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DPP1: EYE PREPARATION (The EYE (1. Cornea (Mechanism of transport…

- - - - Transcellular
        
        For lipophillic drugs
        
        Pass through cells and membranes
        
        Epithelium & Endothelium (Lipophillic)
      - Paracellular
        
        Via fluid-filled Interstellar junctions
        
        For Hydrophillic drugs
    - - Mechanical
        
        Zonula Occludens
      - Chemical
        
        Multi-drug resistance pumps
        
        MRP
        
        BCRP
        
        P-gp
  - - - Retinal blood barrier
        
        oRBB, iRBB
      - Efflux pump expression (P-gp)
      - Tight junctions expression
    - - oRBB
      - iRBB
  - - - Indirectly
        
        Diabetic retinopathy
      - Directly
        
        Glaucoma
        
        Cataract
        
        Infection/trauma
    - - Loss of Drug
        
        Nasolacrimal Drainage
        
        Conjunctiva absorption
        
        Rapid removal
        
        Decreased local effects
        
        GI Tract
        
        Systemic Effects
        
        Salty/bitter taste
        
        Other Issues
        
        Permeability & Metabolic barriers
        
        Frequent instillation
        
        Induce
        
        Toxicity
        
        Cellular damage
        
        Spillage
  - - - Solute/Molecule
        
        Hydrophillic
        
        Diffuse through proteoglycans
        
        Charge
        
        Positive
        
        Lowered permeability
        
        Negative
        
        Increased permeability
        
        Increased Lipid Solubility
        
        Lowered permeability
      - Depends on molecular
        
        Weight
        
        Radius
    - - Proteoglycans (Polar Aq.)
      - Collagen fibers
  - - - Binocular
        
        Depth perception
      - Monocular
        
        Maximized field of view
    - - Collect light
        
        Convert to EI
        
        Via Optic Nerve
      - Sent to Brain
        
        Convert to Image
- - - - Chlorbutol
        
        Chlorinated alcohol, 0.5 % w/v
        
        Anti-fungal, antibacterial activity
        
        Volatile, low stability at high temperature
        
        Absorbed to plastic containers
      - Phenylmercuric salts
        
        0.001-0.04% w/v, organic mercury
        
        Anti-fungal, antibacterial activity
        
        Increased: Phenyl ethanol
        
        Decreased: Disodium adetate
      - Benzalkonium chloride
        
        Activity
        
        Gram +ve: Aromatic alcohol
        
        Gram -ve: Chelating agent
        
        Quaternary ammonium
        
        0.01-0.02% w/v
        
        Surface activity
        
        Dry eyes, corneal irritation
      - Thiomersal
        
        0.005-0.01% w/v, organic mercury
        
        Anti-fungal, antibacterial activity
    - - Buffers
        
        Lachrymal fluid
        
        Slight buffer (pH 7.2 - 7.4)
        
        Principle
        
        Maintains non-irritant
        
        Acidic solution: buffered to reduce stinging
        
        Suitable
        
        Borate (Boric acid/borax): pH 6.8 - 9.1
        
        Phosphate: pH 4.5 - 8.5
        
        Citrate: pH 2.5 - 6.5
      - Antioxidant
        
        Required by amine-containing drugs
        
        Examples
        
        Sodium metabisulphite (Acidic)
        
        Sodium sulphite (Basic)
        
        0.1 % w/v: Prevents oxidation
      - Viscosity Enhancers
        
        Polyvinyl alcohol
        
        1.4% w/v
        
        Good contact time & clarity
        
        Other
        
        PVP
        
        PEG
        
        Dextrin
        
        Methyl-cellulose derivatives
        
        Good solubility & clarity
        
        0.5-2.0% w/v, high conc. cause crust
        
        Hypromellose
        
        Increased viscosity
        
        Increased residence time
        
        Increased penetration & action
      - Chelating agent
        
        Disodium edetate
        
        0.1 % w/v
        
        Removed metal
    - - Plastic
        
        Sterilized with ionizing radiation
        
        Components
        
        Friction plug (with baffle)
        
        Squeezable body
        
        Rigid plastic cap
        
        Polyethylene (PE), polypropylene (PP)
      - Glass
        
        Type I, II : Partially ribbed
        
        Rubber teats
        
        Extemporaneous preps
        
        Constant volume: 10 mL
  - - - 10 μg of solid activant
        
        Not more than 2 particles: greater than 50 μm
        
        No particles: greater than 90 μm
        
        Not more than 20 particles: greater than 25 μm
    - - Isotonic
        
        Same osmotic pressure as plasma
      - Paratonic
        
        Hypertonic
        
        OP more than plasma
        
        Crenation
        
        Dilution
        
        Hypotonic
        
        OP less than plasma
        
        Haemolysis
        
        Addition of adjusters
        
        Glucose
        
        Mannitol
        
        NaCl
    - - Fltration
      - Dry heat
        
        At 160`C for 2 hours
        
        For non-aqueous prps
      - Autoclaving
        
        At 115`C for 30 mins
        
        At 121`C for 15 mins
      - Ionizing radiation
        
        Gamma radiation
        
        Absorbed dose, 25 kGv
    - - Antimicrobial efficacy
      - Particle size control
        
        Lotions
        
        Semisolids
        
        Drops
      - pH control
      - Sterility
      - Powder preps
        
        Uniformity
        
        Mass
        
        Contents
        
        Dosage units
      - Dose reproducility
        
        For multi-dose preps
    - - BP: Strict requirement for absence of particulants
      - Clarification by filtration
        
        Sintered glass filter
        
        Direct into final/temporary container
- - - - Adjust tonicity
      - Stabilize
        
        pH
        
        Preparation
      - Prevent caking
      - To facilitate dissolution
  - - - Comply BP particulate limit
      - Homogeneous appearance
      - Must be steriled
    - - Desired
        
        Permit drug diffusion
        
        Retain drug activity
        
        Non-irritating
      - Incorporation into base
        
        Aseptic techniques
        
        Sterilized apparatus
        
        Sterile drugs
      - Basic
        
        1 part wool fat
        
        8 parts yellow soft paraffin
        
        1 part liquid paraffin
        
        Hard paraffin q.s. ad
    - - Ointments, creams, gels
    - - Less than 10 g collapsible tube
      - O single-use containers
      - Plastic or metal
      - Nozzle
        
        Facilitate administration
        
        Minimize contamination
  - - - pH adjusters
      - Viscosity modifiers
      - Tonicity adjusters
    - - Less than 200 mL
      - Non-irritant
      - Sterile aqueous
      - Free from particles
    - - Impregnating eye dressing
      - Rinsing eye
  - - - Hydrating agents
      - Antibiotics
      - Anaesthetic