Novel Drug Delivery Systems II Lecture Spring 2024 PDF

PHA 339 Learn the mechanism behind some novel drug delivery systems Understand the advantages, disadvantages and future prospective of novel drug delivery systems Improve and Unique Clinical benefits Improved patient compliance and outcomes Reduction in adverse, side, toxic effects Avoidance of cost...

PHA 339 Learn the mechanism behind some novel drug delivery systems Understand the advantages, disadvantages and future prospective of novel drug delivery systems Improve and Unique Clinical benefits Improved patient compliance and outcomes Reduction in adverse, side, toxic effects Avoidance of costly interventions Outpatient therapy management Implants: Implant is an object or material inserted into the body for prosthetic, therapeutic, diagnostic or experimental purposes Factors to be considered: ✓ ✓ ✓ ✓ ✓ Erodibility Irritation Carcinogenicity Dose dumping Duration Polymeric Implants: ✓ Nexplanon ✓ Norplant Small, soft, and flexible birth control containing 68 mg of Etonogestrel. Nexplanon/Implanon consists of a single rod made of ethylene vinylacetate copolymer that is 4 cm long and 2 mm in diameter. Serum levels maintain relatively stable through 36 months. Nexplanon should be removed after three years; however, they can be removed at any time if pregnancy is desired. 15 mg of barium sulphate added to the core, so it is detectable by x-ray Reservoir consisting of 6 capsules containing crystalline levonorgestrel in Silastic® membrane Diffusion controlled Discontinued Duration of use ✓ 5 years ✓ 70 µg/day first few months, ✓ 30 µg/day thereafter ✓ 0.25 ng/mL therapeutic dose (Norplant 20x min dose) Polymer Non-degradable Non-degradable Degradable Degradable Design Reservoir Matrix Reservoir Matrix Release √√√ √√√ √√ √√ Removal √ √ Duration 5 years 2 years 1-2 years < 1 year Examples Norplant® Jadelle® CapronorTM Microspheres https://www.youtube.com/watch?v=XXRLSndJ-x4 Drug-eluting stent (DES) is a peripheral or coronary stent placed into peripheral or coronary arteries that slowly releases a drug to block cell proliferation. ✓ The CYPHER® Stent is a drug-eluting stent. The metal of the stent has a soft, plastic coating that contains the anti-rejection-type medicine Sirolimus. Eighty percent (80%) of the Sirolimus is released during the first 30 days. The rest is released by the end of 90 days. ✓ The TAXUS® stent uses Translute™ Polymer, a proprietary polymer carrier technology, to control drug release. The durable Translute Polymer protects the drug and maintains coating integrity during preparation, delivery, and stent expansion. The polymer controls the release of paclitaxel, which may allow for consistent drug release and more uniform drug distribution. https://www.youtube.com/watch?v=uerMJMjo9_E Ocular Implants: Hydroxypropyl cellulose ophthalmic insert Sterile, translucent, rod-shaped, water soluble, preservativefree, slow-release, prescription lubricant which is placed into the eye Acts to lubricate and protect the eye https://www.youtube.com/watch?v=vnvpiPPGgUo Implant Medication Method of Implantation Size Release Time Ozurdex® Dexamethosone in PLGA matrix (Biodegradable) 22 gauge designer applicator rod-shaped, 0.46 mm diameter, 6 mm long up to 6 months Retisert® Fluocinolone acetonide in PVA/silicone coating (Non-Biodegradable) surgical insertion 1.5 mm diameter, 6 mm long, 2 mm wide up to 2.5 years IIuvien® Fluocinolone acetonide in PVA matrix (NonBiodegradable) injection with 25 gauge needle 3.5 mm × 0.37 mm tube up to 3 years Vitrasert ® Gancyclovir in PVA surgical insertion 4–5 sclerotomy up to 8 months Surodex® Dexamethosone in PLGA 25 gauge needle, placed during cataract surgery 1 mm × 0.5 mm 7–10 days https://www.youtube.com/watch?v=B3Eaui0waLA https://www.youtube.com/watch?v=zBuTpx5XNYI Ion Exchange System: In this system, a charged polymer is used as the matrix and an oppositely charged drug is bound ionically to it. When this medicine is taken by the patient, the drug is exchanged in the biological system for ions of the same charge (either positive or negative) and the drug is released into the body. These ions that exchange are usually as simple as sodium or chloride ions that are found commonly in the body, usually in the intestines. Example: Pennkinetic system as a complex of both coated and uncoated drug-resin. Tussionex® a liquid suspension containing the opiate hydrocodone and the histamine H1 antagonist chlorpheniramine, is an example of a Pennkinetic system Hydrocodone Polistirex: Sulfonated styrene-divinylbenzene copolymer complex with 4,5α-epoxy-3-methoxy-17-methylmorphinan6-one Chlorpheniramine Polistirex: Sulfonated styrene-divinylbenzene copolymer complex with 2-[p-chloro-α-[2-(dimethylamino)ethyl]benzyl]pyridine. Medical device designed to deliver a single dose of a drug usually life saving. Spring-loaded syringes Needles shielded for prevention Self administration possible. Epipen EpiPen (Epinephrine), ATNAA (Atropine and Pralidoxime chloride), Rebiject II (Rebif or interferon beta-1a) https://www.youtube.com/watch?v=ZISbTH3GGq4 It is composed of an insulin cartridge (integrated/separate) and a dial to measure the dose. It is used with disposable pen needles to deliver the dose. ✓ NovoLog, NovoRapid and Levemir by Novo Nordisk ✓ ✓ Lantus and Apidra by Sanofi-Aventis Humulin and Humalog by Eli Lilly and Company Advantages: ✓ Accurate dosages ✓ Convenient and easier to use and transport ✓ Less injection pain (polished and coated needles) Disadvantages: ✓ Mixing different types of insulin ✓ Expensive https://www.youtube.com/watch?v=SfY_jXFapV4 Source: Online Images through google Store new, unopened pens in refrigerator Assign BUD after removal from refrigeration Never share pens Vaginal rings/Intravaginal rings/V-Rings) are polymeric drug delivery devices designed to provide controlled release of drugs over extended periods of time and provides contraception protection. Leaving the ring in for three weeks slowly releases hormones into the body, mainly vaginally administered estrogens and/or progestogens. These hormones stop ovulation and thicken the cervical mucus, creating a barrier preventing sperm from fertilizing an egg. ✓ Estring: Low-dose estradiol-releasing ring uses silicone elastomer. ✓ NuvaRing: Low-dose progestin and estrogen from copolymer of ethylene and vinyl acetate. Pulse delivery -- erodable polymers with different drug loads in different layers of the device. ✓transdermal insulin reservoir could be attached to the skin and generate a minute pulse of electricity to open the skin pores temporarily ✓the device would take a sample of the blood and process it via a glucose-oxidizing enzyme ✓The device will then sense how much acid is formed during the enzymatic reaction and adjust the insulin release accordingly ✓a second electrical pulse would open the skin pores once again to allow the insulin to enter the body Ternary Solid Dispersion ❑ The dispersion of an active ingredient in two polymers or a polymer and surfactant. Drug Polymer 1 or Surfactant Polymer 2 Ternary Solid dispersions ❑Advantages – If developed rationally: ▪ The properties of the carriers can be tailored to the needs of the system ▪ Synergistic advantage: Improved stability and enhanced dissolution. 20 Ultrasonic Nebulizers: Incorporate a piezoelectric crystal at the bottom of the drug reservoir or cup. Crystal mechanically vibrates at a high frequency when subjected to an electric field. Crystal vibrations send shockwaves through the liquidfilled reservoir and cause droplet formation at the liquid surface through turbulence on the liquid surface and by cavitation in the liquid. Cavitation is the creation and implosion of voids in the liquid caused by crystal vibrations. Droplets formed as a gentle aerosol cloud above the liquid reservoir. 21 Vibrating-mesh Nebulizers: Attach a piezoelectric crystal to a laser-drilled metal mesh at the bottom of a drug reservoir or cup. When the crystal is subjected to an electric field, the metal mesh rapidly oscillates and forces the drug liquid through the holes in the mesh. A gentle aerosol is produced with a uniform aerodynamic particle size distribution due to the uniform nature of the laser-drilled holes in the metal membrane. https://www.youtube.com/watch?v=6MAAzxAHPGE 22 Microneedles: Microneedles make use of syringes in the micro range to deliver drugs to the respective sites. Deliver the drug: By increasing the pore size of the skin (Solid MNs) and thereby facilitating the diffusion of the drug applied topically; or by delivering the drugs by coating the drugs on the MNs (Coated MNs); or by delivering the drug via the pore of the syringe (Hollow MNs) https://www.youtube.com/watch?v=6idUWxtJ97g 23 24 Hydrogels: Three-dimensional, cross-linked networks formed from hydrophilic homopolymers, copolymers, or macromers. Cross-links produced through: ✓ Chemical reaction to form covalent bonds ✓ Entanglement of polymers ✓ Hydrogen bonding and van der Walls forces Classification: ✓ ✓ ✓ ✓ Neutral Anionic Cationic Ampholytic 25 26 Microneedle via GI Tract: The prototype device is an acrylic capsule about two centimeters long and one centimeter wide that can be taken orally, roughly the size of a large multivitamin. The capsule is designed to protect the medication inside until it reaches the GI tract. Once the capsule has reached its target destination, it dissolves and exposes the drug reservoir that is covered with five-millimeter-long needles. The needles pierce the intestines when the tissue contracts, delivering the drug directly http://www.iflscience.com/health-and-medicine/new-drug-delivery-system-couldreplace-injections Ref: Ifl Science Online 28 Receptor-mediated drug delivery (Manuscript on Blueline) : Differential expression of receptors between tumors and normal tissues. The strategy can actively transport drugs, such as small molecular drugs, gene medicines, and therapeutic proteins to tumors while minimizing adverse reactions 29 Doxorubicin Effective and widely used cancer drug Crosses the BBB very slowly Transferrin-Doxorubicin Through recombinant protein engineering – HIV type I protease Faster transport rate through the BBB and a 4.63 increased in cell inhibition to C6 tumor brain cell Stronger inhibitory effect on tumor growth Substantial reduction in tumor size of U87 tumor brain cells The worlds first and only FDA approved 3-D printed Drug Used to treat seizures caused by Epilepsy Dissolves instantly when comes in contact with fluid https://www.youtube.com/watch?v=u0E7TDmHBqM Match the following with four options below Which of the following drug delivery systems form 1)spherical vesicles of phospholipid bilayers 2) emulsifies in lipids 3) amorphous drug in polymer matrix 4)nanosized particles A) Liposomes B) Self emulsifying drug delivery systems C) Solid dispersions D) Nanoparticles Which of the following statements are incorrect? A) Ultrasonic nebulizers produces droplets through turbulence on the liquid surface and by cavitation in the liquid. B) Nexplanon is a non-biodegradable implant C) PLGA matrix is biodegradable whereas PVA/Silicone coating is non-biodegradable D) Ternary solid dispersions can only be formed using two polymers and not by adding a polymer with a surfactant. Review Questions 3 Sterile ophthalmic insert of hydroxypropyl cellulose use for lubrication and protection of eye. A) B) C) D) Ocusert Lacrisert Nexplanon Norplant Review Questions 3 Novel drug delivery system that incorporate a piezoelectric crystal at the bottom of the drug reservoir or cup. A) Ultrasonic Nebulizers B) Microneedles C) Hydrogel D) Implants Ansel’s Pharmaceutical Dosage Forms and Drug Delivery Systems; ▪ Chapter 20- Novel Dosage Forms and Drug Delivery Technologies Pharmaceutics: Basic principles and application to pharmacy practice ▪ Chapter 12- Special dosage forms and novel drug delivery systems 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. Ointments, Creams and Gels: Semi-Solid dosage forms USP Chapters: Pharmaceutical Dosage Forms USP Chapters: Qualitative and Quantitative Evaluation Suppositories: Rectal and Vaginal drug delivery systems Nebulizers and Inhalers: Pulmonary drug delivery systems Patches: Transdermal drug delivery systems Novel Drug delivery systems I Novel Drug delivery systems II Calculations: Dosage form Design and Delivery Systems Pharmaceutical Excipients Expectation: More application based (both theoretical and calculation-based problems) compared to straightforward questions. 38