Lec 19- Swelling controlled release systems

Question 1

Swelling Controlled-release systems

Answer 1

• Start with a tab that is made of water-soluble polymer- which dissolves slowly (slow dissolution kinetics)
• The drug is embedded within the tablet
• Over time the polymer will form a gel layer- thickness and diameter of the tablet grows- this is the swelling
• When you increase the size of the tablet you create more space betweent the drug particles and the polymer allowing the drug to be released
• If there is a lower amount of polymer (<10%)- then small individual parts of the tablet swell leading to faster disintegration due to greater spaces created

Question 2

Swelling controlled-release systems

Answer 2

• Absorption of water from the external environment
  
  • Outer layer swells on the entry of water which changes properties
  • Enhances release rate
• Drug release depends upon
  
  • The rate of water uptake
    
    • Poor compression leads pores- leads to increased SA
    • Nature of the polymer
  • The diffusion coefficient of the drug
• Widely used for oral delivery

Question 3

Advantages

Answer 3

• Comparatively simple concept
• Easy to manufacture- similar manufacturing to monolithic systems
• Cheap excipients
• Erodible- no shell

Question 4

Disadvantages

Answer 4

• Drawbacks include
  
  • Release is dependent on 2 processes
    
    • Penetration of water through hydrated mix and diffusion of drug through matrix
    • Lag between dissolution and taking the tablet
  • If outer layer erodes, complicated kinetics- different geometries effect the kinetics

Question 5

Examples of polymers used

Answer 5

• Hydrophilic colloid matrix systems
  
  • Hydroxypropylmethylcellulose (HPMC)
  • Sodium carboxymethylcellulose
• Hydrogel
  
  • A hydrophilic polymer with water-soluble drug
    
    • E.g. poly(hydroxyethyl methacrylate) and theophylline
  • Diffusion in the gel is low but increases as water enters

Question 6

pH control of drug release

Enteric coating

Answer 6

• Generally remain intact in the stomach but will dissolve at higher pH’s along the GI tract
• Coating materials are usually weak acids that remain undissociated at low pH but ionise at pH >5

Question 7

Enteric coating polymers

Answer 7

• Cellulose acetate phthalate (CAP)
  
  • Oldest, pH >6
  • Susceptible to hydrolytic degradation
• Polyvinyl acetate phthalate (PVAP), hydroxypropyl methylcellulose phthalate (HPMCP), hydroxypropyl methylcellulose acetate succinate (HPMCAS)
• Acryclic acid co-polymers are now widely used
  
  • Methacrylic acid- methyl/ethyl methacrylate co-polymer (Eudragit)

Question 8

Question Monolithic dispersion

Answer 8

• The mass of drug (M_t) released from a slab-shaped simple monolithic daspersion at time t is given by:
  
  • M_t= A Sqr(Dt x C_s x (2C₀ - C_s)
• And the initial mass of drug (M₀) in the device by:
  
  • M_o = A x C_o x h / 2
• If the device has a total area of 10cm² and a thickness (h) of 1mm, estimate the time to complete exhaustion if: the diffusion co-efficient (D) of the drug within the device is 5x10^-6cm²S^-1 the initial drug concentration (C₀) is 20mg cm^-3 and the solubility of the drug in the matrix (C_s) is 0.1mg cm^-3

Question 9

Answer

Answer 9

Question 10

Attempt this question

Delivery from the osmotic device

Answer 10

• A push-pull veterinary osmotic device of active area 5cm²
• Uses NaCl as the osmotic attractant
• The osmotic pressure exerted by this solute is 356 atmosphere
• While the semipermeable membrane, of thickness 150 um, has a water permeability coefficient of 1x10^-6 cm²/h atm
• If the drug to be delivered has an aqueous solubility of 0.8g cm^-3 estimate the amount of drug delivered during a four-hour period