Biopharmaceuticals Classification System

• Biopharmaceuticals Classification System


  • Class I: High Permeability, High Solubility
  • Class II: High Permeability, Low Solubility
  • Class III: Low Permeability, High Solubility
  • Class IV: Low Permeability, Low Solubility
• Highly soluble


  The highest dose is soluble in <250 ml water over a pH range of 1 to 7.5
• Highly permeable


  >90% dose absorbed in humans
• Rapidly dissolving


  >85% of labeled amount of drug substance dissolves within 30 minutes
• Stability testing of drug substances at the preformulation level


  • Provides a clear idea about which types of dosage forms can be used
  • Highly unstable protein drug cannot be placed in anything but a highly preserved and protected parenteral form
• Excipients


  Substances other than the active drug substance that are included in the drug delivery system or packaging of a drug product
• Functional roles of excipients


  • Modulating solubility and bioavailability of the active ingredient(s)
  • Enhancing stability of the active ingredient(s) in finished dosage forms
  • Helping active ingredients maintain a preferred polymorphic form or conformation
  • Maintaining pH and osmolarity of liquid formulations
  • Acting as antioxidants, emulsifying agents, aerosol propellants, tablet binders, and tablet disintegrants
  • Preventing aggregation or dissociation
  • Modulating the immunogenic response of active ingredients (e.g., adjuvants)
• Types of excipients


  • Binders
  • Coating
  • Disintegrants
  • Glidant
  • Diluent
  • Lubricant
• Binders


  Help in bringing cohesiveness to the drug, hold the ingredients of tablets and ensure the required mechanical strength of the tablet
• Types of binders


  • Solution binders (dissolved in solvent before adding to tablet, e.g. gelatin, PEG)
  • Dry binders (added as powder, e.g. cellulose, methyl cellulose)
• Coating

  • Mask taste, odour, colour of drugs
  • Control and sequential release of drug from tablet
  • Protect drug from gastric environment of stomach
  • Prevent incompatibility of active ingredients
  • Help in the addition of an adjuvant
  • Improve pharmaceutical elegance
  • Strengthen the drugs
  • Impart aesthetic to the drug
  • Provide protection to the active ingredients
• Coating materials


  • Sugar
  • Titanium dioxide
• Disintegrants


  Inactive substances which expand and dissolve when wet, added to break the tablet in the digestive tract
• Disintegrants


  • Starch
  • Sodium starch glycollate
  • Cross-linked polyvinylpyrrolidone
• Glidant


  Aids powder flow properties during manufacture
• Glidants


  • Colloidal silica
  • Starch
• Diluent


  Bulking agent to adjust tablet weight and ameliorate poor bulk drug properties
• Diluents


  • Lactose
  • Crystalline cellulose
  • Dicalcium phosphate
• Lubricant


  Prevents powder/tablets sticking to punches, aids punch movement
• Formulation types


  • Solid dosage forms (tablets, capsules)
  • Liquid formulations (oral, intravenous, intraspinal, elixirs, lotions, analgesic syringes, inhalator solutions)
  • Semisolids (gels, emulsions, suspensions, creams, ointments)
  • Novel preparations (suppositories, ophthalmic, optics, dental resins, veterinary)
• Intravenous preparations


  • Prepared and delivered using aseptic techniques
  • Therapeutic agents often manufactured in lyophilized or powdered form for stability or ease in handling and shipping
  • Dry form of therapeutic agent reconstituted with sterile diluent
  • Multiple steps and manipulations increase chance of failure in aseptic technique and drug loss/improper dosage
  • Risk of exposure to harmful drug products for healthcare workers
• Typical procedure for reconstitution of an intravenous drug


  1. Withdraw appropriate volume of sterile diluent from container and inject into drug vial

  2. Admix drug and diluent in vial

  3. Transfer reconstituted drug to intravenous delivery system
• Parenteral nutrition


  Feeding method where nutrients go directly into the bloodstream through a catheter placed into a vein
• Elixir


  A sweetened aromatic solution of alcohol and water, serving as a vehicle for medicine
• Types of elixirs


  • Non-medicated elixirs (used as solvents or vehicles)
  • Medicated elixirs (antihistaminic, sedative/hypnotic, expectorant, miscellaneous)
  • East Asian vitamin drinks
• Composition of elixirs


  Hydro-alcoholic solution of at least one active ingredient

  Alcohol used to solubilize ingredients, retard crystallization, preserve, mask taste, enhance flavor
• Other excipients in elixirs


  • Sugar and/or sugar substitutes

  Preservatives and antioxidants

  Buffering agents

  Chelating agents

  Flavoring agents and enhancers

  Coloring agents
• Syrup


  A thick, sweet, sticky liquid, consisting of a sugar base, natural or artificial flavorings, and water, used as a vehicle for medicine
• Semisolid preparations


  Formulation types selected for systemic transdermal products and dermatological products based on requirements of the system and skin
• Ingredients in pharmaceutical formulations


  • Humectants like glycerol and sorbitol
  • Preservatives like parabens and benzoates
  • Antioxidants like butylated hydroxytoluene (BHT) and sodium metabisulfite
  • Buffering agents
  • Chelating agents like sodium ethylenediaminetetraacetic acid (EDTA)
  • Flavoring agents and flavor enhancers
  • Coloring agents
• Syrup


  A thick, sweet, sticky liquid, consisting of a sugar base, natural or artificial flavorings, and water, it is the juice of a fruit or plant boiled with sugar until thick and sticky solution prepares, moreover it is a concentrated solution of sugar in water, often used as a vehicle for medicine
• Semisolid preparations


  • Selection of formulation types for systemic transdermal products, which are designed for application to intact non-diseased skin
  • Selection of formulation type for dermatological products is influenced more by the nature of the skin lesion
• Ointment


  • Any semi-solid containing fatty material and intended for external application
  • Semisolid anhydrous external preparations
• Types of ointment base


  • Hydrocarbon bases
  • Absorption bases
  • Water-removable bases
  • Water-soluble bases
• Hydrocarbon ointment bases


  • Completely anhydrous
  • Contain straight or branched hydrocarbon chain lengths ranging from C16 to C30
  • May also contain cyclic alkanes
  • Used principally in nonmedicated form as emollients or lubricants
  • Typical formulation contains fluid hydrocarbons (mineral oils, liquid paraffins) mixed with longer alkyl chain, higher melting point hydrocarbons (white and yellow soft paraffin, petroleum jelly)
  • The difference between white and yellow soft paraffin is that the white version has been bleached
  • Hard paraffin and microcrystalline waxes are similar to the soft paraffins except that they contain no liquid components
  • Tend to produce formulations which are greasy and unpleasant to use
  • Addition of solid components, such as microcrystalline cellulose, can reduce the greasiness
  • Limited value as topical drug delivery platforms due to relative insolubility of many drugs in hydrocarbons and silicone oils
  • Drug solubility can be increased by incorporating hydrocarbon-miscible solvents, such as isopropylmyristate or propylene glycol
• Emulsions


  • Two-phase preparations in which one phase (the dispersed or internal phase) is finely dispersed in the other (the continuous or external phase)
  • The dispersed phase can be either hydrophobic based (oil-in-water creams, O/W) or aqueous based (water-in-oil creams, W/O)
  • Whether a cream is O/W or W/O is dependent on the properties of the system used to stabilize the interface between the phases
• Emulsion stabilization


  • Achieved by increasing the viscosity of the continuous phase or establishing an energy barrier between the droplets
  • Electrostatic repulsion provided by ionic surfactants adsorbed at the oil-water interface
  • Steric repulsion provided by adsorbed non-ionic surfactant or polymeric material
  • Emulsions stabilized by electrostatic repulsion are sensitive to additional electrolytes
• Emulsifier types


  • Ionic surfactants (suitable for O/W emulsions)
  • Non-ionic surfactants (suitable for both O/W and W/O emulsions)
  • Mixtures of surfactants (create more stable emulsions than individual surfactants)
• HLB (Hydrophilic-Lipophilic Balance)


  • An arbitrary number (usually between 0 and 20) assigned to a particular surfactant to indicate its hydrophilic or lipophilic nature
  • Surfactants with HLB values between 4 and 6 are W/O emulsifiers
  • Surfactants with HLB values between 8 and 18 are O/W emulsifiers
• Other semi-solid and liquid formulation types


  • Sprays
  • Foams
  • Multiple emulsions
  • Microemulsions
  • Liposomal formulations
  • Niosomes
  • Cyclodextrins
  • Glycospheres
  • Dermal membrane structures
  • Microsponges