Modified Release Drug Delivery Systems

Modified Release Drug Delivery System

• Ideal drug delivery systems provide therapeutic concentrations at the site of action for the desired duration of treatment.
• Maintaining a constant "steady state" plasma concentration is achieved through repetitive administration of conventional dosage forms.
• Conventional dosage forms aim for maximal physical/chemical stability and bioavailability, optimized for drug absorption rate and extent.

Problems with Conventional Dosage Forms

• Poor patient compliance, particularly with drugs having short biological half-lives necessitating frequent dosing (2-4 times a day).
• Increased frequency of administration increases the risk of missed doses.
• Significant fluctuations in peak and trough plasma drug levels upon repeated administration can lead to undesirable side effects (high peaks, low troughs).

Modified Release Drug Delivery Systems

• Overcome problems associated with conventional dosage forms by controlling drug release rate.
• Provide a sustained/prolonged therapeutic concentration.
• Examples of terms used interchangeably include controlled release, sustained release, and prolonged release.
• Modified-release dosage forms continuously release drugs at controlled rates to create a prolonged therapeutic effect following a single dose.

Mechanisms for Modified Release Preparations

• Using pharmacokinetic phase:
  • Prolonging absorption, metabolism, or excretion by altering drug absorption, metabolism, or excretion
• Utilizing chemical reactions:
  • Modify drug chemical structure into prodrugs
  • Alter drug solubility, binding to proteins, and partition coefficient
• Utilizing technological processes:
  • Change solvent types
  • Add viscosity enhancers
  • Utilize insoluble adsorbents for drug absorption
  • Encapsulate drug in multilayer structures
• Methods for modified release:
  • Coating, film forming, embedding in matrices, osmotic pressure application

Dissolution Systems

• Drugs with inherently low aqueous solubility naturally exhibit sustained release characteristics.
• Dissolution rate in gastrointestinal medium can be controlled for highly soluble drugs
• Key steps in dissolution:
  • Initial detachment from solid structure to liquid interface
  • Drug molecule diffusion into bulk liquid medium

Diffusion Systems

• Diffusion is the spontaneous transfer of molecules to achieve chemical potential equilibrium.
• Controlled diffusion release through inert polymer barriers.
• Two types of diffusion systems:
  • Reservoir systems: A drug core encapsulated in a polymeric membrane barrier.
  • Matrix systems: Uniformly dispersed drug within an insoluble polymer matrix.

Erosion Systems

• Erosion of the polymer controls drug release.
• Bulk release results from rapid polymer degradation while surface release comes from the boundaries.
• Erosion is dependent on the polymer dissolution and diffusion rates.

Swelling Systems

• Drug is dispersed in polymer, instead of using impermeable polymers, swellable polymers are used.
• Swelling controlled matrices use a combination of diffusion and dissolution.
• Swelling controlled systems are especially effective for drugs with narrow therapeutic indices.

Ion-exchange Resin Systems

• Water-insoluble crosslinked polymers are utilized, with charged ion-exchange groups.
• Drug release is controlled by interaction between drug and the resin, along with factors like ionic environment and diffusion path length.

Osmotic Pump Systems

• Osmotic pressure differences across a semi-permeable membrane drive drug release at a constant rate (zero-order release).
• The system has an osmotic core containing a drug and an osmotically active agent or salt coated with a semi-permeable membrane.
• Water uptake through the membrane creates hydrostatic pressure that expels the drug solution from the dosage form.
• Two types:*
  • Elementary osmotic pumps (EOPs):
  • Oral osmotic pumps (OROS):

Hydrodynamic Pressure Controlled Systems

• Drug release is triggered by hydrodynamic pressure created by swelling.
• A hydrophilic gum layer swells, creating a pressure difference to expel the drug.