Download - Dissolution apparatus POST-LAB
DISSOLUTION APPARATUSPOST-LAB DISCUSSION
6/24/15
Types of Dissolution Apparatus
• USP Dissolution apparatus (official):1. Basket type2. Paddle type3. Reciprocating cylinder4. Flow through cell5. Paddle over disc6. Rotating cylinder7. Reciprocating disc
USP dissolution apparatus (non-official):
1. Rotating bottle method
2. Diffusion cell
3. Peristalisis method
4. Intrinsic dissolution method
• IP Dissolution apparatus:1. Paddle type2. Basket type
BP Dissolution apparatus:1. Basket type apparatus2. Paddle type apparatus3. Flow through cell
IDEAL FEATURES OF DISSOLUTION APPARATUS
• Fabrication dimensions and positioning of all components must be precisely specified and reproducible, run to run.
• Must be simply design easy to operate and useable under variety of conditions.
IDEAL FEATURES OF DISSOLUTION APPARATUS
• Must be sensitive to reveal processes changes and formulations differences but still yield repeatable results under identical conditions.
IDEAL FEATURES OF DISSOLUTION APPARATUS
• Should permit controlled but variable intensity of: mild uniform non-turbulent liquid agitation. Uniform flow is very essential because changes in hydrodynamic flow will modify dissolution
• Nearly perfect sink conditions should be maintained.
• Provide easy means of introducing the dosage form into dissolution medium and holding it, once immersed in a regular and reliable fashion.
• Provide minimum abrasion to the dosage form during test period to avoid disruption of the microenvironment surrounding the dissolving form.
IDEAL FEATURES OF DISSOLUTION APPARATUS
• Special care should be taken that medium must not evaporate from container of apparatus.
IDEAL FEATURES OF DISSOLUTION APPARATUS
• Sample should be easily withdrawn for automatic or manual analysis without interrupting the flow characteristics of liquid.
• Should be capable of allowing the evaluation of disintegrating, non-disintegrating, floating tablets or capsules, finely powdered drugs and novel dosage forms.
IDEAL FEATURES OF DISSOLUTION APPARATUS
APPARATUS NAME DRUG
PRODUCT
I ROATING BASKET
TABLETS
II PADDLE Tab, capsules modified drug products
III RECIPROCATING CYCLINDER
ER drug products
IV FLOW CELL Drugs w/ low water sol drug
APPARATUS NAME DRUG
PRODUCT
V PADDLE OVER DISK
Transdermal
VI CYLINDER Transdermal
VII RECIPROCATING DISK
ER products
VIII NON USP NF ER products
APPARATUS NAME DRUG
PRODUCT
IX NON USP NF Ointments creams
transdermal
PADDLE TYPE
PADDLE TYPE
PADDLE TYPE
• Design
1. Vessel
2. Shaft: the blade passes through the shaft so that the bottom of blade fuses with bottom of shaft.
3. Stirring elements: Made of Teflon/ stainless steel
PADDLE TYPE
4. Waterbath: Maintain at 37 + 0.5C
5. Sinkers: Platinum wire used to prevent capsule tablet from floating.
PADDLE TYPE
PADDLE TYPE
• Consist of a special, coated paddle that minimizes turbulence due to stirring.
• The paddle is attached vertically to a variable-speed motor that rotates at a controlled 40 speed.
PADDLE TYPE
• The tablet or capsule is placed into the round bottom dissolution flask, which minimizes turbulence of the dissolution medium.
• The apparatus is housed in a constant-temperature water hall maintained at 37C similar to a rotating basket method.
• The position and alignment of the paddle are specified in the USP. The paddle method is very sensitive to tilting. Improper alignment may drastically affect the dissolution results with some drug products.
PADDLE TYPE
• The most common operating speed for apparatus II are 50 rpm for solid oral dosage forms and 25 rpm for suspensions
PADDLE TYPE
• Apparatus II is generally preferred for tablets.
• A sinker such as a few turns of platinum wire may be used to prevent a capsule or tablet from floating.
PADDLE TYPE
Dissolution Sampling
• Use of Water is LIMITED
• Additives (enzymes and salt)
• Agitation (50-100 rpm)
• Media temp (37 +/- 0.5C oral)
(38 +/- 0.5C special; rectal)
( 32 +/- 0.5C transdermal)
•Use of sinkers
Dissolution media
• Required major characteristics of a dissolution medium
1. Should be a representative of the liquid phase present in the tract (aqueous)
2. Physiologically, the dissolution medium has to be water or water based.
Dissolution media
Potassium or NaOH soln, although water-based, their use is restricted by their high pH values not found in the GI tract
Types of dissolution media
• Purified water• Dilute acid (0.001 N- 0.1 HCl)• Simulated gastric fluid (w or without
enzymes)• Simulated intestinal fluid(w or wo enzyme)Surfactants ( w or w/o acids or buffers)Buffered aqueous sol’n (pH 4-8)
Selection of dissolution media
• Oral formulation
-physiological pH
pH 1.2-6.8 for IR formulations
pH 1.2- 7.5 for MR formulations
Selection of dissolution media
• Low solubility compounds
Surfactants (eg polysorbate, SLS, bile)
Wetting agent
Solubilizing agent
CALCULATIONS
1. mg/ tablet = Au/ As x conc of std(ug/mL)/1000 X DF X average wt of tab
weight of tab
Where: Au - absorbance reading of sample
As - absorbance reading of standard
DF - Dilution factor
900 X 50 mL = 50,000
0.9 1 tab
2. % of labeled claim=actual amount obtainedX100
labeled claim
USP LIMITSNot less than 80% of the labeled amount of acetaminophen is dissolved in 30 mins.
CALCULATIONS
DISSOLUTION
• Drug Dissolution testing is routinely used to provide critical in vitro drug release information for QC purpose.
Uses:
1. To assess batch consistency of solid DF
2. To predict in vivo drug release profiles
3. To assist in decisions concerning need for bioavailability studies.
Sample Calculation:
Find: mg/ tablet% labelled claim
DATA : 500 mg Mefenamic acidAs - 3.214Au - 3.210Wt of 10 tabs - 6.53 gAve wt - 0.65 gActual wt - 0.653 g
SOLUTION
1. mg/ tablet = Au/ As x conc of std(ug/mL)/1000 X DF X average wt of tab
weight of tab
= __________________
= __________________
SOLUTION
2. % of labeled claim=actual amount obtainedX100
labeled claim
= _______________
= _______________