Drug Delivery Systems

Joab Chen& Kenneth Tsang

Drug Delivery

How do we physically get drugs into our bodies?What are the various systems that are in use today? In the future?We as a class will determine which of these systems is the best currently, and which will have the most potential.

Importance of Delivery Systems

A drug that cannot be properly delivered into the human body is useless.Not only that, but drugs must enter in appropriate amounts and be chemically stable until the desire effect is reached.A delivery system has huge consequences for the quality of life of a patient.

Success of a delivery system

There are 3 criteria’s in judging a system

Efficacy, does it work?Efficiency, how well does it work?Convenience, from a health profession and a patient point of view.

No current system can fully satisfy all three.

Agenda

We’ll be looking at 4 main categories of delivery systems:

OralInjections (briefly)PulmonaryTransdermal

Oral Delivery

Preferred method of drug intake.Self-Administered drug deliveryHowever, about 1/3 of the population has difficulties with orally taken drugs.Usually involves Geriatrics and Pediatrics.Drug is prone to degradation before absorption.Bioavailability limits the amount of drug absorption

Main Goals for Success

Achieving a constant level of the drug in the bloodstreamMaximize bioavailability and minimize the frequency of dosage– Dissolution– Solubility– Diffusion

Dissolution

Drug release can be controlled by adjusting the thickness of the encapsulated membraneThickness usually ranges from 1 to 20 umAids in masking the tasteAlso helps protect drugs from metabolism

Encapsulated Drugs

Solubility

Increasing solubility will increase bioavailabilityDrugs with low solubility usually require more than 250ml of water to dissolve.Using the body’s natural chemicals to perform “Biotransformation”

Nanocrystal Technology

A popular solution for increasing the solubility is to decrease the particle size which increases the surface area.This also increases the bioavailablity

Diffusion

How well a drug diffuses ultimately decides how much of the it is absorbed through a membraneDependent on concentration

Injection Delivery

Quick absorption and circulation of drug Very high bioavailabilityHowever, causes discomfort/pain to the patientRequires a health care professional to administer the dosagesRisk of infection and overdosing

Needleless injections

Shoots liquid drug at high enough velocity to penetrate skinRelatively painlessOnly the injectate penetrates the skin so it does not scar tissueDistributes the drug as opposed to a pooling of drug left by a needle based injection

Needleless injector

Pulmonary

Alveoli passages in the lungs pass CO2 from blood, ideal site to transport high weight moleculesPassages span huge areas, 80-100 m2, providing for fast uptake ratesAlveoli are closely tied to the vascular system through capillaries, thus drugs enter blood stream quickly after administration and diffusion

Traditional Pulmonary Designs

Used aerosol canisters to “particlized” drugsPatients then inhale aerosol mixtureDrug administered does not equal drug availability (average only 10% efficiency)2 major factors affecting effectiveness– Particle size– Breathing/inhaling technique

Factors affecting absorption

Particle size of vital importanceLarge particles (>5um) tend to have too much inertia (Impactation)Smaller particles have too little inertia (Sedimentation)Ideal size of 1-3um

Breathing technique can also affect absorptionWhen the drug is released during inhalation, how fast you inhale, how long you hold your breath after administration, all have effects on depostion

Breathing Technique

•Inhaling quickly and hold breath for 4 secondsLung Volume at release 20% 50% 80%Lung Deposition 11.8 6.5 6.8Extrathoracic 87 92 91.9Exhaled 1.3 1.4 1.3

•Inhale slowly and hold for 10 secondsLung Volume at release 20% 50% 80%Lung Deposition 14.3 14.3 13.8Extrathoracic 84.6 84.6 85.2Exhaled 1 1.1 1

Aradigm’s AERx

Attempts to solve traditional problems using a computer monitored dosing environmentCan generate particles about 1 micron in size consistentlyParticle environment (temperature,humidity, etc.) is adjusted by the computerComputer also monitors the patient’s breathing behaviour and delivers accordingly

Aradigm’s AERx

Aradigm’s AERx

Transdermal Delivery

Skin is the largest organ in the bodyAlthough it is a strong immune barrier, small molecules are still able to permeate through itAs a result, the skin is the ideal delivery site for convenient, painless uptakeSeveral methods, passive, micro-needle, and iontophoresis

General Characteristics

Convenient and easy to useAbsolutely painlessBetter efficiency than oral, avoids metabolism by GI tractDiffusion guarantees a steady delivery rate

Larger molecular drugs cannot be usedHence only a selected few drugs are compatibleDiffusion rate is determined by patientRate is generally low

Passive Transdermal Patches

The most prevalent form of transdermal delivery todayDrug comes in direct contact with skin, diffuses into dermal blood supplyVery few drugs are small enough to be used (nitroglycerin, testosterone, nicotine, and a few others)

Microneedles

Arrays of microscopic needles150 microns long and a tip of about 1 micronAble to reach just below the stratum corneumEnhances uptake rate by penetrating through thickest part of epidermis

Iontophoresis

Uses electricity to move drugs across epidermal layers2 electrodes immersed in a drug solutionVoltage across electrodes ionizes drugs, which then travels from electrodes into the tissueOn demand administrationPatch is, however, bulkier (power supply)

How it works

Factors affecting Iontophoresis

Current

Transport rate (flux) is linearly proportional to the current appliedRate of increase depends on electrochemical properties of drug

Factors affecting Iontophoresis

Concentration

Generally, flux increases as concentration of drug increasesStrong effects by presence of competing ions

Factors affecting Iontophoresis

pH of drug solution

pH has a severe effect on fluxThe pH of human skin is between 4-6, thus drug solution must match it to gain maximum flux

Iontophoresis

Conclusion/Discussion

How would you like your medicine?Which technology do you think has the most potential to be the “perfect” delivery system?

References

BooksSaltzman, W. Mark, Engineering Principles for Drug Delivery. Oxford Press, 2001.Ranade and Hollinger. Drug Delivery Systems. CRC Press, 2003.Johnson and Lloyd-Jones, Drug Delivery Systems. VCH, 1987.Ganteroton and Jones, Drug Delivery to the Respiratory Tract. VCH, 1987

Internet Researchhttp://www.drugdeliverytech.com/cgi-bin/articles.cgi?idArticle=143http://www.3m.com/us/healthcare/manufacturers/dds/jhtml/inhalation_development.jhtmlhttp://www.elan.com/DrugDelivery/drug_delivery/nanocrystal_technology.asphttp://www.bioject.com/index.html