Compendial methods of dissolution
Basically the literal meaning of dissolution is “the process or act of dissolving”. United States Pharmacopeia for drug describes different methods and apparatus for dissolution test .The dissolution test basically performed on variety of drug products like capsules tablets etc.
Elements that disturbs the dissolution process are:
Following are the apparatus:
Flow through cell.
Paddle over disk.
For solids oral dosage form rotating basket and paddle methods are more effective apparatus.
APPARATUS NO #01
This apparatus contain different parts:
A variable motor shaft
Vessel is made up of glass or inert transparent material with the height of 16_21 cm having 9.8 to 10.6 inside diameter.
It consist of concave bottom with 1000ml volume capacity .Sides are flanged near top end to accept a fitted cover to retard evaporation. It consist four ports one is for thermometer one is for motor shaft and other two are for sample removal for analysis.
Basket assembly consist of a basket placed by a motor shaft. The function of basket is to hold the sample under test and then it rotates in a round flask containing dissolution medium. Mesh size is of 40 with wire opening of 0.36 to 0.44 mm
Variable motor shaft
Shaft is placed in such a way that its axis is not more than 2mm at any point from the vertical axis of the vessel and rotates smoothly, without wobble that could affect the result whereas shaft diameter is 6mm and length is 30 cm 100 to 150 rmp is rotating speed for this process. The advantage given by this process is that PH can be changed easily whereas following are the disadvantages :
Turbulence may occur.
Disintegration dissolution interaction.
Clog may be form to 40 mesh screen.
Paddle apparatus consist of following parts:
It basically avoid turbulence because of stirring and allows uniform hydrodynamics.
The vessel of paddle method is same as the vessel of rotating basket.
The dosage form is placed at constant temperature of 37 centigrade.
Typical speed of motor is 50 to 75 rmp in this process.
This is a few turns of platinum wire to prevent the dosage form from floating. It can be used for film coated tablets that sinks to the vessel wall and helps the dosage form to come under the paddle. Drug products tested Solid dosage forms, tablets, capsules, Particulates, suspensions, powders.
The advantages related to this apparatus are as follows:
Ph can be changed.
Easy to use and easy to automated.
Whereas disadvantages are :
In this process sinkers are used.
And this process is limited.
Consist of following elements:
It basically consist set of cylindrical flat bottomed glass vessels which are prepared with reciprocating cylinders
Screens are basically present at the top and bottom of the cylinders and uses for the modified released dosage form, extended dosage form.
Cylinder is moved horizontally by placing the dosage form in it usual speed is 5 to 35 dips/min
The disadvantages of this process is foaming caused by surfactants Whereas it has a advantage of changing pH in GI tract e.g PH 1, pH 4.5 and due to dipping rate hydrodynamic zones are influenced.
Apparatus No# 04
Flow through cell
This apparatus consist of reservoir for dissolution medium and pump that forces dissolution medium through the cell retaining the test sample.
Recirculate media: closed system
Continuous flow: open system
Fresh or recirculated medium:
Dissolution rate can be obtained if the medium is fresh.
Rate of flow
Flow rates are critical maintained at 10_100 ml/min
For specific dosage forms:
For non-harmonized solid dosage forms i.e. suppositories.
One of the benefit of flow through process is smooth renovation of a sink situation for dissolution whereas major disadvantage is it need extensive labor
Paddle over disk
This apparatus use paddle as well as vessel like apparatus 2 with the addition of stainless steel disk assembly. The standard volume of this apparatus is 900ml whereas the temperature of flask is 32 centigrade in which entire preparation is placed with specific medium.
Drug products are: Emulsion, bolus, floaters, ointments, transdermal patch.
Over a disk assembly paddle is placed directly on which according to the size of disk assembly transdermal patch is placed after different interval of time sample are drawn from dissolution medium and top of paddle blade. The advantage is it is standard equipment whereas disadvantage is that it is restrict to patch size
Apparatus no # 06
In this apparatus cylinder is used instead of basket. Cylinder is made up of stainless steel used to hold sample.
37 centigrade is maintained
This apparatus is used for reservoir patches that can’t be cut smaller.
Apparatus No# o7
This apparatus is similar to apparatus number 3 but there are alternations.
The temperature is maintained at 32 centigrade whereas speed is about 20 to 30 cycles per minutes.
QUESTION NO # O2
Integration rules and techniques of solving integration problems
For the determination of volumes, central points, areas and many other useful things integration can be used.
Rules functions integral
Power rule ? x^ n dx (x^(n+1))?((n+1)+C)
Sum rule ? (f+ g)dx ? f dx+? g dx
Multiplication by constant ? cf (x)dx c? f(x) dx
Difference rule ? (f-g)dx ) ? f dx- ? g dx
Example no #1 integral of sin (x)?
From the table directly above it is recorded as being ?cos(x) + C
So it should be written as:
?sin(x) dx = ?cos(x) + C
Example no#2 integral of x3 (?x3 dx?)?
Power rule should be applied where n =3
? x n dx = xn+1/(n+1) + C
?x3 dx = x4/4 + C
Multiplication by constant
Example no # 01 what is?6×2 dx?
6 should be moved outside the integral
?6×2 dx = 6?x2 dx
Now power rule on x2 should be use
= 6 x3/3 + C
Example no #01
What is ?cos x + x dx?
?cos x + x dx = ?cos x dx + ?x dx
= sin x + x2/2 + C
Example #is ?e w ? 3 d w?
?e w ? 3 d w =?e w d w ? ?3 d w
= e w ? 3w + C
Common functions functions Integration
square ???x^2 dx? x^3?3 +C
variable ???x dx? x^2?2 +C
constant ???a dx? Ax +C
reciprocal ??(1?x)dx Ln IxI + C
exponential ???e^x dx? ex + C
trigonometry ???cos?(x)dx? sin(x) + C
Constant function example:
Integral form of zeroth order rate law:
Rate=?d A 0/d t=k
?_Ao^A??A?0d A = ?_to^t??-kdt?
A = A 0?kt
Integrated equation for first order:
Rate=?d A/d t=k A
D A/ A =?k dt
?_Ao^(A)?(dA)/(A) = -?_to^t?kdt
Ln A –ln Ao=?kt
Ln A = ln A o?kt
Rearrange the equation:
Ln A =? kt+ lnAo
As name indicates physico means physical and chemical means chemical properties whereas the physical and chemical properties of substance on bio molecule that interacts with and has influence to cause the chemical substance to elicit therapeutic effect .
Physical properties that affects drug absorption are: route of administration, age emptying stomach, blood flow through the GIT, membrane physiology, and gastrointestinal Ph.
Pharmaceutical factors that affects are dissolution time, distengration time, nature and type of dosage form, manufacturing variable.
Drug solubility and disintegration time.
Salt form of drug.
Drug solubility and disintegration time
Drug absorption occur when it is in the solution form wherein molecules are independent .Absolute solubility can be defined as the maximum amount of solute in solvent dissolved under standard conditions like temperature pH etc.
Rate of dissolution and rate of drug permeation through bio membrane are rate determining steps in absorption of orally administered.
Particle size and surface area:
When drug is poorly soluble then particle size plays an important role in drug absorption e.g digoxin. Dissolution rate will be higher if surface area is smaller because at the surface area of solute dissolution is about to take place.
Polymorphism is the phenomenon in which same material exist in different morphological forms. Polymorphism has significant effect on formulation development as it may have different solubility, dissolution rate hygroscopicity. Some drugs exist in amorphous forms and show high energy state and show more aqueous solubility than crystalline form because crystalline form need more energy to transfer molecule than non-crystalline.
Salt form of drug:
The conversion of drug in its salt form increase its absorption solubility and many other factors like In case of salt of weak acid pH of diffusion layer increases which enhance the solubility dissolution of weak acid and absorption increase.
Applied Biopharmaceutics and Pharmacokinetics
Author Shargel. Leon 1941