DOSAGE FORMS

							    Dosage Forms




.
Introduction
 What is the difference between a
 chemical and a drug?
Chemical: A substance composed of
 chemical elements or obtained by
 chemical process (review chemistry)
Drug: an agent intended for use in the diagnosis,
  mitigation, treatment, cure, or prevention of
  disease in man or other animals
  (biopharmaceutics)
Dosage Forms
   Drug substances are seldom
    administered alone, but rather as a part
    of a formulation in combination with
    one or more non medical agents that
    serve varied and specialized
    pharmaceutical functions.
Pharmaceutical Ingredients
can serve several functions
   solubilize      color
   suspend         flavor
   thicken         fashion medicinal
   dilute           agents into
   emulsify         efficacious and
                     appealing dosage
   stabilize        forms
   preserve
Why use dosage forms?

   Mechanism for the safe and
    convenient delivery of accurate dosage
   Protection of a drug substance from
    destructive influences of atmospheric
    oxygen or humidity
   Protection from influence of gastric
    acid after oral administration
   To mask taste of offensive drugs.
Why use dosage forms?
   To provide liquid preparations of
    substances that are either insoluble or
    unstable
   To provide clear liquid dosage forms
   To provide time-controlled release of
    drugs
   To provide optimal topical
    administration
Why dosage forms?
   To provide for the insertion of a drug
    into one of the body’s orifices
   Provide for placement of drugs into the
    blood stream
   Provide for lung inhalation of drugs
        DIFFERENT TYPES

   SOLID DOSAGE FORMS
   POWDERS
   TABLETS
   CAPSULES
   SPANSULES (coated pellets in capsule)
   SEMISOLID DOSAGE FORMS
   OINTMENTS
   CREAMS
   PASTES
   GELS
   JELLIES
   SUPPOSITORIES
   PESSARIES
   LIQUID DOSAGE FORMS
    ☺   SOLUTIONS
           ORAL SOLUTIONS
           PARENTERALS
    ☺ SUSPENSIONS
    ☺ EMULSIONS
   INHALATIONS
   AEROSOLS
                POWDER
   A powder is a dry, bulk solid composed
    of a large number of very fine particles
    that may flow freely when shaken or
    tilted.
                 TABLET
   A tablet is a mixture of active
    substances and excipients, usually in
    powder form, pressed or compacted
    into a solid.
               CAPSULE
   Capsule - A small gelatinous case
    enclosing a dose of medication
   made both from gelatine and from plant-
    based gelling substances like
    carrageenans and modified forms of
    starch and cellulose.
                OINTMENT
   An ointment is a viscous semisolid
    preparation used topically on a variety of
    body surfaces. These include the skin and the
    mucus membranes of the eye (an eye
    ointment), vagina, anus, glans and nose. An
    ointment may or may not be medicated.

                    CREAMS
   Creams are semi-solid emulsions, that
    is mixtures of oil and water.
   They are divided into two types:
       oil-in-water (O/W) creams which are
        composed of small droplets of oil dispersed
        in a continuous aqueous phase, and
       water-in-oil (W/O) creams which are
        composed of small droplets of water
        dispersed in a continuous oily phase
                  PASTE
   paste is basic pharmaceutical form. It
    consists of fatty base (e.g. petroleum
    jelly) and at least 25% solid substance
    (e.g. zinc oxide).
   Examples include starch pastes,
    toothpaste
              GELS
   Gel - colloidal system in which a porous
    network of interconnected nanoparticles
    spans the volume of a liquid medium
   A suppository is a drug delivery system
    that is inserted either into the rectum (rectal
    suppository), vagina (vaginal suppository) or
    urethra (urethral suppository) where it
    dissolves
                 PESSARY
   A pessary is a small plastic or silicone
    medical device or form of
    pharmaceutical preparation which is
    inserted into the vagina or rectum and
    held in place by the pelvic floor
    musculature
   a solution is a homogeneous mixture
    composed of two or more substances. In
    such a mixture, a solute is dissolved in
    another substance, known as a solvent.
    a suspension is a colloidal dispersion
    (mixture) in which a finely-divided species
    is combined with another species, with
    the former being so finely divided and
    mixed that it doesn't rapidly settle out.
               EMULSION
   An emulsion is a mixture of two
    immiscible (unblendable) substances.
    One substance (the dispersed phase) is
    dispersed in the other (the continuous
    phase).
   An inhaler or puffer is a medical device
    used for delivering medication into the body
    via the lungs
   Medication is most commonly stored in
    solution in a pressurized canister. The
    canister is attached to a plastic, hand-
    operated actuator.
   The standard metered-dose inhaler (MDI) on
    activating releases a fixed dose of medication
    in aerosol form
   Liniment, is a medicated topical
    preparation for application to the skin.
    Preparations of this type are also called
    balm. less viscous than an ointment or
    cream) applied with friction.
   Lotion is a liniment that is applied
    without friction
                  ENEMA
   An enema (plural enemata or
    enemas) is the procedure of
    introducing liquids into the rectum and
    colon via the anus.
TRANSDERMAL PATCH
   A transdermal patch or skin patch is
    a medicated adhesive patch that is
    placed on the skin to deliver a time
    released dose of medication through
    the skin and into the bloodstream.
CONSTITUENTS OF A DOSAGE FORM
   DRUG
   VEHICLE
   PHARMACEUTICAL EXCIPIENTS
     PHARMACEUTICAL EXCIPIENTS

   TABLETS
       Diluents and fillers (lactose)
       Binders (starch)
       Antiadherents or lubricants (Mg.stearate,Ca.stearate)
       Disintegrating agents (starch)
       Colouring agents (amaranth solution, caramel, cupric
        sulfate (blue), ferrous sulfate (red), zinc oxide (pink).
       Sweetening agents (Sucrose, saccharin, aspartame)
       Flavouring agents (cocoa, raspberry, orange, Cinnamon)
   SEMISOLID DOSAGE FORMS
–   Pharmaceutical bases
   SOLUTIONS
       Solvents to dissolve the drug
        substances
       Flavors and sweeteners
       Colorants
       Preservatives
       Stabilizers
        TABLETS

SOLID UNIT DOSAGE FORM OF
MEDICAMENT/S WITH SUITABLE
EXCIPIENTS INTENDED FOR ORAL USE.
ADVANTAGES:
Tablets are most widely used solid dosage forms
because of following advantages
Easy to carry
Easy to swallow
Attractive in appearance
Unpleasant taste masked by sugar coating
Unidosage accuracy
Prolonged stability
Incompatibilities of medicaments are less
Cost of production –low
    DISADVANTAGES

Drugs of amorphous nature-cannot be
compressed
Delayed action
Unconscious patients-not suitable
Swallowing difficult-children
    ESSENTIAL QUALITIES OF
            A GOOD TABLET
Accurate &uniform in weight
Drugs-uniformly distributed
Size & shape-easy administration
Not too hard-disintegration
No incompatibilities
Chemically & physically stable-storage
No breakage-transportation
No crumble-hands
Attractive in appearance
No manufacturing defects
Economical -production
    IDEAL CHARACTERISTICS OF EXCIPIENTS
   Non toxic and acceptable to
    regulatory authorities
   Must be commercially available in
    an acceptable grade
   Cost must be low
   Physiologically inert
   Physically and chemically stable
   Free of microorganisms
   Color compatible
   Must not have effect on bio-
    availability
             DILUENTS

   DILUENTS/FILLERS DESIGNED TO
    INCREASE THE BULK
   LACTOSE
   SPRAY DRIED LACTOSE
   STARCH
   MANNITOL
   DEXTROSE
   SORBITOL
   MICROCRYSTALLINE CELLULOSE
BINDERS AND
ADHESIVES
    To form granules or promote cohesive
     compacts for directly compressed
     tablets
    Acacia and tragacanth gums
    Gelatin
    Starch paste
    Liquid glucose
    Modified natural polymers
            (Poly vinyl pyrrolidone)
          DISINTEGRANTS
   Facilitate break up or disintegration
   Mechanism
       Draws water in to tablet ,swelling and
        causing tablet to burst apart.
   Starch USP and various starch
    derivatives
   Modified starches are primogel and
    explotab
   Pregelatinized starches are employed
       DISINTEGRANTS
 Clays such as veegum HV and
  bentonite(10%)
 Ac-Di-Sol is commonly used

  among cellulose class.- cross
  linked CMC
 PVP (cross linked polymer)
LUBRICANTS,
ANTIADHERENTS AND
GLIDANTS
   Lubricants reduce friction between
    tablets and dye surface during
    ejection of the tablet
   Antiadherents reduce sticking or
    adhesion of tablets to punches
   Glidants to promote flow properties
   Hydrocarbon oils: mineral oil
   Stearic acid and its salts
   Talc
   Colloidal silica, talc, magnesium
    stearate, starch and its
    derivatives – antiadherents
   Glidants:corn starch 5-
    10%,colloidal silica such as Cab-
    O-Sil ,syloid ,or aerosil in 0.25-
    3% conc.
COLOURING AGENTS
   Use of colours and dyes in tablets
       Disguising of off-color drugs
       Product identification
       Production of a more elegant product
   FD&C dyes and D&C dyes- applied
    as solution in granulating agent-
    and the Lake form of these dyes
   A FD&C lake is a pigment consisting
    of a substratum of alumina
    hydroxide on which dye is adsorbed
    or precipitated
SWEETENING AGENTS
  Limited to chewable tablets
  Mannitol is 72% as sweet as

   sucrose
  Saccharin

  Asparatame
FLAVOURING AGENTS

   Usually limited to chewable tablets, lozenges &
    effervescence tablets
   Volatile oils, volatile substances & fruit flavors
   Oil or water soluble liquids or dry powders
   Oil soluble carriers – soya bean and other edible
    oils
   Water soluble carriers- water, ethanol ,
    propylene glycol, glycerine and emulsifiers
   Dry carriers include – maltodextrins, cornsyrup
    solids, modified starches , gumarabic , salts,
    sugars and whey protein.
   Water soluble : less stable
   Flavour range: 0.5 to 0.75
CAPSULE

 Solid unit dosage form of medicament
 in which the drug(s) is enclosed in a
 practically tasteless , hard or soft
 soluble container or shell made up of a
 suitable form of gelatin
ADVANTAGES
   Tasteless, odorless
   Easily administered
   Attractive in appearance
   Easy to handle and carry
   Economical
   Drugs having unpleasant odour &
    taste---tasteless shell
DISADVANTAGES


   Hygroscopic drugs
   Concentrated solutions which require
    previous dilution
TYPES OF CAPSULES
   HARD CAPSULES



   SOFT CAPSULES
HARD CAPSULES
       DIFFERENT SIZES


 000     00    0    1    2   33   4   5




 CAPACITY VARIES:600mg to 30mg
FILLING POSSIBILITY
DIFFERENT SHAPES




  OBLONG ,OVAL & ROUND
Types of solid dosage forms
   Powder
   Tablets
   Capsules
   Sustained release dosage forms
Advantages
   Tablets               Capsules
       Tamper proof          Liquid drugs like oil
       cheaper than           & powder drugs can
        capsules               be encapsulated
                              Mask taste,color and
                               odour
Advantages of tablets

   Unit dosage form and offers highest dose precision &
    least content variation
   Cost is the least of all dosage forms
   Lightest and most compact
   Easiest and cheapest to package and ship
   Product identification is simplest and cheapest
   Greatest ease of swallowing
   Delayed release products can be designed
   Better suited for large scale production
   Best combined properties of chemical,mechanical and
    microbiological stability of all the oral forms
Disadvantages
   Some drugs resist compression in to dense
    compact owing to their amorphous nature or
    flocculent low-density character
   Drugs with poor wetting,slow dissolution
    properties,optimum to larger
    dosages,optimum absorption high in GIT ---
    difficult or impossible to formulate
   Bitter tasting drugs,drugs with objectionable
    odor,oxidisable or hydrolysable drugs ----
    cannot be formulated or should be
    formulated as coated tablets
Properties - Pharmaceutical
   Objective:
       Design and manufacture of the compressed tablet
        to deliver the correct amount of drug
       Should be elegant product having its own identity
        while being free of defects such as
        chips,cracks,discoloration,contamination and the
        like
       Strength to withstand mechanical shocks
       Should have the chemical and physical stability to
        maintain physical attributes
Properties - Pharmacokinetic
   Must be able to release the medicinal
    agents in the body in a predictable and
    reproducible manner
   Chemical stability – prevent interaction
                   Evaluation
   General appearance:
       Visual identity
       Elegance
       Measurement of tablet’s size, shape, color,
        presence or absence of odor, taste ,surface
        texture, physical flaws and consistency.
                 Evaluation
   Size and shape
   Unique identification markings
   Organoleptic properties
   Hardness and friability
   Drug content and release
   Weight variation
   Disintegration
   Dissolution
                Processing problems
   Capping and lamination
   Picking and sticking
   Mottling
   Weight variation
   Granule size and distribution before compression
       Poor flow
       Punch variation
       Hardness variation
       Double impression
Definition of Aerosols
   Pressurized dosage forms that upon
    actuation emit a fine dispersion of liquid
    or solid material containing one or more
    active ingredients in a gaseous medium

   Aerosols expel their contents as fine
    mist, coarse, wet or dry spray, a steady
    steam or a stable or a fast breaking
    foam
Advantages


   Uncontaminated delivery of a portion
    of drug
   Hermetic containers--- protected from
    oxygen
   Opaque containers ----- protected from
    atmospheric light
   Sterility due to aseptic packing
   Topical application feasible
Advantages
   Particle size of the emitted product and
    its physical form may be controlled
   Dosage can be controlled through the
    use of metered valves
   Aerosol application is a clean process
    requiring little or no wash up by the
    user
Principle
   Formulation consists of two component
    parts
       Product concentrate
       Propellant
   Product concentrate is active ingredient
   Combined with antioxidants , surface
    active agents and solvents
Principle
   Propellant is a liquefied gas or a
    mixture of liquefied gases
   Responsible for maintaining pressure
   Acts as solvent or vehicle for the
    product concentrate
   Compressed gases like carbondioxide
    ,nitrogen,nitrous oxide are employed as
    propellants
   Chloro-fluorocarbons were used as
    propellants
Propellants
   Eg:dichloro-difluoro methane, dichloro
    tetrafluoro ethane, trichloromonofluoro
    methane
   Fluorinated hydrocarbons are gases at
    room temperature but can be liquefied
    by cooling or by compression at room
    temp.
Aerosol systems
   Pressure and performance
   Pressure can be controlled by
       Type and amount of propellant
       Nature and amount of product concentrate
                      Types
   Solution system
       Two phase system – vapor phase and
        liquid phase
       Active ingredients are soluble in the
        propellant
   Water based system
       Water replaces the non aqueous solvents
       Depending on the formulation emitted as
        spray or foam.
       Surfactants, cosolvents are used
                     Types
   Suspension or disperse systems
       Foam systems
       Non aqueous stable foams
       Quick breaking foams
       Thermal foams
       Intranasal foams
Selection of a propellant
   Blends of various LG propellants
   Non reactive with formulation
    ingredients or valve components
       Eg:trichloromonofluoro methane tends to
        form hydrochloric acid with water or ethyl
        alcohol
   No physiological effects
   Non irritant
   No effect on the absorption of drugs
   No cardiotoxic effects
Two phase systems
   Contains liquid phase containing
    propellant and product concentrate
   Vapor phase
Three phase systems
   Three phases consisting of
       Immiscible liquid propellant
       Highly aqueous product concentrate
       Vapor phase
   Dip tube extends only up to product
    concentrate (aqueous phase)
   Vapor phase is replenished from the
    propellant
   Comparative evaluation with
    international brand(s) or approved
    Indian brands,
        If applicable
       Pack presentation
       Dissolution
       Assay
       Impurities
       Content uniformity
       pH
   Force degradation study
   Stability evaluation in market
    intended pack at proposed storage
    conditions
   Packing specifications
   Process validation
Parenterals?
   Term refers to the injectable routes of
    administration
       Para – outside
       Enteron – intestine
   Used when rapid drug action is required
   Un co-operative ,unconscious or unable
    to accept or tolerate oral medication
   Under medical supervision
        Types of parenterals

   Subcutaneous patches
   Biologicals
   Vaccines
   Ophthalmic preparations
        Parenteral routes

•Intravenous
•Intramuscular
•Subcutaneous
•Intra-dermal
•Intra-thecal
Injections
   Injections are sterile, pyrogen free
    preparation intended to be administered
    parenterally.
Official types of injections
   Injection
       Liquid preparations that are drug
        substances or solutions thereof (eg: insulin
        injection USP)
   For injection
       Dry solids that upon addition of suitable
        vehicles yield solutions ( eg:Cefuroxime for
        injection USP)
Official types of injections
   Injectable emulsion :
       Liquid preparation of drug substance
        dissolved or dispersed in a suitable
        emulsion medium ( eg: propofol USP)
   Injectable suspension :
       Liquid preparation of solid suspended in a
        suitable liquid medium ( methyl
        prednisolone acetate suspension USP).
Official types of injections
   For injectable suspension
       Dry solid that upon addition of a suitable
        vehicle yields preparation conforming in all
        respects to an injectable suspension
        (Imipenem and Cilastatin for injectable
        suspension USP)
    Pyrogen and pyrogen testing
   Pyrogens are removed by oxidation or
    imparting alkalinity to the solution

   Potassium permanganate is added as
    oxidizing agent

   Barium hydroxide is added to impart alkalinity

   Distillation is repeated to make it chemical
    free
                    Pyrogen testing
   In vivo
       Using rabbits


   In vitro
       Using limulus polyphemus (LAL test)
       Blood cells of horse-shoe crab
       Contains enzyme protein system that coagulates
        in the presence of low levels of polysaccharides.
       Interference of the active ingredients.
           Industrial preparation
   GMP is followed
   In sterilized area
   Required ingredients are dissolved in
    the given vehicle or combination of
    different solvents
   Solution is filtered until sparkling clear
   Solution is transferred to final
    containers as rapidly as possible
   Final product is then sterilized
                Packaging
   Containers should not interact with the
    product
   Colorless, transparent or light amber
    colored bottles are used to enable
    visible inspection.
   Type of glass is stated in the
    monograph
                      Containers
   Single dose containers
       A hermetic container holding a quantity of
        sterile drug intended for parenteral
        administration as a single dose ;when
        opened it cannot be re-used. eg: ampoules
        or single dose vials
   Multiple dose containers
       A hermetic container that permits the
        withdrawal of successive portions of the
        contents without altering the strength,
        quality or purity of the remaining portion
             Labeling requirements
   Label for a preparation must include
       Name of the preparation
       For a liquid preparation , the percentage
        content of drug or the amount of drug in a
        specified volume
       For a dry preparation, the amount of active
        ingredient present and the volume of the
        solvent to be added
       Route of administration
       Names of manufacturer ,distributor,
       Lot number ,manufacturing history of the
        specific package
        Storage requirements
   According to the individual monograph
    specifications
   Biological products like vaccines,
    toxoids ,toxins and related products are
    to be stored under special concern or
    conditions
                 QA/QC
   Strict quality control is followed
   Manufacturing standards should meet
    GMP requirements
                Quality control tests
   Leaker test
   Clarity test
   Pyrogen test
   Sterility test