Ceutics 2 exam 1

Why use modified-release drug delivery?

Change the rate, timing, or site of release → fewer doses, better adherence, fewer peaks/troughs, and fewer adverse effects.

What are the main types of modified release?

Extended/sustained, controlled, delayed, repeat-action/pulsatile, and targeted release.

Extended/sustained vs controlled release?

Extended/sustained = lasts longer. Controlled = releases at a predetermined rate.

Delayed vs repeat-action vs targeted release?

Delayed = releases later. Repeat-action = 2 or more release phases. Targeted = releases at or near the intended site.

What is dose dumping?

Loss of release control causing a large amount of drug to be released too rapidly.

Matrix vs reservoir system?

Matrix = drug is mixed throughout the carrier. Reservoir = drug core is surrounded by a rate-controlling membrane.

What are the main mechanisms controlling modified release?

Dissolution, diffusion, erosion, ion exchange, and osmotic pressure.

How does a swellable hydrophilic matrix release drug?

Water enters → matrix swells and forms a gel → drug dissolves → drug diffuses through the gel.

What factors affect release from a swellable matrix?

Matrix swelling, drug dissolution, water solubility, diffusivity, and gel properties.

Metformin ER demonstrates what system?

HPMC swellable hydrophilic matrix.

How does an erodible matrix release drug?

The matrix erodes and exposes embedded drug; the erosion rate helps control drug release.

How does a hydrophobic matrix release drug?

Water enters slowly → drug dissolves → drug diffuses through pores/channels in the insoluble matrix.

Which products are wax/hydrophobic-matrix examples?

Klor-Con and Urocit-K.

What is a ghost tablet?

An empty or mostly empty insoluble carrier that can appear in stool after the drug has been released.

Important products that may produce a ghost tablet/shell?

OROS products, Klor-Con, metformin ER, Wellbutrin XL/Forfivo XL, OxyContin, Lialda, Allegra-D, Effexor XR, Pristiq, and Urocit-K.

What does free drug + matrix-bound drug accomplish?

Fast initial/loading release followed by slower prolonged release.

OxyContin release design?

Soluble outer coating + hydrophobic matrix → initial rapid release followed by sustained release.

How does a reservoir system release drug?

Water enters the core → drug dissolves → dissolved drug diffuses through the surrounding membrane.

What controls reservoir release?

Membrane thickness, porosity/polymer properties, and drug diffusivity.

What is microencapsulation?

Individually coating drug particles, crystals, or pellets with polymer.

Why can microencapsulation reduce dose-dumping risk?

Release control is divided among many coated particles instead of depending on one outer shell.

Klor-Con vs Klor-Con M, including the counseling difference?

Klor-Con = wax matrix and should be swallowed whole. Klor-Con M = ethyl-cellulose microencapsulated KCl particles; do not crush/chew particles, but the tablet may be split or dispersed in water as directed.

Wellbutrin ER uses what system?

Insoluble shell/reservoir; bupropion diffuses through the coating.

Why shouldn't Wellbutrin ER be crushed or chewed?

Damaging the coating changes the release rate and can cause dose dumping.

Wellbutrin SR vs XL?

SR = 12-hour. XL = 24-hour.

What is OROS?

Osmotic-Controlled Release Oral Delivery System; a reservoir system.

How does OROS work, and why is it relatively predictable?

Water enters → osmotic pressure rises → drug is pumped out through an orifice. It is less affected by food, GI pH, motility, and intestinal conditions.

What controls OROS release rate?

Orifice size/number plus semipermeable membrane thickness/permeability.

Why must OROS products stay intact?

Breaking or chewing destroys the osmotic release mechanism.

Which products should you recognize as OROS?

Cardura XL, Concerta/Relexxii, Glucotrol XL, Invega, Procardia XL, Tegretol XR, Xeljanz XR, oxybutynin ER, and amantadine ER.

What makes oral Invega OROS unusual?

Trilayer push-pull design with two laser-drilled orifices.

Invega vs Invega Sustenna?

Invega = oral paliperidone OROS ER tablet. Invega Sustenna = long-acting IM paliperidone injection, NOT SubQ.

Match these products to their MR system: Slo-Niacin, Coreg CR, Effexor XR, Pristiq.

Slo-Niacin = soluble matrix. Coreg CR = immediate-release + controlled-release beads. Effexor XR = microencapsulated reservoir. Pristiq = monolithic ER tablet.

Claritin-D release pattern?

Initial outer-layer release followed by later/prolonged pseudoephedrine release from the core.

ConZip release pattern?

Biphasic: immediate + extended release.

What does enteric coating accomplish?

Protects an acid-sensitive drug or the stomach by delaying release until a higher GI pH.

If a drug is acid-unstable AND needs prolonged release, what design makes sense?

Enteric protection plus a prolonged-release component.

Can every modified-release capsule never be opened?

No. Product-specific instructions matter; some capsules contain coated beads that can remain intact after opening.

Omeprazole DR counseling if a patient cannot swallow the capsule?

If the product permits, open the capsule and swallow the intact beads with appropriate soft food; do not crush or chew the beads.

Compare IR, delayed, repeat-action, and ER concentration/release curves.

IR = rapid peak. Delayed = lag then release. Repeat-action = multiple phases. ER = slower, prolonged profile.

What curve would you expect from a biphasic product?

An early release followed by a second or prolonged release phase.

Zero-order vs first-order release?

Zero-order = constant amount released per unit time. First-order = release rate depends on the amount remaining.

What should be the rate-limiting step in a good controlled-release product?

Drug release, not absorption/permeability.

What properties favor an oral MR candidate?

Reasonable dose, solubility, and half-life; good GI absorption; adequate stability; limited first-pass problems.

What properties make oral MR difficult?

Huge dose, extreme or pH-dependent solubility, GI instability, narrow absorption window, very short or very long half-life, or major first-pass metabolism.

Why is an absorption window a problem for MR?

Drug may be released after the dosage form has passed its main absorption site.

How does ion-exchange release work?

GI ions displace drug from a water-insoluble resin; release depends on pH and resin properties.

Ion-exchange product example?

Hydrocodone polistirex + chlorpheniramine polistirex extended-release suspension.

Why do parenterals require strict quality standards?

They bypass normal body defenses; products must be sterile, pyrogen-free, particulate-free, stable, compatible, and appropriately tonic/pH adjusted.

Compare IV bolus, IM/SubQ, and IV infusion concentration curves.

IV bolus = high immediately then falls. IM/SubQ = rises, peaks, then falls. IV infusion = rises toward a plateau.

IV bioavailability?

100%.

Constant IV infusion has what type of input?

Zero-order.

What determines steady state during a constant IV infusion?

Time to steady state depends on biologic half-life, not infusion rate; it takes about 4–5 half-lives. Increasing infusion rate raises steady-state concentration but does not shorten the time to steady state.

IV vs IM of the same drug: which generally gives a higher Cmax?

IV, because the drug enters systemic circulation directly.

Why can an IM suspension allow less frequent dosing?

It can form a slow-release depot at the injection site.

General depot release-speed order?

Aqueous solution > oily solution > oily suspension.

What controls depot suspension/emulsion release?

Solubility, viscosity, partition coefficient, and diffusivity.

Important long-acting IM examples?

Haloperidol decanoate, fluphenazine decanoate, and Risperdal Consta.

Benefits of long-acting injectable antipsychotics?

Improved adherence and reduced daily pill burden.

IM vs SubQ?

IM generally allows larger volume and has greater blood flow. SubQ uses smaller volumes and usually has slower absorption.

What determines syringe/needle selection?

Route, formulation viscosity, volume, and patient factors such as body size, muscle mass, and age.

Important SubQ products to recognize?

Insulin, glucagon, Ozempic, Tymlos, Fragmin, Lovenox/Enoxiluv, Arixtra, Vidaza, Eligard, Otrexup/Rasuvo, Furoscix, buprenorphine, methylnaltrexone, Imitrex, and risperidone.

What is hypodermoclysis?

Subcutaneous infusion of fluids, often for hydration.

What does hyaluronidase do in SubQ products?

Temporarily increases tissue permeability, facilitating drug spread and absorption.

Hyaluronidase-containing products?

Herceptin Hylecta, Rituxan Hycela, Darzalex Faspro, and Phesgo.

Important route clue for monoclonal antibody + hyaluronidase products?

The course notes identify these combinations for SubQ administration.

Why are some injectables supplied as sterile powders, and what is lyophilization?

Dry products can be more chemically/physically stable until reconstitution. Lyophilization = freeze-drying to create a stable dry injectable product.

What does Abilify Maintena illustrate?

Aripiprazole long-acting IM sterile powder/suspension; dual-chamber system.

What does Cleviprex illustrate?

Clevidipine IV oil-in-water emulsion.

What do Cinvanti and Aponvie illustrate?

Aprepitant IV emulsions.

What is a liposome and why use one?

A lipid-bilayer carrier that can improve solubility/compatibility, sustain or target delivery, improve efficacy, and reduce toxicity.

AmBisome vs Doxil?

AmBisome = liposomal amphotericin B. Doxil = PEGylated liposomal doxorubicin.

What does PEGylation do for Doxil?

Helps evade immune detection, increases stability/circulation time, and supports targeting.

What is Abraxane?

Albumin-bound paclitaxel nanoparticle (~130 nm).

Why is Abraxane associated with targeted delivery?

The course slides connect nanoparticle delivery to the EPR effect and protein-related targeting concepts.

Main sustained-release parenteral approaches?

Suspension/emulsion depots, implants/devices, micro/nanoparticles, and in-situ depots.

Surface vs bulk erosion?

Surface = erosion occurs externally. Bulk = water enters the matrix and drug dissolves/diffuses outward.

Important implant examples?

Nexplanon, Gliadel, Zoladex, Supprelin LA, Scenesse, and Xaracoll.

What makes Gliadel important?

Carmustine intracranial wafer providing local sustained delivery at the surgical site.

Sterile vs pyrogen-free?

Sterile = no viable microorganisms. Pyrogen-free = no fever-causing endotoxin.

Terminal sterilization vs aseptic processing?

Terminal = sterilize the finished product. Aseptic = sterilized components are combined without contamination.

Match sterilization method to use.

Steam = aqueous/heat-stable. 0.2–0.22 µm filtration = heat-sensitive liquid. Dry heat = oils/powders. Ethylene oxide = gas sterilization. Radiation = gamma/X-ray/electron beam.

0.22 µm vs 0.45 µm vs 1.2 µm?

0.2–0.22 µm = sterilizing filtration. 0.45 µm = sterility-test membrane. 1.2 µm = 30% Intralipid infusion filter.

How are membrane filtration and direct inoculation used for sterility testing?

Membrane filtration = filterable products through a 0.45 µm membrane. Direct inoculation = nonfilterable product placed directly into growth media.

How is a sterility test interpreted?

Incubate at least 14 days; microbial growth/turbidity indicates failure. Antimicrobial products can cause false negatives.

What are endotoxins?

Gram-negative bacterial lipopolysaccharides (LPS); thermostable, water-soluble, and nonvolatile.

What method in the review can prepare endotoxin-free water?

Distillation.

What does a HEPA filter filter?

Air in aseptic workspaces, not IV solution.

SVP vs LVP?

SVP = less than 100 mL. LVP = 100 mL or more, given by IV infusion; LVPs should not contain bacteriostatic preservatives.

Physical vs chemical IV incompatibility?

Physical = visible precipitate, color change, or gas. Chemical = degradation or potency loss that may not be visible.

Hypertonic vs hypotonic effect on cells?

Hypertonic = water leaves cells → cells shrink. Hypotonic = water enters cells → cells swell/lyse.

Important tonicity examples to recognize?

0.9% NS, D5W, and LR = isotonic. 0.45% NaCl = hypotonic. D10 = hypertonic.

WFI vs Sterile WFI vs Bacteriostatic WFI?

WFI = purified water with an added pyrogen-free requirement. Sterile WFI = WFI that is further sterilized and is preservative-free. Bacteriostatic WFI = sterile WFI containing a preservative, usually benzyl alcohol.

Infiltration vs extravasation vs chemical phlebitis vs catheter occlusion?

Infiltration = nonvesicant fluid leaks into surrounding tissue. Extravasation = vesicant/irritant leaks into tissue. Chemical phlebitis = vein inflammation from an irritant. Catheter occlusion = partial/complete blockage, sometimes from precipitate.

What are the main SVP excipient categories and common examples?

Co-solvents (ethanol, PEG, propylene glycol, glycerin); surfactants/fixed oils; antioxidants; buffers; tonicity agents (NaCl, dextrose, mannitol); chelators (EDTA); preservatives (e.g., benzyl alcohol).