NOVEL DRUG DELIVERY SYSTEM

1. NOVEL DRUG DELIVERY
SYSTEM
By
Ms.Prajakta A. Chawale
Lecturer,
Nagpur College of Pharmacy

2.  New drug delivery system delivers are aimed at maximizing the drug
effectiveness or minimizing the side effects.
 Novel Drug Delivery System (NDDS) is an advanced drug delivery system that
improves potency, control drug release to give a sustained therapeutic effect,
provide greater safety, finally it is to target a drug specifically to the desired
tissue.
 In conventional drug delivery system only a fraction of drug administered dose
reaches the blood circulation and hence most of the drug (dose) is wasted and
cause undesirable side effect and toxicity.

3.  Classification of Noval Drug Delivery Systems:
1. Pulmonary drug delivery system/route:eg. Inhalers.
2. Oral drug delivery system/route:(a) Gastroretentive drug delivery system/
Gastricroute.e.g. Insitu gel.(b) Buccal drug delivery system/ Buccal route
3. Nasal drug delivery system/route:e.g. Buccal patches.e.g. Nasal drop, Nasal
spray, Nasal gel, Nasalpowder.
4. Ocular drug delivery system/route:e.g. Occusert
5. Parenteral drug delivery system/route: (a) Implantable drug delivery system.e.g.
Surgical implant(b) Niosomese.g. Niosomal vaccines
6. Transdermal drug delivery system:e.g. Transdermal patches
7. Intrauterine drug delivery system: e.g. IUDC, Copper IUDC
8. Nano particle drug delivery system:e.g. Nasosuspension

4.  Implants
 Liposome
 Nanoparticles
 Resealed Erythrocytes
 Prodrugs
 Film and strips

5. Sustained release
 The sustained release dosage form is the new drug delivery system. They
provide a therapeutic blood level of the drug which is attained rapidly and is
maintained within narrow limits over an extended period, usually for 10 to 12
hours after administration of a single dose.
 Sustained release of dosage is achieved because they are enteric-coated
which get released in a specific part of the body.
 Application: Sustained release forms are used as pain killers. e.g. Diclofenac
sodium helps to reduce gastric irritation.

7.  Sustained Action Dosage Form: Sustained action dosage forms of medicaments
are meant for oral administration release drug slowly and continuously for a
long duration, thus it maintains the effective drug concentration, throughout
the treatment period.
 Merits: (i) Maintain therapeutic effect for a long period after single-dose
administration.
 (ii) Eliminates administration of several time dosage.
 (iii) Reduces chances of missed doses by the patient.
 (iv) Provide a uniform blood concentration level.
 (v) Eliminates the undesirable side effects caused by high blood levels of drug
administered as in conventional dosage form.
 (vi) It controls the rate and site of release of drugs, where the conventional
system fails.

8.  Demerits:
(i) Poisoning due to long-acting preparations is difficult to
treat.
(ii) Some drugs are effective in conventional form as
compared to sustained form. e.g. Aspirin.
(iii) Long-acting dosage forms may not release the drugs.

9. Targeted drug delivery system
 Targeted drug delivery sometimes called smart drug delivery is a method of
delivering medication to a patient in a manner that increased the
concentration of the medication in some parts of the body relative to others.
 e.g. Targeting drugs to a specific tissue in (Gastro-Intestinal Tract) GIT before
their absorption or to a specific receptor site in the body without becoming
part of systemic circulation after absorption.
OR
 Target drug delivery system is a special form of drug delivery system where
the pharmacologically active agent or medicament is selectively targeted or
delivered only to its site of action or absorption and not to the non-target
organs or tissues at cells.

11.  Advantages of TDDS:
(1) Drug administration protocols may be simplified.
(2) Toxicity is reduced by delivering a drug to its target site, thereby reducing
harmful systemic effects.
(3) Drugs can be administered in a smaller dose to produce the desired effect.
(4) Avoidance of hepatic first-pass metabolism.
(5) Enhancement of the absorption of target molecules such as peptides and
particulates.
(6) Dose is less compared to conventional drug delivery systems.
(7) Selective targeting to infections cells that compare to normal cells.

12.  Disadvantages of TDDS:
(i) Rapid clearance of targeted systems.
(ii) Requires highly sophisticated technology for theformulations.
(iii) Immune reactions against intravenous admini stered carrier systems.
(iv) Drug deposition at the target site may produce toxicity symptoms.
(v) Difficult to maintain the stability of dosage form.e.g. Resealed erythrocytes
have to be stored at4°C.
(vi) Drug loading is usually low e.g. as in micelles. Therefore it is difficult to
predict/ fix the dosageregimen.
(vii) Insufficient localization of targeted systems into tumor cells.

13.  Types of Targeted Drug Delivery System:
 (i) Oral System:(a) Targeted to stomach duodenal: e.g. Effervescence tablets
helpful for vitamins,minerals, antibiotic, sedatives etc.(b) Targeted to
intestine:e.g. Enteric coated tablets. (c) Targeted to colon:e.g.
Hydrocortisone, 5-Flurouracil coat of natural and synthetic polymers. (d)
Targeted to lymphatic system:e.g. Streptomycin, Gentamycin
 (ii) Cells and tissues system:(a) Liposomes(b) Colloidal particles
 (iii)Biological carriers: (a)Resealed Erythrocytes(b) Antibodies c) Nanoparticles

14. IMPLANT DRUG DELIVERY SYSTEM
 Implants are hypodermic tablets that are placed under the skin by means of
minor surgery to release the drug over a prolonged period.
 Recently, some magnetically controlled implants have been devised.
 Magnetically Controlled: Implants and capsules consist of body and cap. The
magnetically controlled capsules are meant for implantation in the upper
thigh at depth of 5 mm. The capsules are placed under the skin by means of
surgery. Then a rod magnet helps to release the drug from the capsules to the
body tissue and moves the drag in the desired direction.
 Application: Hypodermic tablets are placed under the skin for prolonged drug
release.

16. The ideal requirements of implantable IDDSS areas follows:
(i) Implants should be environmentally stable.
(ii) It should be biocompatible.
(iii) As implants directly come in contact with body organs or tissue, they should be
sterile.
(iv) Improve patient compliance by reducing the frequency of drug administration over
the entire period of treatment. Release the drug in a rate-controlled manner that
leads to enhanced effectiveness and reduction in side effects.
(v) Readily retrievable by medical personnel to terminate medication.
(vi) Easy to manufacture and relatively inexpensive.

17. Advantages of Implantable Drug Delivery System
1. The drug is distributed locally or in systemic circulation with the least
interference by metabolic or biological barriers.
2. Potential for Bio-Responsive Release:Bio-responsive release from implantable is
an important area of ongoing research.
3. Potential for Intermittent Release: Intermittent release can facilitate drug
release in response to factors such as the pulsatile release of many peptides
and proteins.
4. It has the potential for controlled release and increases patient compliance.
5. Flexibility: In the choice of material, methods of manufacture,degree of drug
loading, drug release rate etc.considerable flexibility is possible.
6. They are used especially for the administration of growth hormones.

18. Disadvantages of Implantable Drug Delivery System
1. Uncomfortable feeling for the patient wearing the device.
2. There may some scar formation at the site of implantation and surgery-related
complications in a very small number of patients.
3. Danger of device failure.
4. Difficult to maintain accurate dose at the end of its lifetime.
5. Limited to Potent Drug:In order to minimize patient's discomfort the size of an
implant is usually kept small. Therefore most implants have a limited loading
capacity thus potent medicines such as hormones may be appropriate for delivery
by implantable devices.
6. Issues of biocompatibility and safety of an implant.
7. There may be a possibility of adverse reactions
8. Discontinuation also need surgical procedure.

19.  The challenges in an implantable drug delivery system are as follows:
(i) Polymer drug interaction.
(ii) Choice of the sterilization process.
(iii) Level of surgical procedure required implantation.
(iv) Size of implants drug release kinetics.
Examples
 Deoxicortisone acetate (Percorten pellet)
 Estradiol and testosterone (Progynon and oreton pellets)
 Silicon polymer containing levonorgesterone (Nuplant)

20. RESEALED ERYTHROCYTES
 Erythrocytes have also been tried in order to achieve controlled release of
drugs.
 The life span of erythrocytes is about 120 days.
 Erythrocytes can allow a drug to circulate in the body for a long time which
helps in the slow release of drug in the serum.
 When the drug is encapsulated in erythrocytes, the drug gets leaked out of
its cell over a prolonged period of time.

22. ADVANTAGES
 They are fully biodegradable, biocompatible, nonimmunogenic
 It can circulates intravascularly for days
 Allow large amount of drug to be carried.
 The drug need not be chemically modified.
 It is protected from immunological detection and enzymatic inactivation.
DISADVANTAGES
 It is difficult to arrange large quantity of erythrocytes.

23. PREPARATION
 Resealed erythrocytes are prepared by immersing them into a buffered
hypotonic solution of drug which causes them to swell and rupture and
release hemoglobin and trap the drug through the open pores.
 When the isotonicity is adjusted the erythrocytes shrink and thus
encapsulating the drug within them.
 These erythrocytes may be suspended in normal saline solution for preparing
injection.

24. APPLICATION
 Resealed erythrocytes of urease have been used in kidney failure to degrade
serum urea.
 Resealed erythrocytes of asparaginase have shown good results in
asparaginase dependent leukemia.
 Resealed erythrocytes of methotrexate and adriamycin have been tried in
cancer therapy. It has shown good results.
 Resealed erythrocytes of prednisolone have shown good results to prolong
the anti-inflammatory action.

25. LIPOSOMES (CARRIER FOR DRUG
DELIVERY SYSTEMS)
 Liposomes are comprehensively used as carriers for numerous molecules in
the cosmetic and pharmaceutical industries.
 Liposomes are small artificial vesicles of spherical shape that can be prepared
from cholesterol and natural non-toxic phospholipids.
 The size of liposomes is in the range of 0.01 - 5.0 um in diameter. Due to their
size, hydrophobic and hydrophilic character, liposomes are promising systems
for drug delivery.
 Liposomes have got the potential advantage of encapsulating hydrophilic as
well as hydrophobic drugs and targeting them to the required diseased site in
the body.
 They are phospholipids that can be transported with hydrophilic and
hydrophobic drugs.

27. Method of preparation of Liposomes
Dissolve lipid in organic solvent/ co-solvent
Remove organic solvent under vaccum
Film deposition solid lipid mixture is hydrated by usign aqueous buffer
Lipid spontaneously swell and hydrate
Liposome
Post hydration vortexing, sonication, freeze thawing and high pressure extrusion

28.  Advantages of Liposomes:
1. Provide selective passive targeting to tumour tissue.
2. Increased efficacy and therapeutic index.
3. Increased stability via encapsulation.
4. Reduction in toxicity of the encapsulated agent.
5. Biocompatible.
6. Improved pharmacokinetic effects.
7. Chemically and physically well-characterized entities.
8. Used as carriers for controlled and sustained delivery drug
9. Can be made into a variety of sizes. Suitable for delivery of hydrophobic,
hydrophilic and amphipathic drugs and agents.
10. Suitable to administer via various tubes.

29.  Disadvantages of Liposomes:
(i) Leakage of an encapsulated drug during storage.
(ii) Uptake of liposomes by the reticulo endothelial system.
(iii) Batch to batch variation.
(iv) Difficult in large scale manufacturing and sterilization.
(v) Once administered, liposomes cannot be to faulty of our removed.
(vi) Possibility of dumping,administration.
(vii) Less stability.(viii) High production cost.
(viii)Sometimes phospholipids undergo hydrolysis and oxidation reactions.

30.  The challenges in liposomal drug delivery are as follows:
(i) Opsonins and vesical destabilization.
(ii) The Reticuloendothelial System (RES) and Liposomes Clearance.
(iii) The Accelerated Blood Clearance (ABC) Phenomenon.
(iv) Compliment Activation Related Pseudo Allergy

31. APPLICATION
 Used in diseases caused by intracellular parasites.ex. Malaria, tuberculosis and
amoebiasis.
 Liposomes entrapped insulin is active orally and can be replaced by intramuscular
administration of insulin.
 Liposomes can be used to transport functional DNA/RNA molecules into cells.
 Liposomes can be used to transport radiopharmaceuticals and immunological
products.
 Liposomal daunomycin has longer duration of action than free daunomycin
which is used in the treatment of neoplasia.
 Liposomes entrapped actinomycin D and nitrogen mustard are more effective
than the parent drug.

32. NANOPARTICLES
 Nanoparticle Drug Delivery System: Nanoparticle drug delivery systems use
nano particles for the targeted delivery and controlled release of therapeutic
agents.
 Nanoparticles act as a vehicle in which a drug is confined to a cavity
surrounded by a polymer membrane, whereas nanospheres are matrix systems
in which the drug is physically and uniformly dispersed.
 Nanoparticles are solid, colloidal particles consisting of macromolecular
substances that change the pharmacokinetic properties of the drug without
changing the active compound.

33. Advantages of Nanoparticles
1. Drugs can be incorporated into the system without any chemical reaction, this is
important factor for preserving the drug.
2. Controlled release and drug degradation characteristics can be readily modulated.
3. There is no wastage of drug and thus enhanced bioavailability of drug at a specific
site.
4. It improves the solubility of poorly water-soluble drugs, prolongs the half-life of drug
systemic circulation by reducing immunogenicity.
5. Release of a drug at a sustained rate and reduce the frequency of administration.
6. Delivered in a more targeted manner to the affected site.
7. Able to control dosage by the trigger, requirement and even time-release.
8. Drug concentration at the affected site is more optimized.
9. Lesser exposure of unaffected sites to drugs.
10. It provides comfort and compliance to the patient and yet improves the therapeutic
performance of the drug over conventional systems.
11. Nanoparticle drug carriers have higher stabilities.

34. Disadvantages of Nanoparticles
1. Nanoparticles preparations require specialized equipment for processing.
2. Polymeric nanoparticles possess limited drug loading capacity.
3. It may decrease their shelf life and include physical and chemical instability,
aggregation and leaking or hydrolysis of the encapsulated drug.
4. It is expensive as compared to the conventional dosage form.

35.  Applications of Nanoparticles:
1. Nanoparticles improve protein and peptides stability, avoids proteolytic degradation as
well as the sustained release of the incorporated molecules.
2. The anticancer drug can deliver at the targeted cell of the tumour.
3. Nanoparticles of topical formulation enhanced the drug efficacy.
4. Nanoparticles are used as gene therapy.
5. Ocular delivery systems use nanoparticles for the prolonged release of drugs to the eye.
6. Implantable delivery systems of nanoparticles produce prolong drug release.
7. Nanoparticles pulmonary drug delivery. As illustrated better therapeutic efficiency on
the bronchial tube.
8. Nanoparticles are used as carries free nasal vaccine delivery.
9. Nanoparticles are used in various cosmetic products like deodorant, soap, toothpaste,
shampoo, hair conditioner, moisturizer etc.
10. Nanoparticles in molecular diagnostics (molecular imaging) are used to characterize and
quantity sub-cellular biological processes include gene expression, protein-protein
interaction and cellular metabolism.
11. Nanoparticles as biosensors and bio-labels are employed for the determination of
various pathological proteins.

36.  The challenges involved in Nanoparticle drug delivery systems are as follows:
(i) In-vivo and In-vitro behavior.
(ii) The key problems that need to be extensively explored using various animal
(in vivo) models are cellular interaction, tissues transfer, diffusion and
biocompatibility.
APPLICATIONS
 Flourescein isothiocyanate nanoparticles-cytotoxic drugs,tumour cells in
cancer chemotherapy
 Nanoparticles with biological maker like immunoglobulin to target drug to
specific site
 99m Technitium nanoparticles-to study morphology, blood flow, functions of
various organs of body

37. PRODRUGS
 The compounds that show desirable pharmacological activity after their
metabolism are called as prodrugs.
 Prodrugs are used to increase solubility, stability and bioavailability of the
drug, masking the unpleasant taste and odour of the parent drug and reducing
the toxicity.

38.  Classification of Prodrugs:Prodrugs are classified into two broad categories. They
are as:
 (i) Carrier Linked Prodrugs. (ii) Bioprecursors.
 (i) Carrier Linked Prodrugs:Carrier linked prodrugs generally consist of the
attachment of a carrier group to the active drug. This is so done to modify its
physicochemical properties and then subsequent enzymatic or non enzymatic
mechanism to release the active drug moiety.
 (ii) Bioprecursor:Bioprecursor by definition is a type of prodrug that is designed to
tackle pharmaceutical, pharmacokinetics or pharmacodynamics shortcomings of a
drug that limit its clinical use, Applications:(i) Procaine penicillin G and
Benzathine penicillin G are prodrugs of penicillin G which shows resistance to
hydrolysis as compared to the parent drug. Clindamycin-2-palmitate the prodrug
ofclindamycin has no bitter taste of the parent drug.
 (iii) Prodrug can be formulated as:(a) Liposomes (b) Niosomes.

41.  Compounds which under goes biotransformation before showing p’cological
action
 Esters or amides of parent drugs
 To improve solubility, stability, bioavailability, masking unpleasant taste &
odour & reducing drug toxicity

42.  APPLICATIONS
 Chloramphenicol palmitate-no bitter taste
 Procaine penicillin G-resistance to hydrolysis
 Clindamycin 2-palmitate –no bitter taste
 Clindamycin 2-phosphate –little pain & irritation at injection site

43. FILMS AND STRIPS
Meant for topical application-slow release of drug for predetermined period of
time.
 Zero order release film
 Buccal strips
 Spray bandages

44. ZERO ORDER RELEASE FILMS
 Called laminates
 Nitroglycerin laminates-propylene glycol & 1 % carbopol resin, neutralized
with sodium hydroxide, 0.1% nitroglycerin
 Placed between polythene sheet 5×5 cm, edges sealed
 Placed pressure sensitive adesive sheet 5.5×5.5 cm
 12 hours release
 Pilocarpine films

45. BUCCAL STRIPS
 Buccal & sublingual tablets replaced by buccal strips
 Thin absorbent base of fabrics, filter paper & cotton
 Prepared by immersing a long piece of fabric of polyamide fibres into molten
mixture of carbowaxes & drug
 Then cool and cut into smaller pieces

46.  SPRAY BANDAGES
 Prepared by spraying the solution of drug in polylactide
 2% solution of purified polylactide is made in chloroform
 Then drug 0.01% to 90% dissolved or dispersed in it.
 Such solution packed in aerosol container
 When spray, form a comfortable bandge.