New Drug Delivery Systems

  • Conventional drug delivery systems (DDSs) are often accompanied by systemic side effects that mainly attributable to their nonspecific bio-distribution and uncontrollable drug release characteristics.
  • The latest pharmacologic research has resulted in development of novel drug-delivery systems to overcome pharmacokinetic glitches such as limited bioavailability, unwanted distribution, drug resistance, and stability
  • A drug delivery system (DDS) is defined as a formulation or a device that enables the introduction of a therapeutic substance in the body and improves its efficacy and safety by controlling drug release and pharmacokinetic parameters
  • Interface between drug and patient
  • Not pharmaceutically active on its own

Aims of DDS Development

  • Improved drug safety & efficacy
  • Improved compliance, Increase bioavailability, Controlled drug delivery
  • Chrono-pharmacological benefits
  • Reduction of cost of drug development
  • Life extension of the products
  • Reduction of risk of failure in new product development


  • Directing active agents and their carriers into the affected tissue with minimal effects on surrounding healthy tissues after systemic administration
  • Conventional DDSàAbsorption across biological membrane ;
  • Targeted DDSà Goal of targeted DDS is to
    • increase efficacy of drug by having prolonged, localized and protected drug interaction with targeted tissues
    • help in reducing the dosing frequency
    • in turn the reduces the fluctuation in circulating drug levels as well as side effects.
  • Various Drug Delivery Systems
  • 1. Carrier-based Drug Delivery System
  • 2. Transdermal DDS
  • 3. Mucoadhesive DDS
  • 4. Osmotically-controlled DDS
  • 5. Drug devices

Drug Delivery Carriers

Special molecule or system, which encapsulates the drug (both hydrophobic & hydrophilic) within

biocompatible polymers.

• Adv –

1) Targeted & controlled release (maintaining therapeutic drug levels)

2) Biodegradable, non-immunogenic, biocompatible & high chemical stability

3) Avoidance of 1st pass metabolism

4) Minimal drug leakage during transit


• Formed by aggregates of amphiphilic molecules.

• Hydrophobic core – encapsulates poorly water soluble drugs, Hydrophilic exterior

• Estradiol — only FDA-approved micelle, – topical Rx for vasomotor symptoms of menopause.


  • One or more concentric lipid bilayers, separated by aqueous buffer compartments
  • Can load both hydrophilic and lipophilic drugs
  • ability to “passively” accumulate at sites of increased vasculature permeability, and for their ability to reduce the side effects of the encapsulated drugs relative to free drugs. This has resulted in an overall increase in therapeutic index
  • The liposome delivery system allows for better microphage penetration and better builds a concentration at the infection site.
  • significant reduction in the side effects of the liposomal drug compared to the free (i.e., unentrapped) drug à An excellent example is the significant reduction in the irreversible cardiotoxicity of free doxorubicin when the drug is entrapped in liposomes

Surface Modifications

  • Peglyated liposomes= long circulation time
  • Immuno-liposomes= Antibodies attached to target antigen


• Non-ionic surfactant-based vesicle

• Stabilized by cholesterol & anionic surfactant.

• Specially designed for skin delivery – facilitated fusion with membranes

– can be superficially modulated (eg. Rx of Herpes)

– full dermal penetration (eg. Transdermal delivery of insulin)

Preferred over liposomes (expensive, chemically unstable)


  • These are nanocarriers for transdermal drug delivery
  • Ethanolic phospholipid vesicles
  • Deliver drugs to deep skin layers and/or systemic circulation.
  • Administered in semi-solid form (gel/cream)
  • Entrap drug molecule with various physiochemical characteristics i.e. of hydrophilic, lipophilic, or amphiphilic.
  • Higher transdermal flux than liposomes as they can permeate through stratum corneum
  • Erythromycin,clindamycin,acyclovir (zovirax by GSK) ethosomal gel. RCT comparing ethosoamal zivorax vs zivorax solution showed increased efficacy


  • Delivery of anti-viral drugs Zidovudine and Acyclovir
  • Topical delivery of DNA for expression of genes in skin cells in treatment of genetic disorders
  • Transdermal delivery of hormones like testosterone
  • Delivery of Anti-parkinsonism drug Trihexyphenidyl
  • Topical delivery of anti-arthritis medications: cannabidol ethosome formulation

Topical delivery of antibiotics like erythromycin


• Liposomes carrying viral proteins.

• Route: Mucosal (nasal, vaginal etc), ID & IM

• Proposed in immunization.

• Eg. HIV1


• Liposomal derivative

• More stable than other lipidic particles

• composed mainly of charged phosphatidylserine

• no internal aqueous space

• Amphotericin B, proteins, peptides & DNA


• Similar to cochleates

• Novel lipid delivery systems

• Cube-like appearance

• Bio-compatible & bioadhesive

• eg. Oral administration of cubosomes loaded with

Insulin à  hypoglycemic effect in rats


  • These are particle between 1-100 nm size
  • Nanoparticles are used as drug carriers in which drug is either dissolved, entrapped or encapsulated
  • Recent advances in applications of nanoparticles
    • Anti-cancer drugs delivery
    • Photodynamic therapy
    • Delivery of proteins
    • Delivery of nucleic acids
  • Nanoparticles & Anti-Cancer drug delivery
  • Conventional Chemotherapy: A/E on normal tissues and development of resistance
  • Nanoparticles enhance intracellular concentration of drugs by both active and passive targeting
  • Active targeting: Trastuzumab and Rituximab have been conjugated to poly(lactic acid) nanoparticles resulting in conjugates that exhibit a six-fold increase in the rate of particle uptake
  • Passive targeting: Enhanced permeability and retention time of nanoparticles in tumour cells due to leaky vasculature
  • Delivery of Photosensitizers in Photodynamic Therapy
  • Principle of PDT: Administer PSà Light irradiation à ROS generationà Cancer cells killed
  • Polymeric (Chitosan) nanoparticles incorporate water insoluble photosensitizers into hydrophobic cores and deliver them into tumor cells
  • Also, it prolongs circulation time and hence more accumulation of photosensitizers in tumor cells
  • Charge-conversional nanoparticles for delivery of proteins
  • Stable at normal pH but disrupts at acidic pH of endosomes. protein-loaded nanoparticles showed efficient endosomal disruption and subsequent diffusion


  • New DDS carrier which possesses solid lipid core matrix
  • Good physical stability, protection of incorporated drugs from degradation, controlled drug release, and good tolerability
  • SLNs do not show biotoxicity as they are prepared from physiological lipids
  • SLNs are especially useful in ocular drug delivery as they can enhance the corneal absorption of drugs and improve the ocular bioavailability of both hydrophilic and lipophilic drugs.
  • Also being used for Oral Intestinal lymphatic delivery of drugs. SLN act as physical sunscreens with increased UV blocking ability. Incorporation of molecular sunscreens into SLN leads to synergetic UV blocking effects


  • Microspheres can be defined as solid, approximately spherical particles ranging in size from 1 to 1000 μm
  • Each microsphere is basically a matrix of drug dispersed in a polymer (biocamptible/biodegradable) from which release occurs by first order process
  • Used for controlled release of drugs mostly by subcutaneous/ intramuscular route
  • Floating/muco-adhesive microspheres have been developed as gastro-retentive delivery systems used in treatment of H.Pylori infections
  • Microsphere-based systems, providing controlled release delivery, can obviate the need for repeat immunizations à Vaccine delivery: Tetanus & toxoid


  • Any multicomponent fluid made of water, oil in combination with one or several surfactants
  • Stable, isotropic and transparent with low viscosity
  • Thermodynamically stable, High solubilization capacity, High diffusion and absorption rates
  • Size: 20-200 nm
  • Drug delivery vehicles for poorly water-soluble drugs
  • Parenteral delivery: Vincristine Paclitaxel
  • Transdermal delivery: Cyclosporine, progesterone
  • Oral delivery: Itraconazole, Acyclovir


  • drug delivery system in which Free drug transferred in lipid based carrier for improving the solubilization of drugs with low aqueous solubility and to stabilize them against hydrolysis or oxidation
  • aka Colloidal drug carriers(Various colloidal drug delivery systems liposomes, niosomes, nanoparticles and microparticles)
  • Heterogeneous dispersions of two immiscible liquids (o/w, w/o, micron, submicron, double or multiple emulsions)
  • Used as vehicles for anesthetic drugs like Propofol and Etomidate


Transdermal Drug Delivery System

• Self contained, discrete dosage forms, applied to skin  delivers drug at controlled rate

• Adv:

1) Avoidance of first pass metabolism & GI incompatibility

2) Greater patient compliance.

3) Enhance therapeutic efficacy

4) Termination of therapy is easy

  • Scopolamine patch – Motion sickness
  • Hydrogel transdermal patch – Rx of burns
  • Insulin patch


• Localized, non‐invasive, convenient and rapid method of delivering LMW drugs & macromolecules into the skin by ultrasonic energy.

• US (20kHz-16MHz) à ↑ skin permeability

• Reverse US technology – extraction of fluid or compounds out of the skin

Laser assisted Transdermal DDS

• New technology of drug delivery

• Effective drug permeation-enhancement approach for facilitating drug delivery into or across the skin.

• Laser à controlled disruption and ablation of the stratum corneum

• Eg. LAD of Mtx LAD of drugs to treat facial scars

Mucoadhesive DDS

• Mucosal membranes – Oral MDDS, ocular, nasal, vaginal drug delivery systems

Osmotically controlled DDS

• Osmotic pressure – driving force to release drug in controlled manner

Oral – eg. GI therapeutic systems (GITS) à Eg. Once-daily Nifedipine GITS tablet

• Based on Osmotic push–pull technology – Approved for Rx of HTN & Px of angina

Parenteral – eg. Implantable pumps

Pulsatile Release System

  • Defined as rapid and transient release of certain amount of drug molecules within a short period of time, after a predetermined off-release period
  • Deliver drug at time and site specific manner
  • Useful in:
    • Chronopharmacotherapy of disease(asthma early morning, heart attack late night, diabetes after meal);
    • Site specific (Colon);
    • For programmed administration of hormone and drug;
    • For drug having short half life(beta blockers)
  • Osmotic Pressure Release System
    • 1. Capsule based
    • 2. Programmed oral release technology
  • Capsular system with polymeric plugs: Pulsincap

Capsule based: Capsule has pelletà Pellet has coreà Core has drug and osmotic agent and enclosed by water permeable but insoluble polymer.

Water absorptionà Goes into pelletà Osmotic agent dissolves and pellet swellsà Hydrogel is for controlling lag time which gets pushed by swelling of pellet and drug is released as pulse

  • Programmed oral release technology


1. Pulsincap—consist of capsule with water soluble cap, an insoluble body filled with drug & sealed with a hydrogel plug . —

2. The length of plug decides lag time. —

3. On administration, soluble cap dissolves thereby allowing the hydrogel plug to swell & expand —

4. After a predetermined lag time, it is swollen to an extent that it is ejected from capsule body thereby releasing the drug.

Ex: Dofetilide for Hypertension

Drug devices

Drug eluting stents

• 1st drug eluting stent approved – coated with Paclitaxel/Sirolimus

• Coronary stent – slow release of drug to block cell proliferation à prevents fibrosis & clot formation à Restenosis

Hormone releasing devices

IUCD, Norplant


• Hold drug in a reservoir

• Implanted into the body under LA

• Released with the help of hand held wireless device

• Chronic conditions requiring careful monitoring & precise therapy

• Compliance is improved

• Eg: PTH for osteoporosis

PCA pump

• Computerized pump – allows patient to control their pain

Insulin delivery devices

Closed loop insulin delivery system, Insulin pen, insulin jet, Inhaled Afrezza

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