DDS lecture 21 Content

Advanced Drug Delivery System Composition

• Drugs: naturally derived or synthetic

• polymers, potential issues associated

Advanced Drug Delivery Sytems

• Mechanical

• Electronic

• Computer

Topically Administered Advanced Delivery Systems

• Iontophoresis

• Phonophoresis

Iontophoresis

• enhanced transport of solute molecules by creating a potential gradient

• applied electrical current or voltage

Advantages of Iontophoresis

• control of delivery rates by variations of current density, pulsed voltage, drug conc., and ionic strength

• eliminating GI incompatibility, erratic absorption, and first pass metabolism

• reducing side effects and variation among patients

• avoiding risks of infection, inflammation, and fibrosis associated with cont. injection or infusion

• enhancing compliance with a convenient and noninvasive therapeutics regimen

• higher transport than transdermal delivery system

Disadvantages of IP

• skin irritation at high current densities; can be eliminated or minimized by reducing current

• cannot use for large amounts of drug

Phonophoresis

• ultrasound, sonophoresis, ultrasonophoresis

• transport of drugs through skin using ultrasound

• drug-containing coupling agent

• ex. hydrocortisone 10% in phonophoresis gel

Orally administered advanced delivery system

• chewable dispersible tablets

• mucoadhesive system

• osmotic pump

• oral inhalation

Chewable Dispersible Tablets

• lamotrigine: anti-convulsant (epilepsy drug)

  • lamictal chewable dispersible tablets

• didanosine

  • videx

Mucoadhesive System

• striant mucoadhesive testeosterone buccal system

• hydrates, testosterone absorbed through gum and cheek surfaces that are in contact

• low dose

• only drugs that can be absorbed in gums/cheeks, cannot have very high doses

Osmotic Pump

• not used for humans

• used in animal research labs

• Alzet (Alza osmotic minipump)

• tool to overcome blood-brain barrier and delivery agents directly to site of action (brain)

• small, implantable pumps

• deliver precise and continuous dose without interference in elaborate behavioral testing and without stress associated with other methods requiring frequent animal handling

• uses water to manipulate osmotic pressure to slowly release drug

Oral inhalation

• advair discus

  • fluticasone propionate

• Foradil aerolizer

  • formoterol fumarate

Vaginally Administered Advanced DDS

• Intravaginal DDS

• intrauterine progesterone DDS

  • progestasert

  • continuous drug release

  • local effect

• Dinoprostone Vaginal insert

  • Cervidil

• Estradiol vaginal ring

  • Estring

• Micronized Progesterone Gel

  • Crinone Gel

Progestasert

• intrauterine progesterone DDS

• slowly releases average of 60 mcg of progesterone per day for one year after insertion

• provides local rather than systemic action

• advantages:

  • provides contraception without need for daily self-medication

  • use natural hormone

  • contain no estrogen

  • T-shaped delivery device ensures comfort, safety, retention, which minimizes mechanically induced irritation

  • confine hormonal action to uterus

• has drug reservoir and rate controlling membrane

Dinoprostone Vaginal Insert

• thick, flat, rectangular polymeric slab enclosed in pouch of knitted polyester retrieval system

• Cervidil vaginal insert, dinoprostone 10 mg

• approved to start and/or continue the ripening of the cervix in pregnant women who are at or near the time of delivery and in whom there is a medical reason for inducing labor

• only inserted by trained pro in hospital setting

• while inserted, doctor carefully monitors

Crinone Gel

• micronized progesterone gel

• bioadhesive vaginal gel

• contains micronized progesterone and polymer polycarbophil in O/W emulsion

• allows absorption of progesterone through vaginal tissue over 25-50 hours

• used in women with fertility issues

Ophthalmic Advanced DDS

• gels

• ophthalmic inserts

  • lacrisert

  • pilocarpine ocusert

Lacrisert

• rod-shaped

• made of water soluble hydroxy propyl cellulose (HPC)

• insert is placed in the inferior cul-de-sac of the eye once or twice daily for treatment of dry eye

• insert softens and slowly dissolves, thickening precorneal tear film and prolonging treat film breakup

Ocusert

• ocular insert

• contains pilocarpine (non-erodible)

• non-biodegradable

• wafter-like insoluble implant

• preprogrammed to release pilocarpine at constant rate of 20 or 40 mcg/hr for a week

• used for glaucoma

• side effects: headache, brow ache, temporary burning or stinging, increased mucus production may occur initially

  • should disappear as body adjusts

  • contact doctor is blurred vision persists more than several hours in morning after bedtime use

• limitations

  • release of insert may be incomplete

  • approx. 20% of all patients lose device without knowing

  • foreign body sensation

  • expulsion from eye

  • difficultly in handling and insertion

Advanced parenterals

• long-acting parenteral systems

• liposomes

• stealth liposomes (PEGylated liposomes)

Liposome

• spherical vesicle having at least one lipid bilayer

• most often composed of phospholipids, esp phophatidylcholine and cholesterol

• liposome can be used as DDS for admin of nutrients and pharmaceutical drugs

  • lipid nanoparticles in mRNA vaccines, DNA vaccines

• aqueous core, lipid wall

  • can incorporate both hydrophilic and hydrophobic drus

• can cross cell membranes bc of lipid wall

• can have less side effects

• targeted delivery: good for anti-cancer drugs

Liposome Injection Examples

• Abelcet Injection: amphotericin B

• AmBisome: amphotericin B

• Amphotec: amphotericin B cholesteryl sulfate

• DaunoXome: daunorubicin citrate liposome injection

Stealth Liposomes

• PEG on outside of liposome to increase retention / protect against immune system

  • adds hydrophilicity

  • lowers freq. of dosing

Examples of Stealth Liposome

• Doxil: doxorubicin hydrochloride liposome injection

PEGlyated dosage forms

• Neulasta

• Pegasys

• PEG-intron

Neulasta

• Pegfilgrastim

• covalent conjugate of recombinant methionyl human granulocyte colony-stimulating factor (G-CSF) and monomethoxy polyethylene glycol

• reduce chance of infection due to a low white blood cell count, in people w some cancers (non-myeloid) who recieve chemo that can cause fever and low WBC count

Pegasys

• peginterferon alfa-2A

• covalent conjugate of recombinant alfa-2a interferon with single branched bis-PEG chain

• used with other HepC meds to treat adults w chronic hepC and certain liver problems

PEG-Intron

• peginterferon alfa-2b powder for injection

• used in people with malignant melanoma (life threatening cancer that begins in skin cells) who had surgery to remove cnacer

• used to reduce chance that malignant melanoma will come back

• must be started within 84 days of surgery

Fusion Protein

• Ontak: denileukin difitox

• fusion protein designed to direct the cytocidal action of diphtheria toxin to cells that express the interleukin (IL)-2 receptor

• indicated for treatment of adult patients with persistent or recurrent cutaneous T-cell lymphoma whose malignant cells express the CD25 component of IL-2 receptor

Implants

• sterile solid drug products made by compression, melting, or sintering

• usually drug and rate-controlling excipients

• Gliadel Wafer implant

• zoladex implant

• vantas implant

• viadur implant

• vitrasert implant

Gliadel Wafer Implant

• Polifeprosan 20 with carmustine implant

• designed to deliver carmustine directly into surgical cavity created when brain tumor resected

Zoladex Impnat

• Goserelin acetate

• subcutaneous injection with continuous release over 28 days

• sterile white to cream-colored cylinder preloaded into special single-use syringe

• indicated for palliative treatment of advanced carcinoma of the prostate

Vantas Implant

• contains 50 mg Histrelin

• deliver histrelin continuously for 12 months upon SubQ implantation

• help relieve symptoms of prostate cancer

  • NOT cure

Viadur implant

• leuprolide acetate implant

• treat advanced prostate cancer

  • NOT cure

• osmotically driven miniaturized implant

• designed to deliver for 12 months

Vitrasert Implants

• Ganciclovir

• intraviteral implantation

• antiviral: treats cytomegalovirus (CMV) retinitis for AIDS patients

• delivers drug over 5-8 month period

Other Novel DDS

• Definity

• Arestin

• Atridox

• Nascobal gel

• Autoinjection systems

Definity

• Perflutren Lipid Microspheres

• injectable suspension

• diagnostic agent: ultrasound constrast

• used for contrast enhancement during indicated echocardiographic procedures

• used for patients with suboptimal echocardiograms to opacify the left ventricular chamber

Arestin Microsphreres

• contains minocycline hydrochloride microspheres

• subgingival sustained-release product

• GEL?

• PGLA bioresorbable polymer

• professional admin into periodontal pockets

• indicated as adjunct to scaling and root planing (SRP) procedures for reduction of pocket depth in patients with adult periodontitis

Atridox

• doxycycline hyclate

• semi-synthetic tetracycline derivative used in local antimicrobial treatment of periodontal pockets

• atrigel delivery system for controlled release in subgingival applications

• injectable

  • 2 syringe delivery system

Cyanocobalamin Nasal Gel

• prevent lack of vitamin B₁₂

Vitamine B12 deficiency caused by

• pernicious anemia (lack of natural substance needed to absorbed vitamin B12 from intestine)

• certain diseases, infections, medications that decrease the amount of vitamine B12 absorbed from food

• vegan diet

Autoinjection systems

• EpiPen

• EpiPen Jr.

• Epinephrine injection

• Emergency IM use