Osmotic-controlled release oral delivery system

Last updated
A 54mg tablet of Concerta, which uses OROS technology. 22% of the drug is contained in the red overcoat, while the remaining 78% is split between two drug layers of differing concentration. The tablet uses an additional push layer that expands as water enters the tablet via the osmotic membrane. The drug is expelled via the laser-drilled hole visible on the left side of the tablet. Concerta 54mg OROS.png
A 54mg tablet of Concerta, which uses OROS technology. 22% of the drug is contained in the red overcoat, while the remaining 78% is split between two drug layers of differing concentration. The tablet uses an additional push layer that expands as water enters the tablet via the osmotic membrane. The drug is expelled via the laser-drilled hole visible on the left side of the tablet.

The osmotic-controlled release oral delivery system (OROS) is an advanced controlled release oral drug delivery system in the form of a rigid tablet with a semi-permeable outer membrane and one or more small laser drilled holes in it. As the tablet passes through the body, water is absorbed through the semipermeable membrane via osmosis, and the resulting osmotic pressure is used to push the active drug through the laser drilled opening(s) in the tablet and into the gastrointestinal tract. OROS is a trademarked name owned by ALZA Corporation, which pioneered the use of osmotic pumps for oral drug delivery. [1] [2] [3]

Contents

Rationale

Pros and cons

Osmotic release systems have a number of major advantages over other controlled-release mechanisms. They are significantly less affected by factors such as 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 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. [1] [4] [5] [6] [7] [8] [9]

Oral osmotic release systems

Single-layer

An illustration of the different components of the Elementary Osmotic Pump. Elementary Osmotic Pump diagram.png
An illustration of the different components of the Elementary Osmotic Pump.

The Elementary Osmotic Pump (EOP) was developed by ALZA in 1974, and was the first practical example of an osmotic pump based drug release system for oral use. [1] [2] [10] [11] [12] It was introduced to the market in the early 1980s in Osmosin (indomethacin) and Acutrim (phenylpropanolamine), but unexpectedly severe issues with GI irritation and cases of GI perforation led to the withdrawal of Osmosin. [1]

Merck & Co. later developed the Controlled-Porosity Osmotic Pump (CPOP) with the intention of addressing some of the issues that led to Osmosin's withdrawal via a new approach to the final stage of the release mechanism. [1] Unlike the EOP, the CPOP had no pre-formed hole in the outer shell for the drug to be expelled out of. Instead, the CPOP's semipermeable membrane was designed to form numerous small pores upon contact with water through which the drug would be expelled via osmotic pressure. The pores were formed via the use of a pH insensitive leachable or dissolvable additive such as sorbitol. [13]

Multi-layer

An illustration of the different components of the Push-Pull Osmotic Pump. Push-Pull Osmotic Pump diagram.png
An illustration of the different components of the Push-Pull Osmotic Pump.

Both the EOP and CPOP were relatively simple designs, and were limited by their inability to deliver poorly soluble drugs. [1] This led to the development of an additional internal "push layer" composed of material (a swellable polymer) that would expand as it absorbed water, which then pushed the drug layer (which incorporates a viscous polymer for suspension of poorly soluble drugs) out of the exit hole at a controlled rate. [1] [4] Osmotic agents such as sodium chloride, potassium chloride, or xylitol are added to both the drug and push layers to increase the osmotic pressure. [1] [4] [5] The initial design developed in 1982 by ALZA researchers was designated the Push-Pull Osmotic Pump (PPOP), and Procardia XL (nifedipine) was one of the first drugs to utilize this PPOP design. [1] [2]

An animation illustrating the exterior/interior compositions of a tablet of Concerta, a PSOP OROS design. Concerta OROS overcoat.gif
An animation illustrating the exterior/interior compositions of a tablet of Concerta, a PSOP OROS design.

In the early 1990s, an ALZA-funded research program began to develop a new dosage form of methylphenidate for the treatment of children with attention deficit hyperactivity disorder (ADHD). [14] Methylphenidate's short half-life required multiple doses to be administered each day to attain long-lasting coverage, which made it an ideal candidate for the OROS technology. Multiple candidate pharmacokinetic profiles were evaluated and tested in an attempt to determine the optimal way to deliver the drug, which was especially important given the puzzling failure of an existing extended-release formulation of methylphenidate (Ritalin SR) to act as expected. The zero-order (flat) release profile that the PPOP was optimal at delivering failed to maintain its efficacy over time, which suggested that acute tolerance to methylphenidate formed over the course of the day. This explained why Ritalin SR was inferior to twice-daily Ritalin IR, and led to the hypothesis that an ascending pattern of drug delivery was necessary to maintain clinical effect. Trials designed to test this hypothesis were successful, and ALZA subsequently developed a modified PPOP design that utilized an overcoat of methylphenidate designed to release immediately and rapidly raise serum levels, followed by 10 hours of first-order (ascending) drug delivery from the modified PPOP design. This design was called the Push-Stick Osmotic Pump (PSOP), and utilized two separate drug layers with different concentrations of methylphenidate in addition to the (now quite robust) push layer. [1] [14]

An illustration of the different inner components of a tablet of Concerta, a PSOP OROS design. Concerta OROS diagram.png
An illustration of the different inner components of a tablet of Concerta, a PSOP OROS design.

List of OROS medications

OROS medications include: [1] [3] [4] [7]

Related Research Articles

<span class="mw-page-title-main">Stimulant</span> Overarching term covers many drugs that increase activity of the central nervous system

Stimulants is an overarching term that covers many drugs including those that increase activity of the central nervous system and the body, drugs that are pleasurable and invigorating, or drugs that have sympathomimetic effects. Stimulants are widely used throughout the world as prescription medicines as well as without a prescription as performance-enhancing or recreational drugs. Among narcotics, stimulants produce a noticeable crash or comedown at the end of their effects. The most frequently prescribed stimulants as of 2013 were lisdexamfetamine (Vyvanse), methylphenidate (Ritalin), and amphetamine (Adderall). It was estimated in 2015 that the percentage of the world population that had used cocaine during a year was 0.4%. For the category "amphetamines and prescription stimulants" the value was 0.7%, and for MDMA 0.4%.

<span class="mw-page-title-main">Pseudoephedrine</span> Pharmaceutical drug

Pseudoephedrine (PSE) is a sympathomimetic drug of the phenethylamine and amphetamine chemical classes. It may be used as a nasal/sinus decongestant, as a stimulant, or as a wakefulness-promoting agent in higher doses.

<span class="mw-page-title-main">Medication</span> Substance used to diagnose, cure, treat, or prevent disease

A medication is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the medical field and relies on the science of pharmacology for continual advancement and on pharmacy for appropriate management.

<span class="mw-page-title-main">Methylphenidate</span> Central nervous system stimulant

Methylphenidate, sold under the brand names Ritalin and Concerta among others, is a central nervous system (CNS) stimulant used medically to treat attention deficit hyperactivity disorder (ADHD) and, to a lesser extent, narcolepsy. It is a primary medication for ADHD ; it may be taken by mouth or applied to the skin, and different formulations have varying durations of effect, commonly ranging from 2–4 hours. Methylphenidate's efficacy as a athletic performance enhancer, cognitive enhancer, aphrodisiac, and euphoriant is supported by research. However, the manner in which methylphenidate is used for these purposes can result in severe unintended side effects.

<span class="mw-page-title-main">Alza</span> Pharmaceutical and medical systems company

Alza Corporation was a pharmaceutical and medical systems company.

<span class="mw-page-title-main">Nifedipine</span> Calcium channel blocker medication

Nifedipine, sold under the brand name Adalat and Procardia, among others, is a calcium channel blocker medication used to manage angina, high blood pressure, Raynaud's phenomenon, and premature labor. It is one of the treatments of choice for Prinzmetal angina. It may be used to treat severe high blood pressure in pregnancy. Its use in preterm labor may allow more time for steroids to improve the baby's lung function and provide time for transfer of the mother to a well qualified medical facility before delivery. It is a calcium channel blocker of the dihydropyridine type. Nifedipine is taken by mouth and comes in fast- and slow-release formulations.

<span class="mw-page-title-main">Transdermal patch</span> Adhesive patch used to deliver medication through the skin

A transdermal patch is a medicated adhesive patch that is placed on the skin to deliver a specific dose of medication through the skin and into the bloodstream. An advantage of a transdermal drug delivery route over other types of medication delivery is that the patch provides a controlled release of the medication into the patient, usually through either a porous membrane covering a reservoir of medication or through body heat melting thin layers of medication embedded in the adhesive. The main disadvantage to transdermal delivery systems stems from the fact that the skin is a very effective barrier; as a result, only medications whose molecules are small enough to penetrate the skin can be delivered by this method. The first commercially available prescription patch was approved by the U.S. Food and Drug Administration in December 1979. These patches administered scopolamine for motion sickness.

<span class="mw-page-title-main">Dexmethylphenidate</span> CNS Stimulant

Dexmethylphenidate, sold under the brand name Focalin among others, is a strong central nervous system (CNS) stimulant medication used to treat attention deficit hyperactivity disorder (ADHD) in those over the age of five years. It is taken by mouth. The immediate release formulation lasts up to five hours while the extended release formulation lasts up to twelve hours. It is the more active enantiomer of methylphenidate.

<span class="mw-page-title-main">Atosiban</span> Chemical compound

Atosiban, sold under the brand name Tractocile among others, is an inhibitor of the hormones oxytocin and vasopressin. It is used as an intravenous medication as a labour repressant (tocolytic) to halt premature labor. It was developed by Ferring Pharmaceuticals in Sweden and first reported in the literature in 1985. Originally marketed by Ferring Pharmaceuticals, it is licensed in proprietary and generic forms for the delay of imminent preterm birth in pregnant adult women.

<span class="mw-page-title-main">Phenylephrine</span> Medication

Phenylephrine is a medication that is used as a nasal decongestant, used to dilate the pupil, used to increase blood pressure and used to relieve hemorrhoids or uncomplicated nasal congestion. It is a selective α1-adrenergic receptor agonist with minimal to no beta-adrenergic activity. It causes constriction of both arteries and veins. Phenylephrine can also be taken by mouth, given by injection into a vein or muscle, or applied to the skin.

<span class="mw-page-title-main">Armodafinil</span> Drug enhancing wakefulness

Armodafinil (trade name Nuvigil) is the enantiopure compound of the eugeroic modafinil (Provigil). It consists of only the (R)-(−)-enantiomer of the racemic modafinil. Armodafinil is produced by the pharmaceutical company Cephalon Inc. and was approved by the U.S. Food and Drug Administration (FDA) in June 2007. In 2016, the FDA granted Mylan rights for the first generic version of Cephalon's Nuvigil to be marketed in the U.S.

<span class="mw-page-title-main">Drug delivery</span> Methods for delivering drugs to target sites

Drug delivery refers to approaches, formulations, manufacturing techniques, storage systems, and technologies involved in transporting a pharmaceutical compound to its target site to achieve a desired therapeutic effect. Principles related to drug preparation, route of administration, site-specific targeting, metabolism, and toxicity are used to optimize efficacy and safety, and to improve patient convenience and compliance. Drug delivery is aimed at altering a drug's pharmacokinetics and specificity by formulating it with different excipients, drug carriers, and medical devices. There is additional emphasis on increasing the bioavailability and duration of action of a drug to improve therapeutic outcomes. Some research has also been focused on improving safety for the person administering the medication. For example, several types of microneedle patches have been developed for administering vaccines and other medications to reduce the risk of needlestick injury.

Modified-release dosage is a mechanism that delivers a drug with a delay after its administration or for a prolonged period of time or to a specific target in the body.

<span class="mw-page-title-main">Metopon</span> Chemical compound

Metopon (5-methylhydromorphone) is an opioid analogue that is a methylated derivative of hydromorphone which was invented in 1929 as an analgesic.

Attention deficit hyperactivity disorder management options are evidence-based practices with established treatment efficacy for ADHD.

<span class="mw-page-title-main">Thiomer</span>

Thiolated polymers – designated thiomers – are functional polymers used in biotechnology product development with the intention to prolong mucosal drug residence time and to enhance absorption of drugs. The name thiomer was coined by Andreas Bernkop-Schnürch in 2000. Thiomers have thiol bearing side chains. Sulfhydryl ligands of low molecular mass are covalently bound to a polymeric backbone consisting of mainly biodegradable polymers, such as chitosan, hyaluronic acid, cellulose derivatives, pullulan, starch, gelatin, polyacrylates, cyclodextrins, or silicones.

<span class="mw-page-title-main">Ethylphenidate</span> Chemical compound

Ethylphenidate (EPH), also known as Baxtercaine in the United Kingdom is a psychostimulant and a close analog of methylphenidate.

Buccal administration is a topical route of administration by which drugs held or applied in the buccal area diffuse through the oral mucosa and enter directly into the bloodstream. Buccal administration may provide better bioavailability of some drugs and a more rapid onset of action compared to oral administration because the medication does not pass through the digestive system and thereby avoids first pass metabolism.

<span class="mw-page-title-main">Ritalinic acid</span> Major metabolite of the psychostimulant drug methylphenidate

Ritalinic acid is a substituted phenethylamine and an inactive major metabolite of the psychostimulant drugs methylphenidate and ethylphenidate. When administered orally, methylphenidate is extensively metabolized in the liver by hydrolysis of the ester group yielding ritalinic acid. The hydrolysis was found to be catalyzed by carboxylesterase 1 (CES1).

References

  1. 1 2 3 4 5 6 7 8 9 10 11 Malaterre, V; Ogorka, J; Loggia, N; Gurny, R (November 2009). "Oral osmotically driven systems: 30 years of development and clinical use". European Journal of Pharmaceutics and Biopharmaceutics. 73 (3): 311–23. doi:10.1016/j.ejpb.2009.07.002. PMID   19602438.
  2. 1 2 3 Theeuwes, F; Yum, SI; Haak, R; Wong, P (1991). "Systems for triggered, pulsed, and programmed drug delivery". Annals of the New York Academy of Sciences. 618 (1): 428–40. Bibcode:1991NYASA.618..428T. doi:10.1111/j.1749-6632.1991.tb27262.x. PMID   2006800. S2CID   31442663.
  3. 1 2 Conley, R; Gupta, SK; Sathyan, G (October 2006). "Clinical spectrum of the osmotic-controlled release oral delivery system (OROS), an advanced oral delivery form". Current Medical Research and Opinion. 22 (10): 1879–92. doi:10.1185/030079906x132613. PMID   17022845. S2CID   42490425.
  4. 1 2 3 4 Gupta, BP; Thakur, N; Jain, NP; Banweer, J; Jain, S (2010). "Osmotically controlled drug delivery system with associated drugs". Journal of Pharmacy & Pharmaceutical Sciences. 13 (4): 571–88. doi: 10.18433/j38w25 . PMID   21486532.
  5. 1 2 Verma, RK; Mishra, B; Garg, S (July 2000). "Osmotically controlled oral drug delivery". Drug Development and Industrial Pharmacy. 26 (7): 695–708. doi:10.1081/ddc-100101287. PMID   10872087. S2CID   35670161.
  6. ↑ van den Berg, G; van Steveninck, F; Gubbens-Stibbe, JM; Schoemaker, HC; de Boer, AG; Cohen, AF (1990). "Influence of food on the bioavailability of metoprolol from an OROS system; a study in healthy volunteers". European Journal of Clinical Pharmacology. 39 (3): 315–6. doi:10.1007/bf00315121. PMID   2257873. S2CID   1838636.
  7. 1 2 Bass, DM; Prevo, M; Waxman, DS (2002). "Gastrointestinal safety of an extended-release, nondeformable, oral dosage form (OROS: a retrospective study". Drug Safety. 25 (14): 1021–33. doi:10.2165/00002018-200225140-00004. PMID   12408733. S2CID   35424637.
  8. ↑ Modi, NB; Wang, B; Hu, WT; Gupta, SK (January 2000). "Effect of food on the pharmacokinetics of osmotic controlled-release methylphenidate HCl in healthy subjects". Biopharmaceutics & Drug Disposition. 21 (1): 23–31. doi:10.1002/1099-081x(200001)21:1<23::aid-bdd212>3.0.co;2-v. PMID   11038435. S2CID   33413277.
  9. ↑ Auiler, JF; Liu, K; Lynch, JM; Gelotte, CK (2002). "Effect of food on early drug exposure from extended-release stimulants: results from the Concerta, Adderall XR Food Evaluation (CAFE) Study". Current Medical Research and Opinion. 18 (5): 311–6. doi:10.1185/030079902125000840. PMID   12240794. S2CID   25994524.
  10. ↑ Theeuwes, F (December 1975). "Elementary osmotic pump". Journal of Pharmaceutical Sciences. 64 (12): 1987–91. doi:10.1002/jps.2600641218. PMID   1510.
  11. ↑ Eckenhoff, B; Yum, SI (April 1981). "The osmotic pump: novel research tool for optimizing drug regimens". Biomaterials. 2 (2): 89–97. doi:10.1016/0142-9612(81)90005-3. PMID   7248427.
  12. ↑ Heimlich, KR (1983). "The evolution of precision drug delivery". Current Medical Research and Opinion. 8 Suppl 2: 28–37. doi:10.1185/03007998309109821. PMID   6851623.
  13. ↑ Haslam, John L.; Rork, Gerald S. "Controlled porosity osmotic pump". Google Patents. United States Patent and Trademark Office. Retrieved 19 March 2016.
  14. 1 2 Swanson, J; Gupta, S; Lam, A; Shoulson, I; Lerner, M; Modi, N; Lindemulder, E; Wigal, S (February 2003). "Development of a new once-a-day formulation of methylphenidate for the treatment of attention-deficit/hyperactivity disorder: proof-of-concept and proof-of-product studies". Archives of General Psychiatry. 60 (2): 204–11. doi: 10.1001/archpsyc.60.2.204 . PMID   12578439.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.