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Sandeep Singh Dhillon
What you need to know about immediate, delayed and extended-release medications – MIMS Malaysia
Formulation Discussion, Pharma Notables
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Recognising correct drug formulation is an important aspect of medical treatment. There are distinct pharmacokinetic differences between oral formulations such as immediate-release, extended-release and delayed-release although the drug composition and strength are identical. Unfortunately, these distinctions may not be apparent to many doctors or pharmacists, and the specific terms may be incorrectly used interchangeably. In addition, new formulations of the same pharmaceutical ingredients frequently enter the market, thus creating more confusion.

Henceforth, it is pivotal for both doctors and pharmacists to understand the fundamental differences between various formulation types to ensure optimum treatment. For pharmacists, failure to recognize and dispense the correct formulation may constitute negligence which can directly cause harm to patients.
Immediate-release formulation

The most commonly seen formulation in Malaysia is the immediate-release medication. These standard drug products are designed to release the active pharmaceutical compound immediately after the outer shell of tablets/capsule dissolves. There is no deliberate attempt to modify the release profile. For highly soluble drugs, this may result in rapid absorption and fast systemic entry into the body, i.e. a prompt increase in blood concentration of that particular drug. The accompanying clinical effect will be seen as soon as the plasma concentration reaches the therapeutic level (1).

There are exceptions to the above-mentioned observation. Some medicines are formulated as pro-drugs, which mean the pharmaceutical compound itself does not have therapeutic effects until it undergoes hepatic metabolism and transformed into the active compound. In this case, the pharmacodynamic effect may not be apparent until there is enough conversion of the pro-drugs into their active form. Alternatively, many drugs which are poorly soluble (i.e. lipophilic) may not be rapidly absorbed, thus delaying its clinical effect (1).
Modified-release formulation

On the other hand, modified-release formulations are specially designed to alter the drug release profile, thereby favourably affecting the absorption time and subsequent pharmacodynamic effects. The term “modified release” is rather all-encompassing, including many different types of formulations currently available in the market such as extended-release and delayed-release formulation.
Extended-release formulation

Extended-release formulation allows at least twofold reduction in dosage frequency as compared to the immediate-release ones, as described in Applied Biopharmaceutics & Pharmacokinetics (1). Several technologies have been successfully employed to control drug release profiles, such as microencapsulation and diffusion systems.
Know the differences

When compared to delayed-release dosage forms, there are many similarities amidst some distinct differences. A delayed-release product is a formulation that only releases the medication until the tablet has passed through the stomach, as explained by Fava and Holquist (2).

To illustrate the differences between extended- and delayed-release, one can refer to the case of Depakote (divalproex sodium) formulations. Depakote received attention from the medical community, especially the US FDA when the agency received a couple of medication errors pertaining to a mix-up of extended- and delayed-release formulation. Depatoke is indicated for the treatment of manic episode in patients with bipolar disorder whom lithium is contraindicated or not tolerated (3).

Existing pharmacokinetic data indicated that there were significant differences between the plasma concentration profile for both dosage forms. The bioavailability of extended-release Depakote was 10% less than an equivalent dose of delayed-release formulation (2).

It is vital for pharmacists to be aware of such differences for many other drugs. These different dosage forms commonly appear to be comparable to each other in terms of visual similarities and sound-alike names. Vigilance is a valuable trait when prescribing or dispensing such medications. MIMS

Reference:
1. Shargel L, Wu-Pong S, Yu A. Chapter 17. Modified-Release Drug Products. Applied Biopharmaceutics & Pharmacokinetics. 6th Editio. New York: McGraw-Hill Medical; 2012.
2. Fava W, Holquist C. FDA safety page: Delayed-release vs. extended-release Rxs [Internet]. Drug Topics – Voice of the pharmacist. 2007 [cited 2016 Jul 20]. Available from: http://drugtopics.modernmedicine.com/drug-topics/news/clinical/pharmacy/fda-safety-page-delayed-release-vs-extended-release-rxs?page=full
3. Sanofi. Depakote 250mg Tablets [Internet]. eMedicine Compendium. 2009 [cited 2016 Jul 20]. Available from: https://www.medicines.org.uk/emc/medicine/25929



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