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DISSOLUTION PROFILE

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             PHARMAQUEST   1
                        CONTENTS :


1. Definition of dissolution profile
2. Importance of dissolution profile
3. Methods to compare dissolution profile
4. Dissolution studies of different dosage forms
        I. Conventional
               Powders
               Tablet
               Capsule
               Suspensions
               Suppository
               Topical dosage forms
         II. Controlled release
                                               PHARMAQUEST   2
COMPARISON OF DISSOLUTION PROFILE HAS EXTENSIVE
 APPLICATION THROUGHOUT THE PRODUCT DEVELOPMENT
PROCESS AND CAN BE USED TO……..

       Develop in vivo- in vitro correlation which can help to reduce
cost and to speed up the product development.



                 DISSOLUTION PROFILE


   It is graphical representation of …
     Conc. Of dissolved drug Vs Time




                                           PHARMAQUEST                  3
IMPORTANCE OF DISSOLUTION PROFILE


 • Variation within same batch or between batch to batch


 • Variation between brand to brand


 • For optimizing the dosage formula by comparing the
 dissolution profile of various formulas of the same A.P.I




                                             PHARMAQUEST     4
       METHODS TO COMPARE DISSOLUTION PROFILE

I.      Graphical method
II.     Statistical analysis
          1. t – test
          2. ANOVA
III.    Model dependent studies
          1. Higuchi model
          2. Hixon - Crowell model
          3. Quadratic model
IV.     Model independent studies
          1. Similarity factor
          2. Difference factor



                                     PHARMAQUEST   5
                         120

% Metoprplol dissolved   100

                          80

                          60

                          40

                          20

                           0
                               5   10   15      20          25   30   45
                                         Time in minutes
                                   A    B     C      D
                                              PHARMAQUEST             6
                          Statistical
                             analysis




             t - test                             ANOVA




One sample   Paired     Unpaired
  t- test
                                        One way       Two way
             t- test     t- test


                                   PHARMAQUEST                  7
              lX–ul           n

t =                    S


                     Steps to perform ANOVA

1. Calculate total sum of squares of variance (SST)
      SST = ∑( xij - u)2
          =   ∑ xij2 – T2/N        Where T= ∑xij
                                          T2/N is called correction factor
                                          u = ∑xij/N


2. Calculate Variance between Samples (SSC)
      Sum of square between samples due to columns
        SSC = h ∑(xij – u)2
                = ∑Cj2/ h – T2/N        Where h = no. of rows
                                                   PHARMAQUEST               8
3. Calculate Variance within samples (SSE)
    sum of squares within samples due to error
     SSE = SST – SSC


4. Calculate F – Ratio
      Fc = (SSC/ k-1) / (SSE/ N- k)


5. Compare Fc calculated with the FT ( table value)




                                              PHARMAQUEST   9
DISSOLUTION STUDIS OF
  DIFFERENT DOSAGE
         FORMS
   a) CONVENTIONAL
   b) CONTROLLED
        RELEASE


            PHARMAQUEST   10
(A) CONVENTIONAL

 Powder
 Tablets And Capsules
        (Uncoated, Plain Coated)
 Suspension
 Suppositories
 Topical Preparations



                         PHARMAQUEST   11
       Powders

   Powder particles dissolves independently of
    each other
 First step in process of dissolution is wetting of
     dissolving surface which is in contact with
     dissolution medium.
 Intrinsic dissolution profile
 Apparatus - II can be used

                                     PHARMAQUEST       12
Dissolution rate of dosage form which can be
  explained by Noyes – Nernst equation

   dC / dt = AD (Cs – C) / h V
       Where, A = Surface area of the dissolving solid
               D = Diffusion coefficient
               h = Diffusion layer thickness
               V = Volume of dissolution medium
               Cs = Solute conc. in diffusion layer




                                            PHARMAQUEST   13
TABLETS AND CAPSULES

 USP apparatus 1 and 2 are used


                  for dissolution of tablets and capsules.




                                       PHARMAQUEST           14
   DISSOLUTION OF TABLETS

 The rate of dissolution of drug substance from tablet
  depends on the (1) solubility of the drug in that solvent
  or gastric fluid and (2) the concentration of the drug in
  the solution.



 Process variables also affect the dissolution rate of the
  dosage form




                                     PHARMAQUEST              15
Tablet           Disintegration           Granules           Deaggregation




                                                             Drug particles in
                                                             Suspension
    Non -
    Disintegrating
                                  Drug in Solution in
                                  GI Fluid




                                  Drug in Blood



                                               PHARMAQUEST                       16
   Surface area Vs Time for different types of tablets



              Non-disintegrating
                   tablets

                                        Disintegrating
                                            tablets
                                       Fine particles
Surface
area
                     Disintegrated
                       granules
          Solid

                       Time
                                     PHARMAQUEST         17
Non disint. Tab.                      Rapidly disint. Tab




  a                                   b
                   Slowly disint. Tab




                           c
        Dissolved drug Vs Time for different type of tablets
                                            PHARMAQUEST        18
DRUG IN      DISSOLUTION OF             DRUG IN
CAPSULE      CAPSULE SHELL              CAPSULE
                                         MASS


 DIFFUSION    DRUG PARTICLES
 THROUGH
 THE SHELL    IN SUSPENSION


               DRUG IN
               SOLUTION


                 DRUG
               IN BLOOD

   DISSOLUTION OF CAPSULE DOSAGE FORM
                          PHARMAQUEST             19
 Different dissolution apparatus for tablet and
 capsules
 As per different pharmacopoeias


 IP                  BP                                  USP


APPARATUS I AND II                FOR UNCOATED & PLAIN
I- PADDLE TYPE                    COATED                   FOR
II- BASKET TYPE                   TABLETS AND CAPSULES     EXTENDED
                                  APPARATUS-I AND II       RELEASE AND
                                                           ENTERIC
                                                           COATED
              APPARATUS
               I, II AND III                               APP-III AND
              I-BASKET TYPE                                IV
              II- PADDLE TYPE
              III-Flow through cell
              type                         PHARMAQUEST                   20
USAGE OF TABLET TO CALIBRATE APPARATUS


   USP Prednisolone Tablets …….. Disintegrating

   USP Salicylic acid Tablets ……… Non-
                           Disintegrating




                                PHARMAQUEST       21
NON-OFFICIAL METHODS FOR TABLETS




                           PHARMAQUEST   22
DISSOLUTION OF SUSPENSION

  Suspension and Post disintegrated tablet ……. Not same dissolution profile
  Problem with suspension : 1. Retention of dissolving material
                               2. Sampling problem


  Direct method : By electronic particle counting device for hydrocortisone
 suspension
  Prednisolone acetate suspension have been evaluated for their dissolution
    rates by employing the spin- filter device which provides magnetically driven
    rotating filter system.
  Flow through apparatus has also been employed.




                                                 PHARMAQUEST                        23
DISSOLUTION OF SUPPOSITORY




               PHARMAQUEST   24
                  BASKET METHOD         MEMBRANE DIFFUSION
BEAKER METHOD
                                             METHOD




  DIALYSIS CELL
     METHOD
                            CONTINUOUS FLOW
                                METHOD
                                    PHARMAQUEST              25
            FLOW-THROUGH BEAD-BED
     DISSOLUTION METHOD FOR SUPPOSITORIES

THERMOREGULATED              INSULATED RESERVIOR
WATER BATH    GLSS HEATING
                COIL




                                                                      SUPPOSITORY
                                            FLOW-
                                           THROUGH
                                             -BED
                                           CHABBER

                                                                      GLASS
                                                                      BEADS




                                                   MAGNETIC STIRRER
 PERISTALTIC PUMP                      PHARMAQUEST                                  26
Topical Dosage Forms


   Official methods (USP)
     -- APP- V (paddle) , VI (Cylinder)
       And VII (Reciprocating holder)
   Non-official methods
         -- Diffusion through cellophane
            Paper


                               PHARMAQUEST   27
        SUPPORT TUBE




       SAMPLE 2 Gms
                                                       500mL
                                                       BEAKER
                                                       WITH 400mL
MEMBRANE 0.8μm                                         WATER AT
                                                       30O



                                               SUPPORT SCREEN
                                               40- MESH STAINLESS



                                                    MAGNETIC
                                                    STIRRER




                       DISSOLUTION OF OINTMENTS
                                 PHARMAQUEST                 28
Dissolution of controlled release
Dosage forms


FOR EXTENDED RELEASE AND
ENTERIC COATED

         APP-III AND IV (USP)




                       PHARMAQUEST   29
   Examples of using different dissolution apparatus for extended
   release tablets in USP



Dissolution                 Example
Apparatus
Apparatus I                 Cefaclor extended release tablets


Apparatus II                Acetaminophen extended release
                            tablets

Apparatus VII               Nifedipine extended release tablets




                                            PHARMAQUEST             30
        Study Questions

1. Which are difficulties in dissolution study of suppositories
   and suspensions
2. Discuss different methods of comparison of dissolution
   profile
3. Discuss dissolution behaviour of tablet and capsules
4. Describe different dissolution apparatus for dissolution study
   of suppositories




                                                  PHARMAQUEST       31
REFERENCES

 Pharmaceutical dissolution testing,
  By Umesh V. Banakar P. No. 251

   Indian Pharmacopoeia -1996
   British Pharmacopoeia,24; 1993
   United States Pharmacopoeia
   JPS 58,10, 1267; 1969
   JPS 86, 6, 691;1995
   JPS,88, 9, 842-850;1999

                              PHARMAQUEST   32

				
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