Modification of surface prop for h.phobic drugs

Question 1

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

Answer 1

because of its associated problems:

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

Question 2

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

Answer 2

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

Question 3

what happens if you decrease aggregation of a hydrophobic drug?

Answer 3

the surface area increases, improves wetting and dissolution rate

Question 4

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

Answer 4

to improve wetting, dissolution rate and hence bioavailability

Question 5

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

Answer 5

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

Question 6

what is solid dispersions?

Answer 6

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

Question 7

what is the aim of solid dispersion?

Answer 7

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

Question 8

when is solid dispersion mostly used?

Answer 8

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

Question 9

give examples of carriers( excipients)

Answer 9

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

Question 10

what are the two common methods of preparing solid dispersions?

Answer 10

1- melting ( fusion) method

2- solvent ( co-precipitation) method

Question 11

what is the melting method?

Answer 11

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.

Question 12

what is the solvent method?

Answer 12

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

Question 13

what are other possible methods of solid dispersions?

Answer 13

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

Question 14

what are the 3 main types of solid dispersions?

Answer 14

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

Question 15

what is eutectic mixtures?

Answer 15

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

Question 16

how do eutectic mixtures differ in some way?

Answer 16

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.

Question 17

what are the results of eutectic mixtures?

Answer 17

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.

Question 18

what are mixed crystals?

Answer 18

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

Question 19

what are interstitial mixed crystals?

Answer 19

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

Question 20

what are substitutional mixed crystals?

Answer 20

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

Question 21

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

Answer 21

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

Question 22

what are the advantages of solid dispersions?

Answer 22

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.

Question 23

what are the disadvantages of solid dispersions?

Answer 23

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.

Question 24

what does surface adsorption of surfactants and polymers do?

Answer 24

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

Question 25

what are some examples of some hydrophilic surfactants?

Answer 25

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)

Question 26

what are examples of hydrophilic polymers?

Answer 26

Polyethylene glycol
Polyvinyl pyrrolidone
Poloxamers

Question 27

what affects the amount of adsorbed surfactant or polymer?

Answer 27

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)

Question 28

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

Answer 28

• 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.