Modified-release drugs

Frequently identifiable by two letters such as m/r, LA, SA, CR, XL or SR at the end of the name. Words such as “Retard” or “Slow” in the title sometimes used instead. For medicine designed to be released over prolonged period, the mechanism for slowing absorption may be damaged if the medication is manipulated. Disruption of a modified release coating may result in the patient experiencing a period of time where the systemic drug concentration is too high, causing toxicity or an overdose, followed by period where the drug concentration is too low to be therapeutically active. Definition The term modified-release drug product is used to describe products that alter the timing and/or the rate of release characteristics of time course and/or location are chosen to accomplish therapeutic or convenience objectives not offered by conventional dosage forms such as solutions, ointments, or promptly dissolving dosage forms. Modified-release dosage and its variants are mechanisms used in tablets (pills) and capsules to dissolve a drug over time in order to be released slower and steadier into the bloodstream while having the advantage of being taken at less frequent intervals than immediate-release (IR) formulations of the same drug. For example, extended-release morphine enables people with chronic pain to only take one or two tablets per day. Most commonly it refers to time-dependent release in oral dose formulations. Timed release has several distinct variants such as sustained release where prolonged release is intended, pulse release, delayed release (e.g. to target different regions of the GI tract) etc. A distinction of controlled release is that not only it prolongs action but it attempts to maintain drug levels within the therapeutic window to avoid potentially hazardous peaks in drug concentration following ingestion or injection and to maximize therapeutic efficiency. Several types of modified-release oral drug products are recognized: Extended-release drug products. A dosage form that allows at least a twofold reduction in dosage frequency as compared to that drug presented as an immediate-release (conventional) dosage form. Examples of extended-release dosage forms include controlled-release, sustained-release, and long-acting drug products. Delayed-release drug products. A dosage form that releases a discrete portion or portions of drug at a time other than promptly after administration. An initial portion may be released promptly after administration. Enteric-coated dosage forms are common delayed-release products. Targeted-release drug products. A dosage form that releases drug at or near the intended physiologic site of action. Targeted-release dosage forms may have either immediate- or extended-release characteristics. Orally disintegrating tablets (ODT). ODT have been developed to disintegrate rapidly in the saliva after oral administration. ODT may be used without the addition of water. The drug is dispersed in saliva and swallowed with little or no water. In addition to pills, capsules and injectable drug carriers (that often have an additional release function), forms of controlled release medicines include gels, implants and devices (e.g. the vaginal ring and contraceptive implant) and transdermal patches. History The earliest SR drugs are associated with a patent in 1938 by Israel Lipowski, who coated pellets which led to coating particles. The science of controlled release developed further with more oral sustained-release products in the late 1940s and early 1950s, the development of controlled release of marine anti-foulants in the 1950s and controlled release fertilizer in the 1970s where sustained and controlled delivery of nutrients following a single application to the soil. Delivery is usually effected by dissolution, degradation or disintegration of an excipient in which the active compound is formulated. Enteric coating and other encapsulation technologies can further modify release profiles. Methods Several different methods can be used to modify the rate of release of a drug from an oral dosage form including the following: - Modifying the pharmaceutical form – by increasing the drug particle size or forming insoluble crystals leads to a reduced rate of release. Coating pellets – coating drug pellets with a slowly dissolving polymer of varying thickness can vary the drug release rate. The pellets can either be compressed into a tablet or put in gelatin capsules. Insoluble matrix – drug is dispersed within an insoluble matrix and as fluid enters the matrix, the drug dissolved and slowly diffuses out. Eroding matrix – the drug is dispersed within a soluble matrix and as the matrix is slowly eroded the drug is released. Osmotic pump – the drug and an osmotic agent are enclosed in a semi-permeable membrane; water is drawn into the matrix and the dissolved drug is released in a controlled manner through a laser drilled hole. Crushing an extended-release preparation may change the drug release characteristics, with the potential for an unintended large bolus dose being delivered rather than controlled release over the intended timescale. The consequence of this would be for a potentially toxic dose of medication to be delivered following administration with an increased risk of adverse effects. While there is the risk of initial overdosing of drug, there will be under dosing at later times which could result in a lack of clinical efficacy. Importance of acronyms An acronym may be added to the end of the medication’s name to an attempt to describe that it is some sort of longer acting or super version of the original medication. Examples of this include: CD (controlled delivery) TR (time release) LA (long acting) ER (extended release) XT (extra time) SR (sustained release) XL (extra long, extra large) SA (sustained action) CR (controlled release) DR (delayed release) EC (enteric coated) HS (bed time dosing) PM (bed time dosing) CC (continuous control, constant control) XR (extra release) As you can see, a number of acronyms are used with little or no definition of their exact meaning related to the medication name they are attached to. The acronym is just an extension of the original product name, thus creating a new trade name for the product. To further confuse the situation, some medications not only have the original release version, but they also have 2 completely different extended versions with completely different acronyms. One particular seizure medication has an EC version with twice-daily dosing, but there is also an ER version with once-daily dosing. Another antidepressant medication has not only an SR version with twice-daily dosing, but also an XL version with once-daily dosing. When interpreting and filling prescriptions, pharmacists need to be vigilant in their review and determination of the appropriately selected product as it relates to the medication’s acronym. by Mehdiyeva B. References: 1. https://en.m.wikipedia.org/wiki/Modified-release_dosage 2. https://accesspharmacy.mhmedical.com/content.aspx?bookid=513&sectionid=41488035 3. https://www.rosemontpharma.com/health-professionals/oral-medication-that-should-not-be-crushed-or-opened 4. https://www.pharmacytimes.com/contributor/steve-leuck-pharmd/2015/01/medication-acronyms-lack-standardization