How many ways can a drug be turned into a slow-release preparation?

Adding a coating – e.g., bupropion-SR (Wellbutrin-SR)

• – A solid pill consisting of active drug is layered with a single, more inert coating that protects the drug from digestion and absorption early in the GIT. This allows absorption to occur more gradually further along the GIT

Adding layers – e.g., zolpidem-ER (Ambien-CR)

• – In this instance, this drug has a tablet consisting of two layers. The initial layer of a more easily digestible coating is dissolved quickly in the GIT allowing onset of action quickly. The second, deeper layer also contains immediate-release drug but the layers are harder to break down and digest so drug release occurs later and further down the GI tract. These drugs actually give two separate releases instead of a longer, single, gradual release

OROS – e.g., methylphenidate (Concerta) and paliperidone (Invega)

• – First, this technique uses a capsule that has a larger hole on one end, and a smaller hole on the other end. Second, inside the capsule is the immediate-release drug and a small sponge-like substance. As this complex capsule travels through the GIT, water from the GIT is drawn into the large hole, saturates the sponge, which expands, thus driving the active drug gradually out the small hole on the other side of the capsule via hydrostatic pressure

Matrix – e.g., trazodone-ER (Oleptro)

• – An insoluble and difficult-to-digest web of material is created and the active drug is inserted throughout the matrix. As this slow-release package is not easily digested, it takes the active drug time to percolate and leak out of the matrix gradually as it traverses the GIT

Prodrugs – e.g., lisdexamfetamine (Vyvanse) and clorazepate (Tranxene)

• – A prodrug is a drug that is not clinically active in its natural state. A prodrug must be swallowed and digested in the GIT and then be passed to the liver. During hepatic metabolism, an enzyme, or series of enzymes, then alters the structure of the prodrug, which is released post-hepatically in this new form into the bloodstream. This digested new metabolite is the active therapeutic drug. The process of hepatic filtration and enzymatic metabolism is the slow-release mechanism. Essentially, the liver slows down production and release of the active drug

SODAS microbeads (spheroidal oral drug absorption system) – e.g., methylphenidate (Ritalin-LA, Focalin-XR)

• – In this process, active drug molecules (beads) are suspended and then are coated with varying numbers of layers, or coats of inert materials, that must be slowly dissolved to release the active drug. The more layers, the slower the release in the GIT per individual bead. By placing spheres with a few layers, some layers, and many layers all in one capsule, the drug is released gradually throughout the day as they are degraded further and further along in the GIT in sequential fashion. Unlike the two-layered tablet, which allows two distinct releases, the SODAS technology allows many differently timed releases throughout the day, giving a picture that resembles a more gradual, or smooth, release process

Transdermal delivery systems (patches) – e.g., methylphenidate (Daytrana) and selegiline (Emsam)

• – Essentially, the active drug is placed into a gel-like substance that is adhered to an impermeable backing. Next, adhesive glue is placed along the perimeter of the patch to adhere it to the patient’s skin. Pressure and constant drug-to-skin contact is ensured and the active drug is gradually absorbed through the skin’s capillaries, allowing for slow, constant absorption

Posttest self-assessment question and answer

What are some usual benefits of slow-release preparation medications?

A. Lower blood plasma levels often allow for less severe adverse effects

B. Extended half-life often allows for once-daily dosing and improved adherence

C. Cost is usually lowered as once-daily dosing is less costly to manufacture

D. Improved effectiveness over the parent immediate-release preparation

E. A and B

F. A, B, and C

G. All of the above

Answer: E

Lower plasma levels often offer less toxicity and thus fewer clinical side effects and make the drug easier to take, usually in once-daily fashion. Cost usually increases due to the technology involved in the slow-release drug mechanism, and in general, slow-release preparations are equally effective but engender less acute side effects, making C and D false.

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Patient file

The Case:

Generically speaking, generics are adequate

The Question:

What to do when using a generic is detrimental to a patient

The Dilemma:

Navigating clinical care when generic medications are not always equal