Lec 14- reservoir systems

Question 1

First-order Kinetics

Answer 1

• Mass v time first order- release drops

Question 2

First-order release- Linearising data

Answer 2

• Ln(M₀-M_t) = Ln(M₀) - K₁t
• Ln(M₀-M_t) is in (amount remaining)
• Instead of having it in original form (graph)
• Don’t remember this equation for exam
• M₀= initial amount of drug
• M_t= amount of drug released at a certain point
• K= rate constant
• t= time

Question 3

First-order release profiles versus time

Answer 3

• drug release decrease gradually until all drug is used up
• Zero order is a straight line

Question 4

First-order release reservoir depletion

Answer 4

• Loss of drug
  
  • From solution
  • Later stages of suspension
• Entry of water
  
  • May dilute liquid fill
  • May dissolve solid residue

Question 5

Oral bioavailability issues

Answer 5

• Short half-life requires multiple dosing
  
  • Overcome with sustained release
• Efficiency depends upon
  
  • pH- degradation of the drug,
    
    • The coating will have acidic moieties on (will not ionise in the stomach) therefore won’t go into dissolution, therefore, tablet and drug will not absorb
  • gastric residence time, intestinal transit, food
  • Absorption window - not necessarily uniform along GIT
    
    • Drugs often have a preference for absorption in the different area’s of the GIT
• GIT transit time is highly variable
  
  • Reduced bioavailability if a release occurs in an area where there is little absorption

Question 6

Microencapsulated Reservoir Systems

Answer 6

• Oral Pelleted Products
• Transport and release from coated pellets
  
  • Avoids dose being all at one point in GIT
  • More uniform passage down GIT
  • Pass through pyloric sphincter when closed- act in a similar way to suspensions
• Tablets, when taken with food, can end up in the bolus of food which slows absorption- Pellets on the other hand like suspensions can bypass this (as well as the pylorus sphincter) leading to faster onset o absorption
• Dose dumping is the main problem with MR products, the dose is distributed out more within the pellets (the chance of all pellets dose dumping at the same time is reduced)

Question 7

Disprin CV®
Micro-encapsulated Aspirin

Answer 7

• Aspirin 100 mg and 300 mg
  
  • Released over 4-5 hours
  • pH-independent release (no coat that changes absorption dependent on pH)- sustained release profile similar to zero order
    
    • Nu-seal pH dependent- does not release within the acidic stomach= delayed release profile (must have a lag time)
  • For use in cardiovascular disease
    
    • reduce risk of myocardial infarction
    • 28-d calendar pack

Question 8

Disprin CV®
Dissolution Profile

Answer 8

• sustained release profile similar to zero order
  
  • Nu-seal pH dependent- does not release within the acidic stomach= delayed release profile (must have a lag time)

Question 9

Spansule Capsule

Answer 9

• Spansule® Capsules
  
  • Drug is released from a group of beads that have coatings of different thickness
  • Beads with thinnest coating provide initial dose- can use 2 different drugs
  • Maintenance of drug levels at later times by beads with thicker coating
  • First introduced in early 1950s (SKF)
  • Stelazine Spansules® (Goldshield Pharmaceuticals-disc)
    
    • trifluoperazine in dark blue, light blue and white pellets

Question 10

Multiple-release Products
Minocin MR®

Answer 10

• MINOCIN MR Capsules have been formulated as a “double pulse” delivery system
• portion of the minocycline dose is delivered in the stomach
• and a second portion of the dose is available for absorption in the duodenum and upper GI tract
• Pulsitile delivery systems are useful for angina
  
  • flushing symptoms during night- One is released during night and another through the morning

Question 11

Minocin MR®

Answer 11

• Minocycline Capsules
  
  • Hard shell capsule
  • Immediate dissolution
    
    • 60 mg of minocycline as yellow, uncoated particles
  • Delayed dissolution
    
    • 40 mg of minocycline as white, coated particles
    • pH-sensitive polymer coat
    • Delays release until pH rises to 4.5
  • Replaces 50 mg bd with 100 mg od
    
    • No significant difference in overall bioavailability - bioequivalent

Question 12

Minocin MR®
Serum profile

Answer 12

Question 13

Multiple-release Products
Elantan LA® Capsules

Answer 13

• Elantan LA50 and Elantan LA25
  
  • Brown/white or brown/pink capsules containing white “micropellets”
  • Isosorbide mononitrate - Angina prophylaxis
    
    • 30% immediate release : 70% sustained release over 6-8 h
  • Fast onset of action
  • Allows a nitrate-low period each 24 h - at night
• Sugar inert core is used to increase particle size = reduce cohesion = better dose uniformity
  
  • Adds as stability, dose uniformity in terms of each core is the same size so same amount of drug is used

Question 14

Problem 2 transdermal patch