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NOVEL DRUG DELIVERY SYSTEMS

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NOVEL DRUG DELIVERY SYSTEMS Introduction Transdermal drug delivery systems These are defined as self-contained, discrete dosage forms which when applied to the ... – PowerPoint PPT presentation

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Title: NOVEL DRUG DELIVERY SYSTEMS


1
NOVEL DRUG DELIVERY SYSTEMS
2
Introduction
  • Transdermal drug delivery systems These are
    defined as self-contained, discrete dosage forms
    which when applied to the intact skin, deliver
    the drug(s) through the skin at a controlled rate
    to the systemic circulation.
  • Advantages
  • Transdermal medication delivers a steady infusion
    of a drug over an extended period of time.
    Adverse effects or therapeutic failures
    frequently associated with intermittent dosing
    can also be avoided.
  • Transdermal delivery can increase therapeutic
    value of many drugs by avoiding specific problems
    associated with the drug (ex- GIT irritation, low
    absorption, decomposition due to hepatic first
    pass effect, formation of metabolites that causes
    side effects, short half life necessitating
    frequent dosing etc).
  • Self administration is possible with these
    systems.
  • The drug input can be terminated at any point of
    time by removing transdermal patch.

3
Transdermal drug delivery systems
  • Dis advantages
  • The drug must have some desirable physicochemical
    properties for penetration through stratum conium
    if the drug dosage required for therapeutic
    value is more than 10mg/day, the transdermal
    delivery will be difficult for administration.
    Daily doses of less than 5mg/day is preferred.
  • Skin irritation or contact dermatitis due to
    drug, excipients and enhancers of drug used to
    increase percutaneous absorption is another
    limitation.
  • Clinical need is another area that has to be
    examined carefully before a decision is made to
    develop a transdermal product.
  • The barrier function of skin changes from one
    site to another on the same person, from person
    to person with age.

4
Kinetics of transdermal penetration
  • Knowledge of skin permeation kinetics is vital to
    the successful development of transdermal
    therapeutic systems. Transdermal permeation of
    drug involves the following steps
  • Sorption by stratum corneum
  • Penetration of drug through viable epidermis
  • Uptake of the drug by capillary network in the
    dermal papillary layer
  • Basic components of transdermal drug delivery
    systems
  • 1) Polymer matrix/matrices Natural polymers
    Cellulose, gelatin, starches.
  • b) Synthetic elastomers polybutadiene,
    polysiloxane, neoprene etc.
  • c) Synthetic polymers PVC, PVA, polyethylene,
    polyurea.
  • 2) Drugs
  • 3) Permeation enhancers These are compound
    which promote skin permeability by altering the
    skin as a barrier to the flux of a desired
    penetrant. A large no of compounds are identified
    as solvents, surfactants, binary systems
    miscellanous chemicals.
  • 4) Other excipients It includes adhesives,
    backing membrane.

5
Approaches used in development of transdermal
systems
  • Membrane permeation controlled systems
  • Nitroglycerin releasing transdermal system,
    clonidine releasing transdermal system.
  • Adhesive dispersion systems
  • Isosorbide dinitrate releasing transdermal system
  • Matrix diffusion controlled
  • Nitro-Dur-I, Nitro-Dur-II
  • Microreservoir / Microsealed dissolution
    controlled systems
  • Nitrodisc (nitroglycerine releasing transdermal
    systems).

6
Ocular drug delivery systems
  • The objective of the ocular drug delivery is to
  • Improve ocular contact time
  • Enhancing corneal permeability
  • Enhancing site specificity
  • Role of polymers in ocular drug delivery
  • Incorporation of polymers into an aqueous medium
    of drug could increase solution viscosity and
    reduces the solution drainage. Increasing the
    solution viscosity of pilocarpine from 1 to 100
    cps by using methyl cellulose reduced the drug
    drainage and 2 fold increase in drug
    concentration in aqueous humor was obtained.
  • Natural polymers such as sodium hyaluronate
    chondroitin sulfate are being investigated as
    viscosity inducing agents.
  • Ophthalmic inserts It offers the potential
    advantage of improving patient compliance by
    reducing dosing frequency. The desired criteria
    for a controlled release ocular insert are
  • a) Comfort b) Ease of handling c) sterility d)
    Ease of manufacture.
  • Controlled release systems for ocular use
    encompass both erodible non-erodible systems.
    The non-erodible inserts are of 2 types
  • Ocusert system
  • Contact lens

7
Ocular drug delivery systems
  • Ocusert systems It is preprogrammed to release
    pilocarpine at constant rate of 20 or 40 µg/hr
    around the clock for 7 days for the treatment of
    glaucoma.
  • Contact Lens Therapeutic soft lenses are often
    used to aid corneal wound healing in patients
    with infection, corneal ulcers characterised by
    thining of cornea.
  • Erodible Inserts Several erodible drug inserts
    have been prepared tested for ocular use.
    Pilocarpine containing CMC wafers, PVA disc or
    rod is a classical example. The three devices of
    erodible inserts have been marketed to date are
    a) The Lacriserts b) SODI (soluble ocular drug
    insert) c) Minidisc.
  • Corneal collagen shields Collagen is a protein
    that can be safely applied to the body and is
    used to promote wound healing and delivers a
    variety of medications to the cornea ocular
    tissues. A study published in 1978 showed that
    wafer shaped collagen inserts impregnated with
    gentamicin produced highest level of drug in tear
    film tissue in the rabbit eye compared to
    drops, ointment conjuctival injection.

8
Buccal drug delivery systems
  • Drugs administered to the oral cavity are removed
    from the site of administration by natural
    clearance mechanisms.
  • For drug delivery purposes, the term bioadhesion
    implies attachment of a drug carrier system at a
    specific biological action. In most instances the
    bioadhesive polymer is in contact with the mucous
    hence the term mucoadhesion is employed.
  • Buccal mucosa The buccal cavity provides a
    highly vascular mucous membrane site for
    administration of drugs.
  • The epithelial lining of oral cavity differs both
    in type (keratinised non-keratinised)
    thickness in different areas the differences
    give rise to regional variations in permeability
    to drugs.
  • The buccal mucosa is being perceived as an
    alternative for peptide protein drug
    administration especially when sustained delivery
    is desired.
  • The future challenge in the development of
    buccoadhesive dosage forms is to modify the
    permeability barrier of the mucosa using safe and
    effective penetration enhancers.

9
Buccal drug delivery systems
  • Mucoadhesive buccal dosage forms have 3 desirable
    features.
  • They are readily localised in the oral cavity to
    improve enhance the bioavailability of drugs.
  • They facilitate intimate contact of the
    formulation with the underlying absorption
    surface.
  • They also prolong residence time of the dosage
    form to permit once or twice a day dosing.
  • Methods to study bioadhesion
  • Study of cellular modifications during
    interpretation
  • Study of adhesion on artificial media
  • Study of adhesion on biological tissues
  • Factors affecting bioadhesion
  • The bioadhesive polymer environment both affect
    bioadhesion. The polymer related factors include
    mol.wt, polymer chain length configuration,
    concentration of active polymer swelling.
  • The environment related factors are pH applied
    strength.

10
Liposomes as drug carriers
  • These are simple microscopic (lipid) vesicles in
    which an aqueous volume is entirely enclosed by a
    membrane composed of lipid molecule.
  • The drug molecules can either be encapsulated in
    aqueous space or intercalated into the lipid
    bilayer.
  • Amphipathic molecules are used to form Liposomes.
    Some examples of amphipathic molecules are
    lecithin, phosphatidyl glycerol etc.
  • The exact location of drug will depend upon its
    physicochemical characteristics the
    composition of lipids.
  • A standard composition of Liposome is egg
    lecithin cholesterol phosphatidyl glycerol in
    molar ratio (0.9 1.0 0.1). These lipids can
    be stored either as solids, or inorganic solution
    at -20 or -70ºC in order to reduce the chances of
    oxidation.
  • Method of preparation of Liposomes It involves
    3 or 4 basic stages
  • Drying down lipids from organic solvent
  • Dispersion of lipids in aqueous media
  • Purification of resultant Liposomes
  • Analysis of final product

11
Liposomes as drug carriers
  • Characterisation of Liposomes
  • The behaviour of Liposomes in both physical
    biological systems is governed by the factors
    such as physical size, membrane permeability,
    entrapped solutes, chemical composition as well
    as quantity purity of starting materials.
  • Therefore the Liposomes are characterised for
    physical attributes (shape, size its
    distribution, drug captured, entrapped volume,
    lamellarity, drug release and chemical
    composition (estimation of phospholipids,
    cholesterol).
  • Applications of Liposomes
  • Liposomes prove to be efficient carrier for
    targeting the drug to site of action, because of
    being biodegradable identical to biological
    membrane.
  • Liposomes can able to produce localised drug
    effect, enhanced drug uptake cell Liposome
    interaction.
  • Liposomes are carriers for vaccines, antigens,
    micromolecules for site specific delivery (oral,
    topical, pulmonary ophthalmic etc).

12
Niosomes as drug carriers
  • Niosomes are non-ionic surfactant vesicles that
    can entrap both hydrophilic and lipophilic drugs
    either in aqueous layer or in vesicular membrane
    made of lipid materials. Niosomes can prolong the
    circulation of entrapped drugs.
  • Some examples of non-ionic surfactants like
    span-40,60,80 tweens are commonly used. These
    surfactants can be combined with cholesterol to
    entrap drugs in vesicles.
  • Formulation of Niosomes It can be formulated by
    lipid layer hydration method, reverse phase
    evaporation techniques or by trans membrane pH
    gradient uptake process.
  • Characterisation Niosomes can be characterised
    by size distribution studies (small niosomes
    100-200 nm, large 800-900 nm, big 2-4 µm).
  • Evaluation Drug entrapment efficiency, drug
    stability, drug leakage in saline plasma on
    storage, PK aspects, toxicity studies drug
    targeting efficiency.

13
Niosomes as drug carriers
  • Loading of drug(s) into Niosomes The use of
    niosomes as drug delivery vehicles naturally
    assumes an ability to efficiently load the
    niosomes with the drug of choice. Passive
    trapping and active trapping are 2 methods used
    to load drug(s) into niosomes.
  • Benefits of Niosomal drug carrier
  • Niosomes are more suitable for parenteral drug
    delivery.
  • As compared to liposomes, about 50 of
    phospholipids can be replaced with non-ionic
    surfactant the vesicle stability may be
    improved.
  • Due to presence of non-ionic surfactants, there
    may be improvement in permeation release of
    drugs entrapped through various barriers of body
    organs which may improve the targeting
    efficiency of drugs.
  • The drug targeting efficiency of niosomes may be
    improved using suitable surface modification with
    the help of other adjuvants.

14
Niosomes as drug carriers
  • Applications of Niosomes
  • Therapeutic agents like anticancer agents, anti
    infectives, anti HIV agents, antivirals,
    anti-inflammatory drugs can be entrapped in
    niosomes to achieve better bioavailability
    targeting properties for reducing the toxicity
    side effects of drugs.
  • Niosomes can be transported by macrophages which
    are known to infiltrate tumour cells.

15
Microspheres as drug carriers
  • Microspheres of biodegradable non biodegradable
    polymers have been investigated for sustained
    release depending on the final application.
  • The most important characteristic of microsphere
    is microphase separation morphology which endows
    it with a controllable variability in degradation
    rate also drug release.
  • Preparation of Microspheres The preparation of
    microspheres from natural polymers involves 3
    steps
  • In the 1st step, the solution of polymer is
    dispersed in a continuous medium such as
    vegetable oil or an organic solvent using
    suitable stabilising agent.
  • Dispersion is accomplished using
    mechanical stirring or by ultrasonication or by
    high speed homogenisation depending on particle
    size required.
  • The 2nd step involves hardening of polymer
    droplets either by heat denaturation or by
    chemical cross linking using suitable cross
    linking agent.
  • The 3rd step involves separation of solid
    microspheres, purification drying.

16
Microspheres as drug carriers
  • Drugs are incorporated into the microspheres
    either during their synthesis or after the
    microsphere is formed.
  • High loading can be achieved by insitu loading
    if drug is insoluble in the dispersion medium
    employed for microsphere stabilisation.
  • Washing the microspheres after their preparation
    to remove surfactants, oils and other impurities
    etc using solvents in which the drug solubility
    is high may result in poor loading efficiency.
  • Mechanism of drug release from microspheres
  • Degradation controlled monolithic system
  • Diffusion controlled monolithic system
  • Diffusion controlled reservoir system
  • Erodable polyagent system

17
Microspheres as drug carriers
  • Microspheres based on natural polymers
  • Albumin microspheres
  • Casein microspheres
  • Gelatin microspheres
  • Polysaccharide microspheres
  • Microspheres based on synthetic polymers
  • Polyester microspheres
  • Polyanhydride microspheres
  • Other biodegradable polymers

18
Nanoparticles as drug carrier
  • Nanoparticles are sub nanosized colloidal
    structures composed of synthetic or semisynthetic
    polymers.
  • The first reported nanoparticles were based on
    non biodegradable polymeric systems
    (polyacrylamide, polymethyl methacrylate
    polystyrene etc).
  • The polymeric nanoparticles can carry drug(s) or
    proteinaceous substances (antigens). The drugs
    may be added during preparation of nanoparticles
    or to the previously prepared nanoparticles.
  • TYPES OF POLYMERS FOR PREPARATION OF
    NANOPARTICLES
  • Natural polymers Lectins, albumin, alginate,
    dextran, chitosan etc.
  • Synthetic polymers poly lactic acid, poly
    lactide co glycolide, polymethyl methacrylate,
    polybutyl cyanoacrylate.

19
Nanoparticles
  • Preparation of Nanoparticles
  • Amphiphilic macromolecule cross linking
  • a) Heat cross linking b) Chemical cross
    linking
  • 2) Polymerisation based methods
  • Polymerisation of monomers insitu
  • Emulsion (micellar) polymerisation
  • Dispersion polymerisation
  • Interfacial condensation
  • Interfacial complexation
  • 3) Polymer precipitation methods
  • Solvent extraction/evaporation
  • Solvent displacement (nanoprecipitation)
  • Salting out

20
Nanoparticles
  • Novel nanoparticulate systems
  • Solid Lipid Nanoparticles (SLN), Copolymerised
    Peptide Nanoparticles
  • Hydrogel nanoparticles, Nanocrystals
    Nanosuspensions
  • Biomimetic nanoparticles , Magnetic nanoparticles
  • Nanoparticles coated with antibodies
  • Characterisation of nanoparticles
  • Particle size size distribution
  • Charge determination, surface hydrophobicity
  • Chemical analysis of surface, carrier-drug
    interaction, drug stability
  • Release profile, nanoparticle dispersion
    stability
  • Applications of Nanoparticles
  • 1) Cancer chemotherapy 4) DNA delivery
  • 2) Ocular delivery 5)
    Oligonucleotide delivery
  • 3) Brain delivery 6)
    Lymph targeting
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