Drug Delivery Systems Overview

Introduction

• Drug delivery systems encapsulate drugs in nanoparticles such as micelles, liposomes, nanocapsules, nanospheres, and others.
• This encapsulation improves therapeutic index and reduces adverse side effects.

Classification of drug delivery systems

• Drug delivery systems (DDSs) are divided into two main types:
  • Conventional DDSs / immediate release formulations
  • Novel drug delivery systems (NDDS)

Conventional DDSs

• These systems provide rapid onset of action for some drugs like analgesics, antipyretics, and vasodilators.
• Includes simple methods like oral, topical, inhaled, or injection.

Limitations of conventional DDSs

• Rapid drug elimination leading to frequent dosing
• Fluctuations in plasma drug levels resulting in adverse effects
• Inability to target specific sites in the body

Novel Drug Delivery Systems (NDDS)

• Focus on controlling pharmacokinetics (ADME), pharmacodynamics, non-specific toxicity, immunogenicity, and drug efficacy.
• Address drug delivery complications that conventional systems cannot minimize.
• Often called "controlled DDS" and use advanced techniques and new dosage forms.

Terminology

• Rate controlled delivery: Delivers drugs at a predetermined rate systemically or locally for a specified period.
• Sustained/prolonged/extended drug delivery: Releases drugs slowly and provides a continuous supply over a prolonged period.
• Targeted drug delivery: Delivers drugs to specific sites in the body.
• Zero-order release: Drug release does not vary with time, maintaining a relatively constant level in the body for longer periods.
• Timed (delayed) release DDS: Releases drugs after a lag time of 4-5 hours.
• Enteric coated dosage: Designed to protect the drug in the stomach and release it in the colon.

Rationale for Developing SR DDS

• Extends the duration of drug action.
• Reduces dosing frequency.
• Minimizes plasma level fluctuations.
• Improves drug utilization.
• Minimizes adverse effects.
• Improves patient compliance.

Conventional vs Controlled Release DDS

• Conventional Release:
  • Frequent dosing (rapid elimination)
  • Fluctuation in plasma levels
  • Limited targeting
• Controlled Release:
  • Reduced dosing frequency
  • Stable plasma levels
  • Targeted delivery

Advantages of Sustained/Controlled Release Dosage Forms

• Reduced drug administration frequency.
• Reduced plasma level fluctuations.
• Avoidance of night-time dosing.
• Increased patient compliance.
• More uniform effect.

Disadvantages of Sustained/Controlled Release Dosage Forms

• Unpredictable or poor in vitro/in vivo correlation.
• Reduced potential for dose adjustment.
• Possibility of dose dumping (sudden release of a large amount of drug).
• Delay in onset of drug action.
• Poor systemic availability in general.

Fick's first law of diffusion

• Calculates the rate of drug released (dm/dt).
• Formula: dm/dt = ADK ΔC/L
  • A = Area
  • D = Diffusion coefficient
  • K = Partition coefficient
  • L = Diffusion path length
  • ΔC = Concentration difference across the membrane.

Diffusion-Controlled Systems

• Reservoir device: Drug is contained in a core reservoir covered by a thin polymeric membrane.
  • Release is by diffusion through the membrane.
  • Rate is governed by membrane thickness, porosity, and drug characteristics.
  • Risk of dose dumping if the membrane ruptures.
  • Difficult for high molecular weight compounds.
• Matrix device: Drug is dispersed throughout a polymer matrix.
  • Release depends on the rate of drug diffusion.
  • Easier to produce than reservoir devices.
  • Can deliver high molecular weight compounds.

Difference between Reservoir and Matrix Systems

• Reservoir:
  • Advantages: Zero-order delivery, variable release rates.
  • Disadvantages: Dose dumping risk, removal required for implants, difficult for high molecular weight.
• Matrix:
  • Advantages: Easier to produce, high molecular weight delivery.
  • Disadvantages: No zero-order release, removal required for implants, potential toxicity if system fails.

Swelling-Controlled Systems

• Dry system swells when it absorbs water or body fluids, increasing the solvent content within the formulation and enabling drug diffusion.
• Common polymers used: hydroxypropyl methylcellulose (HPMC) and methylcellulose (MC).
• Drug release is controlled by the rate of polymer matrix swelling.
• HPMC is a key polymer for hydrophilic matrices due to fast, uniform gel formation, providing a diffusional barrier to control release.

Erodible Systems

• Two major advantages:
  1. Polymers do not need to be removed from the body after drug delivery.
  2. Drugs do not need to be water-soluble.

Biodegradable Polymers for Drug Delivery

• Two types of biodegradation:
  • Bulk erosion: Degradation occurs throughout the polymer by hydrolysis, breaking down large polymers into smaller biocompatible compounds.
  • Surface erosion: Degradation occurs only at the polymer surface.
• Factors affecting degradation:
  • Chemical structure and composition
  • Molecular weight
  • Concentration
  • Hydrophilicity/hydrophobicity
  • Carrier size, shape, and porosity
  • Additives
  • Microenvironmental pH
  • Method of preparation
  • Sterilization
• Examples of successfully used biodegradable polymers:
  • Polylactic acid and polyglycolic acid
  • Polycaprolactone (polyesters: aliphatic homo-polymer)
• Common characteristics of biodegradable polymers:
  • Stability with drug molecules
  • Biocompatible and biodegradable
  • Ease of large-scale manufacture
  • Amenable to sterilization
  • Flexibility for multiple release profiles

Polyesters in Drug Delivery

• Polyesters and copolymers have been tested for injectable drug delivery.
• Applications: implants, nanoparticles, and microspheres for delivering various drugs (narcotic antagonists, contraceptives, local anesthetics, cytotoxics, and antimalarial agents).

Explore the fundamentals of drug delivery systems, focusing on conventional and novel drug delivery methods. This quiz covers the mechanisms, limitations, and advancements in encapsulating drugs to enhance therapeutic effects. Ideal for students and professionals in pharmacology and related fields.