Presented by Dr. Rajesh Kadam JUNIOR RESIDENT Dept of PharmacologyMGM’s Medical college, Aurangabad (ms)
Major route of drug administration are:A) Topical A) Skin B) ConjunctivalA) Enteral A) Oral B) Sublingual or Buccal C) Rectal D) Inhalational E) Nasal
A) Parenteral A) Subcutaneous B) Intramuscular C) Intravenous D) Intradermal injection
Provide increased local concentration of the drug. Improve the compliance of the patient. Make drug utilization more convenient. Reduces toxic effects of the drug. Delivery of drug by conventional route. Reduces side effects. Enhances target specificity. Increases drug bioavailability in required zone
1) Oral control release drug formulations2) Nasal drug delivery system3) Pulmonary drug delivery system4) Transdermal drug delivery system5) Others
All Other Transdermal 2% 8% Implant 10%Oral CR60% Inhalation 27%
Controlled drug delivery is one which delivers the drug at a predetermined rate,for locally or systemically, for a specified period of time.
Control drug release has been achieved by following classes of control drug delivery system:1) Dissolution 1) Matrix 2) Encapsulation1) Diffusion 1) Matrix 2) Reservoir1) Combination of both Dissolution & Diffusion2) Osmotic pressure control system
These systems are most commonly employed for production of enteric coated dosage forms. To protect the stomach from the effects of drug such as aspirin, a coating that dissolves in alkalline media is used. This inhibits release of drug from the device unless it reaches the higher ph of the intestine.
Also called as Monolith dissolution controlled system. It can be either a drug impegnated shere or tablet which will be subjected to slow erosion Dissolution is Controlled by: 1.Altering porosity of tablet. 2.Dissolving at slower rate. Drug release determined by dissolution rate of polymer. Examples: Dimetane extencaps.
Also Called as Coating dissolution controlled system. Drug is coated with a given thickness coating, which is slowly dissolved in the contents of gastrointestinal tract. An alternative method is to administer the drug as group of beads that have coating of different thickness. Since the beads have different coating thickness, their release occurs in a progressive manner.
Diffusion process shows the movement of drug molecules from a region of higher concentration to one of lower concentration across the membrane. Commonly when a water insoluble membrane encloses a core of drug, it must diffuse through the membrane.
Also called as Laminated matrix device. In the system, a water insoluble polymeric material encases a core of drug. Drug will partition into the membrane and exchange with the fluid surrounding the particle or tablet. Additional drug will enter the polymer, diffuse to the periphery and exchange with the surrounding media. Drug core surrounded by polymer membrane which controls release rate.
Rate controlling mechanism - partitioning into membrane with subsequent release into surrounding fluid by diffusion. Commonly used polymers - HPC, ethyl cellulose & polyvinyl acetate. Examples: Nico-400, Nitro-Bid
Advantages: Zero order delivery is possible Release rate is variable with polymer typeDiadvantages: Difficult to deliver high molecular weight compound Potential toxicity if system fails Increased cost as per dosage
Rate controlling steps :Polymeric content in coating, thickness of coating, hardness of microcapsule.
A solid drug is dispersed in an insoluble matrix and the rate of release of drug is dependant on the rate of drug diffusion. Homogenous dispersion of solid drug in a polymer mixture.
Advantages: Easier to produce than reservoir or encapsulated devices High molecular weight compound can be deliverDisadvantages: It cannot provide zero order release
Rate controlling step: Diffusion of dissolved drug in matrix.
A semi permeable membrane is placed around a tablet, particle or drug solution that allows transport of water into the tablet with eventual pumping of drug solution out of the tablet through a small delivery aperture in tablet coating. Two types of osmotically sustained systems are:- Type A contains an osmotic core with drug Type B contains the drug in flexible bag with osmotic core surrounding.
A new system is acquired i.e. GRDDS to increase the time available for drug absorption. Gastro retentive systems can remain in the gastric region for several hours and hence significantly prolong the gastric residence time of drugs.
In this technique the gastro retention is achieved by floatation of the dosage form in gastric fluid. Floating drug delivery system have a bulk density less than gastric fluid & so remain buoyant in the stomach without affecting gastric emptying rate.
The following approaches have been used for the design of floating dosage forms of single- and multiple-unit systems. Single-Unit Dosage Forms: In Low-density approach the globular shells apparently having lower density than that of gastric fluid can be used as a carrier for drug for its controlled release.
Multiple-Unit Dosage Forms: The purpose of designing multiple-unit dosage form is to develop a reliable formulation. Micro spheres have high loading capacity and many polymers have been used such as albumin, gelatin, starch & polymethacrylate. Spherical polymeric micro sponges, also referred to as “micro balloons,” have been prepared. Micro spheres have a characteristic internal hollow structure and show an excellent in vitro floatability.
Effervescent Floating Dosage Forms: These are matrix types of systems prepared with the help of swellable polymers such as methylcellulose and chitosan and various effervescent compounds, e.g., sodium bicarbonate, tartaric acid, and citric acid. They are formulated in such a way that when in contact with the acidic gastric contents, CO2 is liberated and gets entrapped in swollen hydrocolloids, which provides buoyancy to the dosage forms.
Non-effervescent floating dosage forms use a gel forming or swell able cellulose type of hydrocolloids, polysaccharides, and matrix-forming polymers like polycarbonate, polyacrylate.. The formulation method includes a simple approach of thoroughly mixing the drug and the gel-forming hydrocolloid.
After oral administration this dosage form swells in contact with gastric fluids and attains a bulk density The air entrapped within the swollen matrix imparts buoyancy to the dosage form. The so formed swollen gel-like structure acts as a reservoir and allows sustained release of drug through the gelatinous mass
Pulsatile drug delivery system is defined as the rapid and transient release of certain amount of drug molecules within a short time period immediately after a predetermined off-release period, i.e., lag time. Pulsatile drug delivery aims to release drug on programmed pattern i.e. at appropriate time and at appropriate site of action. Example: Pulsincap
Advantages Extended daytime or night-time activity Reduced side effects Reduced dosage frequency Reduction in dose size Improved patient compliance
Lower daily cost to patient due to fewer dosage units are required by the patient in therapy. Drug adapts to suit circadian rhythms of body functions or diseases. Drug targeting to specific site like colon. Protection of mucosa from irritating drugs. Drug loss is prevented by extensive first pass metabolism
The Pulsincap system is an example of such a system that is made up of a water insoluble capsule body filled with drug formulation. The body is closed at the open end with a swellable hydrogel plug. The length of plug decides lag time. The plug material consists of insoluble but permeable and swellable polymers (eg, polymethacrylates)
Definition: Transdermal drug delivery system can deliver the drugs through the skin portal to systemic circulation at a predetermined rate and maintain clinically the effective concentrations over a prolonged period of time.
These are painless, non adhesive way to deliver drug directly into body. They are useful where drugs that are breakdown by the stomach acid, extensively degraded by liver. Useful in controlled, steady delivery of medication over long period of time .
They have very few side effects as compared to oral route. These are easy to use and to remember. It can be used as an alternative to people who cannot take medication orally. Patient compliance. They are cost effective.
TDDS cannot achieve high drug levels in blood / plasma. We cannot give drugs of large molecular size. TDDS cannot deliver in pulsatile manner.
It cannot given if drug or formulation causes irritation to skin. Adhesive may not adhere well to all types of skin. Uncomfortable to wear. May not be economical.
The adhesive layer of this system also contains the drug. In this type of patch the adhesive layer not only serves to adhere the various layers together, along with the entire system to the skin, but is also responsible for the releasing of the drug. The adhesive layer is surrounded by a temporary liner and a backing.
The multi-layer system is different however that it adds another layer of drug-in- adhesive, usually separated by a membrane.
Unlike the Single-layer and Multi-layer Drug-inadhesive systems the reservoir transdermal system has a separate drug layer. The drug layer is a liquid compartment containing a drug solution or suspension separated by the adhesive layer. In this type of system the rate of release is zero order.
The Matrix system has a drug layer of a semisolid matrix containing a drug solution or suspension. The adhesive layer in this patch surrounds the drug layer partially overlaying it.
In this type of patch the adhesive layer not only serves to adhere the various layers together but also to release vapour. They release essential oils for up to 6 hours and are used in cases of decongestion mainly.
Intranasal drug delivery is now recognized to be a useful and reliable alternative to oral and parenteral routes. Recently, the nasal mucosa has seriously emerged as a therapeutically viable route for the systemic drug delivery.
Hepatic first pass metabolism avoided. Rapid drug absorption and quick onset of action. Bioavailability of larger drug molecules can be improved by means of absorption enhancer. Convenient for long term therapy, compared to parenteral medication. Easy and convenient. Easily administered to unconscious patients.
Pathologic conditions such as cold or allergies may alter significantly the nasal bioavailabilty. Relatively inconvenient to patients possibility due to nasal irritation. Nasal cavity provides smaller absorption surface area when compared to GIT.
The respiratory tract is one of the oldest routes used for the administration of drugs. Over the past decades inhalation therapy has established itself as a valuable tool in the local therapy of pulmonary diseases such as asthma or COPD (Chronic Obstructive Pulmonary Disease) .
It is needle free drug delivery system. It requires low and fraction of oral dose. Pulmonary drug delivery having very negligible side effects since rest of body is not exposed to drug. Onset of action is very quick with pulmonary drug delivery. Degradation of drug by liver is avoided in pulmonary drug delivery.
Targeting specificity. Drug irritation and toxicity. Immunogenicity of proteins Drug retention and clearance.
Aerosol preparations are stable dispersions or suspensions of solid material and liquid droplets in a gaseous medium. The drugs, delivery by aerosols is deposited in the airways by: Gravitational sedimentation Inertial impaction Diffusion Mostly larger drug particles are deposited by first two mechanisms in the airways, while the smaller particles get their way into the peripheral region of the lungs by following diffusion.
There are three commonly used clinical aerosols: Nebulizers Metered–dose Inhaler (MDI) Dry-powder inhaler (DPI) The basic function of these three completely different devices is to generate a drug-containing aerosol cloud that contains the highest possible fraction of particles in the desired size range.
Nebulizers are widely used as aerosolize drug solutions or suspensions for drug delivery to the respiratory tract and are particularly useful for the treatment of hospitalized patients. Delivered the drug in the form of mist. There are two basic types: Air jet Ultrasonic nebulizer
DPIs are bolus drug delivery devices that contain solid drug in a dry powder mix (DPI) that is fluidized when the patient inhales. Dry powder formulations either contain the active drug alone or have a carrier powder (e.g. lactose) mixed with the drug to increase flow properties of drug. DPIs are a widely accepted inhaled delivery dosage form, particularly in Europe, where they are currently used by approximately 40% of asthma patients.
Propellant-free. Less need for patient co-ordination. Less formulation problems. Dry powders are at a lower energy state, which reduces the rate of chemical degradation.
Dependency on patient’s inspiratory flow rate and profile. More expensive than pressurized metered dose inhalers. Not available worldwide.
Used for treatment of respiratory diseases such as asthma and COPD. They can be given in the form of suspension or solution. Particle size of less than 5 microns. Used to minimize the number of administrations errors. , It can be deliver measure amount of medicament accurately.
It delivers specified amount of dose. Small size and convenience. Usually inexpensive as compare to dry powder inhalers and nebulizers. Quick to use. Multi dose capability more than 100 doses available.
Difficult to deliver high doses. There is no information about the number of doses left in the MDI. Accurate co-ordination between actuation of a dose and inhalation is essential.
Traditional insulin drug delivery system:Insulin therapy via subcutaneous or other parenteral route in diabetic patient ispreferred but on continuous administration there may be chance of peripheral hyperinsulinemia, formation of thrombus, inflammation & irritation at the site. Also patient suffering from needle phobia hesitate to take it.
Needle free insulin injection provides following advantages: Improve concordance with insulin regiment. Improve the patient health/well-being. Eliminates the need for sharp disposal and avoids needle stick injuries. Emotional benefits of using a needle free devices. No sharp to dispose off. Fast injection, insulin is delivered in less than 0.3 seconds, regardless of dose. No additional pressure required to delivered large doses.
Jet injectors: A jet injector is a type of medical injecting syringe that uses a high-pressure narrow jet of the injection liquid instead of a hypodermic needle to penetrate the epidermis. It is powered by compressed air or gas, either by a pressure hose from a large cylinder, or from a built-in gas cartridge or small cylinder.
Inhalable insulin: Inhalable insulin (Fig: 3) was available from September 2006 to October 2007 in the United States as a new method of delivering insulin, a drug used in the treatment of diabetes.
Insulin spray: The buccal route is another promising alternative for insulin delivery. The buccal area having an abundant blood supply, it offers some advantages such as a means to deliver the acid labile insulin, and elimination of insulin destruction by first pass metabolism.
Insulin Pen: There are two pen systems: 1. A replaceable cartridge pen reuses the pen portion. When the insulin is empty, the vial is replaced by inserting a new one. 2. A prefilled pen is entirely disposable. When the insulin is gone, the entire unit is discarded.
Advantages: More convenient and easier to transport than traditional vial and syringe. Repeatedly more accurate dosages. Easier to use for those with visual or fine motor skills impairments. Less injection pain
Disadvantages: Unlike the traditional syringe, pens are usually restricted to full or half unit dosing. You are also not able to mix two different insulins in the same pen. In addition, insurance coverage for insulin pens in the United States may vary widely.
(a) Transdermal Delivery Systems : Nesterone is a newer progestin. When used as a cream to the skin it provides effective contraception. Combined contraceptive transdermal patches are also found very effective. Patches are used like pills – 3 weeks on and 1 week off.(b) Uniplant : single rod implant, containing 38 mg of nomegesterol (newer progestin) with a release rate of 100 μg/day. It provides contraception for 1 year.
(c) Biodegradable Implants : Available by the name of capronor, releases levonorgesterol from polymer 6- cap-rolactone.(d) Injectable Contraceptives: In the form of microspheres using copolymer (lactide-glycolide) have been studied. Hormone currently used in the microsphere (0.06- 0.1 mm diameter) is either norethindrone or norethindrone combined with ethinyl estradiol. Injection is given over the gluteal muscle.
(e) Vaginal Rings : These contain levonorgestrel covered by a sialistic tubing. These are5-6 cm in diameter. These can be replaced every 90 days.(f) Combined Ring : These are soft & transparent ethylene vinyl rings. These have ethinylestradiol & etonogestrel. The ring is 5 cm in diameter.(g) Quinacrine pellets: These are inserted into the uterine cavity transcervically with the help ofhysteroscope.