pharmaceutics 5 rassoul dinarvand professor of pharmaceutics pharmaceutics 5 1

Pharmaceutics 5

Rassoul DinarvandProfessor of Pharmaceutics

Pharmaceutics 5 1

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دارورسانی طوالنی

دارورسانی به محل اثر

دارورسانی در زمان مورد نیاز

ثبت پتنت جدید و تمدید دوران تولید انحصاری

پپتیدها و دارورسانی مواد موثره خاص(

پروتئینها(

حذف قله ها و دره های غلظت خونی و

کاهش عوارض جانبی

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Drug levels in the blood with (a) traditional drug dosing and (b) controlled-delivery dosing

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استفاده از حاللهای روغنیاستفاده از امالح کم محلول داروها استفاده از پیش داروها(Prodrugs) )استفاده از حاملهای غیرپلیمری )لیپوزومها استفاده از سیستمهای دارو رسانی مکانیکی )پمپهای

دارورسانی( اتصال مولکولهای دارویی به مولکولهای خاص

(PEG)منوکلونال آنتی بادی، پروتئین های خاص،

استفاده از حاملهای پلیمری

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Chemical engineering◦ Less soluble melts◦ Prodrugs◦ Targeting linkages (MAB)◦ Pegylation

Pharmaceutical engineering◦ Oil vehicles◦ Liposomes◦ Polymeric delivery◦ Cell based drug delivery

Particle engineering◦ Solid lipid particles◦ Dendrimers

Mechanical engineering◦ Mechanical pumps

• Large molecule composed of a number of sub-units

- Natural e.g. alginates,

- synthetic e.g. poly(HMPA)

- Function governed by number and arrangement of constitutional repeat units e.g. –[A-]n, -[A-B-]n, -[A-A] n-[B-B] m , --A-A-B-A-B-B-A-

• How are they made?

- Processing of natural products – alginates from seaweeds, celluloses from plants

- Synthesis from chemical feedstocks – poly(olefins), nylons, poly(esters)

• How can they help?

- Protection of therapeutic compound during passage through body, as encapsulant or carrier.

- Mediator or activator of controlled release

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• Matrix (Monolithic) devices

- films with the drug in a polymer matrix

- Easy to fabricate, typically by simple mixing of polymer and drug

- Example: Eudragit RS100 polymer, mixed with sorbitol and Flurbiprofen

• Polymer drug conjugates

- Polymer attached to drug by (covalent) sacrificial linker

- Example: Paclitaxel-albumin conjugate in the market

Docetaxel-albumin conjugate under investigation

• Reservoir devices

- Drug contained by the polymer

- Release is usually diffusion controlled (Fickian) i.e. J = -DC where J =flux, C =

component of concentration across membrane of defined area, and is a differential vector operator

- Example: PharmazomeTM Theophylline release

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• Biodegradable polymers

- Polymer degrades in vivo to release the drug

- Simple release mechanism, but difficult to obtain fine control over degradation

- Does not invoke an inflammatory or toxic response.

- Is metabolized in the body after fulfilling its purpose, leaving no trace

• Examples in use

- Resomer (PLGA)

- Vicryl (PLGA)

• Common biodegradable polymers

- Poly(lactide-co-glycolide) (PLGA)

- Poly(hydroxybutyrate-co valerate) (Biopol)

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Hydrogels

• Three-dimensional, hydrophilic polymeric networks, swollen with water

• Cross-linking between polymer chains determines swelling and gel flexibility

• Natural or synthetic derived – very large number of hydrogels have been produced

• Ionic (acidic, basic) or neutral dependent on desired application

• Inherently biocompatible – strongly hydrated

O

OOH

O

O

O

O

HEMA EGDMA>95 parts <5 parts

polymeriseO

O

OH

O

O

O

O O

O

HO[] [

]

[] [

]

Monomer (water-soluble) Cross-linker Hydrogel

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Mucoadhesives

• 2nd Major class of polymer drug delivery vehicles

- Similar in design features to hydrogels (sub-class)

- Ability to localise at mucus membrane via adhesive interactions

- Contain functional groups for binding to mucosal surfaces – primarily H-bonding

- Pendant chains for intimate contact and interdigitation with mucins

- Inherently biocompatible – strongly hydrated

O

OH

O

O

O

Methacrylic acid(MAA)

Poly(ethyleneglycol)dimethacrylatePEGDMA

polymeriseO

HO

O

O

O

O O

OH

[] [

]

[] [

]Adhesivegroups

O

[]

n

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Controlled release implies controlled release of drugs from polymer drug delivery systems (DDS)

Type of polymer◦ Non-degradable / Degradable

Type of Design

Reservoir Matrix

Release mechanisms◦ Diffusion / polymer degradation / combination

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Drug delivery from a typical matrix drug delivery system

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Drug delivery from a typical reservoir drug delivery system

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Drug delivery from (a) reservoir and (b) matrix swelling-controlled release systems

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Drug delivery from environmentally sensitive release systems.

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Molecular gates for the delivery of insulin triggered by the presence of glucose in the bloodstream

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Drug delivery from (a) bulk-eroding and (b) surface-eroding biodegradable systems

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Polymer Non-degradable Degradable

Design Reservoir Matrix Reservoir Matrix

Release √√√ √√√ √√ √√

Removal √ √

Rupture √ √

Low Mw √ √ √ √

High Mw √ √ √Duration 5 years 5 years 1-2 years Months

Examples Norplant® Jadelle® CapronorTM Microspheres

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Jadelle

Own work

Norplant

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Particulate systems◦ Nanoparticles

Nanocapsules Nanospheres

◦ Microparticles Microspheres Microcapsules

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Films Membranes Fibers Rods Beads Discs Cylinders

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Simultaneous drug loading and polymerisation/device fabrication

Drug loading after device fabrication◦ Drug uptake by polymeric device when immersed in

drug saturated solution◦ Mechanical drug loading

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DiffusionConcentration gradient in polymeric matrix

Chemical reactionPolymer biodegradation

Solvent effectRelease of soluble drugs in hydrogels

Mechanical releaseDrug release from mechanical devices such as

pumps

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Implants Injectables Transdermal Oral Nasal Ophthalmic Vaginal

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Solid tumor

Apply magnetic field to concentrate particles

Modulate field to release drug from particles

Inject NPs IV,NP will circulate through the blood stream

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