Controlled release of naltrexone pamoate from linear poly(ortho esters)

Maa, Y. F.; Heller, Jorge

doi:10.1016/0168-3659(90)90057-z

Cited by 30 publications

(7 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…12 Sustained-release kinetics of naltrexone are related to the implant/depot polymer composition, with a range currently being available such as a naltrexone-poly(lactic acid) composite, 13 70% naltrexone base in poly(L-lactic-co-glycolic acid), 14 naltrexone-copolymer (90% L-lactic acid and 10% glycolic acid) beads, 15 and a naltrexone pamoate linear poly (ortho esters) disk. 16 Although sustained-release preparations help overcome the noncompliance associated with daily medication, they only last for short periods and still incur significant levels of noncompliance. 8,17 Longer lasting sustained-release preparations might offer advantages for patients and the community.…”

Section: Naltrexonementioning

confidence: 99%

“…Injectable depot formulations include Depotrex® (192 or 384 mg naltrexone), which antagonizes the effects of intravenously administered heroin (0–25 mg) for 3–5 weeks,6 although Vivitrol® (formally known as Vivitrex) produces peak naltrexone–plasma levels within 3 days, which drop to an undetectable level (≤1 ng/mL) by 35 days 12. Sustained‐release kinetics of naltrexone are related to the implant/depot polymer composition, with a range currently being available such as a naltrexone‐poly(lactic acid) composite,13 70% naltrexone base in poly( L ‐lactic‐ co ‐glycolic acid),14 naltrexone–copolymer (90% L ‐lactic acid and 10% glycolic acid) beads,15 and a naltrexone pamoate linear poly (ortho esters) disk 16…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Minor pathological changes are induced by naltrexone‐poly(DL‐lactide) implants in pregnant rats

Farid

McCallum

Tait

et al. 2008

J Biomedical Materials Res

View full text Add to dashboard Cite

Oral naltrexone is used to treat alcohol and heroin dependence but is associated with poor patient compliance. Sustained-release preparations have been developed to overcome noncompliance. Many sustained-release preparations are composed of polymers combined with naltrexone. Limited data indicate that polymers induce variable levels of tissue reactivity and that naltrexone may increase this effect. A slow-release subcutaneous naltrexone-poly (DL-lactide) implant is currently being trialed to treat heroin dependence in Western Australia. A minority of women fall pregnant and, although tissue reactivity in nonpregnant humans is relatively minor, detailed chronological data during pregnancy are lacking. Histological changes in pregnant rats were assessed; a single active tablet containing poly[trans-3,6-dimethyl-1,4-dioxyane-2,5-dione] (DL-lactide) loaded with 25 mg of naltrexone was implanted subcutaneously, and tissue response was compared with inactive polymer implantation. Rats were timed mated at 13-26 days postimplant. Tissue assessment up to 75 days by a pathologist showed that naltrexone induced chronic inflammatory response in a dose-dependent manner, although still at a low level. Furthermore, for inactive implants, minimal foreign body reaction and fibrosis, together with low-level inflammation, suggested good long-term biocompatibility. We conclude that the Australian naltrexone-poly(DL-lactide) implant is tolerated in pregnant rats, reinforcing its potential role for managing alcohol and heroin dependence in pregnant humans.

show abstract

Section: Naltrexonementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Minor pathological changes are induced by naltrexone‐poly(DL‐lactide) implants in pregnant rats

Farid

McCallum

Tait

et al. 2008

J Biomedical Materials Res

View full text Add to dashboard Cite

show abstract

“…Narcotic antagonists, compounds having chemical structures similar to those of opiates and which can preferentially occupy the body’s opiate receptors and then block the euphoric effects of opiates thereby making the use of opiates pleasureless with the concomitant removal of addiction, have been found useful for the treatment of addiction 7,8 . NTX is a safer and more potent narcotic antagonist compared with naloxone and cyclazocine; hence, it is the most promising narcotic antagonist used for the treatment of narcotic addiction 9,10 .…”

Section: Introductionmentioning

confidence: 99%

“…Other polymers have been investigated for the design of controlled delivery systems for NTX with some measures of success 9,24 .…”

Section: Introductionmentioning

confidence: 99%

Studies onin vitroavailability, degradation, and thermal properties of naltrexone-loaded biodegradable microspheres

Akala

Wiriyacoonkasem

Pan

2011

Drug Development and Industrial Pharmacy

View full text Add to dashboard Cite

Purpose Following the report that continuous exposure of naltrexone (NTX) to drug-dependent pregnant women is safe and effective, the work was designed to develop NTX-loaded controlled delivery systems capable of making NTX available from 1 month to 4 months or greater by a single parenteral administration. Such drug-delivery systems will be useful in alleviating problems such as fetal alcohol syndrome in pregnant women and other problems associated with alcoholism. Methods These studies were designed to investigate in vitro drug availability and microsphere degradation (investigated by gel permeation chromatography(GPC) peak areas of water-soluble fragments released into incubation medium, changes in molecular weight with degradation time, and changes in the glass transition temperature with degradation time) of NTX-loaded poly(D,L-lactide-co-glycolide) (PDLLAGA) microspheres. Results Data showed that in vitro drug availability and degradation were affected by the initial molecular weight of the copolymers, the type of copolymers (lactide-co-glycolide ratio), the source of the polymer (the manufacturer), and the nature of the drug (anhydrous versus regular NTX). Conclusion Drug-development scientists interested in NTX-loaded microspheres for the design of controlled release devices using these polyesters should take adequate cognizance of the variables that affect drug availability from NTX-loaded microspheres. The copolymers are suitable for the fabrication of NTX-loaded microspheres capable of sustained drug release from 30 to 150 days.

show abstract

“…Many efforts have been made to develop novel systems to maximize patient compliance [8][9][10][11][12]. There have been different studies using biodegradable beads containing naltrexone as an opiate antagonist in animals [13][14][15].…”

mentioning

confidence: 99%

Preparation of a polymeric reservoir naltrexone delivery device: effect of PEG content of the PLA membrane on drug release

Dinarvand

Moghadam²,

Sayar³

et al. 2005

Therapy

View full text Add to dashboard Cite

Background: Naltrexone is an orally active opioid agonist that has the potential for use as a treatment option for opiate addiction. However, in order for the drug to be effective, sufficient blood levels must be maintained for 4 to 8 months, which typically requires selfadministration by the patient, resulting in complications. Aim: The aim of this study was to develop a polymeric reservoir device containing naltrexone. Materials & methods: The reservoir device was prepared using high-molecular-weight poly-L-lactide and the cylindrical device by dipping a stainless-steel rod in a methylene chloride solution of polylactic acid (PLA). High-molecular-weight PLA was used to take advantage of the low biodegradation rate of the polymer, in order to obtain constant drug release from the device based on the diffusion mechanism rather than biodegradation of the polymer. The impact of the polymeric device weight and polyethyleneglycol content of the polymeric membrane of the device on the release of naltrexone from the device was studied. Results: Rate of drug release from the reservoir device was shown to be successfully regulated by controlling the device weight as well as the amount of hydrophilic additive in the polymeric membrane of the device. The higher the amount of the hydrophilic content of the polymeric membrane, the faster the rate of drug release from the device. Conclusion: Prepared reservoir devices released their drug content through the use of a high-molecular-weight PLA. The presence of NaCl as an osmotic agent did not affect the release profile of naltrexone -an indicator that diffusion is the mechanism of release of naltrexone from the PLA reservoir system.

show abstract

Controlled release of naltrexone pamoate from linear poly(ortho esters)

Cited by 30 publications

References 15 publications

Minor pathological changes are induced by naltrexone‐poly(DL‐lactide) implants in pregnant rats

Minor pathological changes are induced by naltrexone‐poly(DL‐lactide) implants in pregnant rats

Studies onin vitroavailability, degradation, and thermal properties of naltrexone-loaded biodegradable microspheres

Preparation of a polymeric reservoir naltrexone delivery device: effect of PEG content of the PLA membrane on drug release

Contact Info

Product

Resources

About