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Modified Release Drug Delivery Systems

Definition of Modified-release Products

  • Overview: Dosage forms that alter the time course and/or location of the drug release from the drug product.

  • Characteristics:

    • Modified release dosage forms can change:

      • Time of release

      • Rate of release

      • Location of drug release

  • Purpose: Target specific locations with certain concentrations.

Types of Modified Release Forms

  • Extended Release (ER): Changes the rate of drug release.

  • Delayed Release (DR): Changes the time of drug release.

  • Targeted Delivery Systems: Changes the location of drug delivery.

  • Oral Disintegrating Tablets (ODT): e.g., Zofran, Spritam.

Other Terminology Associated with Modified Release

  • Extended action, Sustained release, Sustained action, Prolonged action, Repeat action, Controlled release, Delayed action.

  • Prolonged Release: Medication provided over an extended time.

  • Sustained Release: A loading dose followed by a slow release of medication over time.

  • Controlled Release: Provides therapeutic control (temporal or spatial), not necessarily sustained release.

Rationale for Design of Modified Release Systems

  • Mainly follows Pharmacodynamics / ADME (Absorption, Distribution, Metabolism, Excretion).

  • Drug Release & Therapeutic Effect:

    • Drugs in dosage forms must be released and dissolved to be absorbed.

    • Pharmacological effects are only exerted by dissolved drugs.

  • Basic Conditions for Drug Action:

    • Must be absorbed when dissolved.

    • Effect is via molecular interaction.

Pharmacodynamics & Drug Concentration

  • Effect of the drug is proportional to its concentration at the site of action (SOA).

Comparison of Drug Release

In Vitro vs. In Vivo

  • In Vitro:

    • Immediate forms maintain constant concentration (no ADME).

    • Modified release shows steady increase in drug release.

  • In Vivo:

    • Immediate release peaks quickly and falls due to elimination.

    • Modified release maintains consistent blood concentration providing prolonged therapeutic effect.

Pharmacokinetics & Dosage Forms

  • Immediate Release:

    • Drug reaches peak blood concentration and then falls.

  • Modified Release:

    • Maintains plateau in drug concentration over time.

Bolus vs. Constant Rate Delivery

  • Bolus Medications: Straight into bloodstream, peaks immediately, then falls due to ADME.

  • Constant Rate: Similar to modified release, maintains plateau via continuous administration (e.g., IV drip).

Pharmacological Effects with Modified Dosage Forms

  • Can achieve:

    • Constant effect

    • Periodic effect

    • Specific location effect (e.g., cancer medications).

Zero Order Release Kinetics

  • Input Rate Determinants:

    • Dosage forms: controlling drug availability via solubility and dissolution rate.

    • Biological barriers: GI epithelium, locations in GI, Stratum Corneum for skin.

  • Therapeutic Implications for ER and DR:

    • Aim for ideally zero-order kinetics and reduce dosing frequency.

    • Example: Enteric-coated tablets (e.g., Asacol).

Targeted Delivery Mechanisms

  • Delivery at or near Site of Action: Appropriate for immediate, ER, or DR forms.

  • Often used in cancer therapies.

Pharmacokinetic Rationale for Modified Release

  • Maintain therapeutic range between Max Tolerated Concentration (MTC) and Min Effective Concentration (MEC).

  • Steady-state maintenance reduces variability in drug levels.