INSTRUMENTAL FACTORS AFFECTING RATE OF DISSOLUTION

Slide 1: 

Welcome

Slide 2: 

2 Sameer I. Patel (M.Pharm. I ST sem. Dept.of Pharmaceutics. ) Mr. S.A.Payghan (H.O.D ) Department of Pharmaceutics Presented By: Guide : Supervised by: Dr. J. I. Disouza (Principal) Department of Pharmaceutics Seminar On Factors Affecting Rate of Dissolution Related to Dissolution Testing Device DEPARTMENT OF PHARMACEUTICS Tatyasaheb Kore collage of pharmacy,Warnanagar

Outline of seminar: 

Outline of seminar 3 Eccentricity of agitation (stirring)element Vibrations Agitation intensity Stirring element alignment Flow pattern disturbances Sampling probe Filters Dosage form position Type of device Composition of medium

Contd…..: 

Contd ….. 11. pH of medium 12. Viscosity of medium 13. Other factors - Traces of surface ion - Surface tension -Surfactant present -Temperature variation

Eccentricity in Agitating (Stirring) : 

Eccentricity in Agitating (Stirring) 5 /18 I n this factor, the rotating paddle or basket shaft does not rotate smoothly and wobble(move side to side) E ccentricity can induce and propagate changes in hydrodynamic condition ,flow pattern and significantly affect dissolution result. O fficial standard -The shaft should rotate smoothly and not wobble.USP/NH XV state that rotation stirring shaft must not deviate >2mm not affect significant effect on result.

Vibration : 

Vibration 6 /18 C ommon variable that affect dissolution profile by changing flow pattern and inducing unwonted energy to dynamic system. O fficial standard- The speed of rotational device selected by official compendia is 100 rpm(vary with some drug) T o control the speed synchronous motor is used. that lock the frequency(85)

Contd… : 

Contd … 7 /18 L iterature - Bayer and Smith (87) reported six fold increases in dissolution rate of Tolbutamide table when vibration rate increases from 0.05to 0.8 min displacement.

Agitation intensity : 

Agitation intensity 8 /18 T his Is the factor that markedly affecting thickness of diffusion layer. I t depend upon dimension ,geometry of dissolution of dissolution vessel, volume of vessel medium and degree of agitation. L iterature – Wurster and Taylor (90)gives an empirical formula that give relationship of dissolution rate and agitation.

Stirring element alignment : 

Stirring element alignment 9 /18 T he misalignment of rotating shaft axis to the axis of dissolution vessel ,that disturb flow pattern test to test . T he tilt in the axis more than 1.5° may vary dissolution rate 2-25% O fficial standard – USP XX/NF XV states that the axis of stirring must not deviate more than 0.2mm from the axis of dissolution vessel .

Flow pattern disturbances : 

Flow pattern disturbances 10 /18

Geometry and alignment of stirring device, external vibrations and rotational speed are factors that influence flow pattern. The vertical distance of basket or paddle from lowest point also affect flow pattern. Official standard-Official compendia specifies vertical distance of paddle or basket from lowest point is 2.5cm(±2mm) : 

Geometry and alignment of stirring device, external vibrations and rotational speed are factors that influence flow pattern. The vertical distance of basket or paddle from lowest point also affect flow pattern. Official standard - Official compendia specifies vertical distance of paddle or basket from lowest point is 2.5cm(±2mm) 11 Contd …

Sampling probe: 

Sampling probe 12 /18 T oday most of the machines are automoted and using large filter tipped probe immersed in dissolution medium. L arge probe affect hydrodynamic of the system and dissolution rate of dosage form. O fficial standard - USP XX/NF XV Apparatus two dissolution rate determined by using two large and one small capillary probe.

filters: 

filters 13 /18 C hoice of filter depend upon adsorption characteristic of drug and properties of filter material. A ccumulation of particulate matter on filter surface(clogging)may cause significance error. T o avoid this select proper filter and purge the filter with reversed flow of dissolution medium or at each sample interval.

Dosage form position : 

Dosage form position 14 /18 T here are many factors related to dissolution testing device that alter the position of dosage form. for example dissolution testing device containing basket , its screen size ,basket design and many mechanical factor affect dissolution profile. C hanges or modification introduced in the mechanics (design)of dissolution device can alter the position of dosage form.

Type of device: 

Type of device 15 /18

Contd…: 

Contd … 16 T his is one of the most prominent factor that influence the dissolution performance of dosage form. D ifferent dissolution testing device offers different working condition depend upon their mechanics. M any testing device have drawbacks associated with apparatus as well as systematic errors

Composition of dissolution medium and ph: 

Composition of dissolution medium and ph 17 /18 D issolution rate of drug product influenced by both composition and pH of dissolution medium. F luctuation in the composition and pH of medium significantly affect the dissolution profile. F or maintaining composition fix leaching in the solution is avoided, resist change in pH different buffers systems are used. O fficial standard- The composition and pH of the medium is maintained as per individual monograph.

Dissolution medium : 

Dissolution medium 18 /18 C onstituent , nature and overall characteristic of dissolution medium have significant effect on dissolution performance of drug substance. S election of proper dissolution medium depend upon solubility of drug as well as economics and practicality. D issolved gases , medium pH , viscosity of medium significant influence on dissolution rate

viscosity: 

viscosity 19 /18 D issolution rate decreases with increase in viscosity of dissolution medium (In diffusion-controlled dissolution process) L ittle effect in interfacial-controlled dissolution process. L iterature – Kellaway and Najib(120) investigated dissolution rate control by polymer through changes in the properties of bulk solution and conclude that there is predictable relationship between and dissolution rate and viscosi ty .

Other factors: 

Other factors 20 /18 Traces of surface ion -Surface ions may contribute little to change in the dissolution profile. Surface tension - Have inverse relationship with dissolution. The surface tension should be maintain constant or as per given in individual monograph. Surfactant -Surfactant alters the surface properties and dissolution profile .

Contd… : 

Contd … 21 /18 Temperature variation -Major factor that have potential influence in the result of dissolution test is the temperature. Official standard - USP/NF Specifies that dissolution medium must be held at 37°C(±0.5) as drug is temperature dependant so careful monitoring of temperature is important.