Factor effect rapid

release formulation by
way of granulation
GROUP MEMBERS

ALISHBA MARIA RIZWAN RIDA SHABILA SUMAIRA

ABID AMJAD ARIF ARSHAD ISMAIL BIBI
958 1015 948 952 991 987
Rapid release formulation

 Print Section. Most conventional (immediate release) oral drug products,

such as tablets and capsules, are formulated to release the active drug
immediately after oral administration. In the formulation of conventional
drug products, no deliberate effort is made to modify the
drug release rate.
Granulation related factors

Granules are can be made by two ways dry and wet

granulation method.

The first step of both methods ,which is interactive mixing

,play an important part in improving the dissolution of
poorly drug because the mixing of micronized drug with
appropriate additive reduce the cohesiveness of the drug
particles, leading to better dissolution.
Liquid binder

Wet granulation offers an opportunity for transformation of crystal forms and

the choice of liquid binder plays an important role in determining the final crystal
form of drug in the granules obtained.

Transformation usually occur during the addition of liquid binders to the powder
mass during wet massing and drying of formed granules.

Addition of binder could be viewed as suspending drug in the mixture of solvent

and additives ,hence, encouraging transformation of anhydrates to solvate form.

If sufficient liquid binder is added ,this could be see as a solution step and
subsequently drying of granules as the recrystallization step.
Examples
 Theophylline readily convert to monohydrate form upon exposure to
water during wet granulation.
 This conversion could not be prevented by having high water by
absorbing capacity additive such as the silicified microcrystalzline
cellulose because minimal amount of water for effective wet massing
was sufficient to trigger this conversion.
 Theophylline monohydrate under vacuum dehydration forms stable
anhydrous form and in process ,formed bridges within tablet.
 A decrease in dissolution would result if the crystallization were not
prevented.
 The use of water as the liquid binder also effect dissolution of naproxen
sodium because drug hydration result in poor dissolution of drug
 If wet granulation has to carried out for these drugs, and in order to
maintain rapid dissolution ,polymorphic conversion may be prevented by
using ethanol, as a liquid binder
Conti..

 The solubility of drug in liquid binder also of resulting capsule or tablets

made from these granules.
 This was illustrated by a study carried out by wu et al who found a
correlation between dissolution rate, rate constant of zindotrine and
solubility of zindotrine in liquid binder by changing the concentration of
ethanol.
 this was explained by the dissolution of certain amount of zindotrine
followed by the recrystallization of fine crystal during the driving phase of
the granules.
 The subsequent enhancement in dissolution was due to fine crystal form
during recrystallization process
 The drug had undergo microinzation process during granulation.
Quantity of liquid binder

Low amount of liquid binder High amount of liquid binder

At higher amount of liquid

At low liquid binder would
binder use is also
result in production of
expected to increase the
smaller granules and the
hardness of granules
resultant tablet formed
.Hard tablet would result
display dissolution faster.
in poor dissolution.
Moisture content:

This observation was found At moisture content of 1.6% and

2% ticlopidine hydrochloride
to be depend on the dissolution highly depend on
moisture content of tablet. tablet strength.

However, with moisture content

of more than 3% the drug
dissolution was independent of
tablet strength.
Granulating equipment

 The use appropriate granulating equipment play important role in release rate
of drug.
 Acetaminophen beads made from extrusion /spheronization were compared
to beads made from pan coating.
 Beads made from pan coating method displays higher dissolution rate as
compared to former method .
 This was attributed to the disintegration of pan coating beads and the ones
made from extrusions/spheronization were denser and less friable due to
higher energy input during wet massing and thus did not disintegrate during
dissolution.
 The selection of equipment for wet granulation thus affects the hardness of the
granules and ultimately influence drug release.
 Chowhan et al also reported that granules made from high speed shear mixer
were lower in porosity as compared to those prepared from planetary mixer.
 Low porosity did not facilitate the solvent penetration and cause poor drug
penetration.
Wet mass

 Wet massing was found to play an important factor in the dissolution rate
of dyphylline.
 Increasing the time during wet massing resulted in an increase in bulk
density of granules.
 The maximum bulk density value coincided with minimum dissolution rate
indicating that the dissolution of drug require the diffusion of dissolution
medium into granules via pores to dissolve the drug.
 The duration of wet mixing affects the hardness of granules and ultimately
dissolution of drug.
Blending

 The dissolution rate affected by the type of blending equipment employed, the
duration of blending of granules with disintegrate ,glidant and lubricant.
 It was found that the type of blender affected the distribution of magnesium
stearate and hence drug dissolution.
 High speed blender was employed to mix interactive mixture of theophylline with
magnesium stearate before tableting
 It was found that a 15 min duration was sufficient to impair theophylline dissolution
whereas an impairment of dissolution was not observed for lower speed blender.
 The impairment to drug dissolution increased with an increase duration of
blending.
 This was attribute to coating of the granules with a thin film lubricant, a water
repellent and hence compromising the wetting granules.