View source for Medicine:Modified-release dosage

{{short description|Mechanism that delivers a drug with a delay after its administration}}
'''Modified-release dosage''' is a mechanism that (in contrast to immediate-release [[Chemistry:Dose (biochemistry)|dosage]]) delivers a drug with a delay after its [[Medicine:Route of administration|administration]] (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).<ref name=pharm>[http://www.pharmpress.com/files/docs/ft_pharmaceutics_drug_delivery_sample.pdf Pharmaceutics: Drug Delivery and Targeting], p. 7-13</ref>

'''Sustained-release dosage forms''' are [[Medicine:Dosage form|dosage form]]s designed to [[Medicine:Liberation (pharmacology)|release (liberate) a drug]] at a predetermined rate in order to maintain a constant drug concentration for a specific period of time with minimum [[Medicine:Side effect|side effect]]s. This can be achieved through a variety of formulations, including [[Biology:Liposome|liposome]]s and drug-polymer conjugates (an example being [[Chemistry:Hydrogel|hydrogel]]s). Sustained release's definition is more akin to a "controlled release" rather than "sustained".

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.<ref name=pharm/>

Sometimes these and other terms are treated as synonyms, but the United States [[Organization:Food and Drug Administration|Food and Drug Administration]] has in fact defined most of these as different concepts.<ref name=pharm/> Sometimes the term "depot tablet" is used, by analogy to the term for an [[Medicine:Depot injection|injection formulation of a drug which releases slowly over time]], but this term is not medically or pharmaceutically standard for oral medication.

Modified-release dosage and its variants are mechanisms used in [[Medicine:Tablet (pharmacy)|tablet]]s (pills) and [[Medicine:Capsule (pharmacy)|capsules]] to [[Chemistry:Solvation|dissolve]] a drug 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 [[Chemistry:Extended-release morphine|extended-release morphine]] can enable certain chronic pain patients to take only {{nowrap|1{{ndash}}2}} tablets per day, rather than needing to redose every {{nowrap|4{{ndash}}6{{nbs}}hours}} as is typical with standard-release morphine tablets.

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 therapeutic window to avoid potentially hazardous peaks in drug concentration following ingestion or injection and to maximize therapeutic efficiency.

In addition to pills, the mechanism can also apply to 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 [[Medicine:Vaginal ring|vaginal ring]] and [[Medicine:Contraceptive implant|contraceptive implant]]) and transdermal patches.

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

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 ''Journal of Controlled Release'' and ''Drug Delivery and Translational Research'' scientific journals.

==List of abbreviations==

There is no industry standard for these abbreviations, and confusion and misreading have sometimes caused prescribing errors.<ref>{{Citation |author=Pennsylvania Patient Safety Authority |date=December 2004 |title=Drug name suffix confusion is a common source of errors |journal=PA PSRS Patient Saf Advis |volume=1 |issue=4 |pages=17–18 |url=http://patientsafetyauthority.org/ADVISORIES/AdvisoryLibrary/2004/dec1(4)/Pages/17.aspx# |postscript=. |url-status=dead |archive-url=https://web.archive.org/web/20130724105938/http://patientsafetyauthority.org/ADVISORIES/AdvisoryLibrary/2004/dec1(4)/Pages/17.aspx |archive-date=2013-07-24 }}</ref> Clear handwriting is necessary. For some drugs with multiple formulations, putting the meaning in parentheses is advisable.

{| class="wikitable sortable" border="1"
! Abbreviation !! Meaning !! Notes 
|-
| CD || Controlled Delivery || 
|-
| CR || Controlled Release || 
|-
| CC || Continuous Control, Constant Control ||
|-
| DR || Delayed Release || 
|-
| ER || Extended Release || 
|-
| IR || Immediate Release || 
|-
| ID || Initial Depot ||
|-
| LA || Long-Acting || 
|-
| LAR || Long-Acting Release || 
|-
| MR || Modified Release || 
|-
| PR || Prolonged Release || 
|-
| SA || Sustained Action || Ambiguous, can sometimes mean Short-Acting 
|-
| SR || Sustained Release || 
|-
| TR || Timed Release || 
|-
| XL || Extra Long|| 
|-
| XR || Extended/Extra Release || 
|-
| XT || Extended/Extra Time|| 
|-
| LS || Lesser/Lower Strength ||
|-
| DS || Double Strength ||
|-
| DA || Double Action ||
|-
| ES || Extra Strength ||
|-
| XS || Extra Strength ||
|-
|}

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 ''ES'' and ''XS'' (Extra Strength).

==Methods==

Today, most time-release drugs are formulated so that the [[Medicine:Active ingredient|active ingredient]] is embedded in a matrix of insoluble substance(s) (various: some acrylics, even [[Chemistry:Chitin|chitin]]; these substances are often patented) such that the dissolving drug must find its way out through the holes.

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.

[[Chemistry:Micro-encapsulation|Micro-encapsulation]] 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 [[Medicine:Capsule (pharmacy)|capsule]].

There are certain considerations for the formation of sustained-release formulation:
* 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.
* If the absorption of the active compound involves an [[Biology:Active transport|active transport]], the development of a time-release product may be problematic.

The [[Biology:Biological half-life|biological half-life]] 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.<ref name="pharmatutor">Lilesh Khalane, Atulal Kunte, and Arunadevi Blrajdar. Sustained Release Drug Delivery System: A Concise Review. Pharmatutor: pharmacy infopedia. 2016. Accessed: May 30, 2016.</ref> 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.<ref>Sampath Kumar, Debjit Bhowmik, Shweta Srivastava, Shravan Paswan, and A. Dutta. Sustained. Release Drug Delivery System Potential. The Pharma Innovation.  2012. Accessed: May 30, 2016.</ref><ref>Kapil Patil, Prashant Patil , Javesh Patil , and Sunil Pawar. A Basic Approach on Sustained Release Drug Delivery System.  American Journal of PharmTech Research. 2011. Accessed: May 30, 2016.</ref>

The [[Medicine:Therapeutic index|therapeutic index]] 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 [[Medicine:Dose dumping|dose dumping]] which can prove fatal at the conditions mentioned.<ref name="overview">Ratnaparkhi P. and Gupta P. Sustained Release Oral Drug Delivery System – An Overview. International Journal of Pharma Research & Review. 2013. Accessed: May 30, 2016.</ref> For a drug that is made to be released over time, the objective is to stay within the therapeutic range as long as needed.<ref name="pharmatutor" />

There are many different methods used to obtain a sustained release.

===Diffusion systems===

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.<ref name="pharmatutor" />
*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.<ref name="pharmatutor" /> 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.<ref name="Navin" /><ref name="Perrie">Perrie, Y., & Rades, T. Pharmaceutics: Drug delivery and targeting. London: Pharmaceutical Press. Accessed: May 30, 2016.</ref> 
*Matrix devices forms a matrix (drug(s) mixed with a gelling agent)<ref>Tarun Parashar, Soniya, Vishal Singh, Gaurav Singh, Satyanand Tyagi, Chirag Patel, and Anil Gupta. International Journal of Research and Development in Pharmacy and Life Sciences. Novel Oral Sustained Release Technology: A Concise Review. 2013. Accessed: May 30, 2016.</ref> where the drug is dissolved/dispersed.<ref name="Perrie" /> 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.<ref name="Navin" /> 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.<ref name="overview" />

===Dissolution systems===

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.<ref name="pharmatutor" /> It is used for drug compounds with high solubility in water.<ref name="overview" /> 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.<ref name="pharmatutor" /> Dissolution systems can be broken down to subcategories called reservoir devices and matrix devices.<ref name="overview" />
*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.<ref name="overview" />
*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.<ref name="overview" />

===Osmotic systems===
[[File:Concerta 54mg OROS.png|thumb|right|A 54mg tablet of Concerta, which uses OROS technology.]]
Osmotic controlled-release oral delivery systems (OROS) have the form of a rigid [[Medicine:Tablet (pharmacy)|tablet]] with a semi-permeable outer membrane and one or more small [[Engineering:Laser drilling|laser drilled]] holes in it. As the tablet [[Medicine:Route of administration#Gastrointestinal/enteral|passes through the body]], water is absorbed through the [[Physics:Semipermeable membrane|semipermeable membrane]] via [[Physics:Osmosis|osmosis]], and the resulting [[Biology:Osmotic pressure|osmotic pressure]] is used to push the active drug through the opening(s) in the tablet. OROS is a trademarked name owned by ALZA Corporation, which pioneered the use of osmotic pumps for oral drug delivery.<ref name=pmid19602438>{{cite journal|last1=Malaterre|first1=V|last2=Ogorka|first2=J|last3=Loggia|first3=N|last4=Gurny|first4=R|title=Oral osmotically driven systems: 30 years of development and clinical use.|journal=European Journal of Pharmaceutics and Biopharmaceutics|date=November 2009|volume=73|issue=3|pages=311–23|doi=10.1016/j.ejpb.2009.07.002|pmid=19602438}}</ref><ref name=pmid2006800>{{cite journal|last1=Theeuwes|first1=F|last2=Yum|first2=SI|last3=Haak|first3=R|last4=Wong|first4=P|title=Systems for triggered, pulsed, and programmed drug delivery.|journal=Annals of the New York Academy of Sciences|date=1991|volume=618|issue=1|pages=428–40|doi=10.1111/j.1749-6632.1991.tb27262.x|pmid=2006800|bibcode=1991NYASA.618..428T|s2cid=31442663}}</ref><ref name=pmid17022845>{{cite journal|last1=Conley|first1=R|last2=Gupta|first2=SK|last3=Sathyan|first3=G|title=Clinical spectrum of the osmotic-controlled release oral delivery system (OROS), an advanced oral delivery form.|journal=Current Medical Research and Opinion|date=October 2006|volume=22|issue=10|pages=1879–92|pmid=17022845|doi=10.1185/030079906x132613|s2cid=42490425}}</ref>

Osmotic release systems have a number of major advantages over other controlled-release mechanisms. They are significantly less affected by factors such as [[Chemistry:PH|pH]], food intake, GI motility, 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 [[Medicine:Pharmacokinetics|pharmacokinetics]]. 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.<ref name=pmid19602438 /><ref name=pmid21486532>{{cite journal|last1=Gupta|first1=BP|last2=Thakur|first2=N|last3=Jain|first3=NP|last4=Banweer|first4=J|last5=Jain|first5=S|title=Osmotically controlled drug delivery system with associated drugs.|journal=Journal of Pharmacy & Pharmaceutical Sciences |date=2010|volume=13|issue=4|pages=571–88|pmid=21486532|doi=10.18433/j38w25|doi-access=free}}</ref><ref name=pmid10872087>{{cite journal|last1=Verma|first1=RK|last2=Mishra|first2=B|last3=Garg|first3=S|title=Osmotically controlled oral drug delivery.|journal=Drug Development and Industrial Pharmacy|date=July 2000|volume=26|issue=7|pages=695–708|pmid=10872087|doi=10.1081/ddc-100101287|s2cid=35670161}}</ref><ref name=pmid2257873>{{cite journal|last1=van den Berg|first1=G|last2=van Steveninck|first2=F|last3=Gubbens-Stibbe|first3=JM|last4=Schoemaker|first4=HC|last5=de Boer|first5=AG|last6=Cohen|first6=AF|title=Influence of food on the bioavailability of metoprolol from an OROS system; a study in healthy volunteers.|journal=European Journal of Clinical Pharmacology|date=1990|volume=39|issue=3|pages=315–6|pmid=2257873|doi=10.1007/bf00315121|s2cid=1838636}}</ref><ref name=pmid12408733>{{cite journal|last1=Bass|first1=DM|last2=Prevo|first2=M|last3=Waxman|first3=DS|title=Gastrointestinal safety of an extended-release, nondeformable, oral dosage form (OROS: a retrospective study.|journal=Drug Safety|date=2002|volume=25|issue=14|pages=1021–33|pmid=12408733|doi=10.2165/00002018-200225140-00004|s2cid=35424637}}</ref><ref name=pmid11038435>{{cite journal|last1=Modi|first1=NB|last2=Wang|first2=B|last3=Hu|first3=WT|last4=Gupta|first4=SK|title=Effect of food on the pharmacokinetics of osmotic controlled-release methylphenidate HCl in healthy subjects.|journal=Biopharmaceutics & Drug Disposition|date=January 2000|volume=21|issue=1|pages=23–31|pmid=11038435|doi=10.1002/1099-081x(200001)21:1<23::aid-bdd212>3.0.co;2-v|s2cid=33413277 }}</ref><ref name=pmid12240794>{{cite journal|last1=Auiler|first1=JF|last2=Liu|first2=K|last3=Lynch|first3=JM|last4=Gelotte|first4=CK|title=Effect of food on early drug exposure from extended-release stimulants: results from the Concerta, Adderall XR Food Evaluation (CAFE) Study.|journal=Current Medical Research and Opinion|date=2002|volume=18|issue=5|pages=311–6|pmid=12240794|doi=10.1185/030079902125000840|s2cid=25994524}}</ref>

===Ion-exchange resin===
{{main|Chemistry:Ion-exchange resin}}
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.<ref name="pharmatutor" /><ref name="overview" /> 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.<ref name="overview" />

===Floating systems===

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 [[Physics:Buoyancy|buoyancy]] 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.<ref name="pharmatutor" /> Many types of forms of drugs use this method such as powders, capsules, and tablets.<ref name="Dusane">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.</ref>

===Bio-adhesive systems===

[[Chemistry:Bioadhesive|Bio-adhesive]] 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.<ref name="pharmatutor" />

===Matrix systems===

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.<ref name="pharmatutor" />
*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.<ref name="pharmatutor" />
*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.<ref name="pharmatutor" /> 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.<ref>Jaimini Manish and Kothari Abhay. Sustained Release Matrix Type Drug Delivery System: A Review. Journal of Drug Delivery & Therapeutics. 2012. Accessed: May 30, 2016.</ref>
*A lipid matrix uses wax or similar materials. Drug release happens through diffusion through, and erosion of, the wax and tends to be sensitive to digestive fluids.<ref name="pharmatutor" />
*Biodegradable matrices are made with unstable, linked monomers that will erode by biological compounds such as enzymes and proteins.<ref name="pharmatutor" />
*A mineral matrix which generally means the polymers used are obtained in seaweed.<ref name="pharmatutor" />

===Stimuli inducing release===
Examples of stimuli that may be used to bring about release include pH, enzymes, light, magnetic fields, temperature, ultrasonics, osmosis, cellular traction forces,<ref>{{Cite journal|last1=Stejskalová|first1=Anna|last2=Oliva|first2=Nuria|last3=England|first3=Frances J.|last4=Almquist|first4=Benjamin D.|title=Biologically Inspired, Cell-Selective Release of Aptamer-Trapped Growth Factors by Traction Forces|journal=Advanced Materials|language=en|issue=7|pages=1806380|doi=10.1002/adma.201806380|pmid=30614086|pmc=6375388|issn=1521-4095|year=2019|volume=31|bibcode=2019AdM....3106380S }}</ref> and electronic control of [[Engineering:MEMS|MEMS]]<ref name=Maloney>{{cite journal |vauthors=Maloney JM, Uhland S, Polito B, ((Sheppard NF Jr)), Pelta C, ((Santini JT Jr)) | year = 2005| title = Electrothermally activated microchips for implantable drug delivery and biosensing | url = http://john.maloney.org/Papers/Electrothermally_activated_microchips.pdf | journal = Journal of Controlled Release| volume = 109|  issue=1–3 |pages = 244–255| doi = 10.1016/j.jconrel.2005.09.035 | pmid = 16278032}}</ref> and [[Nanoelectromechanical systems|NEMS]].<ref>{{cite journal | pmc = 3002303 | pmid=21114841 | doi=10.1186/1754-1611-4-15 | volume=4 | title=Bioresponsive matrices in drug delivery | year=2010 | journal=J Biol Eng | pages=15 |vauthors=You JO, Almeda D, Ye GJ, Auguste DT | doi-access=free }}</ref>

Spherical hydrogels, in micro-size (50-600&nbsp;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.<ref>{{Cite journal|last1=Ahnfelt|first1=E.|last2=Gernandt|first2=J.|last3=Al-Tikriti|first3=Y.|last4=Sjögren|first4=E.|last5=Lennernäs|first5=H.|last6=Hansson|first6=P.|date=2018-12-28|title=Single bead investigation of a clinical drug delivery system – A novel release mechanism|journal=Journal of Controlled Release|volume=292|pages=235–247|doi=10.1016/j.jconrel.2018.11.011|pmid=30419268|issn=0168-3659|doi-access=free}}</ref>

== Pill splitting ==
[[Image:Split Bupropion XL shell Anchen.jpg|thumb|200px| Empty half-shell of a split [[Chemistry:Bupropion|bupropion]] XL 150mg manufactured by Anchen Pharmaceuticals that was soaked in water overnight and then shaken. ]]
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.<ref>{{cite web|url=http://www.netdoctor.co.uk/medicines/100004842.html|title=Equasym XL (methylphenidate)|date=24 May 2013|website=netdoctor.co.uk|access-date=16 August 2016|archive-url=https://web.archive.org/web/20111208120921/http://www.netdoctor.co.uk/medicines/100004842.html|archive-date=8 December 2011|url-status=dead}}</ref><ref>{{cite journal|last=Vranić|first=E|author2=Uzunović, A|title=Influence of splitting on dissolution properties of metoprolol tablets.|journal=Bosnian Journal of Basic Medical Sciences|date=August 2009|volume=9|issue=3|pages=245–9|pmid=19754482|pmc=5632511|doi=10.17305/bjbms.2009.2815}}</ref>

Among the [[Company:Health information technology|health information technology]] (HIT) that pharmacists use are medication safety tools to help manage this problem. For example, the ISMP "do not crush" list<ref name="ISMP_DoNotCrush">{{Citation |author=Institute for Safe Medication Practices (ISMP) |title=ISMP "do not crush" list: Oral dosage forms that should not be crushed |date=20 November 2017 |url=http://www.ismp.org/Tools/DoNotCrush.pdf }}</ref> 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.

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.

==History==
The earliest SR drugs are associated with a patent in 1938 by Israel Lipowski, who coated pellets which led to coating particles.<ref name="Navin">Navin Dixit, Sheo Dutt Maurya, and Bhanu Sagar. Sustained Release Drug Delivery System. Indian Journal of Research in Pharmacy and Biotechnology. 2013. Accessed: May 30, 2016.</ref> 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 was achieved following a single application to the soil. Delivery is usually effected by dissolution, degradation, or disintegration of an [[Chemistry:Excipient|excipient]] in which the active compound is formulated. [[Chemistry:Enteric coating|Enteric coating]] and other encapsulation technologies can further modify release profiles.

==See also==
*[[Medicine:Depot injection|Depot injection]]
*[[Medicine:Tablet (pharmacy)|Tablet (pharmacy)]]

==Footnotes ==
{{reflist}}

== External links ==
* [http://www.controlledreleasesociety.org/about/Pages/default.aspx Controlled Release Society]
* [http://www.ukicrs.org United Kingdom & Ireland Controlled Release Society]
* [http://web.mit.edu/professional/short-programs/courses/controlled_release_technology.html Controlled Release Technology] 5-day short course at MIT with Professor Robert Langer.
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{{DEFAULTSORT:Sustained Release Dosage Forms}}
[[Category:Dosage forms]]
[[Category:Routes of administration]]
[[Category:Drug delivery devices]]
[[Category:Pharmacokinetics]]

{{Sourceattribution|Modified-release dosage}}