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<title>Modified-release dosage</title>

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<span id="openzim-page-title" class="mw-page-title-main"><span class="mw-page-title-main">Modified-release dosage</span></span>

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</style><div role="note" class="hatnote navigation-not-searchable">"Time release" redirects here. For the novel, see <a href="Time_Release_(novel)" title="Time Release (novel)">Time Release (novel)</a>.</div>

<p><b>Modified-release dosage</b> is a mechanism that (in contrast to immediate-release <a href="Dose_(biochemistry)" title="Dose (biochemistry)">dosage</a>) delivers a <a href="Drug" title="Drug">drug</a> with a delay after its <a href="Route_of_administration" title="Route of administration">administration</a> (delayed-release dosage) or for a prolonged period of time (extended-release [ER, XR, XL] dosage) or to a specific target in the body (targeted-release dosage).<sup id="cite_ref-pharm_1-0" class="reference"><a href="#cite_note-pharm-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup>

</p><p><b>Sustained-release dosage forms</b> are <a href="Dosage_form" title="Dosage form">dosage forms</a> designed to <a href="Liberation_(pharmacology)" title="Liberation (pharmacology)">release (liberate) a drug</a> at a predetermined rate in order to maintain a constant drug concentration for a specific period of time with minimum <a href="Side_effect" title="Side effect">side effects</a>. This can be achieved through a variety of formulations, including <a href="Liposome" title="Liposome">liposomes</a> and drug-polymer conjugates (an example being <a href="Hydrogel" title="Hydrogel">hydrogels</a>). Sustained release's definition is more akin to a "controlled release" rather than "sustained".

</p><p>Extended-release dosage consists of either sustained-release (SR) or controlled-release (CR) dosage. SR maintains drug release over a sustained period but not at a constant rate. CR maintains drug release over a sustained period at a nearly constant rate.<sup id="cite_ref-pharm_1-1" class="reference"><a href="#cite_note-pharm-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup>

</p><p>Sometimes these and <a href="#List_of_abbreviations">other terms</a> are treated as synonyms, but the United States <a href="Food_and_Drug_Administration" title="Food and Drug Administration">Food and Drug Administration</a> has in fact defined most of these as different concepts.<sup id="cite_ref-pharm_1-2" class="reference"><a href="#cite_note-pharm-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup> Sometimes the term "depot tablet" is used, by analogy to the term for an <a href="Depot_injection" title="Depot injection">injection formulation of a drug which releases slowly over time</a>, but this term is not medically or pharmaceutically standard for oral medication.

</p><p>Modified-release dosage and its variants are mechanisms used in <a href="Tablet_(pharmacy)" title="Tablet (pharmacy)">tablets</a> (pills) and <a href="Capsule_(pharmacy)" title="Capsule (pharmacy)">capsules</a> to <a href="Solvation" title="Solvation">dissolve</a> a <a href="Drug" title="Drug">drug</a> over time in order to be released more slowly and steadily 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, orally administered <a href="Extended-release_morphine" title="Extended-release morphine">extended-release morphine</a> can enable certain chronic pain patients to take only <span class="nowrap">1–2</span> tablets per day, rather than needing to redose every <span class="nowrap">4–6<span class="nowrap"> </span>hours</span> as is typical with standard-release morphine tablets.

</p><p>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 it not only prolongs action, but it attempts to maintain drug levels within the <a href="Therapeutic_window" class="mw-redirect" title="Therapeutic window">therapeutic window</a> to avoid potentially hazardous peaks in drug concentration following ingestion or injection and to maximize therapeutic efficiency.

</p><p>In addition to pills, the mechanism can also apply to capsules and injectable <a href="Drug_carriers" class="mw-redirect" title="Drug carriers">drug carriers</a> (that often have an additional release function), forms of controlled release medicines include gels, implants and devices (e.g. the <a href="Vaginal_ring" title="Vaginal ring">vaginal ring</a> and <a href="Contraceptive_implant" title="Contraceptive implant">contraceptive implant</a>) and <a href="Transdermal_patches" class="mw-redirect" title="Transdermal patches">transdermal patches</a>.

</p><p>Examples for cosmetic, personal care, and food science applications often centre on odour or flavour release.

</p><p>The release technology scientific and industrial community is represented by the Controlled Release Society (CRS). The CRS is the worldwide society for delivery science and technologies. CRS serves more than 1,600 members from more than 50 countries. Two-thirds of CRS membership is represented by industry and one-third represents academia and government. CRS is affiliated with the <i><a href="Journal_of_Controlled_Release" title="Journal of Controlled Release">Journal of Controlled Release</a></i> and <i>Drug Delivery and Translational Research</i> scientific journals.

</p>

<div class="mw-heading mw-heading2"><h2 id="List_of_abbreviations">List of abbreviations</h2></div>

<p>There is no industry standard for these abbreviations, and confusion and misreading have sometimes caused prescribing errors.<sup id="cite_ref-2" class="reference"><a href="#cite_note-2"><span class="cite-bracket">[</span>2<span class="cite-bracket">]</span></a></sup> Clear handwriting is necessary. For some drugs with multiple formulations, putting the meaning in parentheses is advisable.

</p>

<th>Abbreviation</th>

<th>Meaning</th>

<th>Notes

</th></tr>

<tr>

<td>Controlled Delivery</td>

<td>

</td></tr>

<tr>

<td>Controlled Release</td>

<td>

</td></tr>

<tr>

<td>Continuous Control, Constant Control</td>

<td>

</td></tr>

<tr>

<td>Delayed Release</td>

<td>

</td></tr>

<tr>

<td>Extended Release</td>

<td>

</td></tr>

<tr>

<td>Immediate Release</td>

<td>

</td></tr>

<tr>

<td>Initial Depot</td>

<td>

</td></tr>

<tr>

<td>Long-Acting</td>

<td>

</td></tr>

<tr>

<td>Long-Acting Release</td>

<td>

</td></tr>

<tr>

<td>Modified Release</td>

<td>

</td></tr>

<tr>

<td>Prolonged Release</td>

<td>

</td></tr>

<tr>

<td>Sustained Action</td>

<td>Ambiguous, can sometimes mean Short-Acting

</td></tr>

<tr>

<td>Sustained Release</td>

<td>

</td></tr>

<tr>

<td>Timed Release</td>

<td>

</td></tr>

<tr>

<td>Extra Long</td>

<td>

</td></tr>

<tr>

<td>Extended/Extra Release</td>

<td>

</td></tr>

<tr>

<td>Extended/Extra Time</td>

<td>

</td></tr>

<tr>

<td>Lesser/Lower Strength</td>

<td>

</td></tr>

<tr>

<td>Double Strength</td>

<td>

</td></tr>

<tr>

<td>Double Action</td>

<td>

</td></tr>

<tr>

<td>Extra Strength</td>

<td>

</td></tr>

<tr>

<td>Extra Strength</td>

<td>

</td></tr>

</tbody></table>

<p>A few other abbreviations are similar to these (in that they may serve as suffixes) but refer to dose rather than release rate. They include <i>ES</i> and <i>XS</i> (Extra Strength).

</p>

<div class="mw-heading mw-heading2"><h2 id="Methods">Methods</h2></div>

<p>Today, most time-release drugs are formulated so that the <a href="Active_ingredient" title="Active ingredient">active ingredient</a> is embedded in a matrix of insoluble substance(s) (various: some <a href="Acrylyl_group" class="mw-redirect" title="Acrylyl group">acrylics</a>, even <a href="Chitin" title="Chitin">chitin</a>; these substances are often <a href="Patented" class="mw-redirect" title="Patented">patented</a>) such that the dissolving drug must find its way out through the holes.

</p><p>In some SR formulations, the drug dissolves into the matrix, and the matrix physically swells to form a gel, allowing the drug to exit through the gel's outer surface.

</p><p><a href="Micro-encapsulation" title="Micro-encapsulation">Micro-encapsulation</a> is also regarded as a more complete technology to produce complex dissolution profiles. Through coating an active pharmaceutical ingredient around an inert core and layering it with insoluble substances to form a microsphere, one can obtain more consistent and replicable dissolution rates in a convenient format that can be mixed and matched with other instant release pharmaceutical ingredients into any two piece gelatin <a href="Capsule_(pharmacy)" title="Capsule (pharmacy)">capsule</a>.

</p><p>There are certain considerations for the formation of sustained-release formulation:

</p>

<ul><li>If the pharmacological activity of the active compound is not related to its blood levels, time releasing has no purpose except in some cases, such as bupropion, to reduce possible side effects.</li>

<li>If the absorption of the active compound involves an <a href="Active_transport" title="Active transport">active transport</a>, the development of a time-release product may be problematic.</li></ul>

<p>The <a href="Biological_half-life" title="Biological half-life">biological half-life</a> of the drug refers to the drug's elimination from the bloodstream which can be caused by metabolism, urine, and other forms of excretion. If the active compound has a long half-life (over 6 hours), it is sustained on its own. If the active compound has a short half-life, it would require a large amount to maintain a prolonged effective dose. In this case, a broad therapeutic window is necessary to avoid toxicity; otherwise, the risk is unwarranted and another mode of administration would be recommended.<sup id="cite_ref-pharmatutor_3-0" class="reference"><a href="#cite_note-pharmatutor-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup> Appropriate half-lives used to apply sustained methods are typically 3–4 hours and a drug dose greater than 0.5 grams is too high.<sup id="cite_ref-4" class="reference"><a href="#cite_note-4"><span class="cite-bracket">[</span>4<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-5" class="reference"><a href="#cite_note-5"><span class="cite-bracket">[</span>5<span class="cite-bracket">]</span></a></sup>

</p><p>The <a href="Therapeutic_index" title="Therapeutic index">therapeutic index</a> also factors whether a drug can be used as a time release drug. A drug with a thin therapeutic range, or small therapeutic index, will be determined unfit for a sustained release mechanism in partial fear of <a href="Dose_dumping" title="Dose dumping">dose dumping</a> which can prove fatal at the conditions mentioned.<sup id="cite_ref-overview_6-0" class="reference"><a href="#cite_note-overview-6"><span class="cite-bracket">[</span>6<span class="cite-bracket">]</span></a></sup> For a drug that is made to be released over time, the objective is to stay within the therapeutic range as long as needed.<sup id="cite_ref-pharmatutor_3-1" class="reference"><a href="#cite_note-pharmatutor-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup>

</p><p>There are many different methods used to obtain a sustained release.

</p>

<div class="mw-heading mw-heading3"><h3 id="Diffusion_systems">Diffusion systems</h3></div>

<p>Diffusion systems' rate release is dependent on the rate at which the drug dissolves through a barrier which is usually a type of polymer. Diffusion systems can be broken into two subcategories, reservoir devices and matrix devices.<sup id="cite_ref-pharmatutor_3-2" class="reference"><a href="#cite_note-pharmatutor-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup>

</p>

<ul><li>Reservoir devices coat the drug with polymers and in order for the reservoir devices to have sustained-release effects, the polymer must not dissolve and let the drug be released through diffusion.<sup id="cite_ref-pharmatutor_3-3" class="reference"><a href="#cite_note-pharmatutor-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup> The rate of reservoir devices can be altered by changing the polymer and is possible be made to have zero-order release; however, drugs with higher molecular weight have difficulty diffusing through the membrane.<sup id="cite_ref-Navin_7-0" class="reference"><a href="#cite_note-Navin-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Perrie_8-0" class="reference"><a href="#cite_note-Perrie-8"><span class="cite-bracket">[</span>8<span class="cite-bracket">]</span></a></sup></li>

<li>Matrix devices forms a matrix (drug(s) mixed with a gelling agent)<sup id="cite_ref-9" class="reference"><a href="#cite_note-9"><span class="cite-bracket">[</span>9<span class="cite-bracket">]</span></a></sup> where the drug is dissolved/dispersed.<sup id="cite_ref-Perrie_8-1" class="reference"><a href="#cite_note-Perrie-8"><span class="cite-bracket">[</span>8<span class="cite-bracket">]</span></a></sup> The drug is usually dispersed within a polymer and then released by undergoing diffusion. However, to make the drug SR in this device, the rate of dissolution of the drug within the matrix needs to be higher than the rate at which it is released. The matrix device cannot achieve a zero-order release but higher molecular weight molecules can be used.<sup id="cite_ref-Navin_7-1" class="reference"><a href="#cite_note-Navin-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup> The diffusion matrix device also tends to be easier to produce and protect from changing in the gastrointestinal tract, but factors such as food can affect the release rate.<sup id="cite_ref-overview_6-1" class="reference"><a href="#cite_note-overview-6"><span class="cite-bracket">[</span>6<span class="cite-bracket">]</span></a></sup></li></ul>

<div class="mw-heading mw-heading3"><h3 id="Dissolution_systems">Dissolution systems</h3></div>

<p>Dissolution systems must have the system dissolved slowly in order for the drug to have sustained release properties which can be achieved by using appropriate salts and/or derivatives as well as coating the drug with a dissolving material.<sup id="cite_ref-pharmatutor_3-4" class="reference"><a href="#cite_note-pharmatutor-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup> It is used for drug compounds with high solubility in water.<sup id="cite_ref-overview_6-2" class="reference"><a href="#cite_note-overview-6"><span class="cite-bracket">[</span>6<span class="cite-bracket">]</span></a></sup> When the drug is covered with some slow dissolving coat, it will eventually release the drug. Instead of diffusion, the drug release depends on the solubility and thickness of the coating. Because of this mechanism, the dissolution will be the rate limiting factor for drug release.<sup id="cite_ref-pharmatutor_3-5" class="reference"><a href="#cite_note-pharmatutor-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup> Dissolution systems can be broken down to subcategories called reservoir devices and matrix devices.<sup id="cite_ref-overview_6-3" class="reference"><a href="#cite_note-overview-6"><span class="cite-bracket">[</span>6<span class="cite-bracket">]</span></a></sup>

</p>

<ul><li>The reservoir device coats the drug with an appropriate material which will dissolve slowly. It can also be used to administer beads as a group with varying thickness, making the drug release in multiple times creating a SR.<sup id="cite_ref-overview_6-4" class="reference"><a href="#cite_note-overview-6"><span class="cite-bracket">[</span>6<span class="cite-bracket">]</span></a></sup></li>

<li>The matrix device has the drug in a matrix and the matrix is dissolved instead of a coating. It can come either as drug-impregnated spheres or drug-impregnated tablets.<sup id="cite_ref-overview_6-5" class="reference"><a href="#cite_note-overview-6"><span class="cite-bracket">[</span>6<span class="cite-bracket">]</span></a></sup></li></ul>

<div class="mw-heading mw-heading3"><h3 id="Osmotic_systems">Osmotic systems</h3></div>

<div role="note" class="hatnote navigation-not-searchable">Main article: <a href="Osmotic_controlled-release_oral_delivery_system" class="mw-redirect" title="Osmotic controlled-release oral delivery system">Osmotic controlled-release oral delivery system</a></div>

<p>Osmotic controlled-release oral delivery systems (OROS) have the form of a rigid <a href="Tablet_(pharmacy)" title="Tablet (pharmacy)">tablet</a> with a semi-permeable outer membrane and one or more small <a href="Laser_drilling" title="Laser drilling">laser drilled</a> holes in it. As the tablet <a href="Route_of_administration#Gastrointestinal/enteral" title="Route of administration">passes through the body</a>, water is absorbed through the <a href="Semipermeable_membrane" title="Semipermeable membrane">semipermeable membrane</a> via <a href="Osmosis" title="Osmosis">osmosis</a>, and the resulting <a href="Osmotic_pressure" title="Osmotic pressure">osmotic pressure</a> is used to push the active <a href="Drug" title="Drug">drug</a> through the opening(s) in the tablet. OROS is a trademarked name owned by <a href="ALZA_Corporation" class="mw-redirect" title="ALZA Corporation">ALZA Corporation</a>, which pioneered the use of osmotic pumps for oral drug delivery.<sup id="cite_ref-pmid19602438_10-0" class="reference"><a href="#cite_note-pmid19602438-10"><span class="cite-bracket">[</span>10<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid2006800_11-0" class="reference"><a href="#cite_note-pmid2006800-11"><span class="cite-bracket">[</span>11<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid17022845_12-0" class="reference"><a href="#cite_note-pmid17022845-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup>

</p><p>Osmotic release systems have a number of major advantages over other controlled-release mechanisms. They are significantly less affected by factors such as <a href="PH" title="PH">pH</a>, food intake, <a href="Gastrointestinal_physiology#Motility" title="Gastrointestinal physiology">GI motility</a>, and differing intestinal environments. Using an osmotic pump to deliver drugs has additional inherent advantages regarding control over drug delivery rates. This allows for much more precise drug delivery over an extended period of time, which results in much more predictable <a href="Pharmacokinetics" title="Pharmacokinetics">pharmacokinetics</a>. However, osmotic release systems are relatively complicated, somewhat difficult to manufacture, and may cause irritation or even blockage of the GI tract due to prolonged release of irritating drugs from the non-deformable tablet.<sup id="cite_ref-pmid19602438_10-1" class="reference"><a href="#cite_note-pmid19602438-10"><span class="cite-bracket">[</span>10<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid21486532_13-0" class="reference"><a href="#cite_note-pmid21486532-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid10872087_14-0" class="reference"><a href="#cite_note-pmid10872087-14"><span class="cite-bracket">[</span>14<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid2257873_15-0" class="reference"><a href="#cite_note-pmid2257873-15"><span class="cite-bracket">[</span>15<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid12408733_16-0" class="reference"><a href="#cite_note-pmid12408733-16"><span class="cite-bracket">[</span>16<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid11038435_17-0" class="reference"><a href="#cite_note-pmid11038435-17"><span class="cite-bracket">[</span>17<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid12240794_18-0" class="reference"><a href="#cite_note-pmid12240794-18"><span class="cite-bracket">[</span>18<span class="cite-bracket">]</span></a></sup>

</p>

<div class="mw-heading mw-heading3"><h3 id="Ion-exchange_resin">Ion-exchange resin</h3></div>

<div role="note" class="hatnote navigation-not-searchable">Main article: <a href="Ion-exchange_resin" title="Ion-exchange resin">Ion-exchange resin</a></div>

<p>In the ion-exchange method, the resins are cross-linked water-insoluble polymers that contain ionisable functional groups that form a repeating pattern of polymers, creating a polymer chain.<sup id="cite_ref-pharmatutor_3-6" class="reference"><a href="#cite_note-pharmatutor-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-overview_6-6" class="reference"><a href="#cite_note-overview-6"><span class="cite-bracket">[</span>6<span class="cite-bracket">]</span></a></sup> The drug is attached to the resin and is released when an appropriate interaction of ions and ion exchange groups occur. The area and length of the drug release and number of cross-link polymers dictate the rate at which the drug is released, determining the SR effect.<sup id="cite_ref-overview_6-7" class="reference"><a href="#cite_note-overview-6"><span class="cite-bracket">[</span>6<span class="cite-bracket">]</span></a></sup>

</p>

<div class="mw-heading mw-heading3"><h3 id="Floating_systems">Floating systems</h3></div>

<p>A floating system is a system where it floats on gastric fluids due to low density. The density of the gastric fluids is about 1 g/mL; thus, the drug/tablet administered must have a smaller density. The <a href="Buoyancy" title="Buoyancy">buoyancy</a> will allow the system to float to the top of the stomach and release at a slower rate without worry of excreting it. This system requires that there are enough gastric fluids present as well as food.<sup id="cite_ref-pharmatutor_3-7" class="reference"><a href="#cite_note-pharmatutor-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup> Many types of forms of drugs use this method such as powders, capsules, and tablets.<sup id="cite_ref-Dusane_19-0" class="reference"><a href="#cite_note-Dusane-19"><span class="cite-bracket">[</span>19<span class="cite-bracket">]</span></a></sup>

</p>

<div class="mw-heading mw-heading3"><h3 id="Bio-adhesive_systems">Bio-adhesive systems</h3></div>

<p><a href="Bioadhesive" title="Bioadhesive">Bio-adhesive</a> systems generally are meant to stick to mucus and can be favorable for mouth based interactions due to high mucus levels in the general area but not as simple for other areas. Magnetic materials can be added to the drug so another magnet can hold it from outside the body to assist in holding the system in place. However, there is low patient compliance with this system.<sup id="cite_ref-pharmatutor_3-8" class="reference"><a href="#cite_note-pharmatutor-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup>

</p>

<div class="mw-heading mw-heading3"><h3 id="Matrix_systems">Matrix systems</h3></div>

<p>The matrix system is the mixture of materials with the drug, which will cause the drug to slow down. However, this system has several subcategories: hydrophobic matrices, lipid matrices, hydrophilic matrices, biodegradable matrices, and mineral matrices.<sup id="cite_ref-pharmatutor_3-9" class="reference"><a href="#cite_note-pharmatutor-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup>

</p>

<ul><li>A hydrophobic matrix is a drug mixed with a hydrophobic polymer. This causes SR because the drug, after being dissolved, will have to be released by going through channels made by the hydrophilic polymer.<sup id="cite_ref-pharmatutor_3-10" class="reference"><a href="#cite_note-pharmatutor-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup></li>

<li>A hydrophilic matrix will go back to the matrix as discussed before where a matrix is a mixture of a drug or drugs with a gelling agent.<sup id="cite_ref-pharmatutor_3-11" class="reference"><a href="#cite_note-pharmatutor-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup> This system is well liked because of its cost and broad regulatory acceptance. The polymers used can be broken down into categories: cellulose derivatives, non-cellulose natural, and polymers of acrylic acid.<sup id="cite_ref-20" class="reference"><a href="#cite_note-20"><span class="cite-bracket">[</span>20<span class="cite-bracket">]</span></a></sup></li>

<li>A lipid matrix uses wax or similar materials. Drug release happens via diffusion through, and erosion of, the wax and tends to be sensitive to digestive fluids.<sup id="cite_ref-pharmatutor_3-12" class="reference"><a href="#cite_note-pharmatutor-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup></li>

<li>Biodegradable matrices are made with unstable, linked monomers that will erode by biological compounds such as enzymes and proteins.<sup id="cite_ref-pharmatutor_3-13" class="reference"><a href="#cite_note-pharmatutor-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup></li>

<li>A mineral matrix which generally means the polymers used are obtained in seaweed.<sup id="cite_ref-pharmatutor_3-14" class="reference"><a href="#cite_note-pharmatutor-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup></li></ul>

<div class="mw-heading mw-heading3"><h3 id="Stimuli_inducing_release">Stimuli inducing release</h3></div>

<p>Examples of stimuli that may be used to bring about release include pH, enzymes, light, magnetic fields, temperature, ultrasonics, osmosis, cellular traction forces,<sup id="cite_ref-21" class="reference"><a href="#cite_note-21"><span class="cite-bracket">[</span>21<span class="cite-bracket">]</span></a></sup> and electronic control of <a href="MEMS" title="MEMS">MEMS</a><sup id="cite_ref-Maloney_22-0" class="reference"><a href="#cite_note-Maloney-22"><span class="cite-bracket">[</span>22<span class="cite-bracket">]</span></a></sup> and <a href="Nanoelectromechanical_systems" title="Nanoelectromechanical systems">NEMS</a>.<sup id="cite_ref-23" class="reference"><a href="#cite_note-23"><span class="cite-bracket">[</span>23<span class="cite-bracket">]</span></a></sup>

</p><p>Spherical hydrogels, in micro-size (50-600 μm diameter) with 3-dimensional cross-linked polymer, can be used as drug carrier to control the release of the drug. These hydrogels are called microgels. They may possess a negative charge as example DC-beads. By ion-exchange mechanism, a large amount of oppositely charged amphiphilic drugs can be loaded inside these microgels. Then, the release of these drugs can be controlled by a specific triggering factor like pH, ionic strength or temperature.<sup id="cite_ref-24" class="reference"><a href="#cite_note-24"><span class="cite-bracket">[</span>24<span class="cite-bracket">]</span></a></sup>

</p>

<div class="mw-heading mw-heading2"><h2 id="Pill_splitting">Pill splitting</h2></div>

<p>Some time release formulations do not work properly if split, such as controlled-release tablet coatings, while other formulations such as micro-encapsulation still work if the microcapsules inside are swallowed whole.<sup id="cite_ref-25" class="reference"><a href="#cite_note-25"><span class="cite-bracket">[</span>25<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-26" class="reference"><a href="#cite_note-26"><span class="cite-bracket">[</span>26<span class="cite-bracket">]</span></a></sup>

</p><p>Among the <a href="Health_information_technology" title="Health information technology">health information technology</a> (HIT) that pharmacists use are medication safety tools to help manage this problem. For example, the ISMP "do not crush" list<sup id="cite_ref-ISMP_DoNotCrush_27-0" class="reference"><a href="#cite_note-ISMP_DoNotCrush-27"><span class="cite-bracket">[</span>27<span class="cite-bracket">]</span></a></sup> can be entered into the system so that warning stickers can be printed at the point of dispensing, to be stuck on the pill bottle.

</p><p>Pharmaceutical companies that do not supply a range of half-dose and quarter-dose versions of time-release tablets can make it difficult for patients to be slowly tapered off their drugs.

</p>

<div class="mw-heading mw-heading2"><h2 id="History">History</h2></div>

<p>The earliest SR drugs are associated with a patent in 1938 by Israel Lipowski, who coated pellets which led to coating particles.<sup id="cite_ref-Navin_7-2" class="reference"><a href="#cite_note-Navin-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup> 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 <a href="Controlled_release_fertilizer" class="mw-redirect" title="Controlled release fertilizer">controlled release fertilizer</a> in the 1970s where sustained and controlled delivery of nutrients was achieved following a single application to the soil. Delivery is usually effected by dissolution, degradation, or disintegration of an <a href="Excipient" title="Excipient">excipient</a> in which the active compound is formulated. <a href="Enteric_coating" title="Enteric coating">Enteric coating</a> and other encapsulation technologies can further modify release profiles.

</p>

<ul><li><a href="Depot_injection" title="Depot injection">Depot injection</a></li>

<li><a href="Tablet_(pharmacy)" title="Tablet (pharmacy)">Tablet (pharmacy)</a></li></ul>

<div class="mw-heading mw-heading2"><h2 id="Footnotes">Footnotes</h2></div>

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<li id="cite_note-Dusane-19"><span class="mw-cite-backlink"><b><a href="#cite_ref-Dusane_19-0">^</a></b></span> <span class="reference-text">Dusane Ratilal, Gaikwad D., Banker H., and Pawar P. A Review On: Sustained Release Technology. International Journal of Research in Ayurveda and Pharmacy. 2011. Accessed: May 30, 2016.</span>

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<li id="cite_note-20"><span class="mw-cite-backlink"><b><a href="#cite_ref-20">^</a></b></span> <span class="reference-text">Jaimini Manish and Kothari Abhay. Sustained Release Matrix Type Drug Delivery System: A Review. Journal of Drug Delivery & Therapeutics. 2012. Accessed: May 30, 2016.</span>

</li>

<li id="cite_note-21"><span class="mw-cite-backlink"><b><a href="#cite_ref-21">^</a></b></span> <span class="reference-text"><cite id="CITEREFStejskalováOlivaEnglandAlmquist2019" class="citation journal cs1">Stejskalová, Anna; Oliva, Nuria; England, Frances J.; Almquist, Benjamin D. (2019). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375388">"Biologically Inspired, Cell-Selective Release of Aptamer-Trapped Growth Factors by Traction Forces"</a>. <i>Advanced Materials</i>. <b>31</b> (7): 1806380. <a href="Bibcode_(identifier)" class="mw-redirect" title="Bibcode (identifier)">Bibcode</a>:<a rel="nofollow" class="external text" href="https://ui.adsabs.harvard.edu/abs/2019AdM....3106380S">2019AdM....3106380S</a>. <a href="Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1002%2Fadma.201806380">10.1002/adma.201806380</a>. <a href="ISSN_(identifier)" class="mw-redirect" title="ISSN (identifier)">ISSN</a> <a rel="nofollow" class="external text" href="https://search.worldcat.org/issn/1521-4095">1521-4095</a>. <a href="PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375388">6375388</a></span>. <a href="PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/30614086">30614086</a>.</cite></span>

</li>

<li id="cite_note-Maloney-22"><span class="mw-cite-backlink"><b><a href="#cite_ref-Maloney_22-0">^</a></b></span> <span class="reference-text"><cite id="CITEREFMaloneyUhlandPolitoSheppard_NF_Jr2005" class="citation journal cs1">Maloney JM, Uhland S, Polito B, Sheppard NF Jr, Pelta C, Santini JT Jr (2005). <a rel="nofollow" class="external text" href="http://john.maloney.org/Papers/Electrothermally_activated_microchips.pdf">"Electrothermally activated microchips for implantable drug delivery and biosensing"</a> <span class="cs1-format">(PDF)</span>. <i>Journal of Controlled Release</i>. <b>109</b> (<span class="nowrap">1–</span>3): <span class="nowrap">244–</span>255. <a href="Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1016%2Fj.jconrel.2005.09.035">10.1016/j.jconrel.2005.09.035</a>. <a href="PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/16278032">16278032</a>.</cite></span>

</li>

<li id="cite_note-23"><span class="mw-cite-backlink"><b><a href="#cite_ref-23">^</a></b></span> <span class="reference-text"><cite id="CITEREFYouAlmedaYeAuguste2010" class="citation journal cs1">You JO, Almeda D, Ye GJ, Auguste DT (2010). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3002303">"Bioresponsive matrices in drug delivery"</a>. <i>J Biol Eng</i>. <b>4</b>: 15. <a href="Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://doi.org/10.1186%2F1754-1611-4-15">10.1186/1754-1611-4-15</a></span>. <a href="PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3002303">3002303</a></span>. <a href="PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/21114841">21114841</a>.</cite></span>

</li>

<li id="cite_note-24"><span class="mw-cite-backlink"><b><a href="#cite_ref-24">^</a></b></span> <span class="reference-text"><cite id="CITEREFAhnfeltGernandtAl-TikritiSjögren2018" class="citation journal cs1">Ahnfelt, E.; Gernandt, J.; Al-Tikriti, Y.; Sjögren, E.; Lennernäs, H.; Hansson, P. (2018-12-28). <a rel="nofollow" class="external text" href="https://doi.org/10.1016%2Fj.jconrel.2018.11.011">"Single bead investigation of a clinical drug delivery system – A novel release mechanism"</a>. <i>Journal of Controlled Release</i>. <b>292</b>: <span class="nowrap">235–</span>247. <a href="Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://doi.org/10.1016%2Fj.jconrel.2018.11.011">10.1016/j.jconrel.2018.11.011</a></span>. <a href="ISSN_(identifier)" class="mw-redirect" title="ISSN (identifier)">ISSN</a> <a rel="nofollow" class="external text" href="https://search.worldcat.org/issn/0168-3659">0168-3659</a>. <a href="PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/30419268">30419268</a>.</cite></span>

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<li id="cite_note-25"><span class="mw-cite-backlink"><b><a href="#cite_ref-25">^</a></b></span> <span class="reference-text"><cite class="citation web cs1"><a rel="nofollow" class="external text" href="https://web.archive.org/web/20111208120921/http://www.netdoctor.co.uk/medicines/100004842.html">"Equasym XL (methylphenidate)"</a>. <i>netdoctor.co.uk</i>. 24 May 2013. Archived from <a rel="nofollow" class="external text" href="http://www.netdoctor.co.uk/medicines/100004842.html">the original</a> on 8 December 2011<span class="reference-accessdate">. Retrieved <span class="nowrap">16 August</span> 2016</span>.</cite></span>

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<li id="cite_note-26"><span class="mw-cite-backlink"><b><a href="#cite_ref-26">^</a></b></span> <span class="reference-text"><cite id="CITEREFVranićUzunović,_A2009" class="citation journal cs1">Vranić, E; Uzunović, A (August 2009). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5632511">"Influence of splitting on dissolution properties of metoprolol tablets"</a>. <i>Bosnian Journal of Basic Medical Sciences</i>. <b>9</b> (3): <span class="nowrap">245–</span>9. <a href="Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.17305%2Fbjbms.2009.2815">10.17305/bjbms.2009.2815</a>. <a href="PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5632511">5632511</a></span>. <a href="PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/19754482">19754482</a>.</cite></span>

</li>

<li id="cite_note-ISMP_DoNotCrush-27"><span class="mw-cite-backlink"><b><a href="#cite_ref-ISMP_DoNotCrush_27-0">^</a></b></span> <span class="reference-text"><cite id="CITEREFInstitute_for_Safe_Medication_Practices_(ISMP)2017" class="citation cs2">Institute for Safe Medication Practices (ISMP) (20 November 2017), <a rel="nofollow" class="external text" href="http://www.ismp.org/Tools/DoNotCrush.pdf"><i>ISMP "do not crush" list: Oral dosage forms that should not be crushed</i></a> <span class="cs1-format">(PDF)</span></cite></span>

</li>

</ol></div></div>

<div class="mw-heading mw-heading2"><h2 id="External_links">External links</h2></div>

<ul><li><a rel="nofollow" class="external text" href="http://www.controlledreleasesociety.org/about/Pages/default.aspx">Controlled Release Society</a></li>

<li><a rel="nofollow" class="external text" href="http://www.ukicrs.org">United Kingdom & Ireland Controlled Release Society</a></li>

<li><a rel="nofollow" class="external text" href="http://web.mit.edu/professional/short-programs/courses/controlled_release_technology.html">Controlled Release Technology</a> 5-day short course at MIT with Professor Robert Langer.</li>

<li><a rel="nofollow" class="external text" href="https://www.researchgate.net/publication/369737573_A_review_of_medicines_with_sustained_release">A review of medicines with sustained release</a> March 2023, World Journal of Biology Pharmacy and Health Sciences</li></ul>

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</style><div id="Routes_of_administration,_dosage_forms650" style="font-size:114%;margin:0 4em"><a href="Route_of_administration" title="Route of administration">Routes of administration</a>, <a href="Dosage_form" title="Dosage form">dosage forms</a></div></th></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="Oral_administration" title="Oral administration">Oral</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:10em;white-space:normal;"><a href="Human_gastrointestinal_tract" class="mw-redirect" title="Human gastrointestinal tract">Digestive tract</a> (<a href="Enteral_administration" title="Enteral administration">enteral</a>)</th><td class="navbox-list-with-group navbox-list navbox-odd" style="padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:5em;white-space:normal;"><a href="Solid" title="Solid">Solids</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="padding:0"><div style="padding:0 0.25em">

<ul><li><a href="Tablet_(pharmacy)" title="Tablet (pharmacy)">Tablet</a></li>

<li><a href="Capsule_(pharmacy)" title="Capsule (pharmacy)">Capsule</a></li>

<li><a href="Pastille" title="Pastille">Pastille</a></li>

<li><a href="Time_release_technology" class="mw-redirect" title="Time release technology">Time release technology</a></li>

<li><a href="Osmotic-controlled_release_oral_delivery_system" title="Osmotic-controlled release oral delivery system">Osmotic delivery system</a></li></ul>

</div></td><td class="noviewer navbox-image" rowspan="2" style="width:1px;padding:0 0 0 2px"><div><span typeof="mw:File"></span><br><span typeof="mw:File"></span></div></td></tr><tr><th scope="row" class="navbox-group" style="width:5em;white-space:normal;"><a href="Liquid" title="Liquid">Liquids</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="padding:0"><div style="padding:0 0.25em">

<ul><li><a href="Decoction" title="Decoction">Decoction</a></li>

<li><a href="Elixir" title="Elixir">Elixir</a></li>

<li><a href="Electuary" title="Electuary">Electuary</a></li>

<li><a href="Emulsion" title="Emulsion">Emulsion</a></li>

<li><a href="Effervescent_tablet" title="Effervescent tablet">Effervescent powder or tablet</a></li>

<li><a href="Herbal_tea" title="Herbal tea">Herbal tea</a></li>

<li><a href="Hydrogel" title="Hydrogel">Hydrogel</a></li>

<li><a href="Molecular_encapsulation" class="mw-redirect" title="Molecular encapsulation">Molecular encapsulation</a></li>

<li><a href="Powder" title="Powder">Powder</a></li>

<li><a href="Softgel" title="Softgel">Softgel</a></li>

<li><a href="Solution_(chemistry)" title="Solution (chemistry)">Solution</a></li>

<li><a href="Suspension_(chemistry)" title="Suspension (chemistry)">Suspension</a></li>

<li><a href="Syrup" title="Syrup">Syrup</a></li>

<li><a href="Tincture" title="Tincture">Tincture</a></li></ul>

</div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:10em;white-space:normal;"><a href="Oral_mucosa" title="Oral mucosa">Oral mucosa</a> (<a href="Buccal_administration" title="Buccal administration">buccal</a>, <a href="Sublabial_administration" title="Sublabial administration">sublabial</a>, <a href="Sublingual_administration" title="Sublingual administration">sublingual</a>, <a href="Supralingual_administration" title="Supralingual administration">supralingual</a>)</th><td class="navbox-list-with-group navbox-list navbox-odd" style="padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:5em;white-space:normal;"><a href="Solid" title="Solid">Solids</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="padding:0"><div style="padding:0 0.25em">

<ul><li><a href="Orally_disintegrating_tablet" title="Orally disintegrating tablet">Orally disintegrating tablet</a></li>

<li><a href="Lollipop#Medicinal_use" title="Lollipop">Lollipop</a></li>

<li><a href="Drop_(liquid)" title="Drop (liquid)">Sublingual drops</a></li>

<li><a href="Throat_lozenge" title="Throat lozenge">Lozenges</a></li>

<li><a href="Effervescent" class="mw-redirect" title="Effervescent">Effervescent</a> tablet</li>

<li><a href="Chewing_gum" title="Chewing gum">Chewing gum</a></li></ul>

</div></td></tr><tr><th scope="row" class="navbox-group" style="width:5em;white-space:normal;"><a href="Liquid" title="Liquid">Liquids</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="padding:0"><div style="padding:0 0.25em">

<ul><li><a href="Mouthwash" title="Mouthwash">Mouthwash</a></li>

<li><a href="Toothpaste" title="Toothpaste">Toothpaste</a></li>

<li><a href="Topical" class="mw-redirect" title="Topical">Ointment</a></li>

<li>Spray</li></ul>

</div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:10em;white-space:normal;"><a href="Respiratory_tract" title="Respiratory tract">Respiratory tract</a> (<a href="Inhalation" title="Inhalation">inhalation</a>)</th><td class="navbox-list-with-group navbox-list navbox-odd" style="padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:5em;white-space:normal;"><a href="Solid" title="Solid">Solids</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="padding:0"><div style="padding:0 0.25em">

<ul><li><a href="Dry-powder_inhaler" title="Dry-powder inhaler">Dry-powder inhaler</a></li>

<li><a href="Smoking" title="Smoking">Smoking</a></li></ul>

</div></td><td class="noviewer navbox-image" rowspan="3" style="width:1px;padding:0 0 0 2px"><div><span typeof="mw:File"></span><br><span aria-hidden="true" style="visibility:hidden;color:transparent;">0</span><br><span aria-hidden="true" style="visibility:hidden;color:transparent;">0</span></div></td></tr><tr><th scope="row" class="navbox-group" style="width:5em;white-space:normal;"><a href="Liquid" title="Liquid">Liquids</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="padding:0"><div style="padding:0 0.25em">

<ul><li><a href="Anesthetic_vaporizer" class="mw-redirect" title="Anesthetic vaporizer">Anesthetic vaporizer</a></li>

<li><a href="Heated_humidified_high-flow_therapy" title="Heated humidified high-flow therapy">Heated humidified high-flow therapy</a></li>

<li><a href="List_of_medical_inhalants" title="List of medical inhalants">Medical inhalants</a></li>

<li><a href="Metered-dose_inhaler" title="Metered-dose inhaler">Metered-dose inhaler</a> (MDI)</li>

<li><a href="Nebulizer" title="Nebulizer">Nebulizer</a></li>

<li><a href="Vaporizer_(inhalation_device)" title="Vaporizer (inhalation device)">Vaporizer</a></li></ul>

</div></td></tr><tr><th scope="row" class="navbox-group" style="width:5em;white-space:normal;"><a href="Gas" title="Gas">Gas</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="padding:0"><div style="padding:0 0.25em">

<ul><li><a href="Oxygen_mask" title="Oxygen mask">Oxygen mask</a> and <a href="Nasal_cannula" title="Nasal cannula">Nasal cannula</a></li>

<li><a href="Oxygen_concentrator" title="Oxygen concentrator">Oxygen concentrator</a></li>

<li><a href="Anaesthetic_machine" title="Anaesthetic machine">Anaesthetic machine</a></li>

<li><a href="List_of_medical_inhalants" title="List of medical inhalants">Medical inhalants</a></li>

<li><a href="Relative_analgesia_machine" title="Relative analgesia machine">Relative analgesia machine</a></li></ul>

</div></td></tr></tbody></table><div></div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="Ophthalmic_drug_administration" title="Ophthalmic drug administration">Ophthalmic</a>,<br><a href="Ear" title="Ear">otic</a>, <a href="Nasal_administration" title="Nasal administration">nasal</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em">

<ul><li><a href="Nasal_spray" title="Nasal spray">Nasal spray</a></li>

<li><a href="Ear_drop" title="Ear drop">Ear drops</a></li>

<li><a href="Eye_drop" title="Eye drop">Eye drops</a></li>

<li><a href="Topical" class="mw-redirect" title="Topical">Ointment</a></li>

<li><a href="Hydrogel" title="Hydrogel">Hydrogel</a></li>

<li><a href="Insufflation_(medicine)" title="Insufflation (medicine)">Insufflation</a></li>

<li><a href="Bioadhesive" title="Bioadhesive">Mucoadhesive microdisc</a></li></ul></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="Genitourinary_system" title="Genitourinary system">Urogenital</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em">

<li><a href="Topical" class="mw-redirect" title="Topical">Ointment</a></li>

<li><a href="Pessary" title="Pessary">Pessary</a></li>

<li><a href="Vaginal_ring" title="Vaginal ring">Vaginal ring</a></li>

<li><a href="Douche" title="Douche">Douche</a></li>

<li><a href="Intrauterine_device" title="Intrauterine device">Intrauterine device</a> (IUD)</li>

<li><a href="Extra-amniotic_administration" title="Extra-amniotic administration">Extra-amniotic infusion</a></li>

<li><a href="Urinary_bladder" class="mw-redirect" title="Urinary bladder">Intravesical infusion</a></li>

</div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="Rectal_(medicine)" class="mw-redirect" title="Rectal (medicine)">Rectal</a> (<a href="Enteral_administration" title="Enteral administration">enteral</a>)</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em">

<ul><li><a href="Topical" class="mw-redirect" title="Topical">Ointment</a></li>

<li><a href="Suppository" title="Suppository">Suppository</a></li>

<li><a href="Enema" title="Enema">Enema</a>

<ul><li><a href="Solution_(chemistry)" title="Solution (chemistry)">Solution</a></li>

<li><a href="Hydrogel" title="Hydrogel">Hydrogel</a></li></ul></li>

<li><a href="Murphy_drip" title="Murphy drip">Murphy drip</a></li>

<li><a href="Nutrient_enema" title="Nutrient enema">Nutrient enema</a></li></ul></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="Dermis" title="Dermis">Dermal</a> (<a href="Topical_medication" title="Topical medication">topical</a>)</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em">

<li><a href="Topical" class="mw-redirect" title="Topical">Ointment</a></li>

<li><a href="Topical_cream" class="mw-redirect" title="Topical cream">Topical cream</a></li>

<li><a href="Topical_gel" class="mw-redirect" title="Topical gel">Topical gel</a></li>

<li><a href="Liniment" title="Liniment">Liniment</a></li>

<li><a href="Paste_(rheology)" title="Paste (rheology)">Paste</a></li>

<li><a href="Dimethyl_sulfoxide" title="Dimethyl sulfoxide">DMSO</a> solution</li>

<li><a href="Iontophoresis" title="Iontophoresis">Iontophoresis</a></li>

<li><a href="Hydrogel" title="Hydrogel">Hydrogel</a></li>

<li><a href="Liposome" title="Liposome">Liposomes</a></li>

<li><a href="Transfersome" title="Transfersome">Transfersome vesicles</a></li>

<li><a href="Cream_(pharmaceutical)" class="mw-redirect" title="Cream (pharmaceutical)">Cream</a></li>

<li><a href="Lotion" title="Lotion">Lotion</a></li>

<li><a href="Shampoo" title="Shampoo">Medicated shampoo</a></li>

<li><a href="Dermal_patch" title="Dermal patch">Dermal patch</a></li>

<li><a href="Transdermal_patch" title="Transdermal patch">Transdermal patch</a></li>

<li><a href="Transdermal_spray" title="Transdermal spray">Transdermal spray</a></li>

<li><a href="Jet_injector" title="Jet injector">Jet injector</a></li></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><div style="display: inline-block; line-height: 1.2em; padding: .1em 0;"><div class="plainlist"><ul><li><a href="Parenteral" class="mw-redirect" title="Parenteral">Parenterals</a></li><li><a href="Injection_(medicine)" title="Injection (medicine)">Injections</a></li><li><a href="Infusion_pump" title="Infusion pump">infusions</a></li></ul></div><br><small><i>(into tissue/blood)</i></small></div></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:10em;white-space:normal;"><a href="Human_skin" title="Human skin">Skin</a> (<a href="Transdermal" title="Transdermal">transdermal</a>)</th><td class="navbox-list-with-group navbox-list navbox-even" style="padding:0"><div style="padding:0 0.25em">

<li><a href="Intradermal_injection" title="Intradermal injection">Intradermal</a></li>

<li><a href="Subcutaneous_injection" class="mw-redirect" title="Subcutaneous injection">Subcutaneous</a>

<ul><li><a href="Injector_pen" title="Injector pen">Injector pen</a></li></ul></li>

<li><a href="Transdermal_implant" title="Transdermal implant">Transdermal implant</a></li>

</div></td><td class="noviewer navbox-image" rowspan="4" style="width:1px;padding:0 0 0 2px"><div><span typeof="mw:File"></span></div></td></tr><tr><th scope="row" class="navbox-group" style="width:10em;white-space:normal;"><a href="Human_anatomy#Major_organ_systems" title="Human anatomy">Organs</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="padding:0"><div style="padding:0 0.25em">

<ul><li><a href="Intracavernous_injection" title="Intracavernous injection">Intracavernous</a></li>

<li><a href="Intravitreal_administration" title="Intravitreal administration">Intravitreal</a></li>

<li><a href="Intra-articular_injection" class="mw-redirect" title="Intra-articular injection">Intra-articular</a></li></ul>

</div></td></tr><tr><th scope="row" class="navbox-group" style="width:10em;white-space:normal;"><a href="Central_nervous_system" title="Central nervous system">Central nervous system</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="padding:0"><div style="padding:0 0.25em">

<ul><li>Intracerebral</li>

<li><a href="Intrathecal_administration" title="Intrathecal administration">Intrathecal</a></li>

<li><a href="Epidural_administration" title="Epidural administration">Epidural</a></li></ul>

</div></td></tr><tr><th scope="row" class="navbox-group" style="width:10em;white-space:normal;"><a href="Circulatory_system" title="Circulatory system">Circulatory</a>,<br><a href="Human_musculoskeletal_system" title="Human musculoskeletal system">musculoskeletal</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="padding:0"><div style="padding:0 0.25em">

<ul><li><a href="Intravenous" class="mw-redirect" title="Intravenous">Intravenous</a></li>

<li><a href="Intracardiac_injection" title="Intracardiac injection">Intracardiac</a></li>

<li><a href="Intramuscular_injection" title="Intramuscular injection">Intramuscular</a></li>

<li><a href="Intraosseous_infusion" title="Intraosseous infusion">Intraosseous</a></li>

<li><a href="Intraperitoneal_injection" title="Intraperitoneal injection">Intraperitoneal</a></li>

<li><a href="Nanocell" title="Nanocell">Nanocell injection</a></li>

<li><a href="Patient-controlled_analgesia" title="Patient-controlled analgesia">Patient-controlled analgesia</a> pump</li>

</div></td></tr></tbody></table><div></div></td></tr></tbody></table></div></div><div><div class="zim-footer">

This article is issued from <a class="external text" title="Last edited on 2025-07-28" href="https://en.wikipedia.org/wiki/?title=Modified-release_dosage&oldid=1303004093">Wikipedia</a>. The text is available under <a class="external text" href="https://creativecommons.org/licenses/by-sa/4.0/deed.en">Creative Commons Attribution-Share Alike 4.0</a> unless otherwise noted. Additional terms may apply for the media files.

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