Extended-release formulations of psychotropic medications

Extended-release formulations of psychotropic medications

Several pharmaceutical technologies are employed to create extended-release formulations of psychotropic medications like quetiapine, paliperidone, venlafaxine (Effexor), and paroxetine (Seroxat/Paxil). Here’s an overview of the key technologies used:

Matrix Systems

• Hydrophilic matrix systems (HPMC-based)
  • Medications like extended-release quetiapine use hydroxypropyl methylcellulose (HPMC) polymers
  • Drug release occurs through diffusion and erosion of the gel layer
  • Example: Quetiapine XR uses GeomatrixTM technology with multiple HPMC layers
• Hydrophobic matrix systems
  • Utilize waxes, fatty acids, or polymers like ethylcellulose
  • Used in some paroxetine CR formulations
  • Release controlled through diffusion through tortuous pathways

Osmotic Pump Technologies

• OROS® (Osmotic Release Oral System)
  • Used in paliperidone ER (Invega)
  • Consists of a semipermeable membrane with laser-drilled delivery orifice
  • Osmotic pressure drives drug release at controlled rate
  • Provides near zero-order release kinetics independent of GI conditions

Multiparticulate Systems

• Coated pellets/beads in capsules
  • Used in venlafaxine XR (Effexor XR)
  • Drug-containing cores coated with release-controlling polymers
  • Different coating thicknesses create staged release profiles
  • Example: Spheroidal Drug Absorption System (SODAS®) technology
• Mini-tablets
  • Multiple small tablets with different release characteristics in a single capsule
  • Used in some newer extended-release formulations

Specialized Coating Technologies

• Acrylic polymer coatings (Eudragit®)
  • pH-dependent release profiles
  • Used in paroxetine CR (Seroxat/Paxil CR)
  • Different Eudragit types dissolve at specific pH ranges along GI tract
• Ethylcellulose coatings
  • Create semipermeable membranes controlling drug diffusion
  • Often combined with pore-forming agents like HPMC

Specific Examples

• Paliperidone ER (Invega): OROS® push-pull system with non-deformable tablet core that maintains delivery rate throughout GI transit
• Quetiapine XR (Seroquel XR): Multilayered matrix system with erosion-controlled release
• Venlafaxine XR (Effexor XR): Diffusion-controlled spheroid technology in capsules
• Paroxetine CR (Paxil CR): Geomatrix™ technology with enteric coat and hydrophilic matrix core

These technologies allow for once-daily dosing, improved therapeutic profiles, reduced peak-trough fluctuations, and potentially fewer side effects compared to immediate-release formulations