Journal of pharmaceutics & pharmacology最新文献

{"title":"Aticaprant (Clinically Developed Kappa-Opioid Receptor Antagonist) Combined With Naltrexone Prevents Alcohol \"Relapse\" Drinking.","authors":"Y Zhou,&nbsp;D C Zhou,&nbsp;M J Kreek","doi":"10.13188/2327-204x.1000032","DOIUrl":"https://doi.org/10.13188/2327-204x.1000032","url":null,"abstract":"<p><p>Alcohol relapse is the treatment target for medications development for alcohol dependence. Aticaprant, a selective and short-acting kappa-opioid receptor (KOR) antagonist, has recently been under development for new clinical implications (depression or anhedonia). Recent studies have also found that aticaprant reduces alcohol intake and prevents stress- triggered alcohol seeking in rodents via a KOR-mediated mechanism. Here, we further investigated whether aticaprant alone or in combination with naltrexone (mu-opioid receptor [MOR] antagonist) altered alcohol relapse-like drinking using a mouse alcohol deprivation effect (ADE) paradigm to mimic the relapse episodes in human alcoholics. A long-acting and selective KOR antagonist nor-BNI was used as a reference compound for the effects of the KOR antagonism on the ADE. After 3-week intermittent-access alcohol drinking (two-bottle choice, 24-h access every other day), male and female mice displayed excessive alcohol intake and then pronounced ADE after 1-week abstinence. Aticaprant alone decreased alcohol ADE in a dose- dependent manner (1-3 mg/kg) in both males and females. Aticaprant at a lower dose (0.3 mg/kg) than the effective one (3 mg/kg) combined with a low dose of naltrexone (1 mg/kg) reduced the ADE in both sexes, and the combination was effective after a multi-dosing regimen (5 daily injections during the abstinence) without development of tolerance, suggesting synergistic effects of the combination. In contrast, nor-BNI alone or with naltrexone had no effect on the ADE in either sex. Our present study suggests that a combination of clinically developed, short-acting KOR antagonist aticaprant with low-dose naltrexone has therapeutic potential in alcohol \"relapse\" treatment.</p>","PeriodicalId":89990,"journal":{"name":"Journal of pharmaceutics & pharmacology","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9275124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40503063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential for the Use of Adamantanes for the Prevention and Treatment of the Neurological Complications of COVID-19","authors":"R. Butterworth","doi":"10.13188/2327-204x.1000037","DOIUrl":"https://doi.org/10.13188/2327-204x.1000037","url":null,"abstract":"","PeriodicalId":89990,"journal":{"name":"Journal of pharmaceutics & pharmacology","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84068215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repurposing of Adamantanes for the Treatment of COVID-19: Rationale and Perspectives","authors":"R. Butterworth","doi":"10.13188/2327-204x.1000035","DOIUrl":"https://doi.org/10.13188/2327-204x.1000035","url":null,"abstract":"Intensive efforts are underway in the search for novel antiviral agents and in the repurposing of existing antivirals with the potential to mitigate the effects of COVID-19. Amantadines represent a large family of tricyclic agents some of which are known to manifest efficacy against a range of viruses including influenza A and several human and animal coronaviruses including SARS-CoV and HCoV-OC43 with neuroinvasive characteristics. The adamantane derivative memantine improves clinical scores and motor disabilities while reducing HCoVOC43 viral replication in a dose-dependent manner. Anti-viral actions of memantine against HCoV are independent of the agent’s action as a non-competitive NMDA receptor antagonist. Amantadine and the novel spiroadamantane amine possess significant activity against coronavirus 229E. Mechanisms proposed to date to account for the antiSARS CoV-2 actions of adamantanes include blocking of the viroporin channel of the virus E protein preventing release of viral nucleus into the host-cell cytoplasm and down-regulation of the host protease CTSL and lysosomal disruption leading to decreased viral replication. Further investigations are now required including the assessment of other adamantanes as antivirals in the experimental setting and controlled clinical trials to assess their safety and efficacy for the prevention and treatment of COVID-19.","PeriodicalId":89990,"journal":{"name":"Journal of pharmaceutics & pharmacology","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73912576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innovative Approaches to Enhance Dissolution Rate of a Hydrophobic Drug Glimepiride","authors":"A. Usman","doi":"10.13188/2327-204x.1000036","DOIUrl":"https://doi.org/10.13188/2327-204x.1000036","url":null,"abstract":"Method: In the proposed study, USP analytical method was validated for the determination of glimepiride in its formulations. The calibration curve was linear over the concentration range of 2.5-12.5 μg/ml with a regression analysis (r2 = 0.9999). For getting an idea about the release of drug from its dosage form, innovator brands were picked and estimated for pharmaceutical parameters. On the basis of this information, 10 experimental batches of tablets were prepared. The optimized batch was prepared by using 2:1 ratios of tween 80 and PVP K30 by slurry technique. Pre-compression and post-compression parameters were evaluated to confirm the validity of the design and development of processes. The optimized batch was subjected to stability studies for 03 months at 40±2 °C & % RH: 75±5%.","PeriodicalId":89990,"journal":{"name":"Journal of pharmaceutics & pharmacology","volume":"153 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84804081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adamantanes for the Prevention of COVID-19: A Review of Case Reports","authors":"Cortes A Borra","doi":"10.13188/2327-204x.1000034","DOIUrl":"https://doi.org/10.13188/2327-204x.1000034","url":null,"abstract":"Clinical evidence is reviewed for the possible use of the adamantanes amantadine and memantine, for the prevention and/or treatment of COVID-19. Literature searches revealed three series of case reports authored by independent teams of international investigators. Subjects were comprised principally of patients receiving amantadine or memantine for several weeks as part of their treatment regimen for Parkinson’s disease, Multiple Sclerosis or Cognitive impairment prior to their infection by SARS-CoV-2. All patients tested positive for SARSCoV-2 confirmed by RT-PCR of nasopharyngeal swabs. Interestingly, the majority of cases manifested age-related vulnerabilities to COVID-19 as well as the presence of co-morbidities resulting from either severe neurological disorders or type-2 diabetes. Amantadine appeared to prevent the appearance of typical COVID-19related clinical manifestations of infectious disease in 23/24 cases. In addition, one patient with type-2 diabetes treated with amantadine for 14 days showed clear improvements in clinical status and in oxygen saturation levels; by day 6 he could breathe without the need for oxygen supplementation and was discharged from hospital on day 14. It is necessary to now confirm these findings by randomized controlled trials in order to objectively evaluate the use of these agents for the prevention and/or treatment of COVID-19.","PeriodicalId":89990,"journal":{"name":"Journal of pharmaceutics & pharmacology","volume":"32 1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80360291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amantadine for the Treatment of SARS-Cov-2: Case Report","authors":"GE Aranda-Abreu","doi":"10.13188/2327-204x.1000033","DOIUrl":"https://doi.org/10.13188/2327-204x.1000033","url":null,"abstract":"","PeriodicalId":89990,"journal":{"name":"Journal of pharmaceutics & pharmacology","volume":"48 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78572111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preparation and Evaluation of Glaucocalyxin A SustainedRelease Pellets Based on Phospholipid Complex System with Enhanced Bioavailability","authors":"","doi":"10.13188/2327-204x.1000030","DOIUrl":"https://doi.org/10.13188/2327-204x.1000030","url":null,"abstract":"Objective: Glaucocalyxin A (GLA) suffers from low oral bioavailability and rapid in vivo metabolism. Therefore, the purpose of this study was to develop a new formulation to enhance the oral bioavailability simultaneously sustained release of GLA. Material and methods: GLA-phospholipid complex was firstly formulated by solvent-evaporation method to improve the solubility of GLA. Differential scanning calorimetry, powder X-ray diffraction, scanning electron microscopy, and solubility study were used to characterize the GLA-phospholipid complex. And then, the optimized GLA-phospholipid complex was selected to prepare GLA-phospholipid complex sustained release pellets by extrusion-spheronization and fluidized bed coating technology. The prepared pellets were studied by in vitro drug release study and administered to beagle dogs to evaluate the oral bioavailability of GLA-phospholipid complex and GLA-phospholipid complex sustained release pellets. Results: The results illustrated that GLA in GLA-phospholipid complex was either molecularly dispersed or in an amorphous form with 13.8fold water solubility than the free GLA. The pharmacokinetic studies in beagle dogs demonstrated that GLA-phospholipid complex and GLAphospholipid complex sustained-release pellets showed 2.19-fold and 2.07-fold improvement than the free GLA by oral dosage, respectively. Further, steady plasma concentration, and prolonger Tmax were simultaneously obtained from GLA-phospholipid complex sustained release pellet. Conclusion: These outcomes suggested that the combination of phospholipid complex and sustained release pellets could enhance the oral bioavailability and prolong the action time in vivo which provided a promising delivery system for GLA.","PeriodicalId":89990,"journal":{"name":"Journal of pharmaceutics & pharmacology","volume":"718 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85417963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Sars-Cov-2 Viroporin E and its Interaction with Amantadine an Analysis","authors":"Aranda Abreu Ge","doi":"10.13188/2327-204X.S200003","DOIUrl":"https://doi.org/10.13188/2327-204X.S200003","url":null,"abstract":"This article discusses the function of the SARS-Cov-2 virus E-channel and its interaction with amantadine.In this analysis it is proposed that amantadine is able to enter the E-channel of the coronavirus, inhibiting the viral content to enter the cell avoiding viral replication. Therefore, amantadine is a drug that can help decrease the symptoms of coronavirus. It is also mentioned how amantadine may be acting with the Spike protein, through a molecular docking study. Introduction At the end of 2019, a new virus called COVID-19 was spreading in an alarming way in Wuhan City in China. This virus belongs to the family Coronoviridae and it is structurally formed by 4 proteins, E and M are part of the viral envelope, N is the one that binds to the viral genome and S (spike) is the one that binds to the human receptor ACE2 [1,2]. Aspects of channel E Viroporin E structurally consists of 5 protein chains, formed by 75 amino acids, where 33.33% form an alpha-helix structure (hydrophobic region), 53.33% random-coil, and 13.33% extended chain [3,4]. The E protein is well conserved among the 3 corona virus groups and shows limited homology across the different groups [5,6]. It has been shown that by deleting the E gene, viral replication decreases by 100 to 1000 times that of recombinant wild strains and that this decrease is accompanied by less inflammation in hamster lungs infected with the virus that possesses the E gene deletion [7]. The E protein was mainly located in the Endoplasmic ReticulumGolgi Intermediate Compartment (ERGIC) of the cells, where it participates in assembly, budding and intracellular trafficking, in addition to possessing ion channel activity [8,9]. Studies have shown that E is involved in critical aspects of the corona virus life cycle, which could make it a good candidate for the development of vaccines or drugs such as amantadine [1,4]. Amantadine molecular function Amantadine has been used as an antiviral therapy against the influenza virus, the proposed mechanism being that it blocks the early stage of replication. When the viral particle enters the cell, an endosomal structure is formed which has a pH of 5, this protein channel is formed by the M2 protein, which carries protons into the virion. Amantadine by its lipophilic nature is able to cross the endosome membrane and interrupt the release of the virion into the cell. Similarly, amantadine can enter the E-channel of the corona virus by preventing the release of the viral nucleus into the cell [10]. Molecular docking studies have shown that amantadine may interact with the amino acids ALA22 and PHE26 by blocking the protein channel [4] (Figure 1). A mechanism has also been proposed where the entry of SARS-Cov-2 into a cell depends on the binding of the viral spike protein (S) to the cell receptor and the cleavage of the spike protein by host cell proteases such as Cathepsin L (CTSL) and Cathepsin B (CATSB). CTSL/B is a crucial element of the lysosome pathway and both enzy","PeriodicalId":89990,"journal":{"name":"Journal of pharmaceutics & pharmacology","volume":"7 19","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72388346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lysosomotropic Action of Amantadine: Basis for Treatment of COVID-19","authors":"SP Smieszek","doi":"10.13188/2327-204x.1000031","DOIUrl":"https://doi.org/10.13188/2327-204x.1000031","url":null,"abstract":"SARS-coronavirus 2 is the causal agent of the COVID-19 outbreak. SARSCov-2 entry into a cell is dependent upon binding of the viral Spike (S) protein to cellular receptor and on cleavage of the spike protein by the host cell proteases such as Cathepsin L and Cathepsin B (CTSL/B). They are crucial elements of lysosomal pathway and both enzymes are almost exclusively located in the lysosomes. CTSL disruption offers potential for CoVID-19 therapies. The mechanisms of disruption include: decreasing expression of CTSL, direct inhibition of CTSL activity and modification of the CTSL environment (increase pH in the lysosome). We have conducted a high throughput drug screen gene expression analysis to identify compounds with the capacity to downregulate the expression of CTSL/CTSB. One of the most significant results shown to downregulate the expression of the CTSL gene is Amantadine(10uM). We confirmed Amantadine’s lysosmal trapping capacity in an invitro Lysosomal Trapping Assay. In addition, to downregulating CTSL, Amantadine disrupts the lysosomal pathways, hence, interferes with the capacity of the virus to replicate. It acts as a lysosomotropic agent altering the CTSL functional environment. We propose that Amantadine could decrease the viral load in SARS-CoV-2 positive patients and as such it may serve as a potent therapeutic decreasing the replication and infectivity of the virus likely leading to better clinical outcomes. Clinical studies are currently needed to examine the therapeutic efficacy of Amantadine in COVID-19 infection.","PeriodicalId":89990,"journal":{"name":"Journal of pharmaceutics & pharmacology","volume":"48 11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83795427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preparation and Evaluation of Controlled-Release Solid Dispersion Granules Containing a Poorly Water-Soluble Drug, Hydrated Silicon Dioxide, and Polyvinylpyrrolidone","authors":"","doi":"10.13188/2327-204x.1000029","DOIUrl":"https://doi.org/10.13188/2327-204x.1000029","url":null,"abstract":"The study aim was to develop controlled-release, solid dispersion granules containing a poorly water-soluble drug, Hydrated Silicon Dioxide (HSD), and Polyvinylpyrrolidone (PVP), and to elucidate the mechanism underlyingsustained release from the soliddispersion granules. To achieve this purpose, we used the wet granulation method to prepare the first-release granules containing a poorly water-soluble drug and HSD. Then, the effect of PVP on the dissolution of the poorly water-soluble drug was estimated. Initially, the selection of a binder and contentsof drug and binder were investigated to determine the optimum formulation fora rapidly dissolving granule with HSD. Firstrelease granules containing Nifedipine (NIF) as a poorly water-soluble drug, erythritol as a binder, and HSD were developed. Differential scanning calorimetry confirmed reduced NIF crystallinity in the granules. To investigate the first-release granules’ applicabilityto other drugs, six poorly water-soluble drugs (griseofulvin, indomethacin, ibuprofen, carbamazepine, progesterone, and phenytoin) were prepared. Rapid dissolutionof all tested drugs from the granule with the same NIF formulation was observed. These findings suggest that HSD is useful for improving dissolution ratesof poorly water-soluble drugs insoliddispersion granules. Next, we investigated PVP’s effect on the dissolution of drug from the first-release granules. The effects of PVP on sustained release from the granules containing the seven drugs weredivided into three types: Type 1 was no effect (rapid dissolution), type 2 was a middle effect, and type 3 was a strong effect (sustained release). To elucidate the mechanism underlying sustained release from the solid dispersion granules, the intermolecular interactions between the drugs and HSD or PVP were investigated by Fourier transform infrared spectroscopy. The results suggested that the balance between the interaction of a drug and HSD and the interaction of a drug and PVP is important for sustained release of the drug.","PeriodicalId":89990,"journal":{"name":"Journal of pharmaceutics & pharmacology","volume":"41 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82017203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}