Dissolution of tablet,capsules and granules:

Using instruments

1-Hansen paddle equipment (book page 15)

simulating of conditions od dissolution inside the body.

*temp :37 +-0.5c

*liq: acc to tablet diss. In stomach (use 10N Hcl PH=1.2) or in intestine (usijng phosphate buffer at PH=6.8-7.2 )

*stir

*at diff time intervals take sample then analyse drug in it (dissol. Rate l by time) , pharmacopia give specification of each drug eg. Hydrochlorothiazide 60% of drug should be dissolve in 30 min to give therapeutic effect.

 Criticism of this method is :SA of tablet exposed is not const by time so mofification is req.

 

 

2-research design to ensure const SA

figue in ook

it has the same principal as Hanse  but it is provided by a holder of specific area to control exposed SA .

*air jacket to maintain the temp at 37c

 

3-USP  made rotating basket apparatus :

*container from plastiglass (its vol is 1L) contain 900ml of

gastric juice or intestinal fluid

*it is covered by 4 holes :

1-in the center contain paddal (stirrer )with motor ,and at the

 end of paddal there is a basket which determine exposed SA

 of the tablet 

basket :is small container contain meshes (mesh size =12-18)

acc to fine particle of powder

mesh size =no of meshes per linear inch.

*tablet is put with pedal in the same line

2-thermometer :to maintain temp at 37 by puttinf in W.B

and there is also thermostat

3-hole for pipette by which you can take the sample and analyse it .

4-hole behind paddle to compensate liq of withdrawal sample to keep vol all the time const at 900ml.

 

 

Factors afeecting rate of dissolution

1-particla size :

l p.s   l  dissolution rate

2-structure of the crystals

a:polymorphism

drug is in more one form agree in chemical properties and not in physical one

 eg chloramphenicol

b/; hydration of crystal : no of water molecules in formulation of drug

3-solubility :

 

l sol  l  dissolution rate       l  effectiveness of drug

 

4-complexation :drug +other sub  =water insol complex  l dissolution rate

tetracyclines form water insol complexex with Ca,Mg,Al,Fe  so it should not be taken with dairy products or with Fe as it is not absorbed

5-surfactant : with drug  l wettability of drug (good effect) as it make drug miscible with water and body fluids so l solubility.

Some drugs are hydrophobic  with surfactant  l wettability  l sol  ldissolution of drug

 

6-reactive additives  LPH at which drug will dissolve)  acidic or alkaline  .

acc to site of absorp. In stomach or intestine addn of acid or alkali or buffer  ,,at this PH l solubility

 

7-density ,viscousity and wettability :

particles if are dense = l settiling  adhere to mucous membrane of stomach or intestine ,, exposed from one side ,,less dissolution . ,,if it is not dense  :better as it is suspended 

viscousity: thin med is more dissolving than thick (viscousity hinders solubility)

eg sol in glycerine is much les sol in water .

wettability :if drug is hydrophobic :take longer time to dissolve the drug

8-adsorption : drug is unavailable to be dissolved  so l dissolution rate  and  l sol

 

 

difference between disintegration and dissolution :

dissolution :is solubility of drug in liquid .

disintegration :tablet disintegrate into particles (granules)

similarities bet them 1-shape of the curve(S) shaped curve .

 

differences :

1- disintegration  has poor indicator of bioavailability of drug

 

for dissolution depend on sol of the drug so can determine absorption

 

2- dissolution depend on sol ,particle size and crystal structure (poly morphism )  but disinteg. Depends only on disint. Agent.