This slide outlines the evaluation methods of various Controlled Drug Delivery Systems (CDDS) used in the pharmaceutical industry. The controlled Drug Delivery Systems release the drug to the plasma at a controlled, pre-determined level to ensure prolonged and adequate drug supply for a longer time. The slide analyses the various evaluation methods, its pharmacokinetic properties and applications of the evaluation methods in various scenario.

1. EVALUATION OF
CDDS
Presented by:
Muhammed Fahad
1st M.Pharm
Dept. of Pharmaceutics
Al-Shifa College of
Pharmacy

2.  Mainly used is in-vitro dissolution
tests.
 Dissolution studies together with
bioavailability studies—used to predict
in-vitro-in-vivo correlation (IVIVC).
INTRODUCTION
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3. DISSOLUTION STUDIES
Criteria:
 Reproducibility of medium
 Proper choice of the medium
 Maintenance of sink conditions
 Dissolution rate as a function of pH
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4. Parameters to be taken care of:
1. Lack of dose dumping
2. Complete drug release from the
dosage form—at least 75-80% to be
released at the last sampling interval
3. pH dependence/independence of the
dosage form
DISSOLUTION STUDIES
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5. In-Vitro-In-Vivo Correlations
(IVIVC)
Different degrees of correlations exist:
 Correlation Level A
 Correlation Level B
 Correlation Level C
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6. Correlation Level A
 Highest level of correlation (ideal).
 relationship exist.
 Here, direct comparison of in-vitro
dissolution curve with plasma drug
concentration–time curve can be
done.
 Advantage: simply perform in-vitro
tests.
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7.  Correlation is less than Level A.
 Mean Residence Time (MRT) of the
drug in body and mean dissolution
time in vitro are determined and
correlated.
Correlation Level B
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8.  Weakest level of correlation—only
partial relationship between absorption
and dissolution exist.
 Uses a single point in the dissolution
curve to correlate to plasma drug
concentration–time data.
 E.g. t50%, t90%
Correlation Level C
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9. Pharmacokinetic Studies
 Various types of pharmacokinetic
studies may be required by the FDA.
 Extended-release dosage form should
be available in several dosage
strengths.
 Reference—full NDA-approved
conventional, immediate-release
dosage form given in equal daily dose
 Both single- and multiple-dose steady-
state crossover studies are done. 9

10. Waivers:
 Done when 2 drug products are:
 In same dosage form.
 Proportionally similar in active & inactive
ingredients.
 Differ only in strengths of the medication.
 Bioequivalence study of lower strength(s)
can be waived.
 Only comparative in vitro dissolution test is
required to establish bioequivalency.
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Pharmacokinetic Studies

11. Case One:
 Extensive
pharmacodynamic/pharmacokinetic
data exist for the IR formulation of an
ER formulation.
 Both single- and multiple-dose steady-
state crossover studies are required.
 Study also performed as fasting state
vs fed state (high-fat meal).
Pharmacokinetic Studies
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12. To determine:
 Need for labeling specifications of
special conditions w.r.t meals.
 Whether the absorption pattern of the
ER dosage compares to that for IR
(conventional) form of the same drug.
Pharmacokinetic Studies
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13. Case Two:
 Concerned with non-oral extended-
release dosage forms.
 Usually require studies of Case but
doesn’t need fed state study.
 E.g. isoproterenol  form sulfate
conjugation orally; i.v. forms 3-O-
methylated derivative via COMT.
Pharmacokinetic Studies
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14. Case Three:
 Involve generic equivalent of an NDA-
approved, extended-release product.
 Establishment of bioequivalence is
done.
Pharmacokinetic Studies
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15. Evaluation of In-Vivo
Bioavailability Data
Pharmacokinetic Profile:
 Calculate Ka using Wagner-Nelson
method.
 Should not have significant dose-
dumping.
 Bioavailability data should
demonstrate extended-release
characteristics.
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16. Rate of Drug Absorption:
Evaluation of In-Vivo
Bioavailability Data
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17. Occupancy Time:
Evaluation of In-Vivo
Bioavailability Data
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18. Evaluation of TDDS
Thickness:
 Using digital micrometer screw gauge
at 3 diff. places and the mean value is
calculated.
Folding endurance:
 Folding endurance at the same place till
the patch breaks.
Tensile strength:
 Weight is gradually increased till the
patch breaks. 18

19. Evaluation of TDDS
Weight variation:
 Individually weighing 10 random
patches.
Drug content:
 Using suitable analytical methods.
Percentage of moisture content:
 Weighed and placed in desiccator
containing activated silica at room
temperature for 24 hours.
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20. Evaluation of TDDS
Percentage of moisture uptake:
 Kept in dessicator for 24 hrs; exposed
to 84% RH (saturated sol. of NH4Cl).
In vitro diffusion studies:
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21. REFERENCE:
 Shargel. L, Applied Biopharmaceutics
and Pharmacokinetics, 5th edition, Mc
Graw Hill, Singapore, 2005.
 Brahmankar. D. M, Biopharmaceutics
and Pharmacokinetics—A Treatise, 1st
editon, Vallabh Prakashan, 2006.
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