Novel Drug Delivery Systems

Dr.Maulik M PatelAssistant Professor

Aims for new drug delivery systems

Selective targeting of drugs to the site of acton

Try to make “ideal” drugs

increase the bioavailability. provide controlled delivery of drug transport the drugs intact to the site of action

avoiding the non diseased tissue

stable and delivery be maintained under various physiological variables.

easy to administer , safe and reliable

cost effective

Characteristics of ideal DDS

Medical-optimum dose , at the right time and at the right location

Industrial-Efficient use of expensive ingredients, reduction in production cost

Social-Beneficial to patients, better therapy, improved compliance and standard of living

Benefits

Modified-release drug formulations-Sustained and Controlled PolymersMicellesLiposomesEthosomesNenotechnology

ProdrugsTransdermal Drug delivery systemsOcusertInsulin jet and Micro pump controlled delivery systemPatient controlled analgesia(PCA)Drug eluting stentsGene therapyPersonalised medicine

Novel Drug delivery systems

Modified-release Drug

formulations

A way of formulating a medicine so that it is released into the body steadily, over a long period of time, Increases duration of action of a drug Reducing dosing frequency Once-daily oral preparations Long lasting depot injections(e.g.

contraceptives, hormone replacements, antipsychotic drugs)

Sustained Release drug formulations

Water

Hydratable dry polymer

Drug Drug

Dry polymer containing immobile drug

Hydratable gel containingDiffusible drug

It closely mimics the way by which the body naturally produces hormones such as insulin.

A way of formulating the medicine so it is released into the body in respond to specific stimuli e.g.

Exposure to light, Changes in pH or temperature.

Controlled Release drug formulations

Disintegrate when temperature is increased

Local heating of a tumour will cause the drug to be released at that site

Temperature sensitive liposomes

Used to delay the release of acid sensitive drugs( Peptides)

Drug delivery targeted to regions of low pH ,

Such as inflamed or hypoxic tissues

pH sensitive polymers

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pH Sensitive CR Formulation

Pharmaceutical Polymers

Biodegradability and biocompatibility

Biodegradation is generally described by two steps, (1) water penetrates polymeric matrix, attacking the chemical bonds by hydrolysis and metabolism of the fragments (2) surface erosion of the polymer

Biocompatibility refers to specific properties of a material not having toxic or injurious effects on biological systems.

Consist of aggregates of a few hundred amphiphilic molecules

That contains distinct Hydrophilic regions facing the surrounding water And Hydrophobic regions forming an inner core.

Micelles

Typically have diameter of 10-80 nm, Small enough not to sediment under gravity

But large enough –Can’t cross tight capillary endothelium (BBB)

Malignant tumors and inflamed tissues have large fenestrated capillaries, so transfer into such tissues more rapid than normal tissues

Absorption directly to the lymphatic system rather than vascular system to bypass first pass metabolism

Protect the drug from metabolic degradation, so half life is prolonged

Advantages of Micelles

First discovered in 1965 and proposed as drug carriers afterwards

Microscopic vesicles formed when an aqueous suspension of phospholipid is exposed to ultrasonic agitation

Large multilayered vesicles or small single layered vesicles may be formed.

Liposomes

Cholesterol/Phospholipid bilayer

Polymer coat(PEG)

TargettingMolecules(Antibody)

Drug substance

Liposome

Ethosomes are the slight modification of well established drug carrier- liposome.

Ethosomes are lipid vesicles containing phospholipids with high concentrations of ethanol and water.

These are vesicles tailored for enhanced delivery of active agents

Ethosomes

Ethanol causes skin disruption ↓

More permeability through skin ↓

Ethosomes permeate inside ↓

Fuse with skin lipids ↓

Release drug into deep skin layers

Mechanism of Action

Nanotechnology is the technology useful for synthesis of materials, devices and system by controlling shape and size at nanometer scale, (1-100 nm).

Achievements: -once daily oral Ciprofloxacin -tumor targeted delivery -improved ophthalmic delivery -oral insulin -oral administration of other peptides

Nanotechnology based DDS

Prodrugs

Transdermal DDSActive ingredient is delivered across the skin for systemic distribution.Example: transderm scopolamine, nitroglycerine , nicotine, Fentanyl

Avoid the risk and inconveniences associated with parenteral/ oral routes.

Increase the bioavailability - bypassing hepatic first pass metabolism

Bypass the variation in absorption and metabolism.

continuous drug administration Reduce the chance of over or under dosing

Advantages of transdermal DDS

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Ocular Insert- Occusertto increase the contact time between the preparation and the conjunctival tissue to ensure a sustained release suited to topical or systemic treatment.

Delivers insulin subcutaneously without using needle Achieved by pressurizing the liquid through a small

orifice which creates high speed jet that can penetrate the skin and underlying tissue.

Insulin jet

It is a computerized syringe which delivers insulin into the subcutaneous tissue every few minutes in tiny amount 24 hours a day through a canula placed in the subcutaneous tissue.

Micro pump insulin delivery system

Patient can control the release of analgesic drug depending on the pain – this can be useful in cancer pain

Patient Controlled Analgesia

Genetic Transfer System Under evaluation & III Phase clinical trials

for Adenovirus & HIV

means prescription of specific treatment and therapeutics best suited for an individual. It is also referred to as individualized or individual based therapy based on the patient genotype, circadian rhythm, biochemical and hematological parameters.

Example: Isoniazid , Sch , G-6 PD, p-glycoprotein ,Malignant hyperthermia by halothane

Personalized medicine-ultimate goal of new DDS