Controlled-Release Carbamazepine

							Controlled-Release Carbamazepine
Granules and Tablets Comprising Lipophilic
and Hydrophilic Matrix Components
                                   By
                                SOUMYA.T
                                 M.PHARM-I.P
                                     I-SEM.
                             UNDER THE GUIDANCE OF
                                Dr.V.P.REDDY
OBJECTIVE:

   To investigate the effect of lipophilic
    (Compritol® 888 ATO) and hydrophilic
    components (combination of HPMC and
    Avicel) on the release of carbamazepine
    from granules and corresponding tablet.
   To evaluate the physical characteristics of
    the prepared granules and matrix tablets.
                  INTRODUCTION
   Hydrogels can be applied for the release of both hydrophilic
    and hydrophobic drugs and charged solutes. Hydrogel provide
    the basis for implantation, transdermal and oral controlled-
    release systems.
   Hydrophilic polymers, in particular cellulose derivatives(e.g.
    HPMC) have beenwidely used in the formulation of hydrogel
    matrices which satisfy the key criteria for the development of
    controlledrelease oral solid dosage forms.
   hydrophobic polymers, Glyceride such as Compritol® (glyceryl
    behenate) have been used for the preparation of controlled
    release formulations since they possess some very interesting
    characteristics, i.e., chemical inertness against other materials
    and excellent flow properties.
MATERIALS:


   Carbamazepine,
   Compritol®,
   Hydroxypropyl methylcellulose &
   Microcrystalline cellulose
Preparation and Evaluation of Granules


 By using wet granulation technique.
 The granules were evaluated on the basis of
  CBZ content, angle of repose, bulk (BD) &
  tap (TD) density. Also, the Carr’s index was
  calculated by using the following equation:
           CI = TD - BD * 100/TD.
Preparation of Matrix Tablets
   Magnesium stearate 1% w/w was added to the dried
    granules and tumbled mixed for 5 min. An accurately
    weight portion of lubricated granules from each
    formula containing CBZ equivalent to 200 mg was
    fed manually to the die of a single punch tabletting
    machine equipped with flat faced punch of 9-mm
    diameter and compressed at the maximum
    compaction pressure of 4,034 kg/cm2.
   These matrix tablets were evaluated for CBZ
    content, friability, weight variation, thickness and
    diametral tensile strength.
Table I. Composition of CBZ Wet Granulations Comprising Lipophilic–Hydrophilic Matrix
Components
      DRUG-EXCIPIENT STUDIES

   Differential Scanning Calorimeter :
    About 2–5 mg either pure drug or pure excipient, or
    drug: excipient physical and granulated mixture was
    analyzed in a Perkin-Elmer differential scanning
    calorimeter, at a heating rate of 10°C/min, from
    25°C to 200°C. The samples were heated in sealed
    aluminium pans, under a nitrogen flow (20 mL/min)
    and an empty sealed pan was used as reference.
    The apparatus was calibrated with indium (99.98%,
    m.p. 156.65°C).
Fourier Transform Infrared Spectroscopy
(FT-IR)
   IN VITRO RELASE STUDIES:
 The in vitro drug release was evaluated by using the USP/NF
  dissolution apparatus II
 The CBZ content was determined using a UV spectrophotometer at
  285nm.

Water Uptake (Swelling) of Compacted Matrix
 Components:
 % of swelling (S%) was calculated according to the following
  relationship:
         S% =(Ws- Wd)/Wd*100
   RESULTS AND DISCUSSION

Physical Properties of the Granules:
 Carr’s index-15 & 25,
 angle of repose-28° and 35.5°.
Evaluation of the Tablet Properties:
 drug content-96.49% and 100.55%
 tensile strength-6.65 to 8.3 kg/cm2
 Friability of all formulations was less than 1%.
Differential scanning calorimetric studies:

DSC curve of CBZ displayed a single
 sharp endothermic peak at 1980c
 corresponding to its m.p,Compritol at
 720c,60-1600c range for HPMC & Avicel.
The DSC curve of physical mixture also
 shows identical peaks to pure
 components,this indicates no
 incompatibility b/w the drug & excipients.
DSC
FT-IR SPECTRA:

IR bands of CBZ are observed at
 3474,1686,1603,1593cm-1 due to -NH,-
 CO-R,-C=C=,-C=O vibrations respectively,
Similar peaks were observed for physical
 mixture of drug & excipients ,this indicates
 no interaction of excipients with the drug.
IN VITRO DRUG RELEASE KINETICS
FROM GRANULATION:
 The release pattern of CBZ showed fast dissolution &
  burst effect during first hour.
 In case of A1,A2,A3(weight ratio of compritol:HPMC is
  more than 1) the drug release was not effected by the
  content of HPMC.
 In case of A4 & A5 (weight ratio less than 1)burst effect
  decreased,sustaining effect increased.
 This indicates HPMC concentration plays a major role.
 Drug release from granules follows Higuchi & korsmeyer
  et al model.
IN VITRO DRUG RELEASE KINETICS
FROM MATRIX TABLETS:
The release rate from the control tablets
 was very slow,HPMC content affect the
 release behaviour.
A gradual disintegration of the matrix
 tablets was observed due to axial
 expansion of the tablet.
It follows diffusion controlled release & fits
 into zero order model due to erosion.
RELEASE PATTERN
              CONCLUSION
 Combination of compritol with HPMC & Avicel as
  matrix former offers a flexible system for
  sustained release of CBZ(85% release after 7
  hrs).
 Hydration ability,mechanical strength of the gel
  & stress applied in stomach,intestine influences
  in vivo drug release.
 Formulation containing 75% w/w CBZ in a matrix
  composed of compritol:HPMC:Avicel at
  1:8:1(A5) Ratio was selected for further in vivo
  study in dogs.
REFERENCES
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