Drug Delivery System

1. DRUG DELIVERY SYSTEM
Assignment
SAMEEN ARIF
BPD02173219
APRIL 29, 2022
UNIVERSTY OF LAHORE
DEPARTMENT OF PHARMACY

2. OSMOTIC CONTROL DRUG DELIVERY SYSTEM
INTRODUCTION
Osmotic drug delivery uses the osmotic pressure of drug or other solutes (osmogens or
osmagents) for controlled delivery of drugs. Osmotic drug delivery has come a long way since
Australian physiologists Rose and Nelson developed an implantable pump in 1955.
ADVANTAGES OF OSMOTIC DRUG DELIVERY SYSTEM
1. The delivery rate of zero-order (which is most desirable) is achievable with osmotic
systems.
2. Delivery may be delayed or pulsed, if desired.
3. For oral osmotic systems, drug release is independent of gastric ph and hydrodynamic
conditions which is mainly attributed to the unique properties of semipermeable
membrane (SPM) employed in coating of osmotic formulations.
4. Higher release rates are possible with osmotic systems compared with conventional
diffusion-controlled drug delivery systems.
5. The release rate of osmotic systems is highly predictable and can be programmed by
modulating the release control parameters.
6. A high degree of in vivo–in vitro correlation (IVIVC) is obtained in osmotic systems
because the factors that are responsible for causing differences in release profile in vitro
and in vivo (e.g., agitation, variable ph) affect these systems to a much lesser extent.
7. The release from osmotic systems is minimally affected by the presence of food in the
gastrointestinal tract (GIT). This advantage is attributed to design of osmotic systems.
Environmental contents do not gain access to the drug until the drug has been delivered
out of the device.
8. Production scale up is easy.
DISADVANTAGES OF OSMOTIC DRUG DELIVERY SYSTEM

3. 1. Expensive
2. Chance of toxicity due to dose dumping
3. Rapid development of tolerance
4. Hypersensitivity reaction may occur
5. Integrity and consistency are difficult
6. Release of drug depends on
 Size of hole/aperture
 Surface area
 Thickness and composition of membrane
BASIC COMPONENTS OF OSMOTIC PUMP DRUG
Drug itself may act as an osmogen and shows good aqueous solubility
E.g.
 Potassium chloride pumps
But if the drug does not possess an osmogenic property, osmogenic salt and other sugars can
be incorporated in the formulation
OSMOGEN / OSMAGENT / OSMOTIC DRIVING AGENT
For the selection of osmogen, the two most critical properties to be considered are osmotic
activity and aqueous solubility.
Osmotic agents are classified as
1. Inorganic water soluble osmogens
 Magnesium sulphate,
 Sodium chloride,
 Sodium sulpahte,
 Potassium chloride,
 Sodium bicarbonate etc.
2. Organic polymeric osmogens:
 Na CMC
 HPMC
 HEMC
3. Organic water soluble osmogens:
 Sorbitol,
 Mannitol,etc.
SEMIPERMEABLE MEMBRANE
1. Semipermeable membrane must possess certain performance criteria:

4.  It must have sufficient wet strength and water permeability
 It should be selectively permeable to water and biocompatible. 
2. Cellulose acetate is a commonly employed semipermeable membrane for the
preparation of osmotic pumps.
3. Some other polymers such as
 Agar acetate
 Amylose triacetate
 Betaglucan acetate
 Poly (vinyl methyl) ether copolymers
 Poly (orthoesters)
 Poly acetals
 Poly (glycolic acid)
 Poly (lactic acid) derivatives.
HYDROPHILIC AND HYDROBHOBIC POLYMERS
1. These polymers are used in the formulation development of osmotic systems containing
matrix core.
2. The selection of polymer is based on the solubility of drug as well as the amount and
rate of drug to be released from the pump.
3. The highly water soluble compounds can be co-entrapped in hydrophobic matrices and
moderately water soluble compounds can be co-entrapped in hydrophilic matrices to
obtain more controlled release.
Examples of hydrophilic polymers
 Hydroxy ethyl cellulose
 Carboxy methyl cellulose
 Hydroxyl propyl methyl cellulose
Examples of hydrophobic polymers
 Ethyl cellulose
 Wax materials,
WICKING AGENTS
It is defined as a material with the ability to draw water into the porous network of a delivery
device.
The function of the wicking agent is to draw water to surfaces inside the core of the tablet,
thereby creating channels or a network of increased surface area.

5. Example
 Colloidon silicon dioxide
 Kaolin,
 Titanium dioxide
 Alumina
 Niacinamide
 Sodium lauryl sulphate (SLS),
 Low molecular weight polyvinyl pyrrolidone (PVP)
 Bentonite
 Magnesium aluminium silicate
 Polyester
 Polyethylene,etc.
SOLUBILIZING AGENTS
Non swellable solubilizing agents are classified into three groups
1. Agents that inhibits crystal formation of the drugs or otherwise act by complexation of
drug e.g.
 PVP
 PEG
 Cyclodextrins)
2. A high HLB micelle forming surfactant, particularly anionic surfactants
E.g
 Tween 20, 60, 80,
 Poly oxy ethylene
 Polyethylene containing surfactants and other long chain anionic surfactants
such as SLS).
3. Citrate esters and their combinations with anionic surfactants
E.g
 Alkyl esters particularly triethyl citrate)
SURFACTANTS
They are added to wall forming agents.
The surfactants act by regulating the surface energy of materials to improve their blending in to
the composite and maintain their integrity in the environment of use during the drug release
period. Examples:
 Polyoxyethylenated glyceryl recinoleate
 Polyoxyethylenated castor oil having ethylene oxide
 Glyceryl laurates, etc.
COATING SOLVENTS

6. Solvents suitable for making polymeric solution that is used for manufacturing the wall of the
osmotic device include inert inorganic and organic solvents.
Examples
 Methylene chloride
 Acetone
 Methanol
 Ethanol
 Isopropyl alcohol
 Ethyl acetate cyclohexane
PLASTICIZERS
Permeability of membranes can be increased by adding plasticizer, which increases the water
diffusion coefficient.
Examples:
 Dialkyl phthalates
 Trioctyl phosphates,
 Alkyl adipates
 Triethyl citrate
 Other citrates, propionates, glycolates, glycerolates, myristates, benzoates,
sulphonamides and halogenated phenyls.
FLUX REGULATORS
Flux regulating agents or flux enhancing agent or flux decreasing agent are added to the wall
forming material; it assist in regulating the fluid permeability through membrane.
Poly hydric alcohols such as poly alkylene glycols and low molecular weight glycols such as poly
propylene, poly butylene and poly amylene,etc. Can be added as flux regulators.
PORE FORMING AGENTS
These agents are particularly used in the pumps developed for poorly water soluble drug and in
the development of controlled porosity or multiparticulate osmotic pumps.
The pore formers can be inorganic or organic and solid or liquid in nature.
For example
 Alkaline metal salts such as sodium chloride, sodium bromide, potassium chloride, etc.
 Alkaline earth metals such as calcium chloride and calcium nitrate
 Carbohydrates such as glucose, fructose, mannose,etc.
TRANSDERMAL DRUG DELIVERY SYSTEM

7. TDDS are adhesive-drug containing device of defined surface area that deliver a predetermined
amount of drug to the surface of intact skin at programmed rate to reach the systemic
circulation
ADVANTAGES
 Avoids chemically hostile GI environment (drug degradation in acidic and basic
environments is prevented).
 No GI distress and the factors like Gastric emptying, intestinal motility, transit time,
donot effect this route as in oral route.
 Avoidance of significant presystemic metabolism (degradation in GIT or by the liver) and
therefore need lower doses.
 Allows effective use of drugs with short biological half-life.
 Allow administration of drugs with narrow therapeutic window because drug levels are
maintained within the therapeutic window for prolonged periods of time.
 Reduced inter and intra patient variability.
 Enhance therapeutic efficacy, reduced fluctuations (rapid blood level spikes-low and
high) due to optimization of blood concentration – time profile.
 Reduction of dosing frequency and enhancement of patient compliance.
 Provides controlled plasma levels of very potent drugs.
 Can provide adequate absorption of certain drugs.
 Avoids the risk and inconveniences of parenteral therapy (Painless method of drug
administration). Drug input can be promptly interrupted simply by removal of the patch
when toxicity occurs.
 Provides suitability of self medication.
DISADVANTAGES OF TDDS
 Drugs that require high blood levels cannot be administered – limited only to potent
molecules, those requiring a daily dose of 10mg or less.
 Transdermal administration is not a means to achieve rapid bolus type drug input,
rather it is usually designed to offer slow, sustained drug delivery.
 Adequate solubility of the drug in both lipophilic and aqueous environments, to reach
dermal microcirculation and gain access to the systemic circulation.
 The molecular size of the drug should be reasonable that it should be absorbed
percutaneously.
 Tolerance inducing compounds are not an intelligent choice for this mode of
administration unless an appropriate wash out period is programmed in between the
dosing regimen.
 Difficulty of permeation of the drug through human skin –barrier function of the skin.

8.  Skin irritation or dermatitis due to excipients and enhancers of drug delivery system
used for increasing percutaneous absorption is another major limitation.
 Adhesive may not adhere well to all types of skin.
 Uncomfortable to wear.
 May not be economical.
FACTORS INFLUENCING TRANSDERMAL DRUG:
Effective transdermal drug delivery can be formulated by considering three factors as Drug,
Skin, and the vehicles. So the factors affecting can be divided in to classes as biological factors
and physicochemical factors.
Biological factors:
Skin condition:
Acids and alkalis, many solvents like chloroform methanol damage the skin cells and promote
penetration. Diseased state of patient alters the skin conditions. The intact skin is better barrier
but the above mentioned conditions affect penetration
Skin age:
The young skin is more permeable than older. Children are more sensitive for skin absorption of
toxins. Thus, skin age is one of the factors affecting penetration of drug in TDDS.
Blood supply:
Changes in peripheral circulation can affect transdermal absorption.
Regional skin site: Thickness of skin, nature of stratum corneum, and density of appendages
vary site to site. These factors affect significantly penetratio
Skin metabolism:

9. Skin metabolizes steroids, hormones, chemical carcinogens and some drugs. So skin
metabolism determines efficacy of drug permeated through the skin.
Species differences:
The skin thickness, density of appendages, and keratinization of skin vary species to species, so
affects the penetration
Physicochemical factors:
Skin hydration:
In contact with water the permeability of skin increases significantly. Hydration is most
important factor increasing the permeation of skin. So use of humectants is done in
transdermal delivery.
Temperature and ph:
The permeation of drug increase ten fold with temperature variation. The diffusion coefficient
decreases as temperature falls. Weak acids and weak bases dissociate depending on the ph and
pka or pkb values. The proportion of unionized drug determines the drug concentration in skin.
Thus, temperature and ph are important factors affecting drug penetration
Diffusion coefficient:
Penetration of drug depends on diffusion coefficient of drug. At a constant temperature the
diffusion coefficient of drug depends on properties of drug, diffusion medium and interaction
between them.
Drug concentration:
The flux is proportional to the concentration gradient across the barrier and concentration
gradient will be higher if the concentration of drug will be more across the barrier.

10. Partition coefficient:
The optimal K, partition coefficient is required for good action. Drugs with high K are not ready
to leave the lipid portion of skin. Also, drugs with low K will not be permeated.
Molecular size and shape:
Drug absorption is inversely related to molecular weight; small molecules penetrate faster than
large ones. Because of partition coefficient domination, the effect of molecular size is not
known
7. COMPOSITION OF TDDS:
 Polymer matrix.
 Drug.
 Permeation enhancers.
 Pressure sensitive adhesives (psas).
 Backing membrane.
 Release liner.
 Other excipients
Polymer matrix / Drug reservoir:
Polymer matrix, prepared by the dispersion of a drug in a suitable polymer, controls the release
of the drug from the device. Polymers used in TDDS should be stable, compatible and non-
reactive with the drug and other components of the system, should provide effective release of
the drug throughout the device. They should be easily fabricated to the desired product.
Polymers and their degradation products must be non-toxic and non- antigenic to the host

11. Natural polymers:
Hydroxypropyl methyl cellulose (HPMC), sodium carboxy methyl cellulose (sodium CMC),
cellulose acetate, methyl cellulose, ethyl cellu-lose, gelatin, chitosan, sodium
carboxymethylguar, sodium alginate, polymerized rosin etc
Synthetic polymers:
Polyvinyl alcohol, polyethylene, polyethylene glycol, polyvinylpyrrolidone, eudragits, ethylene
vinyl acetate copolymer, ethyl vinyl acetate, silicon rubber etc
IDEAL REQUIREMENTS FOR TDDS:
Shelf life up to 2 years
Small size patch (i.e., less than 40 cm2)
Convenient dose frequency (i.e., once a day to once a week)
Cosmetically acceptable (i.e., clear, white colour)
Simple packaging (i.e., minimum number of pouches and steps required to apply the system)
Adequate skin adhesion (i.e., no fall off during the dosing interval and easy removal without
skin trauma)
No residue i.e., cold flow, around the edge of the patch in storage or after application to skin or
beneath the patch after removal)
MAGNETIC OSMOTIC CONTROL DRUG DELIVERY SYSTEM
Magnetic drug delivery systems have been emerged as a prominent technique for site-specific
targeting of various pharmacological agents throughout the last few decades. With the support

12. of a magnetic field, it avoids reticuloendothelial system and directs the drugs to reach the
target precisely.
2. Principle of Magnetic Drug Targeting Magnetic targeting is one of the productive methods to
deliver the drug at diseased site by virtue of a magnetic compound. These drug delivery
systems contain magnetic responsiveness being integrated from different substances like
magnetite, iron, cobalt, nickel, iron-boron or samarium-cobalt. The drug along with the
magnetic compound is injected into the patient’s blood circulation system and a magnetic field
is applied at the target site to block it. Thus, considerable less amount of drug concentration
can be achieved at specific site which minimizes the unwanted effects due to the high drug
concentrations of freely circulating drug
Advantages of Localization of Drugs
 Magnetic carriers localize the drug at targeted diseased sites, to accomplish following
advantages
 Efficient drug delivery to the target tissues (increase up to 60%)
 Reduced toxicity risk
 Minimizes side effects risk
 Free drug concentration in blood stream is reduced by factor of 100
 Decline in normal cell tissue damage rate.
CLASSIFICATION OF MAGNETIC DRUG DELIVERY SYSTEMS
 Magnetic nanoparticles
 Magnetic microspheres
 Magnetic liposomes
 Magnetic emulsions
 Magnetic Nanoparticles
These nanoparticles show super magnetic behavior above blocking temperature and acts like
paramagnetic atoms showing less resonance
Advantages of Magnetic Nanoparticles
 Excess amount of drug is reduced minimizing unwanted effects
 Frequency of administration is reduced
 Reduced side effects of drugs as compared to conventional dosage forms
 Targeted organ receive prolonged delivery of drug
 Diseased organ receive sustained drug delivery

13. Microemulsions
Microemuslion is widely used technique for formation of uniform particle sized magnetic
nanoparticles due to water in oil type emulsion.It is an identical thermodynamic scattering of
water and oil, stabilized by surfactant molecules which lower the surface tension between the
liquids to form a transparent solution
Magnetic Microspheres Magnetic microparticles comprise of different materials, having strong
magnetic moment which can successfully deliver non-magnetic substances like cells, antibodies,
drugs, nucleic acids and enzymes to the magnetic field. To avoid unwanted distribution of drug
to non target organ help in drug localization and avoid toxicity
Magnetic Liposomes Magnetic liposomes consist of bilayered compositional structure in which
lipid layer and aqueous layer are designed in alternative patterns. These are biocompatible
vesicular shaped structure having nanometric size, being used to encapsulate water soluble and
oil soluble therapeutic agents. Water soluble active ingredients are incorporated in aqueous
layer of magnetic liposomes and lipid soluble active drugs are incorporated in lipid layer of
magnetic liposomes
Magnetic Emulsion Emulsion is a colloidal system consisting of two immiscible liquids (water
and organic solvent) and being stabilized by polymers or surfactants known as emulsifying
agents. Water compose oil in water type emulsion when it is based as continuous external
phase while as internal dispersed phase, it constitutes reverse water in oil type emulsion.
Magnetic emulsion is an emulsion type in which ferrofluids, containing the stable dispersion of
magnetic nanoparticles, constitutes the internal phase.
APPLICATIONS
Applications Magnetic drug delivery system since its origination has shown tremendous
applications in biomedical and biophysical fields of science. We will discuss here some of its
main contributions towards modern drug delivery.
Treatment of Tumors
Magnetic microspheres can be used in chemotherapy of anti-cancer drugs in their delivery to
tumors e.g. Doxorubicin. For such kind of site-specific targeting, magnetically modulated drug
targeting systems have been successfully applied Magnetic field in such cases is applied to
concentrate the drug at tumor site thus eliminating systemic side effects.
Targeting of Radioactive Compound

14. Radioisotopes in therapeutic range can be delivered under magnetic field to target tissues.
Dose can be increased rendering damage to the normal tissues with improved anti-tumor
activity
Magnetic Hyperthermia
Magnetic hyperthermia has been established to destroy the diseased tissues with the help of
elevated temperature as they are more sensitive to the temperature compared to the healthy
tissues
The other advantage is its restriction to the diseased tissues only (Green 2005). Recently
liposomal nanoparticles have been established according to this mechanism as successful
approach to the cancer therapy. Magnetic liposomes have also been prepared and studied for
hyperthermia treatment of cancer through magnetic particles coated with phospholipids