PILOT STUDY OF TABLETS AND CAPSULES.ppt

Document Sample
PILOT STUDY OF TABLETS AND CAPSULES.ppt Powered By Docstoc
					By

Dr. Basavaraj K. Nanjwade   M. Pharm., Ph. D
                  CONTENTS
      Introduction

     Objectives of the Pilot Plant

     Reasons for pilot plant

     Significance of pilot plant

     Importance of the Pilot Plant

     Pilot plant design for tablets

     Pilot plant scale-up techniques for capsules

     References
08 June 2009         SRTM University, NandedDept. of Pharmaceutics   2
                  Introduction
      What is Pilot plant :
                         “Defined as a part of the pharmaceutical
     industry where a lab scale formula is transformed into a viable
     product by the development of liable practical procedure for
     manufacture.”

                 R&D                                 Production

                           Pilot Plant

     Scale-up :
              “The art of designing of prototype using the data
     obtained from the pilot plant model.”
08 June 2009       SRTM University, NandedDept. of Pharmaceutics       3
      Objectives of Pilot Plant
            “Find mistakes on small scale and make profit on
       large scale.”
       To produce physically and chemically stable therapeutic
       dosage forms.
       Review of the processing equipment.
       Guidelines for productions and process control.
       Evaluation and validation.
       To identify the critical features of the process.
       To provide master manufacturing formula.

08 June 2009        SRTM University, NandedDept. of Pharmaceutics   4
  REASONS FOR BUILDING A PILOT PLANT

  To evaluate on process of large change in scale up
   operation.
  To find and examine all by-products or waste .
  To produce a trail lot of quantities of material.
  Clinical studies ,analytical development ,process
   development, stability testing.




08 June 2009    SRTM University, NandedDept. of Pharmaceutics   5
SIGNIFICANCE OF PILOT PLANT
  Examination of formulae.
  Review of range of relevant processing equipments.
  production rate adjustment.
  Idea about physical space required.
  Appropriate records and reports to support GMP.
  Identification of critical features to maintain quality.




08 June 2009    SRTM University, NandedDept. of Pharmaceutics   6
  Importance of Pilot Plant
     Examination of formulae.

     Review of range of relevant processing equipments.

     The specification of the raw materials.

     Production rates.

     The physical space required.

     Appropriate records and reports to support GMP.

08 June 2009       SRTM University, NandedDept. of Pharmaceutics   7
      Pilot Plant design for Tablets
      The primary responsibility of the pilot plant staff is to
      ensure that the newly formulated tablets developed by
      product development personnel will prove to be
      efficiently, economically, and consistently reproducible on
      a production scale.
      The design and construction of the pharmaceutical pilot
      plant for tablet development should incorporate features
      necessary to facilitate maintenance and cleanliness.
      If possible, it should be located on the ground floor to
      expedite the delivery and shipment of supplies.

08 June 2009       SRTM University, NandedDept. of Pharmaceutics   8
    Extraneous and microbiological contamination must be
    guarded against by incorporating the following features in the
    pilot plant design:
1. Fluorescent lighting fixtures should be the ceiling flush
        type.
2. The various operating areas should have floor drains to
        simplify cleaning.
3. The area should be air-conditioned and humidity controlled.
4. High -density concrete floors should be installed.
5. The walls in the processing and packaging areas should be
        enamel cement finish on concrete.
6. Equipment in the pharmaceutical pilot plant should be
        similar to that used by production division- manufacture of
        tablets.
08 June 2009          SRTM University, NandedDept. of Pharmaceutics 9
08 June 2009   SRTM University, NandedDept. of Pharmaceutics   10
08 June 2009   SRTM University, NandedDept. of Pharmaceutics   11
               Material handling system
     In the laboratory, materials are simply scooped or poured by
     hand, but in intermediate- or         large-scale operations,
     handling of this materials often become necessary.
     If a system is used to transfer materials for more than one
     product steps must be taken to prevent cross contamination.
     Any material handling system must deliver the accurate
     amount of the ingredient to the destination.
     The type of system selected also depends on the
     characteristics of the materials.
     More sophisticated methods of handling materials such as
     vacuum loading systems, metering pumps, screw feed
     system.
08 June 2009       SRTM University, NandedDept. of Pharmaceutics   12
               Vacuum loading machine
08 June 2009       SRTM University, NandedDept. of Pharmaceutics   13
                   Dry Blending
     Powders to be used for encapsulation or to be granulated
     must be well blended to ensure good drug distribution.
     Inadequate blending at this stage could result in discrete
     portion of the batch being either high or low in potency.
     Steps should also be taken to ensure that all the
     ingredients are free of lumps and agglomerates.
     For these reasons, screening and/or milling of the
     ingredients usually makes the process more reliable and
     reproducible.

08 June 2009      SRTM University, NandedDept. of Pharmaceutics   14
         The equipment used for blending are:
       V- blender
       Double cone blender
       Ribbon blender
       Slant cone blender
       Bin blender
       Orbiting screw blenders vertical and horizontal high
         intensity mixers.
         SCALE UP CONSIDERATIONS
        Time of blending .
        Blender loading.
        Size of blender.
08 June 2009     SRTM University, NandedDept. of Pharmaceutics   15
       V – cone blender                              Double cone blender
08 June 2009       SRTM University, NandedDept. of Pharmaceutics           16
               Ribbon blender

08 June 2009    SRTM University, NandedDept. of Pharmaceutics   17
                      Granulation
   The most common reasons given to justify granulating
   are:
 1. To impart good flow properties to the material,
 2. To increase the apparent density of the powders,
 3. To change the particle size distribution,
 4. Uniform dispersion of active ingredient.


   Traditionally, wet granulation has been carried out using,
  Sigma blade mixer,
  Heavy-duty planetary mixer.
08 June 2009    SRTM University, NandedDept. of Pharmaceutics   18
   Sigma blade mixer                                Planetary mixer
08 June 2009     SRTM University, NandedDept. of Pharmaceutics        19
     Wet granulation can
     also be prepared using
     tumble blenders
     equipped with high-
     speed chopper blades.




08 June 2009      SRTM University, NandedDept. of Pharmaceutics   20
            More recently, the use of multifunctional “processors” that
            are capable of performing all functions required to prepare
            a finished granulation, such as dry blending, wet
            granulation, drying, sizing and lubrication in a continuous
            process in a single equipment.




08 June 2009 15, 2012
Tuesday, May            Dept. University, NandedDept. of Pharmaceutics
                        SRTMof Pharmaceutics                             21
     Binders:

     Used in tablet formulations to make powders more
     compressible and to produce tablets that are more resistant
     to breakage during handling.

     In some instances the binding agent imparts viscosity to
     the granulating solution so that transfer of fluid becomes
     difficult.

     This problem can be overcome by adding some or all
     binding agents in the dry powder prior to granulation.
08 June 2009       SRTM University, NandedDept. of Pharmaceutics   22
     Some granulation, when prepared in production sized
     equipment, take on a dough-like consistency and may
     have to be subdivided to a more granular and porous mass
     to facilitate drying.
     This can be accomplished by passing the wet mass
     through an oscillating type granulator with a suitably large
     screen or a hammer mill with either a suitably large screen
     or no screen at all.




08 June 2009       SRTM University, NandedDept. of Pharmaceutics   23
                                 Drying
      The most common conventional method of drying a
      granulation continues to be the circulating hot air oven,
      which is heated by either steam or electricity.
      The important factor to consider as part of scale-up of an
      oven drying operation are airflow, air temperature, and the
      depth of the granulation on the trays.
      If the granulation bed is too deep or too dense, the drying
      process will be inefficient, and if soluble dyes are involved,
      migration of the dye to the surface of the granules.
      Drying times at specified temperatures and airflow rates
      must be established for each product, and for each particular
      oven load.
08 June 2009        SRTM University, NandedDept. of Pharmaceutics   24
    Fluidized bed dryers are
    an attractive alternative to
    the circulating hot air
    ovens.
    The      important    factor
    considered as part of scale
    up fluidized bed dryer are
    optimum loads, rate of
    airflow,      inlet      air
    temperature and humidity.




08 June 2009       SRTM University, NandedDept. of Pharmaceutics   25
           Reduction of Particle size
      Compression factors that may be affected by the particle
      size distribution are flowability, compressibility,
      uniformity of tablet weight, content uniformity, tablet
      hardness, and tablet color uniformity.
      First step in this process is to determine the particle size
      distribution of granulation using a series of “stacked”
      sieves of decreasing mesh openings.
      Particle size reduction of the dried granulation of
      production size batches can be carried out by passing all
      the material through an oscillating granulator, a hammer
      mill, a mechanical sieving device, or in some cases, a
      screening device.
08 June 2009       SRTM University, NandedDept. of Pharmaceutics   26
 Oscillating type granulator                            Hammer mill
08 June 2009      SRTM University, NandedDept. of Pharmaceutics       27
      As part of the scale-up of a milling or sieving operation,
      the lubricants and glidants, which in the laboratory are
      usually added directly to the final blend, are usually added
      to the dried granulation during the sizing operation.

      This is done because some of these additives, especially
      magnesium stearate, tend to agglomerate when added in
      large quantities to the granulation in a blender.



08 June 2009        SRTM University, NandedDept. of Pharmaceutics   28
                            Blending
     Type of blending equipment often differs from that using
     in laboratory.
     In any blending operation, both segregation and mixing
     occur simultaneously are a function of particle size, shape,
     hardness, and density, and of the dynamics of the mixing
     action.
     Particle abrasion is more likely to occur when high-shear
     mixers with spiral screws or blades are used.
     When a low dose active ingredient is to be blended it may
     be sandwiched between two portions of directly
     compressible excipients to avoid loss to the surface of the
     blender.
08 June 2009       SRTM University, NandedDept. of Pharmaceutics   29
     Equipments used for mixing
     Sigma blade mixer.
     Planetary mixer.
     Twin shell blender.
     High shear mixer



08 June 2009     SRTM University, NandedDept. of Pharmaceutics   30
               Slugging (Dry Granulation)
     A dry powder blend that cannot be directly compressed because
     of poor flow or compression properties.
     This is done on a tablet press designed for slugging, which
     operates at pressures of about 15 tons, compared with a normal
     tablet press, which operates at pressure of 4 tons or less.
     Slugs range in diameter from 1 inch, for the more easily
     slugged material, to ¾ inch in diameter for materials that are
     more difficult to compress and require more pressure per unit
     area to yield satisfactory compacts.
     If an excessive amount of fine powder is generated during the
     milling operation the material must be screened & fines
     recycled through the slugging operation.
08 June 2009       SRTM University, NandedDept. of Pharmaceutics   31
                  Dry Compaction
     Granulation by dry compaction can also be achieved by passing
     powders between two rollers that compact the material at
     pressure of up to 10 tons per linear inch.
     Materials of very low density require roller compaction to
     achieve a bulk density sufficient to allow encapsulation or
     compression.
     One of the best examples of this process is the densification of
     aluminum hydroxide.
     Pilot plant personnel should determine whether the final drug
     blend or the active ingredient could be more efficiently
     processed in this manner than by conventional processing in
     order to produce a granulation with the required tabletting or
     encapsulation properties.
08 June 2009        SRTM University, NandedDept. of Pharmaceutics   32
08 June 2009   SRTM University, NandedDept. of Pharmaceutics   33
08 June 2009   SRTM University, NandedDept. of Pharmaceutics   34
                      Compression
     The ultimate test of a tablet formulation and granulation
     process is whether the granulation can be compressed on a
     high-speed tablet press.

   During compression, the tablet press performs the
   following functions:
 1. Filling of empty die cavity with granulation.
 2. Precompression of granulation (optional).
 3. Compression of granules.
 4. Ejection of the tablet from the die cavity and take-off of
     compressed tablet.
08 June 2009      SRTM University, NandedDept. of Pharmaceutics   35
   When evaluating the compression characteristics of a particular
   formulation, prolonged trial runs at press speeds equal to that to
   be used in normal production should be tried.
   Only then are potential problems such as sticking to the punch
   surface, tablet hardness, capping, and weight variation detected.
   High-speed tablet compression depends on the ability of the
   press to interact with granulation.
   Following are the parameters to be considered while choosing
   speed of press.
1. Granulation feed rate.
2. Delivery system should not change the particle size
      distribution.
3. System should not cause segregation of coarse and fine
                                                  static charges.
      particles, nor it should induce of Pharmaceutics
08 June 2009         SRTM University, NandedDept.                  36
     The die feed system must be able to fill the die cavities
     adequately in the short period of time that the die is
     passing under the feed frame.
     The smaller the tablet , the more difficult it is to get a
     uniform fill a high press speeds.
     For high-speed machines, induced die feed systems is
     necessary.
     These are available with a variety of feed paddles and with
     variable speed capabilities.
      So that optimum feed for every granulation can be
     obtained.

08 June 2009       SRTM University, NandedDept. of Pharmaceutics   37
  After the die cavities are filled ,the excess is removed by the feed
  frame to the center of the die table.
  Compression of the granulation usually occurs as a single event
  as the heads of the punches pass over the lower and under the
  upper pressure rollers.
  This cause the punches to the penetrate the die to a preset depth,
  compacting the granulation to the thickness of the gap set
  between the punches.
  The rapidity and dwell time in between this press event occurs is
  determined by the speed at which the press is rotating and by the
  size of compression rollers.
  Larger the compressions roller, the more gradually compression
  force is applied and released.

08 June 2009      SRTM University, NandedDept. of Pharmaceutics     38
   Slowing down the press speed or using larger compression
   rollers can often reduce capping in a formulation.
      The final event is ejection of compressed tablets from die
      cavity.
      During compression, the granulation is compacted to form
      tablet, bonds within compressible material must be formed
      which results in sticking.
      High level of lubricant or over blending can result in a soft
      tablet, decrease in wettability of the powder and an
      extension of the dissolution time.
      Binding to die walls can also be overcome by designing the
      die to be 0.001 to 0.005 inch wider at the upper portion
      than at the center in order to relieve pressure during
      ejection.
08 June 2009        SRTM University, NandedDept. of Pharmaceutics 39
                      DIFFERENT PUNCHES &DIES




08 June 2009   SRTM University, NandedDept. of Pharmaceutics   40
        HIGH SPEED ROTARY
                                                         MULTI ROTARY MACHINE
             MACHINE


08 June 2009       SRTM University, NandedDept. of Pharmaceutics                41
               DOUBLE ROTARY
                                                                UPPER PUNCH AND
                  MACHINE
                                                                  LOWER PUNCH


08 June 2009           SRTM University, NandedDept. of Pharmaceutics              42
                  SINGLE ROTARY MACHINE



08 June 2009   SRTM University, NandedDept. of Pharmaceutics   43
                   Tablet Coating
     Sugar coating is carried out in conventional coating pans,
     has undergone many changes because of new
     developments in coating technology and changes in safety
     and environmental regulations.
     The conventional sugar coating pan has given way to
     perforated pans or fluidized-bed coating columns.
     The development of new polymeric materials has resulted
     in a change from aqueous sugar coating and more recently,
     to aqueous film coating.
     The tablets must be sufficiently hard to withstand the
     tumbling to which they are subjected in either the coating
     pan or the coating column.
08 June 2009      SRTM University, NandedDept. of Pharmaceutics   44
     Some tablet core materials are naturally hydrophobic, and
     in these cases, film coating with an aqueous system may
     require special formulation of the tablet core and/or the
     coating solution.
     A film coating solution may have been found to work well
     with a particular tablet in small lab coating pan but may be
     totally unacceptable on a production scale.
     This is because of increased pressure & abrasion to which
     tablets are subjected when batch size is large & different
     in temperature and humidity to which tablets are exposed
     while coating and drying process.

08 June 2009       SRTM University, NandedDept. of Pharmaceutics   45
08 June 2009   SRTM University, NandedDept. of Pharmaceutics   46
                             METHODS
DRY BLENDING                  WET                                  DRY
                           GRANULATION                         GRANULATION

   WEIGHING                 WEIGHING
                                                                WEIGHING
     SIZING                   SIZING
                                                                  SIZING
   BLENDING                GRANULATION
                                                                BLENDING
  LUBRICATION                DRYING
                                                               COMPACTION
  COMPRESSION               BLENDING
                                                                 MILLING
    COATING                LUBRICATION
                                                               LUBRICATION
                           COMPRESSION
                                                               COMPRESSION

08 June 2009   SRTM University, NandedDept. of Pharmaceutics            47
      Compression rates of typical production
      presses




08 June 2009   SRTM University, NandedDept. of Pharmaceutics   48
  Pilot Plant scale-up techniques
            for Capsule
   Capsules are solid dosage forms in which the drug
   substance is enclosed in either a hard or soft soluble
   container or shell of a suitable form of gelatin.
   Steps in capsule production
 1. Mixing of ingredient
 2. Granulation and lubrication
 3. Making of capsules
 4. Filling of capsules
 5. Uniformity testing
 6. Packing and labeling
08 June 2009   SRTM University, NandedDept. of Pharmaceutics   49
     The manufacturing process for capsulated products often
     same to that tablets.
     Both tablets & capsules are produced from ingredients that
     may be either dry blended or wet granulated to produce a
     dry powder or granule mix with uniformly dispersed
     active ingredients.
     To produce capsules on high speed equipment ,the powder
     blend must have the uniform particle size distribution,
     bulk density & compressibility required to promote good
     flow properties & result in the formation of compact of the
     right size and sufficient cohesiveness to be filled in to
     capsule shells.
08 June 2009       SRTM University, NandedDept. of Pharmaceutics   50
         Manufacture of Hard Gelatin
                 Capsules
 1. Shell composition :
    Gelatin :
  Prepared by the hydrolysis of collagen.
  Gelatin in its chemical and physical properties,
    depending upon the source of the collagen and
    extraction.
  There are two basic types of gelatin:
   Type – A and Type – B.
  The two types can be differentiated by their isoelectric
    points (7.0 – 9.0 for type A and 4.8 – 5.0 for type B) and
    by their viscosity and film forming characteristics.
08 June 2009     SRTM University, NandedDept. of Pharmaceutics   51
 Combination of pork skin and bone gelatin are often used
  to optimize shell characteristics.
 The physicochemical properties of gelatin of most interest
  to shell manufactures are the bloom strength and viscosity.

   Colorants :
 Various soluble synthetic dyes (“coal tar dyes”) and
   insoluble pigments are used.
 Not only play a role in identifying the product, but also
   may play a role in improving patient compliance.
 E.g., white, analgesia; lavender, hallucinogenic effects;
   orange or yellow, stimulants and antidepressants.
08 June 2009    SRTM University, NandedDept. of Pharmaceutics   52
 Opaquing agents :
Titanium dioxide may be included to render the shell
 opaque.
Opaque capsules may be employed to provide protection
 against light or to conceal the contents.

 Preservatives :
When preservatives are employed, parabens are often
 selected.




08 June 2009   SRTM University, NandedDept. of Pharmaceutics   53
   2) Shell manufacture :




08 June 2009    SRTM University, NandedDept. of Pharmaceutics   54
I.        Dipping :
         Pairs of the stainless steel pins are dipped into the dipping
          solution to simultaneously form the caps and bodies.
  The pins are at ambient temperature; whereas the dipping
          solution is maintained at a temperature of about 500C in a
          heated, jacketed dipping pan.
  The length of time to cast the film has been reported to be
          about 12 sec.
 II. Rotation :
  After dipping, pins are elevated and rotated 2-1/2 times
          until they are facing upward.
  This rotation helps to distribute the gelatin over the pins
          uniformly and to avoid the formation of a bead at the
          capsule ends. University, NandedDept. of Pharmaceutics
08 June 2009           SRTM                                           55
 III. Drying :
  The racks of gelatin coated pins then pass into a series
      of four drying oven.
  Drying is mainly done by dehumidification.
  A temperature elevation of only a less degrees is
      permissible to prevent film melting.
  Under drying will leave the films too sticky for
      subsequent operation.
 IV. Stripping :
  A series of bronze jaws strip the cap and body portions
      of the capsules from the pins.

08 June 2009    SRTM University, NandedDept. of Pharmaceutics   56
 V. Trimming :
  The stripped cap and body portions are delivered to
     collects in which they are firmly held.
  As the collects rotate, knives are brought against the
     shells to trim them to the required length.
 VI. Joining :
  The cap and body portions are aligned concentrically in
     channels and the two portions are slowly pushed
     together.



08 June 2009    SRTM University, NandedDept. of Pharmaceutics   57
 3) Sorting :
  The moisture content of the capsules as they are from
    the machine will be in the range of 15 – 18% w/w.
  During sorting, the capsules passing on a lighted moving
    conveyor are examined visually by inspectors.
  Defects are generally classified according to their nature
    and potential to cause problems in use.
 4) Printing :
  In general, capsules are printed before filling.
  Generally, printing is done on offset rotary presses
    having throughput capabilities as high as three-quarter
    million capsules per hour.
08 June 2009    SRTM University, NandedDept. of Pharmaceutics   58
      5) Sizes and shapes :
       For human use, empty gelatin capsules are
         manufactured in eight sizes, ranging from 000 to 5.
       Capsule capacities in table:
               Size                         Volume                     Fill weight(g) at 0.8
                                                                      g/cm3 powder density
               000                            1.37                            1.096
               00                             0.95                            0.760
                0                             0.68                            0.544
                1                             0.50                            0.400
                2                             0.37                            0.296
                3                             0.30                            0.240
                4                             0.21                            0.168
                5                             0.15                            0.104
08 June 2009          SRTM University, NandedDept. of Pharmaceutics                        59
 The largest size normally acceptable to patient is a No: 0.
 Three larger size are available for veterinary use: 10, 11,
   and 12 having capacities of about 30, 15, and 7.5 g,
   respectively.
 The standard shape of capsules is traditional, symmetrical
   bullet shape.
 Some manufactures have employed distinctive shapes.
 e.g. Lilly’s pulvule   tapers to a bluntly pointed end.
      Smith Kline Beacham’s spansule capsules        taper at
      both the cap and body ends.


08 June 2009    SRTM University, NandedDept. of Pharmaceutics   60
 6) Sealing :
  Capsules are sealed and somewhat reshaped in the
    Etaseal process.
  This thermal welding process forms an indented ring
    around the waist of the capsule where the cap overlaps
    the body.
 7) Storage :
  Finished capsules normally contain an equilibrium
    moisture content of 13-16%.
  To maintain a relative humidity of 40-60% when
    handling and storing capsules.

08 June 2009    SRTM University, NandedDept. of Pharmaceutics   61
      Filling of hard gelatin capsules
  Equipment used in capsule filling operations involves one
  often of two types of filling systems.
  Zanasi or Martelli encapsulator:
 Forms slugs in a dosatar which is a hollow tube with a
  plunger to eject capsule plug.
  Hofliger-Karg machine:
 Formation of compacts in a die plate using tamping pins
  to form a compact.


08 June 2009    SRTM University, NandedDept. of Pharmaceutics   62
     ZANASI AUTOMATIC                             HOFLIGER KARG AUTOMATIC
  CAPSULE FILLING MACHINE                         CAPSULE FILLING MACHINE

08 June 2009    SRTM University, NandedDept. of Pharmaceutics           63
     In this both system, the scale-up process involve bulk
     density, powder flow, compressibility, and lubricant
     distribution.
     Overly lubricated granules are responsible for delaying
     capsule disintegration and dissolution.




08 June 2009      SRTM University, NandedDept. of Pharmaceutics   64
                             OSAKA MODEL R-180
                           SEMI AUTOMATIC CAPSULE
                              FILLING MACHINE


08 June 2009   SRTM University, NandedDept. of Pharmaceutics   65
       Manufacture of Soft Gelatin
               Capsules
 I. Composition of the shell:
  Similar to hard gelatin shells, the basic component of
    soft gelatin shell is gelatin; however, the shell has been
    plasticized.
  The ratio of dry plasticizer to dry gelatin determines the
    “hardness” of the shell and can vary from 0.3-1.0 for
    very hard shell to 1.0-1.8 for very soft shell.
  Up to 5% sugar may be included to give a “chewable”
    quality to the shell.
  The residual shell moisture content of finished capsules
    will be in the range of 6-10%.
08 June 2009     SRTM University, NandedDept. of Pharmaceutics   66
 II. Formulation :
  Formulation for soft gelatin capsules involves liquid,
     rather than powder technology.
  Materials are generally formulated to produce the
     smallest possible capsule consistent with maximum
     stability, therapeutic effectiveness and manufacture
     efficiency.
  The liquids are limited to those that do not have an
     adverse effect on gelatin walls.
  The pH of the lipid can be between 2.5 and 7.5.
  Emulsion can not be filled because water will be
     released that will affect the shell.
08 June 2009   SRTM University, NandedDept. of Pharmaceutics   67
     The types of vehicles used in soft gelatin capsules fall in
     to two main groups:
      1.       Water immiscible, volatile or more likely more volatile
               liquids such as vegetable oils, mineral oils, medium-chain
               triglycerides and acetylated glycerides.
      2.       Water miscible, nonvolatile liquids such as low molecular
               weight PEG have come in to use more recently because
               of their ability to mix with water readily and accelerate
               dissolution of dissolved or suspended drugs.
  All liquids used for filling must flow by gravity at a
   temperature of 350c or less.
  The sealing temperature of gelatin films is 37-400C.

08 June 2009             SRTM University, NandedDept. of Pharmaceutics   68
 III. Manufacture process :
 A. Plate process :
      The process involved
              Placing the upper half of a plasticized gelatin sheet over
               a die plate containing numerous die pockets,
              Application of vacuum to draw the sheet in to the die
               pockets,
              Filling the pockets with liquor or paste,
              Folding the lower half of gelatin sheet back over the
               filled pockets, and
              Inserting the “ sandwich” under a die press where the
               capsules are formed and cut out.
08 June 2009          SRTM University, NandedDept. of Pharmaceutics     69
 B. Rotary die press:
  In this process, the die cavities are machined in to the
    outer surface of the two rollers.
  The die pockets on the left hand roller form the left side
    of the capsule and the die pockets on the right hand
    roller form the right side of the capsule.
  Two plasticized gelatin ribbons are continuously and
    simultaneously fed with the liquid or paste fill between
    the rollers of the rotary die mechanism.
  As the die rolls rotate, the convergence of the matching
    die pockets seals and cuts out the filled capsules.

08 June 2009    SRTM University, NandedDept. of Pharmaceutics   70
08 June 2009   SRTM University, NandedDept. of Pharmaceutics   71
 C. Accogel process:
  In general, this is another rotary process involving
              A measuring roll,
              A die roll, and
              A sealing roll.
  As the measuring roll and die rolls rotate, the measured
   doses are transferred to the gelatin-linked pockets of the
   die roll.
  The continued rotation of the filled die converges with
   the rotating sealing roll where a second gelatin sheet is
   applied to form the other half of the capsule.
  Pressure developed between the die roll and sealing roll
   seals and cuts out the capsules.
08 June 2009           SRTM University, NandedDept. of Pharmaceutics   72
 4. Bubble method:
  The Globex Mark II capsulator produces truly seamless,
    one-piece soft gelatin capsules by a “bubble method”.




08 June 2009   SRTM University, NandedDept. of Pharmaceutics   73
  A concentric tube dispenser simultaneously discharges
   the molten gelatin from the outer annulus and the liquid
   content from the tube.
  By means of a pulsating pump mechanism, the liquids
   are discharged from the concentric tube orifice into a
   chilled-oil column as droplets that consists of a liquid
   medicament core within a molten gelatin envelop.
  The droplets assume a spherical shape under surface
   tension forces and the gelatin congeals on cooling.
  The finished capsules must be degreased and dried.



08 June 2009    SRTM University, NandedDept. of Pharmaceutics   74
 IV. Soft/Liquid-filled hard gelatin capsules:
  Important reason: the standard for liquid filled capsules
   was inability to prevent leakage from hard gelatin
   capsules.
  As banding and of self-locking hard gelatin capsules,
   together with the development of high-resting state
   viscosity fills, has now made liquid/semisolid-filled
   hard gelatin capsules.
  As with soft gelatin capsules, any materials filled into
   hard capsules must not dissolve, alter or otherwise
   adversely affect the integrity of the shell.
  Generally, the fill material must be pumpable.
08 June 2009    SRTM University, NandedDept. of Pharmaceutics   75
 Three formulation strategies based on having a high
     resting viscosity after filling have been described.
          1. Thixotropic formulations,

          2. Thermal-setting formulations,

          3. Mixed thermal-Thixotropic systems.

  The more lipophilic contents, the slower the release rate.

  Thus, by selecting excipients with varying HLB balance,
        varying release rate may be achieved.

08 June 2009          SRTM University, NandedDept. of Pharmaceutics   76
                CAPSULE                                               AUTO MATIC
               POLISHING                                               CAPSULE
                MACHINE                                              ARRANGEMNT
08 June 2009         SRTM University, NandedDept. of Pharmaceutics                 77
                     References
 1. The theory and practice of industrial pharmacy. Leon
    Lachman, Herbert A. Lieberman, Joseph L. Kanig. Third
    edition. Varghese publishing house. Page no. 681-703.
 2. Pharmaceutical dosage forms: Tablets. Volume 3. second
    edition. Leon Lachman, Herbert A. Lieberman, Joseph
    B. Schwartz. Page no. 303-365.
 3. Pharmaceutical process scale –up edited by Michael
    Levin.
 4. Modern pharmaceutics. Edited by Gilbert S. Banker &
    Christopher T. Rhodes. 4th edition.
 5. www.google.com
08 June 2009    SRTM University, NandedDept. of Pharmaceutics   78
                        E-mail: bknanjwade@yahoo.co.in
                        Cell No: 09742431000




Tuesday, May
08 June 2009 15, 2012     Dept. University, NandedDept. of Pharmaceutics
                          SRTMof Pharmaceutics                             79

				
DOCUMENT INFO
Shared By:
Categories:
Tags:
Stats:
views:127
posted:5/16/2012
language:English
pages:79
handongqp handongqp
About