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mental > Pharm Tech > Flashcards

Pharm Tech Flashcards

1
Q

advantages of parenteral delivery

A

1) bypass first pass
2) control dosage (customisable)
3) sustained release
4) ideal for non-compliant, unconscious or dysphagic patient

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2
Q

disadvantages/barrier for parenteral delivery

A

1) IM, IV, SC need to cross BBB
2) problems with dilution and distribution
3) reticuloendothelial system: immune cells phagocytose drug
4) invasive
5) need trained medical professional
6) need sterility

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3
Q

blood to brain delivery - general

A
  • reticuloendothelial system (RES)
  • drug will distribute everywhere if no active targeting
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4
Q

blood to brain delivery - crossing BBB

A

1) paracellular, transcellular
2) active efflux transporters

  • remove drugs from organs (brain) into lumen (blood)
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5
Q

blood to brain delivery - crossing BBB - types of efflux transporters

A

1) carrier mediated transporters (CMT)

  • drug form complex w carrier at apical side (face outside) -> transported across membrane
  • drug diffuse through epithelial cell -> form another complex at basal side (face inside) -> enter brain interstitial fluid/CSF

2) receptor-mediated transporters (RMT)

  • drug bind to receptor -> internalised by membrane -> exocytosis into brain interstitial fluid/CSF
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6
Q

Lipinski’s rule of 5 for IV, IM, SC

A
  • weight < 500 Da
  • H bond donor ≤ 5
  • H bond acceptor ≤ 10
  • Log P < 5
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7
Q

Lipinski’s rule of 5 for CNS

A
  • weight < 450 Da
  • H bond donor < 3
  • H bond acceptor < 7
  • Log P: 1 - 3
  • unionised
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8
Q

ideal properties for parenteral

A
  • pH ideally 7.4, IM 3-11, SC 3-6
  • tonicity 280-290 mOsm/L, hypertonic > hypotonic
  • X visible particles
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9
Q

excipients list for parenteral

A

1) diluent/solvent

  • sesame oil (form depot in IM space)

2) buffer

  • sodium acetate, citrate, phosphates, lactate

3) buffer/pH adjuster

  • L-methionine (antioxidant)

4) preservatives

  • minimal for intrathecal cuz might inflamme brain
  • benzyl alcohol, chlorbutanol, methylparaben, propylparaben, phenol, thiomersal

5) tonicity adjusting agent + cryoprotectant

  • mannitol

6) tonicity adjusting agent

  • NaCl

7) solvent

  • ethanol, PEG, propylene glycol

8) solvent + tonicity adjusting agent

  • glycerin, glycerol, glycine

9) surfactant

  • polysorbate 20 and 80
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10
Q

types of packaging for parenteral drug

A

1) glass ampoules (scored for breakage)
2) glass vials w rubber stopper (for powder that need reconstitution, sterile water included w product)
3) pre-filled syringes

(all these need to withstand sterilisation process)

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11
Q

advantages of transdermal delivery

A

1) controlled release via reservoirs and duration of contact = decrease dosing frequency
2) no GI degradation/irritation
3) bypass hepatic first pass
4) easy termination of output
5) non-invasive

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12
Q

disadvantages and barriers of transdermal delivery

A

1) variability between people and location of administration
2) stratum corneum slow absorption
3) skin irritation
4) can be removed by patients
5) metabolic enzymes on skin
6) systemic SE
7) need to cross BBB

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13
Q

factors affecting transdermal delivery

A

1) skin condition

  • affected by age, disease, injury, site
  • can become dry, scaly, hydrophilic

2) skin thickness
3) hydration of skin

  • water occupy and swell intercellular space -> more plump -> increased transport

4) stimulation of skin

  • sound, ionisation, heat

5) physicochemical properties of drug
6) permeation enhancers

  • reversibly reduce barrier resistance of stratum corneum wo damaging viable cells

7) concentration gradient
8) area of contact between formulation and skin

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14
Q

ideal drug properties for transdermal

A

Lipinski rule of 5

  • weight < 500 Da
  • H bond donor ≤ 5
  • H bond acceptor ≤ 10
  • Log P 1 - 3
  • unionised
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15
Q

explanation of excipients for transdermal delivery

A

1) preservatives

  • patch exposed to pathogens in air once open packaging
  • patch placed on skin for long periods of time

2) solvent/co-solvent
3) viscosity modifier

  • determine how much drug released over time
  • more viscos = slower diffusion, release and absorption

4) permeation enhancer

  • interact with bilayer and improve absorption
  • placed on adhesive surface

5) adhesives

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16
Q

transdermal delivery excipients example list

A

1) cyclodextrin

  • permeation enhancer

2) glyceryl monooleate

  • ester w hydrophobic and hydrophilic region so can reduce membrane integrity
  • permeation enhancer, bio adhesive, sustained release agent

3) ethanol, propylene glycol

  • solvent, permeation enhancer

4) carboxymethylcellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose

  • viscosity modifier, matrix polymer

5) hyaluronate sodium

  • viscosity modifier, humectant, matrix polymer

6) calcium alginate

  • viscosity modifier, adhesive, matrix polymer

7) carbomer, poly(methyl vinyl ether/maleic anhydride)

  • viscosity modifier, adhesive

8) ascorbyl palmitate, silicon metabisulfite, DL-alpha-tocopherol

  • antioxidant

9) povidone, ethylene-vinyl acetate

  • polymer matrix

10) silicone adhesive
11) polyester backing layer

17
Q

factors affecting drug release from polymer matrix

A

1) drug diffusion coefficient
2) surface area
3) concentration
4) porosity/tortuosity of polymer matrix

  • polymer string -> intramolecular interactions (cross linking, H bonds) -> fold on itself -> create matrix
  • more tortuous (complicated) = more distant drug has to diffuse out of to access edge of patch = sustained release over time
18
Q

packaging and storage of transdermal delivery patche

A

1) patches sealed in individual pouches

  • plastic/polymer lining
  • aluminum lining protect API/excipients that are light sensitive

2) sealed packaging

  • maintain integrity of adhesive
  • maintain integrity of product
  • maintain hydration
19
Q

design of transdermal patches tldr

A

1) backing layer
2) drug containing portion
3) adhesive
4) liner

20
Q

design of transdermal patches - backing layer

A
  • protection of drugs and contents
  • water-impermeable polymer which prevent formulation and moisture from leaving
  • act as occlusive layer for drug formulation
21
Q

design of transdermal patches - drug containing portion

A
  • composition/chemistry, porosity/tortuosity determine release rate
  • types

1) membrane
** depot -> membrane -> adhesive
** drug released in separate depot
** rate-controlling membrane limit amount of drug released over time
** disadvantage: more bulky

2) matrix
** matrix -> adhesive
** drug incorporated in polymer matrix separate to adhesive layer

3) drug in adhesive matrix
** only adhesive, drug released directly from there
** multifunctional excipients useful
** advantages: lesser chemical interactions w other excipients, less obvious

22
Q

design of transdermal patches - adhesive

A
  • silicone, rubber, adhesives, adhesive enhancer
  • can put permeation enhancers
23
Q

design of transdermal patches - liner

A

protect adhesive

24
Q

special considerations for transdermal patches

A

1) release rate from patch

  • make sure drug released at constant rate over time
  • potential for leaching and extraction of drug into backing/other layer
  • make sure no interaction between drug and backing layer
  • temperature may increase rate of release -> overdose
  • crystallinity of drug over time -> affect drug solubility and diffusion -> affect release rate

2) strength of adhesion

  • between layers
  • influenced by sweat or hair

3) disposal

  • excess drug in patch after use -> need to dispose properly

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