Drug Delivery System

Modified Release Dosage Form (MRDF)

• Introduction:
The goal of any drug delivery system is to provide a therapeutic amount of drug to a proper site in the
body so that the desired drug concentration can be achieved promptly and then maintained. Thus the
two objectives are;
1. Spatial Placement: drug targeting to specific organ
2. Temporal delivery: Controlling the rate of drug delivery to target site. Thus maintaining drug
concentration.

The conventional dosage form has potential problems these are;

3. Lack of temporal delivery
4. Repeated dosage after specific interval. If the interval is not proper there will be large peaks and valleys
5. Patient non compliance
6. Increased untoward effects

The above problems of conventional dosage form stimulates the formulator both in industry and
laboratory level to develop modified release dosage form
 • Method or process of administering an active pharmaceutical
ingredient (API) to achieve therapeutic effect in humans or animals.
• Modify drug release profile and pharmacokinetic parameters for the
benefit of improving product efficacy as well as patient convenience
and compliance.
• Aims to deliver the drug at a rate directed by the needs of the body
during the period of treatment, and target the active entity to the
site of action
Disadvantages in current /Conventional therapy
• Inactivation by gastric juice
• Metabolism before reaching target cell – First pass metabolism in
lung / liver / Intestine
• Too many adverse reactions
• How to overcome these Problems
• By improving rate of drug delivery
• Decreasing biodegradation
• Time release medications
• Site-specific targeting
• Costly, multiple-dose, long-term therapies → Inexpensive, potent,
time-releasing or self- triggering formulations.
Classification of Modify Drug Delivery
System
1.Delayed Release
2. Extended Release
3. Site Specific Targeting
4. Receptor Targeting
5. Fast Dissolve Drug Delivery System (Flash)
• Delayed Release:
• Example include enteric coated tablets , where a timed release is
achieved by barrier coating repeated action tablets or spansules.
• Extended Release:
• These include any dosage form that maintains therapeutic blood or
tissue level of drug for prolong time.
• Site Specific Targeting:
• In such system the drug delivery is targeted adjacent to or in the
diseased organ or tissue.
• Receptor Targeting
• In such system the target is a particular receptor with in an organ or
tissue.
• Fast Dissolve Drug Delivery System (Flash)
• It is type of solid dosage form that dissolves or disintegrate in the oral
cavity without the help of water or chewing.
Advantages

1.Avoid patient compliance problem

2.Less total drug incorporation

• a) Minimize or eliminate local side effects

• b) Minimize or eliminate system side effects
• d) Minimize drug accumulation with chronic use
3.Improve efficiency in treatment

• a) Cure or control condition more promptly

• b) Reduce fluctuation in drug level
• c) Improve bioavailability of some drugs
• d) Make use of special effects (e.g. sustained release aspirin for
morning relief of arthritis by dosing before bedtime)

• 4. Economic Savings.
The ideal drug delivery system should be inert,
biocompatible, mechanically strong,
comfortable for the patient, capable of
achieving high drug loading, safe from
accidental release, simple to administer and
remove, and easy to fabricate and sterilize.

Drug levels in the blood with

(a)traditional drug dosing and
(b)controlled-delivery dosing.
In general, the sustained - release dosage form is designed to maintain
therapeutic blood or tissue levels of the drug for an extended period of
time. This is accomplished by attempting to obtain zero - order release
from the designed dosage form.
Zero order release constitutes drug release from the dosage form that
is independent of the amount of drug in the delivery system at a
constant release rate.
A number of variables, such as drug properties including stability,
solubility, partitioning characteristics. charge and protein binding
behavior, routes of drug delivery, target sites, acute or chronic therapy,
the disease, and the patient, must be considered to establish the
criteria for designing controlled release products.
1. Physicochemical Factors
Physicochemical properties, such as aqueous solubility, partition
coefficient and molecular size, drug stability, and protein binding
Ionization, p K a , and Aqueous Solubility Most drugs are weak acids or
bases. It is important to note the relationship between the p K a of the
compound and the absorptive environment. Delivery systems that are
dependent on diffusion or dissolution will likewise be dependent on the
solubility of drug in the aqueous media.
• Partition Coefficient
• Following administration, drugs and other bioactive compounds must
traverse a variety of membranes to gain access to the target area.
The partition coefficient and molecular size influence not only the
permeation of drug across biological membranes but also diffusion
across or through a rate controlling membrane or matrix. The
partition coefficient is generally defined as the ratio of the fraction of
drug in an oil phase to that of an adjacent aqueous phase
Drugs with extremely high partition coefficient (i.e., those that are
highly oil soluble) readily penetrate the membranes, while the
excessive high aqueous soluble compounds, having low oil/water
partition coefficients, cannot penetrate the membranes. A balance in
the partition coefficient is needed to give an optimum flux for
permeation through the biological and rate controlling membranes.

Drug Stability
The stability of drug in the environment where it is to be exposed is an
essential physicochemical factor to be considered before designing
controlled dosage forms . For example, orally administered drugs are
subjected to both acid – base hydrolysis and enzymatic degradation
• For drugs that are unstable in the stomach, the dosage forms can be
designed in so that they can be placed in a slowly soluble form or
have their release delayed until they reach the intestine. This type of
approach can be ineffective and the drug may be unstable in the small
intestine or undergo extensive gut wall metabolism. To obtain better
bioavailability for such types of drugs, which are unstable even in the
intestine, a different route of administration (e.g., transdermal with
controlled - release dosage forms) can be a better option . A
transdermal patch of nitroglycerin is a good example.
Technology of ER Dosage Forms
• 1. ER Coated Granules or Microspheres
• Granules of drug may be coated with lipid materials such as
beeswax, carnuba wax, glycerylmonostearate, acetyl alcohol, etc. •
Careful blending of coated and un-coated granules and with
coatings of different thicknesses will provide drug release of desired
characteristics.
• Example: Toprol-XL (Metoprolol succinate)
2. Multitablet system
• Small spheroid compressed tablets 3 to 4 mm in diameter may be
prepared to have varying drug release characteristics.
• They may be placed in gelatin capsule shells to provide the desired
pattern of drug release.
• Each capsule may contain 8 to 10 minitablets, some uncoated for
immediate release and others coated for extended drug release.
3. Microencapsulated drug
• MICROENCAPSULATION is a process by which very tiny droplets or
particles of liquid or solid material are surrounded or coated with a
continuous film of polymeric material. The product obtained by this
process is called as Microcapsules.
• The typical encapsulation process usually begins with dissolving the
wall material, say gelatin, in water.
• The material to be encapsulated is added and the two-phase mixture
thoroughly stirred.
• With the material to be encapsulated broken up to the desired
particle size, a solution of a second material, usually acacia is added.
• This additive material concentrates the gelatin into tiny liquid
droplets.

• One of the advantages of microencapsulation is that the

administered dose of a drug is subdivided into small units that are
spread over a large area of the gastrointestinal tract, which may
enhance absorption by diminishing localized drug concentration.
4. Embedding drug in slowly eroding or
hydrophilic matrix system
• By this process, the drug substance is combined and made into
granules with an excipient material that slowly erodes in body
fluids, progressively releasing the drug for absorption.
• When these granules are mixed with granules of drug prepared
without the excipient, the uncombined granules provide the
immediate drug effect whereas the drug-excipient granules provide
extended drug action.
5. Osmotic Pump
1.The system is composed of a core tablet surrounded by a
semipermeable membrane coating have a 0.4 mm diameter hole
produced by laser beam.
• Osmotic core containing drug Osmotic delivery orifice Semipermeable
membrane Osmotic pressure-controlled drug delivery system
• The system is designed such that only a few drops of water are drawn
into the tablet each hour. The rate of inflow of water and the function of
the tablet depends upon the existence of an osmotic gradient between
the contents of the bi-layer core and the fluid in the GI tract. Drug
delivery is essentially constant as long as the osmotic gradient remains
constant.