New Construction of Functionalized CuO/Al2O3 Nanocomposite-Based Polymeric Sensor for Potentiometric Estimation of Naltrexone Hydrochloride in Commercial Formulations

Electrically conductive polymeric nanocomposites with nanoparticles are adaptable types of nanomaterials that are prospective for various applications. The extraordinary features of copper oxide (CuO) and aluminium oxide (Al2O3) nanostructures, encourages extensive studies to prospect these metal oxide nanocomposites as potential electroactive materials in sensing and biosensing applications. This study suggested a new CuO/Al2O3 nanocomposite-based polymeric coated wire membrane sensor for estimating naltrexone hydrochloride (NTX) in commercial formulations. Naltrexone hydrochloride and sodium tetraphenylborate (Na-TPB) were incorporated in the presence of polymeric polyvinyl chloride (PVC) and solvent mediator o-nitrophenyloctyl ether (o-NPOE) to form naltrexone tetraphenylborate (NTX-TPB) as an electroactive material. The modified sensor using NTX-TPB-CuO/Al2O3 nanocomposite displayed high selectivity and sensitivity for the discrimination and quantification of NTX with a linearity range 1.0 × 10−9–1.0 × 10−2 mol L−1 and a regression equation EmV = (58.25 ± 0.3) log [NTX] + 754.25. Contrarily, the unmodified coated wire sensor of NTX-TPB exhibited a Nernstian response at 1.0 × 10−5–1.0 × 10−2 mol L−1 and a regression equation EmV = (52.1 ± 0.2) log [NTX] + 406.6. The suggested modified potentiometric system was validated with respect to various criteria using the methodology recommended guidelines.

Study of Acute Toxicity and Irritant Effect of Nasal Spray Naltrexone Hydrochloride

Introduction. Acute toxicity of naltrexone hydrochloride nasal spray during intragastric administration to mice and local irritant effect on rabbits was studied. At all stages of the experiment, observations were made on the General condition of the animals. The state of homeostasis was evaluated using functional, hematological and morphometric methods. According to the results of research, there was no local irritant effect on the eyes of rabbits, as well as no toxic effect of high doses of the drug on animals. Introduction. Naltrexone hydrochloride in doses of 1.5– 5 mg/day has shown its effectiveness in the treatment of a number of diseases. Due to the lack of such a "low-dose" naltrexone registered on the pharmaceutical market, we have developed the composition of the nasal spray naltrexone hydrochloride. One of the stages of our research is to study the safety of the drug being developed. The first step in this direction was to study its acute toxicity and local irritant effect.Aim. Study of acute toxicity and local irritant effect of naltrexone hydrochloride nasal spray.Materials and methods. The object of the study was a nasal spray of naltrexone hydrochloride. Acute toxicity studies were performed on outbred adult mice (females). Study of local irritant effect on Soviet chinchilla rabbits (males).Results and discussion. The study of acute toxicity showed that the drug, at a dose significantly higher than the estimated maximum daily therapeutic dose for humans, did not have a significant toxic effect on the body of laboratory animals. The presence of a local irritant effect in the studied drug was not established in the framework of the experiment.Conclusion. As part of the experiment, the drug under study did not have a local irritant or toxic effect on the animal body. The results obtained allow us to continue the development and study of the nasal spray naltrexone hydrochloride.

Probing the Release of Bupropion and Naltrexone Hydrochloride Salts from Biopolymeric Matrices of Diverse Chemical Structures

In the last decades, the notion of including excipients in the formulations, as inert substances aiding production processes, has changed and they are recently viewed as multifunctional discrete entities. It is now well documented that excipients serve several roles, spreading from the stabilization and modified release, to providing biocompatible properties and targeting moieties. The aim of this study was to develop matrix-based oral drug delivery systems of bupropion hydrochloride (BUP·HCl) and naltrexone hydrochloride (NTX·HCl), suitable for releasing these active substances in a modified manner, providing a stable level of drug release, which is simultaneously therapeutically effective and non-toxic, thus reducing side effects, after a single dose administration, throughout the gastrointestinal tract. The new formulations, employing hydroxypropylmethycellulose (HPMC K15M) (a cellulosic polymer, which, generally hydrates to form a gelatinous layer that is critical to prevent wetting and rapid drug release from the matrices), poly(methacylic acid-co-ethyl acrylate) 1:1 (Eudragit® L100-55: effective for site specific drug delivery in intestine), poly(ethylene oxide) (PEO) (7 × 106: a high molecular weight polymer, water-soluble, in micro-granular powder form), as the rate controlling polymers, were chosen to lead to a “soothing out” release pattern of these drugs, at 0 ≤ t ≤ 120 min. Moreover, the release of the two drugs from the ulvan-based tablets, was found to follow the desired profile, throughout the entire course of the dissolution experiments.

Quantitative Determination of Benzalconium Chloride in the Naltrexone Hydrochloride Nasal Spray

Introduction. Benzalkonium chloride is widely used as a conservation agent in medicines. For quantitative determination, the methods described in the European and American Pharmacopoeias by chromatography using columns with nitrile sorbent are often used. However, in order to unify the methods and simplify the quality control technology in the production process, it is advisable to adapt the existing methods for new goals and objectives.Aim. To develop a method for the quantitative determination of benzalkonium chloride in a nasal spray containing a thermosensitive polymer Poloxamer 407 and validate it.Materials and methods. As an object of research, a naltrexone hydrochloride nasal spray was used. The quantitative determination of naltrexone in the test sample was developed using a Dionex UltiMate 3000 high-performance liquid chromatograph (Thermo Fisher Scientific, USA) equipped with a diode-matrix detector.Results and discussion. The paper explored the possibility of using an earlier developed method for the quantitative determination of naltrexone hydrochloride for the quantitative determination of benzalkonium chloride in the composition of a nasal spray. Based on the results obtained, changes were made to the quantitative determination method, and the sample preparation of the samples under study was adapted.Conclusion. As a result of the studies carried out, the most acceptable conditions for the preparation of the nasal spray for the quantitative determination of the preservative were selected. The developed technique provides for the chromatographic conditions previously used for the determination of naltrexone hydrochloride, which makes it possible to use the equipment as efficiently as possible in the analysis of the finished drug. The method has been validated and its specificity, linearity, correctness and precision have been proven.

Microbiological Estimation of Nasal Spray Containing Naltrexone Hydrochloride

Introduction. In order to standardize the quality indicators during the expected shelf life of the developed drug naltrexone hydrochloride in the form of a nasal spray containing a high concentration of poloxamer and benzalkonium chloride as a preservative, a microbiological study was carried out. The possibility of using the membrane filtration method for testing prototypes recommended by the State Pharmacopoeia XIV.Aim. Study and selection of test conditions for the «microbiological purity» indicator of nasal spray samples containing naltrexone hydrochloride.Materials and methods. As an object of research, a naltrexone hydrochloride nasal spray was used. When analyzing the microbiological purity, the membrane filtration method recommended in the State Pharmacopoeia XIV.Results and discussion. As part of the study, it was found that the samples of the drug meet the requirements for a microbiological indicator for drugs of category 2. Testing the suitability of the method for samples of the dosage form showed that the antimicrobial effect of the drug was completely removed by washing the filter, which was proved by inoculation of indicator test microorganisms, the quantitative and qualitative nature of growth, which did not differ from the control without the drug.Conclusion. As a result of the studies carried out, the optimal test conditions for the «Microbiological purity» indicator for the nasal spray containing naltrexone hydrochloride were selected and substantiated.

Quantitative Determination of Naltrexone Hydrochloride in a Nasal Spray by High-performance Liquid Chromatography

Introduction. Naltrexone, an antagonist of µ-opioid receptors, is promising for the treatment of various autoimmune and oncological diseases when used in doses of 1.5–5 mg/day. To date, there are no medications that provide such dosages of naltrexone.Aim. Development and validation of a method for the quantitative determination of naltrexone hydrochloride in a nasal spray by high performance liquid chromatography (HPLC).Materials and methods. As an object of research, a naltrexone hydrochloride nasal spray was used. The quantitative determination of naltrexone in the test sample was developed using a Dionex UltiMate 3000 high-performance liquid chromatograph (Thermo Scientific, USA) equipped with a diode-matrix detector.Results and discussion. The possibility of using isocratic and gradient chromatographic modes for the quantitative determination of naltrexone hydrochloride in the nasal spray was studied. Based on these results, a new method of determination using the gradient mode is proposed, which allows minimizing the influence of the polymer component in the test sample on the analysis results.Conclusion. A new technique of high-performance liquid chromatography (HPLC) is proposed that allows identification and quantification of naltrexone hydrochloride in a nasal spray containing a high concentration of water-soluble heat-sensitive poloxamer as a thickener. The developed method was validated according to the parameters: correctness, precision, specificity, linearity.