Lecture 26: Principes Of Depot Injections Flashcards
(44 cards)
What are the advantages of long acting injectable? (7)
- Predictable drug-release profile during a defined period of time following each injection
- Better patient compliance
- Ease of application
- Improving systemic availability by avoidance of first-pass metabolism
- Reduced dosing frequency
- Decreasing incidence of side effects
- Cost reduction of medical care
Two types of routes for long acting injections
Subcutaneous (SC) and Intramuscular (IM)
What are the advantages for subcutaneous injections and what is the volume limited to and primary route for what?
Greater surface area for target Injection sites, use of shorter needles, ease of self-administration, less discomfort, better safety profile
– primary route for delivery of protein-based drugs
– the volume of SC injection are usually limited to no more than 1-2 mL
What are the advantages for intramuscular injections?
- Greater injection volume (2-5 mL) in the large skeletal muscles (these muscles are less richly supplied with sensory nerves)
What are the 3 types of long acting injections?
- Oil based solutions (Control the release of active drug for weeks)
- Drug suspensions (weeks)
- Polymer-based
What are the polymer- based acting times?
- Particulate: microsphere (months) upto 3
- In situ-based gelling systems (months)
When may oils based long acting injectable be used for?
- Steroid esters (contraception’s and hormone replacement therapy). antipsychotics
What are 3 important formulation considerations for long acting injections
- drug solubility in oil vehicles
- drug partitioning between oil and aqueous interface
- vehicle viscosity `
What oil is usually used for long-acting injections?
Vegetable oils
Why are vegetable oils usually used in long-acting injections?
- Contains various triglycerides in different proportion,
- which influences vehicle density and viscosity.
What in vegetable oil, cause a risk of oxidation?
- They contain triglycerides, which contain fatty acids
- Castor oil had high content of fatty acids with hydroxyl group (due to ricinolein acid)
What are some alternative oils used for long acting injections?
- Synthetic fatty acid esters such as isopropyl myristate and ethyl oleate as alternative vehicles
What other biocompatible cosolvents may be used in formulations? (3)
- aliphatic alcohols
- benzyl benzoate
- ethyl acetate
What is the partition coefficient (P) of a drug substance?
- Ratio of drug activities (at equilibrium) in two immiscible solvents comprising the portioning system.
How to enhance drug affinity for the oil phase
Need to manipulate partition coefficients by transiently masking the drug in the form of a lipophilic prodrug.
How does a prodrug work (haloperidol e.g.)?
- Long lipophilic carbon chain attached to drug via an ester bond.
- The carbon chain will be in oily phase
- The other part will be in aqueous phase
- Hydrolysis of the ester bond will release the drug in active form.
What is the rate-limiting step of drug absorption in drug suspension?
The dissolution of drug particles in the formulation or in tissue fluid surrounding the drug formulation.
What type of formulation can be used to control dissolution rate of drug particles, to prolong the absorption?
- Poorly water-soluble salt formulations
- Larger particle sizes
What does Polysorbate 80 do in olanzapine pamoate
- Non-ionic surfactant
- Improves the dispersion of the formulation by a repulsive effect
What does hydrochloric acid and sodium hydroxide do in olanzapine pamoate
Allows for pH adjustment
What are Polymer-based systems used for?
For macromolecules (proteins and peptides)
Advantages of polymer-based systems?
- In-vitro and in vivo stabilization of macromolecules
- Extension of biological half-life
- Improvement of systemic availability
Types of polymer-based systems
- Microspheres
- In situ forming gels
How are microspheres formed?
- Polymer dissolved in solvent and gradually remove solvent.
- This will then form structure called microspheres.
- Drugs may also be adsorbed onto microsphere after.
