Osmotic-controlled release oral delivery system

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A 54 mg 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 54 mg 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

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Stimulants are a class of drugs that increase the activity of the brain. They are used for various purposes, such as enhancing alertness, attention, motivation, cognition, mood, and physical performance. Some of the most common stimulants are caffeine, nicotine, amphetamines, cocaine, methylphenidate, and modafinil.

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

Pseudoephedrine, sold under the brand name Sudafed among others, is a sympathomimetic medication which is used as a decongestant to treat nasal congestion. It has also been used off-label for certain other indications, like treatment of low blood pressure. At higher doses, it may produce various additional effects, including psychostimulant, appetite suppressant, and performance-enhancing effects. In relation to this, non-medical use of pseudoephedrine has been encountered. The medication is taken by mouth.

<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. For ADHD, the effectiveness of methylphenidate is comparable to atomoxetine but modestly lower than amphetamines, alleviating the executive functioning deficits of sustained attention, inhibition, working memory, reaction time and emotional self-regulation.

<span class="mw-page-title-main">Atomoxetine</span> Medication used to treat ADHD

Atomoxetine, sold under the brand name Strattera, is a selective norepinephrine reuptake inhibitor medication used to treat attention deficit hyperactivity disorder (ADHD) and, to a lesser extent, cognitive disengagement syndrome. It may be used alone or along with psychostimulants. It enhances the executive functions of self-motivation, sustained attention, inhibition, working memory, reaction time and emotional self-regulation. Use of atomoxetine is only recommended for those who are at least six years old. It is taken orally. The effectiveness of atomoxetine is comparable to the commonly prescribed stimulant medication methylphenidate.

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

Alza Corporation was an American pharmaceutical and medical systems company.

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

Nifedipine, sold under the brand name 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 potent central nervous system (CNS) stimulant 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">Sympathomimetic drug</span> Substance that mimics effects of catecholamines

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<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.

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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.

Attention deficit hyperactivity disorder management options are evidence-based practices with established treatment efficacy for ADHD. Approaches that have been evaluated in the management of ADHD symptoms include FDA-approved pharmacologic treatment and other pharmaceutical agents, psychological or behavioral approaches, combined pharmacological and behavioral approaches, cognitive training, neurofeedback, neurostimulation, physical exercise, nutrition and supplements, integrative medicine, parent support, and school interventions. Based on two 2024 systematic reviews of the literature, FDA-approved medications and to a lesser extent psychosocial interventions have been shown to improve core ADHD symptoms compared to control groups.

<span class="mw-page-title-main">Ethylphenidate</span> Stimulant analog of methylphenidate

Ethylphenidate (EPH) is a central nervous system (CNS) stimulant and a close analog of methylphenidate.

<span class="mw-page-title-main">3,4-Dichloromethylphenidate</span> Stimulant drug

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

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References

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