THE RISE AND RISE OF DRUG DELIVERY

ORAL ROUTE Released drug is absorbed in small intestine. Advantages: - patient acceptance - convenient Disadvantages: - poor uptake — rapidly metabolized - chemical instability in GI tract Traditional: Tablets, capsules

Tablets: A tablet is a hard, compressed medication in round, oval or square shape. Types of tablets: 1- Disintegrating tablet (conventional or plain tablet) Disintegrating tablet is the most common type of tablets that is intended to be swallowed.

Types of Tablets (Cont.) Single layer tablet

Types of Tablets (Cont.) 2- Chewable tablets Chewable tablets are to be chewed and thus mechanically disintegrated in the mouth. Advantages of chewable tablets: - Provide quick and complete disintegration of the tablet and thus obtain a rapid drug effect - Easy administration, especially for infants and elderly people.

Types of Tablets (Cont.)

3- Effervescent tablets - Effervescent tablets are dropped into a glass of water before administration during which CO2 is liberated.

Types of Tablets (Cont.) Advantages of effervescent tablets: 1- To obtain rapid drug action, for example analgesics and antacids.

Types of Tablets (Cont.)

2- To facilitate drug intake, for example vitamins

Types of Tablets (Cont.) 4- Sublingual and Buccal tablets They are used for drug release in mouth followed by systemic uptake of the drug. A rapid systemic drug effect can thus be obtained without first-path liver metabolism. Sublingual tablets are placed under the tongue.

Types of Tablets (Cont.)

Buccal tablets are placed in the side of the check for absorption through oral mucosa.

Types of Tablets (Cont.) 5- Lozenges They are tablets that dissolve slowly in the mouth and so release the drug dissolved in the saliva. Lozenges used for - Local medications in the mouth or throat, e.g. local anaesthetics, antiseptics and antibiotics.

Types of Tablets (Cont.) Hard candy lozenges, e.g. Halls®

Capsules: A capsule is a medication in a gelatin container. 1- Hard gelatin capsules - The capsule consists of two halves and filled with powder.

Capsules: 2 Soft gelatin capsules: The capsule consists of one part and used for oils and for active ingredients that are dissolved or suspended in oil. chewable soft gelatin capsules of omega-3

Novel oral delivery systems: 1- Fast dissolving oral film: -It consists of a very thin polymeric film strip incorporating and delivering pharmaceutical active ingredients (alone or in combination). -It has the size of a stamp and – once placed in the mouth – dissolves in a few seconds and is swallowed with the saliva without the need of taking water.

Novel oral delivery systems:

Advances in Controlled / Sustained Release Drug Delivery System: Benefits of modified drug delivery system: - Decreased in dosing frequency - Sustained & Consistent blood level within the therapeutic window. - Enhanced bioavailability - Reduced side effects - Improved patient compliance

Advances in Controlled / Sustained Release Drug Delivery System: Some technologies of modified release drug delivery system: I. Osmotic Drug Delivery Devices: They fall in two categories 1- Implantable E.g. Implantable Miniosmotic pump

Osmotic Drug Delivery Devices: 2- Oral osmotic Pump Single chamber osmotic pump Multi chamber osmotic pump Specific types E.g. Elementary osmotic pump E.g. Push pull osmotic pump E.g. Osmotic pump with non expanding second chamber E.g. Elementary osmotic pump

Novel oral delivery systems: 2- Controlled drug delivery systems I. The osmotic-controlled release oral delivery system, OROS: - It is an advanced drug delivery technology that uses osmotic pressure as the driving force to deliver pharmacotherapy, usually once-daily, in several therapeutic areas.

Novel oral delivery systems: A- The elementary osmotic pump

Novel oral delivery systems: Following ingestion, water is absorbed into the system, dissolving the drug, and the resulting drug solution is delivered at the same rate as the water entering the tablet. Disadvantage: It is only suitable for the delivery of water- soluble drugs.

Novel oral delivery systems: B- The two-layer osmotic push–pull tablet - The polymeric expanding compartment (push layer) provides additional force on the drug layer to ensure that the drug is delivered through the delivery orifice at the target rate.

The osmotic push–pull tablet

Novel oral delivery systems: C- The advanced longitudinally compressed tablet multilayer formulation - It consists of an osmotic push layer and can be configured to contain several drug layers. - The option of multiple drug layers provides increased flexibility and control over the pattern of release of medication from the system.

The advanced longitudinally compressed tablet multilayer formulation

Novel oral delivery systems: D- The L-OROS system - provide controlled delivery of liquid drug formulations in a capsule form. - This system consists of a semipermeable membrane coating that encloses a liquid drug layer and osmotic push layer.

Novel oral delivery systems:

E- Sandwiched Osmotic Tablets (SOTS) - It is composed of polymeric push layer sandwiched between two drug layers with two delivery orifices. - When placed in the aqueous environment the middle push layer containing the swelling agents swells and the drug is released from the two orifices situated on opposite sides of the tablet and thus SOTS can be suitable for drugs prone to cause local irritation of the gastric mucosa.

Sandwiched Osmotic Tablets

Novel oral delivery systems: F- OROS-CT - OROS-CT is used as a once or twice a day formulation for targeted delivery of drugs to the colon. - The OROS-CT can be a single osmotic agent or it can be comprise of as many as five to six push pull osmotic unit filled in a hard gelatin capsule.

OROS-CT

Novel oral delivery systems: II. pH sensitive systems

38 Transdermal Route Transdermal patch is a medicated adhesive patch that is placed on the skin to deliver a specific dose of medication through the skin and into the bloodstream. Transdermal drug delivery offers an attractive alternative to the conventional drug delivery methods of oral administration and injection.

Transdermal Route Advantages of Transdermal drug delivery system over Conventional Dosage Forms: -Avoids vagaries associated with gastrointestinal absorption due to pH, enzymatic activity, drug-food interactions etc. -Substitutes oral administration when the route is unsuitable as in case of vomiting, diarrhea. - Avoids hepatic “first pass” effect. - Avoids the risks and inconveniences of parenteral therapy.

Transdermal Route - Reduces daily dosing, thus, improving patient compliance. - Rapid termination of drug effect by removal of drug application from the surface of the skin. - Suitability for self-administration.

Transdermal Route Limitations of Transdermal drug delivery: - The drug must have some desirable physicochemical properties for penetration through stratum corneum. - Skin irritation or contact dermatitis due to the drug, excipients and enhancers of the drug used to increase percutaneous absorption is another limitation. - The barrier function of the skin changes from one site to another on the same person, from person to person and with age.

Transdermal Route (Cont.) Traditional : controlled release patches

Transdermal Route (Cont.) Device Designs A-membrane based : Release rate constant (rate-limited by diffusion through membrane) laminated layers:

Transdermal Route (Cont.) B- monolithic patch - C 0 >> C s drug dissolution in polymer matrix controls release rate. ⇒

Transdermal Route (Cont.) The Latest Approaches for Enhancing Transdermal Drug Delivery - Various technologies have been developed to bypass or modulate the barrier function of the skin. I. Iontophoresis: Iontophoresis is an effective and painless method of delivering medication to a localized tissue area by applying electrical current to a solution of the medication.

Transdermal Route (Cont.) The diagram below illustrates the basic mechanism. Like electrical charges repel. Therefore, application of a positive current will drive positively charged drug molecules away from the electrode and into the tissues; similarly, a negative current will drive negatively charge ions into the tissues.

What is iontophoresis ?

Iontophoretic Patches

Iontophoresis & Beauty Iontophoresis, a widely used method in the fields of dermatologist, emits feeble electric current to the skin to lower the skin barriers, and used electical repulsion to deliver the nutrients of cosmetics to deep under the skin

Transdermal Route (Cont.) II. Reverse iontophoresis: Iontophoresis can be used in reverse to remove molecules from the circulation. One example, the GlucoWatch, a needleless means of monitoring blood glucose levels in diabetic patients, uses an electrical signal that is proportional to the amount of glucose in the extracellular fluid.

GlucoWatch & principle

Transdermal Route (Cont.) II. Electroporation: This process, in which brief, intense electric charges create small pores in the phospholipid bilayer of cell membranes, can assist in the transdermal delivery of drugs. Electroporation appears to reversibly disrupt the lipid bilayers in the stratum corneum, and the channels it creates are said to promote the passage of hydrophilic drugs through the skin.

Electroporation ii) When the electric field is applied, the ions move according to their charge. iii) Pathways are formed across the cell membrane allowing DNA to enter. iv) When the electric field is deactivated, the membrane heals.

Electroporation

Transdermal Route (Cont.) III.Phonophoresis (sonophoresis) : - The use of ultrasound of a suitable frequency to enhance skin permeability seems to be a useful alternative technique for delivering drugs through the skin and can be applied to vaccination and gene therapy.

Mechanism of action of phonophoresis: Enhanced Transdermal Permeation by Cavitation upon application of Ultrasound

Phonophoresis (sonophoresis)

Transdermal Route (Cont.) IV. Microneedles (Microporation): - patches coated with hundreds of microscopic needles (microneedles) that pierce only the stratum corneum. - They are generally one micron in diameter and range from microns in length. - The microneedles are usually drug-coated projections of solid silicon or hollow, drug-filled metal needles. - They can deliver proteins, nanoparticles, and both small and large molecules through the skin. - Because the nerves located deeper in the skin are not stimulated, the patient does not experience pain or discomfort. - Instead, patients feel the texture of sandpaper or a cat's tongue.

Microneedles An array of stainless steel microneedlesAn array of stainless silicon microneedles

Microneedles Microscope image shows an array of hollow microneedles next to a hypodermic needle typical of those now used to inject drugs and vaccines

Patch Microneedles

Transdermal Route (Cont.) V. Needleless Jet Injectors: - Needleless jet injectors combine the advantages of transdermal and parenteral drug delivery methods. - It fires fine, solid particles through the stratum corneum using high-pressure helium gas or uses nitrogen gas to propel liquid drug formulations through the skin. - The high velocity jet stream pierces the skin and the drug disperses into the subcutaneous adipose tissue.

Transdermal Route (Cont.) - Drug delivery is painless because the injectors use particles that are too small to trigger pain receptors.

Needleless Jet Injectors:

Transdermal Route (Cont.) VI. Medicated Tattoos: - modified the temporary tattoo popular with children and young adults to contain an active drug for transdermal delivery