Lec 17- Osmotic delivery system

Question 1

Osmosis

Answer 1

• Osmosis- flow of water through a semi-permeable membrane from a lower to a higher concentration of solute
• Semi-permeable membrane (doesn’t allow drug through)- water will move from low solute to high solute to equal out the water potential difference between compartments

Question 2

Concept of osmotic pump

Answer 2

• We have tablet containing drug molecules which are covered by a semi-permeable membrane
• Some excipients exert high osmotic pressure they are known as an osmogene- this causes water to pass through the semi-permeable membrane via osmosis
• As water enters drug dissolves- and pushes the drug through a pre-designed orifice on the tablet (sometimes you can have multiple holes)
  
  • Strict controlled release of the drug- specifically sustained release due to one exit point of the drug from the tablet
  • this type of dosage form doesn’t rely on the physiological conditions of the body such as pH, concentration gradient

Question 3

Zero order release profiles

Answer 3

*

Question 4

Full Release Profile

Answer 4

• Lag time is first to hydrate the system- drug molecules to under dissolution and diffusion before absorption can occur

Question 5

Zero Order Release Rate

Answer 5

• Rate of drug release= dM/dt = AK’π_sC_s / h
• A = area of semi-permeable membrane
• K’ = Permeability constant (different membrane are more or less resistant to water)
• π_s = Osmotic pressure of saturated salts in device
• C_s= Concentration of drug (Solubility)
• h= thickness of semi-permeable membrane
• Maintain π_s constant by having excess solid osmotic agent other parameters are constant
• dM/dt = constant - zero order release

Question 6

Design Variables

Answer 6

• Membrane permeability- Nature of polymer (structure, MW, permeability)
• The surface area of the device
• Membrane thickness- weight and density
• Osmotic pressure
  
  • Nature of osmotic agent
    
    • Saturated NaCl- 356 atmospheres
    • Saturated KCl - 245 atmospheres
    • Saturated Dextrose- 82 atmospheres
• Drug solubility or concentration
• Release orifice (size of the orifice)- greater the orifice the greater the release

Question 7

Advantages

Answer 7

• Zero-order release is possible
• The release of the drug is independent of the external environment or physiological conditions
• Reformulation is not required for different drugs- Because of the specificity of the release you don’t have to reformulate the medicine
• Lower risk of dose dumping

Question 8

Disadvantages

Answer 8

• Systems can be expensive
  
  • Precise drilling of a hole
  • Semi-permeable membrane (e.g. polymer of cellulose acetate)
• Quality control is more extensive than conventional systems
• These were created by certain companies- they hold the patent- you then have to pay for it

Question 9

Elementary Osmotic Pump Oros

Answer 9

• Drug release from osmosis- controlled single-unit tablet
• Oros (Oral Osmotic Delivery)
• The drug is mixed with the water-soluble core material
• Core surrounded by a water-insoluble semipermeable membrane
• Water molecules diffuse into the core through the membrane to form a concentrated solution
• The drug is pushed out of the pre-drilled orifice
• The core may be an inert salt, water-soluble polymer of the drug itself (if saturated solution generate sufficient osmotic pressure)

Question 10

Push-pull osmotic pump

Answer 10

• Modification to include a flexible membrane for poorly water-soluble drugs
• The drug in pull layer
• Push layer contains excipients that will increase and swell (HPMC)
• As expansion occurs drug will be pushed put through the orifice at a rate set by the swelling rate
• If the drug is the osmogene this may be the best
• The solubility of the drug- with poorly soluble drugs (with the previous method the would not want to diffuse through the orifice)- this is overcome by the push the drug out of the orifice
  
  • E.g. Adalat LA, Ditropan XL
  • Adalat LA consists of
    
    • Semipermeable cellulose acetate coating
    • Swellable hydrogel layer of polyoxyethylene glycol and HPMC (push layer)
    • Drug chamber of nifedipine in HPMC and PEG (Pull layer)

Question 11

Alzet Minipump

Answer 11

• Miniature, implantable pumps used for research in laboratory animals
• Continuously deliver drugs, hormones, and other test agents at controlled rates from one day to four weeks without the need for external connections or frequent handling
• Eliminates the need for repeated night-time or weekend dosing

Question 12

Concerta (Methylphenidate)

Answer 12

• One dose gives a similar PK profile from a TDS profile
• Overcoat contains drugs which dissolve quickly to give an immediate dose
• Then swelling- MR release

Question 13

Osmosin

Answer 13

• Osmotic delivery system for indomethacin
• Withdrawn in 1983
• Intestinal perforation- capsule would get stuck in the small intestine in the same spot giving out NSAID for a long time leading to Ulcers