Novel Drug Delivery Systems (NDDS)

Novel Drug Delivery Systems (NDDS)

1. Definition, scope & rationale

• A drug delivery system (DDS) is the formulation/technology that governs where, when and how fast a drug enters the body and reaches its site of action; "novel" delivery systems are technologies that go beyond the conventional pill/injection to deliberately control release rate and/or localisation (Golan 4e Ch.55, p.979).
• Conventional drug administration is dominated by the pill or injection, both of which offer limited control over release rate and over localisation of the drug — NDDS exist to overcome these two limitations (Golan 4e Ch.55, p.979).
• The unifying goal of NDDS is to alter one or more of the four pharmacokinetic processes so as to improve the therapeutic index (Golan 4e Ch.55, p.979):
  • Absorption — including the time-course over which drug is released into the systemic circulation or at its site of action.
  • Distribution — directing drug to the whole body vs a specific tissue/organ (targeting).
  • Metabolism — either avoided entirely (e.g. bypassing hepatic first-pass) or exploited (prodrug → active conversion).
  • Elimination — modulating the rate of clearance.
• Core therapeutic advantages that motivate NDDS (Golan 4e Ch.55, p.984; Shargel 8e Ch.9):
  • Maintain drug levels continuously within the therapeutic window (avoiding peak–trough fluctuation).
  • Reduce adverse effects by abolishing transient high peak blood levels.
  • Reduce the total dose required (e.g. advanced inhaler designs) and reduce dosing frequency → improved adherence.
  • Enable delivery of agents with short half-lives (peptides, proteins) via controlled-release polymer systems.
• A modern definition from the formulation side: a modified-release (MR) dosage form is one in which the time course and/or location of drug release is deliberately chosen to accomplish therapeutic or convenience objectives not offered by conventional dosage forms (Shargel 8e Ch.9).
• New concerns introduced by advanced DDS that must be designed against (Golan 4e Ch.55, pp.984–5):
  • Each material and its degradation products must be evaluated for toxicity (critical for synthetic polymers).
  • Risk of unwanted rapid release (dose dumping) from a system meant for sustained release.
  • Discomfort of the delivery device or its insertion.
  • Increased cost to patients, insurers and hospitals.

Conventional ("immediate-release", IR) dosage forms as the baseline

• IR oral products (tablets, capsules, solutions) are formulated to release the active pharmaceutical ingredient (API) immediately after administration; no deliberate effort is made to modify release rate (Shargel 8e Ch.9).
• IR products generally give relatively rapid absorption and onset of pharmacodynamic (PD) effect — but not always: a conventional prodrug is delayed by the time needed for hepatic/intestinal/chemical conversion, and a poorly soluble (lipophilic) drug shows gradual absorption due to slow dissolution (Shargel 8e Ch.9).
• The classic dosage forms (KDT framing) are the substrate onto which NDDS are built (KDT 8e Ch.1):
  • Solid — powders, tablets, pills, capsules, suppositories/pessaries.
  • Liquid — syrups, elixirs, emulsions, suspensions, injections.
  • Semisolid — ointments, creams, pastes, gels.