Drug loading and release properties of ion-exchange resin complexes as a drug delivery matrix

Since the advent of ion exchange resin, it has been widely used in many fields, including drug delivery systems. The drug binds to the resin through an exchange reaction to form a drug–resin complex, which can gradually release drugs through the exchange of physiological ions in the gastrointestinal tract, to realize functions such as taste masking and regulating release. In this study, the complexes of methylphenidate hydrochloride and Amberlite IRP69 were prepared and evaluated to explore the mechanism of complexation, influencing factors and release mechanism at a molecular level. Firstly, with the properties of the selected complexes, molecular dynamics simulation was innovatively used to find that the intermolecular interaction between drug molecules and ion exchange resin molecules is mainly caused by the stacking effect of π and salt bridges. Secondly, with the drug loading status as an indicator, the factors affecting the compounding process of the drug and resin were explored. Finally, the release mechanism of the drug–resin complex was studied by mathematical model fitting. In summary, a variety of methods were used to study the mechanism of complexation and release between drug and resin, providing a theoretical basis for promoting the marketing of ion−exchange resin−mediated oral preparations.

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31 A Modified-Release Drug Delivery Technology Containing Amphetamine-Ion Exchange Complexes

CNS Spectrums ◽

10.1017/s1092852919000257 ◽

2019 ◽

Vol 24 (1) ◽

pp. 191-191 ◽

Cited By ~ 1

Author(s):

Barry K. Herman ◽

Thomas R. King ◽

Judith C. Kando ◽

Antonio Pardo

Keyword(s):

Drug Delivery ◽

Ion Exchange ◽

Extended Release ◽

Active Drug ◽

Exchange Resin ◽

Drug Product ◽

Immediate Release ◽

Ion Exchange Resin ◽

Post Dose ◽

Chewable Tablet

AbstractThe proprietary, immediate and extended drug delivery technologyLiquiXR® utilizes an ion-exchange resin that complexes with amphetamine or any active moiety that can be protonated and is water-soluble. The active ingredient of the drug product forms a complex with an ion exchange polymer of the resin resulting in micron-sized particles. A portion of these particles is then coated with an aqueous, pH-independent polymer designed to provide sustained release of drug product. The polymer coating applied to the ion-exchange resin particles is of varying thickness, allowing for extended release of active drug while uncoated particles provide for immediate release of drug.The micron-sized particles lend themselves to being formulated into an appropriate dosage form: solid/chewable tablet, liquid suspension, orally disintegrating tablet, film, or capsules. Active ingredient of drug product is subsequently released from the dosage form in millions of particles, with release driven by a combination of ion exchange and diffusion. After drug release, the ion-exchange resin particles are excreted in the feces.The release characteristics of LiquiXR allow for customized, sustained release of active drug ∼24hours post dose. Mechanistically, drug particles enter the gastrointestinal (GI) tract. As positively-charged ions from GI fluids diffuse across the coating, it displaces drug ions from product and they diffuse through the coating and into the GI fluids for absorption. As the coating is of variable thickness, some drug product takes longer to diffuse and absorb, providing for the delayed drug release characteristics.The LiquiXR drug delivery technology has already been successfully utilized in the development of treatment options (liquid suspension and chewable tablet) that offer rapid absorption and sustained plasma levels after once-daily dosing. LiquiXR is utilized in Dyanavel® XR (amphetamine extended-release oral suspension; AMPH EROS), which is indicated for treatment of ADHD. It comprises 2.5mg/mL amphetamine base and uses LiquiXR technology to provide an immediate release component followed by an extended-release profile.Efficacy of AMPH EROS was established in children 6 to 12 yr in a Phase 3, placebo-controlled laboratory classroom study. In that study, ADHD symptoms in children on an individually optimized dose of amphetamine (range 10–20mg/day) were statistically significantly improved compared with symptoms in children treated with placebo. For children treated with AMPH EROS, onset of effect was demonstrated at 1hour after dosing, and efficacy was observed through 13hr post-dose. The effect size (ES) was comparable to ES demonstrated for other psychostimulants tested in studies using a similar design. The efficacy data reported for AMPH EROS provides an excellent example of the potential utility and clinical application for other active drug products requiring an immediate and extended release profile.Funding Acknowledgements: Support provided by Tris Pharma, Inc.

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Ion-Exchange Resins as Controlled Drug Delivery Carriers

Journal of Scientific Research ◽

10.3329/jsr.v2i3.4991 ◽

2010 ◽

Vol 2 (3) ◽

pp. 597 ◽

Cited By ~ 28

Author(s):

M. V. Srikanth ◽

S. A. Sunil ◽

N. S. Rao ◽

M. U. Uhumwangho ◽

K. V. Ramana Murthy

Keyword(s):

Drug Delivery ◽

Ion Exchange ◽

Exchange Resin ◽

Cation Exchange Resin ◽

Controlled Drug Delivery ◽

Ion Exchange Resin ◽

Ion Exchange Resins ◽

Exchange Cation ◽

Therapeutic Applications ◽

Exchange Resins

Ion exchange resins (IER) are insoluble polymers that contain acidic or basic functional groups and have the ability to exchange counter-ions within aqueous solutions surrounding them. Based on the nature of the exchangeable ion of the resin as a cation or anion, it is classified as cationic or anionic exchange resins, respectively. The efficacy of ion exchange resins mainly depends upon their physical properties such as degree of cross-linking, porosity, acid base strength, stability, purity and particle size. Modified release of drugs from resinate (drug-resin complexes) is another potential application of ion exchange resins. Due to the versatile utility of ion exchange resins, they are being used for various drug delivery and therapeutic applications. Resins used are polymers that contain appropriately substituted acidic groups, such as carboxylic and sulfonic for cation exchangers; or basic groups, such as quaternary ammonium group for anion exchangers. This review addresses different types of ion exchange resin, their properties, the chemistry; role of IER in controlled drug delivery systems, its therapeutic applications, methods of preparation of IER along with their resonates. Keywords: Anion exchange; Cation exchange; Resin; Controlled release; Resinates; Drug delivery. © 2010 JSR Publications. ISSN: 2070-0237 (Print); 2070-0245 (Online). All rights reserved. DOI: 10.3329/jsr.v2i3.4991 J. Sci. Res. 2 (3), 599-613 (2010)

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Sustained-Release Drug Delivery System I: Coated Ion-Exchange Resin System for Phenylpropanolamine and Other Drugs

Journal of Pharmaceutical Sciences ◽

10.1002/jps.2600700409 ◽

1981 ◽

Vol 70 (4) ◽

pp. 379-384 ◽

Cited By ~ 87

Author(s):

Y. Raghunathanx ◽

L. Amsel ◽

O. Hinsvark ◽

W. Bryant

Keyword(s):

Drug Delivery ◽

Ion Exchange ◽

Sustained Release ◽

Drug Delivery System ◽

Delivery System ◽

Exchange Resin ◽

Ion Exchange Resin ◽

Resin System ◽

Release Drug

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Formulation of Dextromethorphan Oral Disintegrating Tablet Using Ion Exchange Resin

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.201-203.1384 ◽

2011 ◽

Vol 201-203 ◽

pp. 1384-1387

Author(s):

Wipada Samprasit ◽

Praneet Opanasopit ◽

Prasert Akkaramongkolporn ◽

Tanasait Ngawhirunpat ◽

Kaewnapa Wongsermsin ◽

...

Keyword(s):

Ion Exchange ◽

Drug Release ◽

Bitter Taste ◽

Exchange Resin ◽

Drug Loading ◽

Ion Exchange Resin ◽

Physical Mixture ◽

Disintegration Time ◽

Mouth Feel ◽

Tablet Hardness

The purpose of this research was to mask the bitter taste of dextromethorphan hydrobromide using a cationic ion exchange resin, Amberlite® IRP-69, to formulate oral disintegrating tablets (ODTs). The drug was loaded (resinate) were prepared in drug to resin ratio of 1:1 and 1:2. The resinate or physically mixed with the resin (physical mixture) was incorporated into ODTs by direct compression. The formula was developed to acquire the optimal formulations of taste masked ODTs, hardness and mouth feel and disintegration time. The ODTs were further evaluated for weight, friability, disintegration time, drug content, degree of bitter taste and drug release, respectively. The weight and friability of the tablet with resinate were not significantly different from those with physical mixture. The tablet with resinate had a lower tablet hardness due to drug loading might be reduced compressibility. The addition of Avicel®PH102 could be increased tablet hardness. Both ODTs with resinate and physical mixture provided a sustained pattern of drug release. However, only ODTs with resinate successfully masked bitter taste of the drug. In conclusion, the loaded drug in ion exchange resin as resinate could increase the palatability and acceptability of ODTs containing bitter drugs.

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89 A Novel, Modified-Release Drug Delivery Technology Containing Amphetamine-Ion Exchange Complexes

CNS Spectrums ◽

10.1017/s1092852919000671 ◽

2019 ◽

Vol 24 (1) ◽

pp. 220-220

Author(s):

Barry K. Herman ◽

Thomas R. King ◽

Judith C. Kando ◽

Antonio Pardo

Keyword(s):

Drug Delivery ◽

Ion Exchange ◽

Extended Release ◽

Active Drug ◽

Exchange Resin ◽

Drug Product ◽

Immediate Release ◽

Ion Exchange Resin ◽

Post Dose ◽

Delivery Technology

AbstractThe proprietary immediate and extended drug delivery technology LiquiXR™ utilizes an ion-exchange resin that complexes with amphetamine or any other active moiety that can be protonated and is water-soluble. The active drug product forms a complex with ion-exchange polymers contained in the resin, which is then formed into micron-sized particles. Some of these particles are coated with an aqueous, pH-independent polymer designed to provide immediate or sustained release of active drug product. The polymer coating applied to the ion-exchange resin particles is of varying thickness, allowing for programmed, extended release of active drug product. Solid, coating-free particles provide for immediate release of active drug product.The micron-sized particles are formulated into an appropriate dosage form (solid or chewable tablet, liquid suspension, orally disintegrating tablet, film, or capsules). Active drug product is subsequently released from the dosage form in millions of particles, with the release driven by a combination of ion exchange and diffusion. After drug release, the ion-exchange resin is excreted in the feces.The release characteristics of LiquiXR™ are programmable and allow for a customized, sustained release of active drug product for up to 24hours post-dose. Mechanistically, drug particles enter the gastrointestinal tract. As positively-charged ions from gastrointestinal (GI) fluids diffuse across the coating, ionically-charged drug product diffuses through the coating and into the GI fluids for absorption. As the coating is of variable thickness, some drug product takes longer to diffuse and absorb, providing for the programmable delayed drug release characteristic.The LiquiXR™ drug delivery technology is utilized in Dyanavel® XR (amphetamine extended-release oral suspension; AMPH EROS), which is indicated for the treatment of attention-deficit hyperactivity disorder. It comprises 2.5mg/mL amphetamine base complexed with LiquiXR technology to provide an immediate release component followed by an extended-release profile. The efficacy of AMPH EROS was established in children ages 6 to 12 years in a Phase 3, placebo-controlled laboratory classroom study. In that study, attention-deficit/hyperactivity disorder (ADHD) symptoms in children on an individually optimized dose of amphetamine (range 10–20mg/day) were statistically significantly improved compared with symptoms in children treated with placebo. For children treated with AMPH EROS, onset of effect was demonstrated at 1hour after dosing, and efficacy was observed through 13hours post-dose. The effect size was comparable to effect sizes demonstrated for other psychostimulants tested in studies using a similar design. The efficacy data reported for AMPH EROS provides an excellent example of the potential utility and clinical application for other active drug products requiring an immediate release and extended release profile.Funding Acknowledgements: This work was funded by Tris Pharma, Inc.

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Development and Evaluation of Sustained Release Tablet of Betahistine Hydrochloride Using Ion Exchange Resin Tulsion T344

ISRN Pharmaceutics ◽

10.5402/2012/438342 ◽

2012 ◽

Vol 2012 ◽

pp. 1-5

Author(s):

Vijay D. Wagh ◽

Nilesh Pawar

Keyword(s):

Ion Exchange ◽

Sustained Release ◽

Exchange Resin ◽

Mixing Time ◽

Drug Loading ◽

Cation Exchange Resin ◽

Ion Exchange Resin ◽

Activation Effect ◽

Weight Variation

An attempt was made to sustain the release of Betahistine hydrochloride by complexation technique using strong cation-exchange resin, Tulsion T344. The drug loading onto ion-exchange resin was optimized for mixing time, activation, effect of pH, swelling time, ratio of drug : resin, and temperature. The resinate was evaluated for micromeritic properties and characterized using XRPD and IR. For resinate sustained release tablets were formulated using hydoxypropyl methylcellulose K100M. The tablets were evaluated for hardness, thickness, friability, drug content, weight variation, and in vitro drug release. Tablets thus formulated (Batch T-3) provided sustained release of drug over a period of 12 h. The release of Betahistine HCl from resinate controls the diffusion of drug molecules through the polymeric material into aqueous medium. Results showed that Betahistine HCl was formulated into a sustained dosage form as an alternative to the conventional tablet.

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