• Ease of administration compared with solid dosage forms • Increased rate of drug absorption from solutions • Taste of medicines may be effectively masked

Answer 264

- Difficult to formulate drugs that possess poor chemical stability - Difficult to formulate liquids for drugs that possess poor solubility (Specialist techniques may be required to enhance solubility) - Require specialist formulation strategies (Taste masking, Appearance, Viscosity)

Answer 265

drugs with a higher melting point will have poorer solubility than that of a drug with a lower melting point

Answer 266

a water miscible liquid that has less hydrophilic properties than water

Answer 267

• Salts with large anions or cations that are soluble in water may increase the solubility of non-electrolytes - Due to the dissolution of the solute in oriented clusters of the hydrotrope - Large concentrations of hydrotrope required (20-50%)

Answer 268

– Maximum solubility is achieved in a particular solvent systems at a defined dielectric constant – The dielectric constant is equal to the capacitance of the condenser filled with some reference material (Cx) divided by the standard (Co)

Answer 269

– Thermodynamic measure of the cohesive forces that exist in a substance – Maximum solubility is achieved whenever the solubility parameters of the solvent and solute are identical

Answer 270

they are far less toxic than ionic surfactants

Answer 271

– Why the preservative is included – Proof of its effectiveness – Methods and standards for its control in the product – Labelling details on the product – Relevant safety information

Answer 272

- preservation must be available in the aqueous phase - they need to be unionised (if they are ionised them they will cross the membrane of microorganism and therefore undergoing a dilution event = overall available amount of preservative available decreased.

Answer 273

Widely used as disinfectants and preservatives • 0.5% solution of phenol will kill most vegetative bacteria • Activity markedly diminished by dilution and presence of organic matter • Numerous incompatibilities • Odour, toxicity and volatility issues

Answer 274

- Partitioning into oil/aqueous or biophase - Ionic status & pH - Adsorption & Permeation to container & Closure - Temperature & Surfactant - Status in tablets, suspensions, gels, creams, nasal and eye drops - Physical or Chemical interaction with other formulation components - Microbial Challenge (dilution of the preservative as microorganisms take it in the overall concentration available reduces)

Answer 275

• Mixture of o-, m- and p-methylphenol • Poor solubility • 0.3 – 0.5% effective concentration ranges in suitable formulations • Similar activity range to phenol but less caustic and less poisonous • Activity not reduced in presence of organic matter

Answer 276

- Series of alkyl esters of p-hydroxybenzoicacid • Less readily ionised than parent acid • pKa values around 8.0 -8.5 • Exhibit good preservative activity even at pH 7-8 • Mixtures of esters to protect the various phases in a multiphase formulation

Answer 277

- The test may be conducted in either five original market containers or in five sterile, capped bacteriological containers into which a sufficient volume of the formulation has been transferred - Each container is inoculated with one of the prepared and standardised inoculum to give a final concentration of microorganisms in the test formulations of 10^5 – 10^6 cfu per mL or per g of the product, - mixed thoroughly to ensure homogeneous distribution of microorganims throughout the formulation - Incubate the inoculated containers at 22.5 +/-2.5C (USP)/20-25C protected from light (BP) and sample each container at appropriate intervals, over a maximum of 28 days, according to the type of product. - BP suggests 1 mL or 1 g sample sizes taken at the appropriate intervals, starting from zero hour - The number of viable organisms in each sample is determined by plate count (USP) or by plate count or membrane filtration (BP) - Any changes to the appearance of the product should also be recorded - its important to quench the reacrtion at the time points so that we dont get a better result than we actually did

Answer 278

• Lipophilic Unionised species diffuses across membrane • Encounter cytoplasmic pH near neutrality • Forced to Dissociate to charged ions • Charged ions cannot return across membrane – Anions concentrate in cytoplasm • Dissociation of acid derives proton • Cytoplasm acidification • Growth is Inhibited

Answer 279

• Inhibition of glycolysis • Inhibition of folic acid synthesis • Prevents Active Transport • Interference/ Inhibition of signal transduction

Answer 280

• Elegant (must look like how its meant to) • Efficacious • Stable • Safe All throughout their intended life

Answer 281

product water activity - In complex formulations, microorganisms must compete for water against other components of the formulation which interact with water - Certain products may be protected by manipulation of Aw (ready availability of water to contaminants), to values below those required for growth it can be lowered to give preservation effects by addition of water binding low molecular weight solutes

Answer 282

they completely wipe out any preservative

Answer 283

An objectionable organism is a microorganism that, if present in a product or manufacturing environment, poses a risk to product quality, safety, or compliance with regulatory standards.

Answer 284

Substances added to pharmaceutical formulations/medicines to prevent microbial spoilage, retard deterioration, and restrain organismic growth to low levels

Answer 285

it must demonstrate: – Adequate mixing of the inoculum with the product – Effectiveness of the inactivator or method used to neutralize preservative activity within the sample – Lack of microbiological toxicity of the inactivator which would interfere with the test data and; – Ability of the procedure to bring about the necessary reductions in viable count of the starting inoculum within the formulation/product.

Answer 286

by law they need to be added to any formulation which is to be used more than once from the same container

Answer 287

pH dictates the type of spoilage that occurs Eg • Low pH fruit juice-flavoured medicines inhibit bacterial growth but favour fungal growth • Higher pH anatacids etc. favour growth of pseudomonads

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