Modification of surface prop for h.phobic drugs Flashcards

1
Q

why do we need to modify the surface properties of hydrophobic drugs?

A

because of its associated problems:

  • poor aq solubility
  • adhesion/ agglomeration
  • poor dissolution rate/ bioavailability
  • poor powder flow and poor drug content uniformity
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2
Q

what is the limiting step in the absorption of hydrophobic drugs?

A

In the absorption of hydrophobic drugs, the dissolution rate is the rate limiting step from Noyes-Whitney equation

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3
Q

what happens if you decrease aggregation of a hydrophobic drug?

A

the surface area increases, improves wetting and dissolution rate

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4
Q

why do we want to modify the surface properties of hydrophobic drugs?

A

to improve wetting, dissolution rate and hence bioavailability

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5
Q

what are the different techniques used to improve wetting, dissolution and bioavailability of poorly-water soluble drugs

A
  • solid dispersion formulations
    -surface adsorption of surfactants and polymers
    complexation
    particle size reduction
    alternative polymorphic form
    interactive powder mix
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6
Q

what is solid dispersions?

A

the incorporation of poorly-water soluble drugs in inert water soluble carriers

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7
Q

what is the aim of solid dispersion?

A

Is to alter the crystallinity of the drug in an attempt to enhance: dissolution ratein vivo absorptionsolubility wettability

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8
Q

when is solid dispersion mostly used?

A

is used as a way for improving the bioavailability of poorly water soluble drugs

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9
Q

give examples of carriers( excipients)

A

acids such as citric and succinic acids
sugars such as: xylitollactose and mannitol
polymers such as: polyethylene glycol and polyvinyl pyrrolidone
surfactants for example poloxamers
bile salts
urea

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10
Q

what are the two common methods of preparing solid dispersions?

A

1- melting ( fusion) method

2- solvent ( co-precipitation) method

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11
Q

what is the melting method?

A

The drug and the excipient are melted and the molten mass is cooled rapidly. The formed solid requires grinding; the drug and the excipient must have an acceptably thermal stability.

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12
Q

what is the solvent method?

A

the drug and the carrier are dissolved in a suitable solvent, which is then evaporated rapidly to dryness. The resulting solid mass needs grinding.

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13
Q

what are other possible methods of solid dispersions?

A

spray drying/ melt granulation/ lyophilization /freeze drying/ microwave irrdaitation/
co-precipitation/ kinetisol/ electrospinning/ hot melt extrusion

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14
Q

what are the 3 main types of solid dispersions?

A

Two-component crystalline dispersion, NO mixed crystals
Two-component crystalline dispersion, mixed crystals
Non-crystalline dispersion (amorphous or glassy systems)

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15
Q

what is eutectic mixtures?

A

For pharmaceutical uses, they are formed from drug substances and a water-soluble carrier.

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16
Q

how do eutectic mixtures differ in some way?

A

They differ, at least, in a superficial way from someof properties of the pure substances as follow:
The drug solubility is increased due to particle size reduction
Possible solubilisation effect by the carrier
There are no aggregation and agglomeration of drug particles as the drug is highly dispersed in the carrier.

17
Q

what are the results of eutectic mixtures?

A

The drug wettability is improved, due to the intimate contact between the particles in the drug–carrier mixture.
Possible crystallisation of the drug in a metastable polymorphic form, which results in an increased dissolution rate.
The drug dissolution rate is increased due to the larger surface area of the finely dispersed small particles.

18
Q

what are mixed crystals?

A

are solutions of molecules of one chemical (solute) in the crystal lattice of the second chemical (solvent)

19
Q

what are interstitial mixed crystals?

A

Solute molecules fit between rows of molecules in the solvent crystal lattice. Solute molecule volume is less than 20% of that of the solvent.

20
Q

what are substitutional mixed crystals?

A

solute molecules replace molecules in the crystal lattice of the solvent…..equal volumes

21
Q

what are Non-crystalline dispersion (amorphous or glassy systems)?

A

These systems can be obtained using solvent methods by application of some technique, for example spray drying technique.

22
Q

what are the advantages of solid dispersions?

A

Particle size reduction and reduced agglomeration
Increase dissolution rate of hydrophobic drugs with poor water solubility
Increase the rate and extent of drug absorption
Possible reduction of dose
Grinding (fusion method) may be avoided by liquid filling into hard capsules.

23
Q

what are the disadvantages of solid dispersions?

A

Change in crystallinity or polymorphic form on storage: polymorphic forms can change back into thermodynamically more stable forms.
Bulk properties are often unsuitable:(particle size, shape, bulk volume, flow and melting temperature). The low melting point can cause stickiness.

24
Q

what does surface adsorption of surfactants and polymers do?

A

Adsorption of these substances (hydrophilic) improves wetting and may be solubility of hydrophobic drugs>
enhancing the drug dissolution

Also adsorption of hydrophilic surfactants and polymers in small quantities onto the surface of hydrophobic drug particles improves the wetting of these particles > increase the effective surface area and hence the drug dissolution

25
Q

what are some examples of some hydrophilic surfactants?

A

Ionic surfactants (e.g. sodium lauryl sulphate, docusate sodium, hexadecyl trimethyl ammonium bromide (HTAB)Non-ionic surfactants, less toxic (e.g. Poloxamers(block co-polymers of polyoxyethylene and polyoxypropylene)

26
Q

what are examples of hydrophilic polymers?

A

Polyethylene glycol
Polyvinyl pyrrolidone
Poloxamers

27
Q

what affects the amount of adsorbed surfactant or polymer?

A

Degree of the drug hydrophobicityDrug particle size, shape, porosity and surface chemical structure
Adsorbent or hydrophobic drug)

Chemical structure and molecular weight ofthe adsorbed surfactant or polymerConcentration of the surfactant or polymer inthe solution(Adsorbateor surfactant or polymer)

28
Q

how does the experimental conditions affect the amount of adsorbed surfactant or polymer?

A
  • Solvent used, the extent of adsorption of the surfactant or polymer onto the surface of drug particles is inversely proportional to the solubility of the surfactant or polymer in the solvent used.
  • The pH of the solvent (it affects the ionisation and the solubility of the surfactant or polymer).
  • The temperature influences the solubility of the surfactant or polymer.