T2 - Modified-Release Drug Products and Other Drug Devices Flashcards
What are modified-release drug products?
Products that alter the timing and/or rate of release of the drug substance from the formulation
What are modified-released dosage form?
Formulation in which the drug-release characteristics of time and/or location are chosen for therapeutic effect or convenience
What are the categories of modified-release?
- Extended-release drug products
- Delayed-release drug products
What is delayed release?
- Dosage form that releases a small portion of drug at a time other than the immediate release after administration
- An initial portion may be released after administration
What is an example of a delayed-release?
Enteric-coated dosage forms
What is extended release?
A dosage form tha allows at least a 2fold reduction in dosage frequency as compared to immediate release
What is the purpose of using extended release?
- Prevents very rapid absorption of drug
- Extended action at a predetermined rate for a specific duration
- Release at a specific site
What are the advantages of using extended-release formulations?
- Less fluctuation in drug blood levels
- Frequency reduction in dosing
- Enhanced convince and compliance
- Reduction in adverse side effects
- Reduction in overall health care costs
How does extended-release cause less fluctuation in drug blood levels?
Controlling rate of release eliminates peaks and valleys of blood levels
How does extended-release allow frequent reduction in dosing?
Deliver more than a single dose, hence may be taken less often than conventional forms
How does extended-release enhance convince and compliance?
With less frequency of dosing, a patient is less apt to neglect taking a dose, greater convince with day and night administration
How does extended-release reduce adverse side effects?
Fewer blood levels outside therapeutic range
How does extended-release reduce overall health care costs?
Overall cost of treatment may be less due to enhanced therapeutic benefits
What are the disadvantages of extended-release?
- Dose dumping
- Less flexibility in accurate dose adjustment
- Less possibility for high dosage
What is dose-dumping?
The release of more than the intended fraction of drug or as the release of drug at a greater rate than the customary amount of drug per dosage interval
Why is extended-release less flexible in accurate dose adjustment?
More difficult to remove drug or adjust dose if adverse effect occurs
Why is it less possible to receive high doses for extended release?
Product may contain two or more times the dose given at more frequent intervals, drugs that require high single doses may have to be too large for the patient to swallow easily
What are examples of extended release dosage formulations?
- Pellets
- Granules
- Microspheres
Describe the formulation of slow-release seeds or beads?
- Sugar
- Starch
- Lactose
- Microcrystalline cellulose spheres (more durable)
What is a multi-tablet system?
- Usually capsules containing multiple mini-tablets (8-10)
- Tablets can have different release characteristics
What is micro encapsulations?
A process of encapsulating microscopic drug particles with a special coating material, making the drug particles more desirable in terms of physical and chemical characteristics
What are the advantages of micro encapsulation?
Administered dose of a drug is subdivided into small units that are spread over a large area of the GIT, which may enhance absorption by diminishing local drug concentration
What are the types of matrix systems?
- Gum-type
- Polymeric
What are the characteristics of gum-type matrix systems?
- Methycellulose, veegum, alginic acid, tragacanth
- Biodegradable
- Alter degradation based on hydration control, pH dependence, thickness and viscosity
What are the characteristics of polymeric matrix?
- Nonbiodegradable or biodegradable
- Hydrophilic or phobic
- Non-biodegradable is cautioned for reduced GI motility
- Used for implants and oral admin
How do you prepare a less soluble drug in a matrix?
The drug may be granulated with an excipient to slow dissolution of the drug
What happens when ionic exchange resin is exposed in the GIT?
Cations in the gut (K+ and Na+) will displace the drug from the resin releasing the drug
What are layers of an osmotic pump core?
- Active: containing drug
- Push: pharmacologically inactive, but osmotically active
What happens to an osmotic tablet when it enters the GIT?
Pressure increases in the osmotic later and pushes against the drug layer, releasing the drug from the laser drilled orifice. Altering size of orifice will affect the release rate
How fast is the drug delivery for osmotic pump tablets?
Constant as long as the osmotic gradient remains constant
What are osmotic pump tablets?
- The tablet is placed in water, osmotic pressure is generated by the osmotic agent within the core.
- Water moves into the device, forcing the dissolved drug to exit the tablet through an orifice
What are the clinical considerations of modified drug-release products?
- Patients should be advised of the dose and dosing frequency of modified drug-release products.
- Patients should not use extended-release products interchangeably or concomitantly with immediate-release forms of the same drug unless directed by a physician
- Patients stabilized on a modified-release product should not be changed to an immediate-release product without consideration of any existing blood level concentrations of the drug
- Patients should be advised that modified-release tablets and capsule should not be crushed or chewed, because such action compromises their drug-release features
- Patients and caregivers should be advised that nonerodable plastic matrix shells and osmotic tablets remain intact throughout gastrointestinal transit and the empty shells or ghosts from osmotic tablets may be seen in the stool
What is categories of transdermal drug delivery?
- Matrix
- Reservoir
- Multilaminate
- Drug-in-adhesive
What is the process of transdermal delivery?
- Diffusion of drug into a rate controlling membrane
- Dissolution within and release from the formulation
- Sorption by stratum corneum and penetration through viable epidermis
- Uptake of drug by capillary network in the dermal papillary layer
- Effect on the target organ
What are the physical properties for transdermal permeation?
- Iontophoresis
- Electroporation
- Sonophoresis
- Microneedles
What are the factors affecting percutaneous absorption?
- Drug concentration per unit surface area
- The larger the area of application, the more drug is absorbed. The longer the contact time, the more drug will be absorbed
- Drugs with molecular weights of 100-800 kDa and adequate lipid and aqueous solubility can permeate the skin (ideally 400 or less
- Hydration of the skin generally favors percutaneous absorption (occlusive layer increases hydration
- Patch applied to thin skin rather than thicker skin
What are the advantages of transdermal systems?
- Bypass GI absorption and first past metabolism issues
- Substitute for oral administration when unsuitable (vomiting or diarrhea)
- Noninvasive
- Extended therapy, improving compliance
- Short half-life drugs are extended through the reservoir of drug
- Therapy can be terminated by removal
- Easily identified during emergencies
In what ways can transdermal systems bypass GI absorption and first pass metabolism?
- pH, enzymes, food, drink, other drugs
- Avoiding deactivation by liver and digestion
What are the disadvantages of transdermal systems?
- Only relatively potent drugs are suitable due to limits of drug entry imposed by skin impermeability
- Skin conditions such as contact dermatitis, psoriasis, topical steroid withdrawal syndrome make it difficult for use of transdermal systems depending on the effected area
How should we counsel patients on transdermal patches?
- The preferred general application site is stated in the package insert for each product
- Advise the importance of using the recommended site and rotating locations
- Rotating locations is important to allow the skin beneath a patch to regain its normal permeability after being occluded and to prevent skin irritation
How can hair and skin affect transdermal adhesion?
- Wet or moist skin will affect permeation
- Oily skin can impair the adhesive
- Hair will affect adhesive and permeation
- Should not be shaven or epilated due to the integrity of skin being altered
How should we counsel a patient on transdermal patch application?
- Use of skin lotion should be avoided
- Do not cut patches. 3. This alters the releasing mechanisms and integrity of the system
- Patches should be pressed to the skin firmly for about 10 seconds to ensure uniform contact and adhesion
- Do not touch the adhesive layer with fingertips when removing the protective layer of adhesive
- Patches should be worn in place where they will not rub off (belt line)
- May be left on while swimming, showering, or bathing
What happens if a patch falls off?
May reapply or apply a fresh pathc
How should patients apply a patch?
- Patches should be worn for full period stated in the instructions, removed, then a new one applied
- Clean hands thoroughly after applying patches
- Reevaluation is needed if a sensitivity or intolerance forms to a transdermal patch
- Upon removing a patch, fold in half with the adhesive layer together so that it cannot be reused
- Discarded in a manner safe to children and pets
What are the techniques that use living organisms in the production or modification of products?
- Recombinant DNA
- Monoclonal antibodies
- Polymerase chain reactions
- Gene therapy
- Antisense tech
- Peptide tech
What is recombinant DNA?
Use rDNA in nonhuman cells to manufacture proteins identical to those produced in human cells
What were the first rDNA products to become available for patient use?
human growth hormone and insulin
How do you preform recombinant DNA?
Isolate specific pieces of DNA within a large molecule
What is monoclonal antibodies?
Produced by perpetuating the expression of a single B lymphocyte
What are the 4 types of Mabs?
- -omab
- -ximab
- -zumab
- -umab or -mumab
What is the suffix -omab?
Indicates murine, the earliest Man derived entirely from mice
What is the suffix -ximab?
Indicates chimeric, which has a human constant region and a murine variable region
What is the suffix -zumab?
Indicates a humanized May, 90% human and 10% murine in variable region
What is the suffix -umab or -mumab?
Created in mice whose murine genes are inactivated and replaced with human sequences
What is PCR?
Biotechnologic process where there is substantial applification of a target gene (nucleic acid sequence)
When would PCR be used?
Tissue typing, precision medicine, genetic modification
What is gene therapy?
Process in which exogenous genetic material is transferred into somatic cells to correct an inherited or acquired gene defect
Intended to introduce a new function or property into cells
When would gene therapy be used?
Cystic fibrosis, hemophilia, sickle cell anemia, and diabetes
What is antisense technology?
The study of function of specific proteins and intracellular expression
What is a sense sequence?
The sequence of a nucleotide chain that contains the info for protein synthesis
What is an antisense sequence?
The nucleotide chain that is complementary to the sense sequence
What are antisense drugs?
Binds to the nucleotide sense sequence of specific mRNA molecules, preventing synthesis of unwanted proteins and destroying the sense molecules in the process
What is peptide technology?
Entails screening for polypeptide molecules that can mimic larger proteins
Why is peptide tech used for?
- Afford relatively simple products that can be stable and easy to use
- Peptides can serve as either protein receptor agonists or antagonists
What are the issues of peptide tech?
- High molecular weight and potential for aggregation
- Other proteins could copurify with drug in the manufacturing process causing immunogenic potential
- Constituted products can be less stable than lypophilized products
- The effect of agitation on a product’s stability
- Possible interaction of the product with the inner wall of container and with elastomeric closure
- The effectiveness of the preservative if a multidose product is mixed with other products
- Potency issues
Which method of biotechnology utilizes B cells in order to produce the drug?
Monoclonal antibodies
Which method of Biotechnology utilizes rDNA in nonhuman cells to manufacture proteins identical to those produced in human cells?
Recombinant DNA
What are ophthalmic delivery systems for novel drug products?
- Ocusert
- Lacrisert
What are ocusert?
thin, flexible wafers placed under the eyelid to provide a week’s dose of pilocarpine in the treatment of glaucoma
What are lacrisert?
- Rod-shaped water-soluble form of hydroxypropyl cellulose.
- The insert is placed in the inferior cul-de-sac of the eye once or twice daily for the treatment of dry eyes.
What are long acting parenteral achieved?
- Use of crystal or amorphous drug forms having prolonged dissolution characteristics
- Slowly dissolving chemical complexes of the drug entity
What are the chemical complexes that have slow dissolution for long acting parenteral?
- Solutions, suspensions of drug in slowly absorbed carriers or vehicles
- Large particles of drug suspension
- Injection of slowly eroding microspheres of drug
What are liposomes?
Composed of small vesicles of a bilayer of phospholipid encapsulating an aqueous space ranging from about 0.03 to 10 mm in diameter
How are stealth liposomes developed?
With PEG on the outside of the membrane to avoid detection by the body’s immune system
What are implants?
Long-acting dosage forms that provide continuous release of the drug, often for periods of months to years
How are implants administered?
- By parenteral route for systemic delivery
- Placed subcutaneously for local delivery
- Placed in a specific region of the body
What are implants made of?
- Pellets
- Polymer
- Gel/solid
- Metal/plastic
- Drug eluding stents
