cool approaches to delivery of medicines

what are the different types of controlled release?

• diffusion-controlled: matrix systems, membrane reservoirs

• chemically-activated: biodegradable polymers

• solvent-activated: swellable gels, osmotic systems

• pulsatile: pH- or temperature-sensitive; electric/ultrasonic

what is "smart" drug delivery?

• the future of drug delivery systems will involve smart systems

• address the issue of keeping the drug at the desired therapeutic level in the body thus avoiding frequent administration

• systems will use detection of chemical signals in the body to prompt the release of drugs

what is the ultimate goal of "smart" drug delivery?

to administer drugs at the right time, at the right dose anywhere in the body with specificity and efficiency

what is 3D printing?

as part of personalized medicines development, this platform gives manufacturers the ability to design and develop medicines dependent on consumer need

what are digital pills?

monitor the adherence of the consumer's consumption of the medicine

what is the paradoxical overdose-resistant activating system (PODRAS)?

• these products automatically regulate the bioavailability of the drug to avoid abuse/overdose
• provides deterrence against intentional (drug abuse) and unintentional dose dumping

in the future, what are pharmaceutical manufacturers likely to focus technology on?

• high-speed automation lines in manufacture of generics
• smart machines that can access compiled data and provide historical and predictive analysis
• use of robotics for repeating tasks and containment
• continuous manufacturing
• various tools such as NIR, image processing, lasers
• increased efficiency in scientific scale-up studies due to AI use
• digitization, machine learning, and improved AI

what is unigel?

• patented fixed-dose combination oral dosage form where tablets, granules, pellets, or capsules are filled into a large, soft gelatin capsule
• advantage: ability to combine active ingredients, at least one in a liquid/semi-solid state, with different release profiles or with chemical incompatibility problems

what are multilayer tablets designed for?

• separation of incompatible active pharmaceutical ingredients (APIs)
• to control the rate of release of one or two different active pharmaceutical ingredients
• controlling the release of an API from one layer by taking advantage of the functional properties of the other layer (e.g. osmotic properties)
• to modify the total surface area of the API layer utilizing a spacer with one or two inactive layers to obtain swollen/erodible modified-release barriers
• possibility to implement fixed-dose combination drugs (PDCs), develop new drug delivery systems, thus extending the life cycle of a medicinal product (patent extension)

what are multilayer tablets?

2 incompatible drugs + third drug layer/inert polymer layer in between

what is the process of stellate dosage form administration?

1. capsule disintegration and stellate opening
2. controlled drug dissolution over 7 days

• the capsule releases a large star that remains in the stomach to provide a constant release of the drug

1. dosage form disintegration and passage

• after the drug is released, the matrix breaks down into smaller components that pass safely through the digestive tract

what are the components of the stellate dosage form?

• drug-loaded arm: controls drug release
• elastomeric core: allows folding and recoil
• disintegrating matrices: gradually weaken to allow separation of components

what is sytem-responsive therapy?

• control-based design of biomedical systems
• configurational biomimetic imprinting
• making "artificial locks" for "molecular keys"

what is the molecular key?

• template molecule
• small molecules: drug substances, amino acids, steroid hormones
• large molecules: nucleic acids, proteins
• cells and viruses

what is the artificial lock?

• polymer building blocks
• functional monomers
• cross-linkers

what is the bioMEMS sensor platform?

• pattern environmentally responsive hydrogels onto silicon microcantilevers to create a bioMEMS/MEMS sensor device
• a change in analyte, pH, temp, etc. causes the hydrogel to swell

what is the importance of system-responsive therapy?

• need for advanced intelligent materials, more reliable devices, miniaturized systems
• society asks for improved treatment of disease, advanced detection and therapy, and cost-effective processes
• improvement of the quality of life is important

what are the newest approaches to overcome skin barrier?

decrease/eliminate the barrier by making holes in the skin or applying an electric current to the skin

what is the stratum corneum?

thinnest uppermost layer of skin responsible for the majority of the barrier property of skin (e.g. large MW drugs)

what is the ViaDerm system?

• microelectrode array is snapped onto the control unit
• light pressure creates RF-microchannels within a few seconds
• beep tone and light indicate RF-microchannels present
  release button ejects disposable microelectrode array from tretment site
• release liner removed from patch and drug patch is applied to skin

what are the different approaches to transdermal drug delivery?

ointment, patch, microneedle, sonophoresis, electroporation, iontophoresis

what is the mechanism of the e-skin used for iontophoresis?

what is the microneedle approach?

• minimally invasive, painless
• consist of small arrays of needles made of silicon, metal, biodegradable polymers, sugars (dissolvable)
• uses MEMS (micro electro mechanical systems): microfabrication, micromachining, microelectronic circuitry

what are biodegradable polymer microneedles?

• advantage: if broken in the skin, they are biodegradable and biocompatible
• poly(lactic acid) (PLA), poly(glycolic acid) (PGA), or PLGA used
• beveled-tip needles: length 600 µm, 10 µm tip
• 120 needle arrays made of PGA

how are microneedles used for transdermal delivery?

• needles 300 and 600 microns in length are used to deliver drug solutions through the stratum corneum
• the skin is pierced with the needles with a force of 5-10 lbs in 20 sec
• this painless delivery method is being investigated for delivery of macromolecules and vaccines

what is zosano?

• macroflux skin patch technology
• array of solid titanium microneedles which can either be coated with drug to give bolus effect, with reservoir to give passive delivery, or with iontophoresis to enhance delivery
• length 200 µm, width 170 µm, thickness 35 µm
• 321 microneedles/cm^2 on a 2 cm^2 patch
• useful for delivery of large MW drugs: ex. desmopressin 110 Da (intranasal and oral gives low bioavailability) for diabetes

what is the process of the glucowatch G2 biographer?

• based on reverse iontophoresis

1. glucose pulled through the skin by charged molecules
2. ions migrate to the anode and cathode
3. glucoes reacts with glucoes oxidase to form hydrogen peroxide
4. the reaction produces an electrochemical signal measured by the autosensor
5. reverse iontophoresis: insulindelivery method in response to glucose

what is the combination of insulin delivery and sensor?

• Medtronic Minimed Paradigm insulin pump combined with becton dickinson glucose monitor
• integrated system reduces errors and enhances convenience for patients

what's next for approaches to drug delivery?

• devices applied in or on the body: replace tissue, release drugs
• drugs will be more specific to the disease state (siRNA)
• drug release in a controlled manner: pumps, release devices
• MEMS, tissue engineering, and nanotechnology will provide novel approaches and concepts
• future will be a device, drug(s), delivery system with or without a (bio)sensor: i.e. a multicomponent combination device
• up-scaling and screening of formulations will be performed by AI systems