One should remember that drugs(in solid form) which are administered via oral route are not immediately available for the biological system or the systemic circulation, while those taken in other forms like solution or reconstitutable powders or those which are taken via other route like those of injectables, transdermals, nasal powders, buccal and sublingual tablets and patches etc..will be available to systemic circulation witout much struggle.
Estimating the available drug from the latter forms is simple and easy but, the problem arises with those of former ones. once the drug enters the stomach via oral route it has to cross many hurdles and sustain the harsh acid conditions of the stomach and should get disintegrated (splitting of larger particles into smaller particles) and then get dissolved (mass tranfer from the solid surface to the liquid phase) and later the dissolved form should diffuse across the bilogic membranes of the gut wall into the systemic circulation this differs from drug to drug or same drug with different formulations.(1). The therapeutic effectiveness of the drug can be judged by the ability of the dosage form to deliver the API (active pharmaceutical ingredient) at the site of action and also rate and extent of such delivery so as to elicit therapeutic response (2).The pharmaceutical factors affecting such release of drug from a dosage form can be tested using dissolution testing devices. Apart from quality control these devices are also helpful during developemnt of doage form.These are most reliable predictors of invivo performance.Though the basic principle lies under three major aspects like use of simulated fluids(gastric or intestinal) at normal body temperature, an agitating device at fixed speed, seperation of disintegrated product from the rest of the product.
Many devices have been reported.
CLASSIFICATION OF DISSOLUTION TESTING DEVICES:
The devices can be classified based on intrinsic, total/apparent dissolution rate or the more useful agitation intensity. Since the rate at which the stationary film thickness is altered will directly influence the dissolution rate. the disadvantage of the latter is that the difference in the agitation speeds for the same apparatus.Overcoming such a problem, the next classification on based the way the concentration is maintained.If the concentration is decreased then the condition is called non-sink and for those whose concentration is maintained constant its called sink conditions.
1) NATURAL CONVECTION NONSINK METHODS
a) Klein solvmeter method
b) Nelson Hanging Pellet Method
c) Levy static Disk Method
2) FORCED CONVECTION NON SINK METHODS
a) Tumbling method
b) Levy Method Or Beaker Method
c) Rotating Disk Method
d) Particle Size Method
e) Oscillating Tube Method
f) USP Rotating Basket Apparatus
3) FORCED CONVECTION SINK DEVICES
a) Wurster Pollis adsorption method
b) Partition method
c) Dialysis method
d) Rotating disk apparatus
4) CONTINUOUS FLOW/FLOWTHROUGH METHODS
a) Pernarowski method
b) Langenbucher method
c) Baun and Walker
d) Tingstad and Reigelman
f) Modified column apparatus
g) Cakiryildiz method
h) Takenaka method
NATURAL CONVECTION NONSINK METHOD: In this method the density difference is utilized for replacing the surrounding
Klein solvmeter method: There is a carrier device surrounded by float and is immersed in dissolution medium.The measuring bar connects float to the to the calibration scale above. when dosage form is placed in the boat the bar moves down and as dosage form dissolves it moves upwards. Amount of the dosage from dissolved is revealed frm the difference in the height of the bar movement.This methods suffers from loop holes like dosage from disintegrated cannot be evaluated and concentration effects on dissolution rate and measuring system is not accountable.
Nelson Hanging Pellet Method: there is aluminium strip, having provision for holding dosage form which is inturn connected to a perfectly maintained balance arm of strip. the dosage form is mounted on the aluminium strip with the help of wax. since only one part of the dosage form is exposed to the dissolution, this method can be employed to know the intrinsic dissolution rate. To prevent the disintegration further high pressures can be applied and also constant surface area can be maintained by reducing permeability of the compact.
Levy static Disk Method: Acrylic holder containing dosage form is inserted into a known volume of medium (25ml) through rubber stopper. The vial is inverted and is placed in a incubator at 37 0C.at specified time intervals the vial is removed from the incubator and the samples are analysed. Intrinsic dissolution is possible if the dosage form is mounted on to the acrylic holder such that only one face of it is exposed. This device has disadvantages like effect of concentration on the dissolution medium is ignored and the surface area of the doage form while dissolving is assumed constant which is not impractical.
FORCED CONVECTION NON SINK METHODS: As the name indicates the devices are agitated to induce relative motion between dissolution medium and the dissolved particles. Agitation is implemented by stirring, rotation or oscillation.
Tumbling method: dosage form with the dissolution medium is placed in test tube that is inturn clamped to the revolving drum which is rotated at a speed of 6 to 12 rpm in a water bath at 37 0C. The test tubes are removed and the medium is assayed at regular time points for the dissolved drug amount.
Levy Method Or Beaker Method: 400ml beaker is placed in a constant temperature bath kept at 37 0 C. A 5 centimetered three blade polyethlene stirrer is centered and rotated at 59 rpm. The tablet is dropped at the side of the beaker and samples are taken at specified time points fro analysis. This method is ammenable to measure intrinsic dissolution rate.
Rotating Disk Method: This method is ideally suitable for measurement of the intrinsic dissolution rate with those which maintain a constant surface area. The dosage forms which are prepared by hydraulic press are mounted onto the plexiglass holder that is in turn attached to metal shaft which is stirred at a constant speed. This holder is immersed at a depth of 1 inch in a 500ml dissolution medium that is maintained ta 37 0C and rotated at 555rpm.
Particle Size Method: The primary purpose of this device is to incorporate vigorous agitation so as to suspend the dissolved particles.The changes in the particles size is measured with the help of coulter counter. The particle size and the surface area
data together will enable to know the dissolution kinetics. but, practically chemical analysis outweigh the partice size analysis and this method is not suitable for dosage forms.
Oscillating Tube Method: Broadbent et.al have employed BP (British pharmacopoeia) disintegration apparatus for dissolution.
The difference is that only one tablet is placed instead of five and immersed in 200 ml of dissolution medium. The unique advantage of this method is that both disintegration as well as dissolution can be observed simultaneously. With the help of this device only total dissolution rate can be determined because constant surface area cannot be maintained due to the extreme agitation and abrasion caused by the mesh. Increasing solute concentration, lack of reproducibility, intensity of agitation and constancy of agitation constitute the other limitations.
USP Rotating Basket Apparatus:
The SS basket of 10 mesh is placed at a distance of 2.5 cm from the bottom of the vessel, is centered within 2 mm of the centreline of the vessel. The shaft is rotated at 100 rpm and temperature of the medium is maintained at 37 0C. Aliquots should preferably be withdrawn midway between the surface of the medium and the bottom of the vessel and midway the cylindrical edge of the basket and wall of the vessel.
Magnetic basket dissolution apparatus:
The uniqueness of this device is that it enables reproducible and presice placement of the dosage form.It consists of a beaker (800 ml)and a magnetic basket of 50 mm long and 11 mm inner diameter whose exact placement is ensured by a magnetic bar placed outside the beaker at the bottom.The additional modifications include the basket is constructed of epoxy resin that inert is both acididc and basic environment. the agitation is provided by a three bladed, blades of 18 mm diameter set at an angle of 60 0 angle and 45 0 from the vertical shaft of 7 mm, propeller with a diameter of 51 mm.The dissolution container, of 600 ml of medium is inturn immersed in a water bath so as to maintain the deisred 37 0 c. t propeller is immersed at a depth of 41 mm of the beaker
For the adjustment of the pH electrodes are placed at a depth of 27 mm from the vertical top and 7 mm from the horizontal beaker walls. With all these the device can be used to characterize inter product variation of products.
Modified USP Basket apparatus:
It is known fact that the flow of the medium should be sufficient for the dosage form such that the disintegrated particles during the dissolution should be swept by the medium from the basket screen. in order to fulfill this, the effort done was to change the direction of the basket by the angle of 90 0 by bending the stirring rod so as to get L- shaped configuration. a cylindrical SS screen of 24-mesh was seam welded and fitted over the teflon holder so as to hold the tablet firmly. This device facilitates the increase in the dissolution rate because of the enhanced flow of the medium. wandering of the dosage form within the basket is the major disadvantage while the advantages include economically feasible and simple construction, dual functionality i.e. both holding the dosage form as well as stirring of the holder.
Rotating Filter-Stationary Basket Apparatus:
This device consists of stationary basket, a fluid container and filter assembly with an external magnetic stirrer.the dissolution medium is contained in a fluid container of 1.5 l volume capacity.There are a total of 4 ports: For sample, for glass tube to favor the withdrawal of the aliquots, another for replacement of the fresh medium and other for thermometer to check the temperature. the basket is of 12 mesh which is kept stationary held at 2 to 5 cm from the bottom of the fluid container. the dosage form is placed in the filter providing different intensities of agitation.
USP Paddle method:
It is also called USP apparatus-2, the paddle should be centered within 0.2 cm of the centerline of the vessel, 2.5 + 0.2 cm from the bottom of the vessel. the shaft should rotate at a spped of 100 rpm with a temperature of about 37 0 C. the dosage form should experience some movement under the paddle till disintegration progresses. once disintegration occurs, aliquots should be drawn preferably from midway upper endge of the paddle and the surface of the medium between the wall of the vessel and stirrer shaft. the lowwer portion of vessel should be hemispherical and uniform in all aspects of weight, inside diameter and curvature.in case of floating dosage forms statinless steel or glass helix is attached to the dosage form. in this case excess abrasion and wear of the doage forms due to the friction from the inner surfaces is observed, affecting the micro environment adversely.
Forced Convection Sink Devices:
An ideal dissolution process is one which will mimic the invivo conditions by maintaining perfect sink conditions. these perfect sink conditions can be maintained by either of the following systems:
a) Fixed fluid volume.
b) Multiple phase
c) Continuous fluid flow
a) Fixed fluid volume: in this system the fluid volume is kept fixed such that the volume is sufficient to maintain the drug concentration below 10-20% of its solubility. fro example USP apparatus I and II.
b) Multiple phase: upon dissolution, the drug is either partitioned into water immiscible phase or adsoebed onto the solid interface.
c) Continuous fluid flow: this system helps to know the solubility irrespective of its solubility or dosage strength. the dissolved drug along with the medium is removed constantly and is replaced by fresh medium.
Wurster-Polli Adsorption Method:
in this method the dissolved drug is adsorbed by charcoal or bentonite. care should be taken regarding the adsorbent, adsorbent should not alter the viscosity of the medium
In this device organic phase is employed to remove the dissolved drug such that the drug would partition between the lipophilic and hydrophillic phases. selection of organic phase plays a critical role.
In this method dialysis membrane having minimal equilibrium time, adequate physical strength and solid particle retention is employed.in this device dissolution medium is placed on one side of the membrane and the next side is dosage form and the assembly is rotated at 15 rpm speed. aliquots are withdrawn at the distal end. the advanced method included baffled rotating round bottomed flask at 37 0C such that sloshing action is provided.
Rotating Flask apparatus:
In this method a flask containing dissolution medium is rotated around its horizantal axis in a water bath kept at a temperature of 370 C.The flask has a provision of sampling such that aliquots can be withdrawn and the fresh medium can be replaced back. This apparatus is best suited for oral solid dosage forms like tablets and capsules since they donot require much agitation.
Flow Through Devices:
For the drugs which saturate rapidly in large volumes of medium, USP apparatus will not serve the purpose. For this the suitable device is flow through device. In this device unlimited quantity of fresh dissolution is available.
A dosage form is placed in a small cell and is subjected to a stream of fresh dissolution media.
The various advantages include:
- Changing of pH is simple and convenient.
- number of parameters affceting are minimal.
- Has method has built in filtration.
- There is no problem of sample position.
- Ideal hydrodynamic conditions for mild agitation, homogenicity and calculated solvent flow pattern are exercised.
- Can be either open or closed type.
The basic design principle involved is that there is a vertical cylindrical cell of small dimensions having the capacity to taken in a small volume. The dissolution medium is pumped with the help of pump from the bottom of the
cell top of cell. there is filtration device that prevents the movement of undissolved material and the obatined outflow fluid is clear solution that can be directly assayed. Temperature control, position of the dosage form and liquid agitation
can be controlled.
Continuous Flow Apparatus by Pernarowski et.al.-
It consists of 10 mesh stainless steel basket stirrer assembly with an adjustable stirrer. the chamber is 3 necked flask of 33 mm and the rest two of 20 mm diameter. 1L of medium is employed within the flask. the dissolution characteristics are dependent upon the amount of medium pumped through the dissolution chamber.
Langenbucher Column-type flow through Method:
This device is according to the dissolution basic design (as discussed above).The screen is constructed such that the medium flows equally through the entire cross section in a laminar pattern. This is again closed by a secondary screen, filter which prevents the undissolved drug from being eluted.
Continuous Flow apparatus by Baun and walker:
Also called as constant- circulation apparatus. This consists of a cell, holding dosage form, a reservior with dissolution medium, a pump and water bath. there is a constant circulation apparatus that can be altered depending upon the dosage form.
Continuous flow apparatus by Tingstad and Riegelman:
a cylindrical glass cell of 6.1 cm long and 1.9 cm in diameter constructed with two glass filter funnels is used. The dissolution cell has filter membranes which prevents the solid particles from being analyzed. There are also external valves to control the excess flow of solvent into the system. the air trap averts air bubbles. The complete assembly is immersed in a temperature bath kept at 37 0C.
Flow-Through Modified Column apparatus:
The device consists of filter of 14 M -size made of nylon. the tubing from the pump is connected to the dissolution cell. the teflon faced stainlesssteel supports the screen resting on the bottom half of the filter holder. The direction of the flow is such that the particles donot fall through the screen. the rest of the process is the same.
Multichamber Continuous Flow Apparatus by Cakiryildiz et. al.:
The word multi indicates that there are six chambers with 6 peristaltic pumps, a termperature bath with magnetic stirring palte for 6 beakers, analyzer, With five identical dissolution chambers and the rest one is for recirculation of a reference solution.The dosage form is placed on the top of the bed of glass beads in the dissolution cell and later it is closed. then, medium goes from reservoir to the bottom of the dissolution cell to its top then to analysis.
Continuous flow apparatus by Takenaka et.al.:
The release of drug is measured with the aid of in vitro simulator device consisting of flow type dissolution container. The dosage form is placed in the basket rotating at 94 rpm with 300 ml of medium. then the medium is removed by collecting reservior using peristaltic pump. aliquots are withdrawn using syringe and then filtered using Whatman filter paper and the same volume is replaced immediately with fresh medium.
" This book page doesnot contain plagiarized material"
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