Administration Of Capsules Research Articles

Efficacy of guar gum-based ronidazole capsules as a treatment for Tritrichomonas foetus infection in cats.

Objectives The aims of the study were to determine the in vitro drug release of guar gum-coated capsules of ronidazole, and to evaluate the pharmacokinetics and efficacy of this formulation for the treatment of cats naturally infected with Tritrichomonas foetus. Methods The pharmacokinetics of ronidazole were evaluated in five healthy cats and five cats infected with T foetus. In a second step, the clinical efficacy of these capsules was evaluated by a controlled, randomised, double-blind clinical trial performed in 47 infected cats from French catteries. In this study, cats were randomly allocated to either the ronidazole treatment group (n = 25) or a placebo group (n = 22). Ronidazole (30 mg/kg) q24h for 14 days was administered to the treated cats. After 14 days of treatment, the presence of T foetus was tested by conventional PCR assay. Results In the pharmacokinetic study, a delayed peak plasma concentration was observed in healthy and infected cats, with no significant difference between these two groups (mean geometric mean of 9 h for time to maximum plasma concentration [Tmax], 21.6 µg/ml for time to maximum plasma concentration [Cmax] and 467.4 μg/h/ml for the area under the curve [AUC] in healthy cats; and 9.4 h for Tmax, 17.1 µg/ml for Cmax and 481 μg/h/ml for AUC in infected cats). In the clinical trial, T foetus was detected in 16% of cats from the treated group and 82% of cats from the placebo group at the end of the study ( P <0.001). No clinical signs of adverse drug reactions were observed. Conclusions and relevance Oral administration of guar gum-coated capsules of ronidazole at a dose of 30 mg/kg once daily for 14 days delays the peak plasma concentration and eradicates infection in most cases.

Ghost-Pill-Buster: A Case Study of Intact Levetiracetam Extended-Release Tablets after Dissolution Testing.

Orally administered medications in extended-release (ER) dosage forms continue to play a pivotal role in the treatment of various central nervous system disorders. For certain ER dosage forms, pharmaceutical scientists have been familiar with the passage of intact tablet-like objects in patients' feces after administration of ER tablets or capsules based on water-insoluble or slowly dissolving excipients. Nevertheless, because of lack of awareness of the "ghost pill" phenomenon, anxiety has ensued among some patients and clinicians, who have less understanding of how drugs are released from these tablets once ingested. It has been brought to the attention of the US Food and Drug Administration (FDA) that epilepsy patients administered with Teva's levetiracetam ER tablets have noticed intact tablets in their stools and been concerned that they were not getting the needed dose of the drug. In response to neurologists' clinical reporting, the FDA has conducted investigations to confirm a minimal risk of incomplete drug release of Teva's drug product. The objective of this study was to evaluate the risks of incomplete drug release associated with the passing of intact levetiracetamER tablets, by conducting invitro dissolution testing. Dissolution testing of Teva's drug product was performed in accordance with the USPharmacopeia monograph for levetiracetamER tablets in phosphate buffer and bio-relevant buffers at different pH values. In addition, dissolution testing was conducted with split and crushed tablets. At the end of the dissolution testing, all samples were visually inspected for any undissolved pieces. Approximately 90% of levetiracetam had been released in all dissolution media after 8h of dissolution. The levetiracetamER tablets after dissolution testing remained fully intact in all dissolution media. The rates of drug release were significantly faster from split and crushed tablets than that from whole tablets. On the basis of these findings, Teva's levetiracetamER tablets may appear intact in the stools but have released the drug successfully. The FDA has requested Teva to revise its product labeling to include remarks regarding the potential passing of intact tablets. Since patients who notice ghost pills in their stools may impetuously crush or split the tablets of subsequent doses on their own, healthcare providers should instruct patients to swallow whole tablets throughout the treatment, in accordance with the drug label.

Osimertinib Western and Asian clinical pharmacokinetics in patients and healthy volunteers: implications for formulation, dose, and dosing frequency in pivotal clinical studies.

Osimertinib (AZD9291) 80mg once daily is approved by the US FDA for the treatment of patients with metastatic EGFR T790M-positive NSCLC whose disease has previously progressed on EGFR-TKI therapy. Osimertinib PK was evaluated to define the dose and dosing interval, whether a fixed-dosing approach can be used globally, and the impact of formulation and food on exposure. AURA (NCT01802632): single- and multiple-dose PK of osimertinib (20-240mg daily) was determined in patients with advanced NSCLC. Bioavailability study (NCT01951599): single-dose PK of osimertinib (20mg) was determined in healthy volunteers with administration of capsule, solution, or tablet formulations fasted, and as a tablet in the fed and fasted state. Osimertinib was slowly absorbed and displayed dose-proportional increases in exposure from 20 to 240mg. Distribution was extensive and clearance low to moderate, resulting in a mean half-life of 48.3h. Steady state was achieved by 15days of dosing, consistent with single-dose PK, with a peak-to-trough ratio of 1.6. Two active metabolites circulated at ~10% of osimertinib exposure. Ethnicity did not appear to affect exposure. Osimertinib PK profiles in healthy volunteers were similar to those in patients and were unaffected by formulation. Food caused a clinically insignificant increase in exposure. Osimertinib PK supports once-daily dosing; the same dose for Asian and non-Asian populations; a fixed-dosing approach; a minimal effect of food on exposure; and a switch to tablet formulation without alteration to dose or schedule. Osimertinib plasma concentrations are sustained throughout the dosing period, which is considered optimal for efficacy.

Urinary Branched-Chain 2-Oxo Acids as a Biomarker for Function of B-Group Vitamins in Humans

To find a functional biomarker of B-group vitamins, we collected 24-h urine samples from young Japanese women who lived in the community (n=29) to measure branched-chain 2-oxo acids such as 2-oxo-3-methylbutanoic acid, 2-oxo-3-methylpentanoic acid, and 2-oxo-4-methylpentanoic acid because B-group vitamins are involved in the catabolism of branched-chain amino acids. The relationships between each pair of the three urinary 2-oxo acids were very high (2-oxo-3-methylbutanoic acid and 2-oxo-3-methylpentanoic acid, p<0.001; 2-oxo-3-methylbutanoic acid and 2-oxo-4-methylpentanoic acid, p<0.001; 2-oxo-3-methylpentanoic acid and 2-oxo-4-methylpentanoic acid, p<0.001). The participants were divided into three groups using the upper (n=10), middle (n=9), and lower tertiles (n=10) based on the urinary excretion amounts of the sum of the three branched-chain 2-oxo acids. The administration of capsules containing the daily necessary amounts of B-group vitamins led to a decrease in the urinary excretion of the sum of the three types of branched-chain 2-oxo acids in participants belonging to the upper tertile. A similar phenomenon was observed in the middle tertile, but not in the lower tertile. Intakes of B-group vitamins and the urinary excretion amounts of B-group vitamins were not observed to be significantly different among the upper, middle, and lower tertiles. These results indicate that some young Japanese women need much higher levels of B-group vitamins than the Dietary Reference Intakes for Japanese. Thus, urinary branched-chain 2-oxo acids are useful functional biomarkers for B-group vitamins in humans.

Therapeutic effects of mifepristone combined with Gestrinone on patients with endometriosis.

Objective:To evaluate the clinical therapeutic effects of mifepristone combined with gestrinone on patients with endometriosis.Methods:A total of 150 endometriotic patients treated in our hospital between January 2014 and December 2015 were randomly divided into a control group and a treatment group (n=75). The control group began to orally take gestrinone capsules on the second day after menstruation started (2.5 mg/time, twice/week). The treatment group orally took mifepristone tablets (12.5 mg/time, once/day), and the dosage and administration of gestrinone capsules were the same as those of the control group. After 24 weeks of consecutive treatment, the clinical therapeutic effects of the two groups were assessed, and the pelvic symptom score, clinical sign score, serum sex hormone levels and pregnancy outcomes were compared.Results:The total effective rates of control and treatment groups were 77.3% and 90.7% respectively, between which the difference was statistically significant (P<0.05). After treatment, the scores of pelvic symptoms (dysmenorrhea, dyspareunia, pelvic pain) and clinical signs (pelvic tenderness, induration) significantly reduced (P<0.05). Each score of the treatment group decreased more significantly than that of the control group did (P<0.05). The serum follicle hormone, luteinizing hormone, estrogen and progesterone levels were significantly lower than those before treatment (P<0.05). Each level of the treatment group dropped more significantly than that of the control group did (P<0.05). The pregnancy rates in the 6th and 12th months of follow-up were 28.0% and 13.3% in the control group respectively, and 42.7% and 29.3% in the treatment group respectively. Such rates of the two groups were significantly different at each follow-up time point (P<0.05).Conclusion:Mifepristone combined with gestrinone had satisfactory clinical therapeutic effects on endometriosis by reducing hormone levels and improving pregnancy outcomes. Therefore, this regimen is worthy of promotion and application in clinical practice.

Model Based Description of the Pharmacokinetic Behavior of Pentobarbital in Fasted Male Volunteers after Oral Administration of 10 mg of Pentobarbital

The goal of the current study was to present a further example which showed a model based description of the pharmacokinetic behavior of pentobarbital in fasted male volunteers after oral administration of 10 mg pentobarbital. The current study is a companion piece of the earlier study by Smith et al.; therefore the data published in the study cited here were used. For modeling purposes, an advanced modeling method based on the theory of dynamic systems was employed. All mathematical models developed, more or less successfully described the data of healthy male volunteers after oral administration of capsules containing 50 mg of sodium pentobarbital. The modeling method used in the current study is universal and uniform. Therefore, it can be used to develop mathematical models not only in pharmacokinetics but also in several other scientific and practical fields. This modeling method could augment, or in future replace, a variety of different modeling methods traditionally used in pharmacokinetics.

Use of patency capsule in patients with established Crohn's disease.

Video capsule endoscopy (VCE) is invaluable in the diagnosis of small-bowel pathology. Capsule retention is a major concern in patients with Crohn's disease. The patency capsule was designed to evaluate small-bowel patency before VCE. However, the actual benefit of the patency capsule test in Crohn's disease remains unclear. The aim of this study was to evaluate the clinical impact of patency capsule use on the risk of video capsule retention in patients with established Crohn's disease. This was a retrospective, multicenter study of patients with established Crohn's disease who underwent VCE for clinical need. The utilization strategy for the patency capsule was classified as selective (only in patients with obstructive symptoms, history of intestinal obstruction or surgery, or per treating physician's request) or nonselective (all patients with Crohn's disease). The main outcome was video capsule retention in the entire cohort and within each utilization strategy. A total of 406 patients who were referred for VCE were included in the study. VCE was performed in 132 /406 patients (32.5 %) without a prior patency capsule test. The patency capsule test was performed in 274 /406 patients (67.5 %) and was negative in 193 patients. Overall, VCE was performed in 343 patients and was retained in the small bowel in 8 (2.3 %). In this cohort, the risk of video capsule retention in the small bowel was 1.5 % without use of a prior patency capsule and 2.1 % after a negative patency test (P = 0.9). A total of 18 patients underwent VCE after a positive patency capsule test, with a retention rate of 11.1 % (P = 0.01). Patency capsule administration strategy (selective vs. nonselective) was not associated with the risk of video capsule retention. Capsule retention is a rare event in patients with established Crohn's disease undergoing VCE. The risk of video capsule retention was not reduced by the nonselective use of the patency capsule. Furthermore, VCE after a positive patency capsule test in patients with Crohn's disease was associated with a high risk of video capsule retention.

Application of liquid chromatographic/tandem mass spectrometric method to a urinary excretion study of subutinib and active metabolite in human urine.

A novel and selective liquid chromatographic-mass spectrometric method (LC-MS/MS) has been established and validated for simultaneous determination of subutinib and active metabolite in human urine. Urine samples were extracted by liquid-liquid extraction with ethyl acetate and separated on a Wondasil C18 (150 × 2.1 mm, 3.5 µm), with methanol-0.2% formic acid solution (73:27, v/v) as mobile phase at flow rate of 0.2 mL/min. The linear range was 0.5000-200.0 ng/mL for subutinib and active metabolite, with a lower limit of quantitation of 0.5000 ng/mL. Intra- and inter-run precisions were all <11.8 and 14.3%, and the accuracies were all <4.5 and 5.4%, with the extraction recoveries 88.8-97.5 and 93.8-99.4% for the two analytes, respectively. The carryover values were all <15% for the two anayltes. The method was successfully applied to study urinary excretion of subutinib and active metabolite in human after oral administration of subutinib maleate capsules in fed and fasting states.

Long-term effectiveness of rivastigmine patch or capsule for mild-to-severe Alzheimer’s disease: a meta-analysis

Aim: To evaluate the long-term effectiveness of rivastigmine patch or capsule on mild to severe Alzheimer’s disease (AD). Method: We performed a meta-analysis of 17 studies regarding the treatment effectiveness of rivastigmine patch or capsule on mild-to-severe AD. Results: Significant difference exists between treatment with rivastigmine patch or capsule and placebo groups (p-value < 0.001). In the Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-Cog) score evaluation, a negative weighted mean difference (WMD) was observed in overall and mild-moderate groups after rivastigmine treatment. And in ADAS-ADL score evaluation, a positive WMD was observed in overall groups after rivastigmine treatment. Moreover, WMD value is lower in patch administration subgroup compared to that of capsule administration subgroup. Conclusion: Rivastigmine treatment shows a positive result of improving the condition of patients with mild-to-severe AD. Patch administration shows a stronger effect on decreasing ADAS-Cog score compared to capsule administration.

Simultaneous determination of subutinib and its active metabolite in human plasma by LC-MS/MS: Application to pharmacokinetic study.

A selective liquid chromatographic-mass spectrometric method (LC-MS/MS) has been established and validated for simultaneous determination of subutinib and its active metabolite in human plasma. Plasma samples were extracted by liquid-liquid extraction with ethyl acetate and separated on a Wondasil C18 (150mm×2.1mm, 3.5μm), with methanol-0.2% formic acid solution (73:27, v/v) as mobile phase at flow rate of 0.2ml/min. The linear range was 0.25-100ng/mL for subutinib and 0.125-50.0ng/mL for its active metabolite, with lower limit of quantitation of 0.25ng/mL and 0.125ng/mL, respectively. Intra- and inter-run precision were within 7.0 and 13.1%, and the accuracies (relative errors) were<7.0 and 8.0%, with the extraction recoveries 97.0-101.2% and 93.0-98.1% for the two analytes, respectively. The validated method was successfully applied to a pharmacokinetic study of subutinib and its active metabolite in human after oral administration of subutinib maleate capsules.

Naltrexone Maintenance Decreases Cannabis Self-Administration and Subjective Effects in Daily Cannabis Smokers.

Given that cannabis use is increasing in the United States, pharmacological treatment options to treat cannabis use disorder are needed. Opioid antagonists modulate cannabinoid effects and may offer a potential approach to reducing cannabis use. In this double-blind, placebo-controlled human laboratory study, we assessed the effects of naltrexone maintenance on the reinforcing, subjective, psychomotor, and cardiovascular effects of active and inactive cannabis. Nontreatment-seeking, daily cannabis smokers were randomized to receive naltrexone (50 mg: n=18 M and 5 F) or placebo (0 mg; n=26 M and 2 F) capsules for 16 days. Before, during, and after medication maintenance, participants completed 10 laboratory sessions over 4-6 weeks, assessing cannabis' behavioral and cardiovascular effects. Medication compliance was verified by observed capsule administration, plasma naltrexone, and urinary riboflavin. Relative to placebo, maintenance on naltrexone significantly reduced both active cannabis self-administration and its positive subjective effects ('good effect'). Participants in the placebo group had 7.6 times (95% CI: 1.1-51.8) the odds of self-administering active cannabis compared with the naltrexone group. This attenuation of reinforcing and positive subjective effects also influenced cannabis use in the natural ecology. Naltrexone had intrinsic effects: decreasing ratings of friendliness, food intake, and systolic blood pressure, and increasing spontaneous reports of stomach upset and headache, yet dropout rates were comparable between groups. In summary, we show for the first time that maintenance on naltrexone decreased cannabis self-administration and ratings of 'good effect' in nontreatment-seeking daily cannabis smokers. Clinical studies in patients motivated to reduce their cannabis use are warranted to evaluate naltrexone's efficacy as a treatment for cannabis use disorder.

Optimizing the Interpretation of Capsule Endoscopic Images: Shortsighted or Taking the Long View?

Capsule endoscopy (CE) has become the preferred method of investigating the small intestine [1, 2]. Although capsule administration is a relatively straightforward task in the absence of medical complications, reading of CE videos is laborious, with outcome and reporting dependent not only on reviewer attentiveness and expertise but also on several other specific perceptual and interpretational factors [3, 4]. When viewing a soporific stream of often repetitive nondistinct images in a quiet, dark room, a significant risk of loss of concentration can lead to inaccuracy of reported findings [4, 5]. Nevertheless, practicing gastroenterologists may be considered adequately trained in CE reporting after a short, 1-day training program [6]. Moreover, formal training in CE during gastrointestinal (GI) fellowship, defined only loosely, includes completion of a hands-on course with a minimum of 8 h of continuing medical education (CME) credit, followed by review of CE studies by a credentialed capsule endoscopist [6]. There is currently no standardization of national or international training programs, although guidelines are being developed [7]. Furthermore, only limited evidence-based information on the optimal reading mode of CE review is currently available [3, 4, 8]. The past has taught us a great deal about medical image perception, not only in ‘‘classical’’ image-based specialties such as radiology and pathology, but also in other clinical specialties that use imaging technology—such as gastroenterology, laparoscopic surgery, or dermatology [9–11]. Medical images and videos represent a significant source of information that aid clinicians with diagnostic and therapeutic decisions [11]. Yet, the correct interpretation of medical images relies on a host of factors, with significant health andmedicolegal issues accruing from their inaccurate interpretation,which consists of two basic processes—visual perception (image inspection) and cognition (rendering an interpretation) [10, 11]. The use and development of computer-based models to predict human performance has also been a topic of interest for which a paucity of perceptionoriented research exists, yet the opportunities abound. The American Society of Gastrointestinal Endoscopy (ASGE) recommends a minimum number of 20 supervised procedures to provide adequate experience for those intending to practice CE independently [6]. Commercially available software provides a diverse range of viewing modes (VM) and frame rates (FR), in addition to other image enhancement tools such as digital chromoendoscopy [3, 12, 13]. No consensus has been reached for the latter technique according to a number of studies, its optimal mode of application yet to be determined [2, 3]. The use of differing VM has been, to date, the subject of only two studies [14, 15]. In the most recent large cohort study, Zheng et al. [15] reported that the low lesion detection rates observed were not influenced by increasing CE experience. Detection rates are significantly higher when reading in single VM/FR15 (single screen with FR 15/s) and quad VM/FR20 (four screens with FR 20/s) compared with reading in single View/FR25 (single screen with FR 25/s). Increasing viewing speed in quad VM from FR20 to FR30 appears to have no significant effect on detection ability. Therefore, the investigators suggested that quality control measures to compare and improve lesion detection rates need further study. A. Koulaouzidis (&) Endoscopy Unit, Royal Infirmary of Edinburgh, 51 Little France Crescent, Edinburgh EH16 4SA, Scotland, UK e-mail: Tassos.Koulaouzidis@luht.scot.nhs.uk URL: http://www.drkoulaouzidis.com

Quantitation of pregabalin in dried blood spots and dried plasma spots by validated LC–MS/MS methods

In this paper, novel LC–MS/MS methods for the determination of antiepileptic drug pregabalin in dried matrix spots (DMS) are presented. This attractive technique of sample collection in micro amount was utilized in the form of dried blood spots (DBS) and dried plasma spots (DPS). Following a pre-column derivatization procedure, using n-propyl chloroformate in the presence of n-propanol, and consecutive liquid–liquid extraction, derivatized pregabalin and its internal standard, 4-aminocyclohexanecarboxylic acid, were detected in positive ion mode by applying two SRM transitions per analyte. A YMC-Pack Octyl column (50mm×4.0mm, 3μm particle size) maintained at 30°C, was utilized with running mobile phase composed of acetonitrile: 0.15% formic acid (85:15, v/v). Flow rate was 550μL/min and total run time 2min. Established methods were fully validated over the concentration range of 0.200–20.0μg/mL for DBS and 0.400–40.0μg/mL for DPS, respectively, while specificity, accuracy, precision, recovery, matrix-effect, stability, dilution integrity and spot homogeneity were found within acceptance criteria. Validated methods were applied for the determination of pregabalin levels in dried blood and plasma samples obtained from patients with epilepsy, after per os administration of commercial capsules. Comparison of drug level in blood and plasma, as well as correction steps undertaken in order to overcome hematocrit issue, when analyzing DBS, are also given.

Pharmacokinetic analysis of orally administered puerarin in human saliva using an indirect competition ELISA

The pharmacokinetics of puerarin in human saliva following oral administration of pueraria capsules were successfully studied by an icELISA method.

Levothyroxine Malabsorption Induced by Diabetic Gastroparesis Exacerbated During Pregnancies: Effect of Intramuscular Levothyroxine Injections and Levothyroxine Soft Gel Capsules

ABSTRACT Objective: We report a case of severe hypothyroidism with levothyroxine (LT4) malabsorption induced by diabetic gastroparesis. This was exacerbated during the patient's 2 pregnancies. Management was improved by intramuscular (IM) LT4) injections and LT4 soft gel capsules. Methods: Case report with literature review. Results: A 23-year-old Hispanic female with type 1 diabetes (DM) and hypothyroidism developed diabetic gastroparesis with unpredictable responses to LT4. She had 2 pregnancies during which her oral LT4 was switched to weekly IM injections of LT4 that maintained her euthyroid state. An LT4 absorption test with 1,000 mcg LT4 revealed reduced LT4 absorption. A gastric emptying scan showed delayed emptying, and endoscopy demonstrated a large amount of residual food in the patient's stomach after an overnight fast. Weekly IM injections of LT4 and LT4 soft gel capsules maintained her euthyroid state after her last pregnancy with a follow-up longer than 1-year. A repeat LT4 absorption test with a 1,000-mcg LT4 soft gel capsule preparation demonstrated improved absorption compared to the initial LT4 absorption test. Conclusion: This may be the first patient described in the literature in whom diabetic gastroparesis was associated with impaired oral LT4 absorption and exacerbation during pregnancies. Our experience with this patient suggests that rational management of this problem may include IM LT4 injections or oral LT4 soft gel capsule administration. Abbreviations: CHF congestive heart failure DM diabetes mellitus IM intramuscular LT4 levothyroxine T4 thyroxine TFTs thyroid function tests TSH thyroid-stimulating hormone

Mechanism of Bailemian capsules in the treatment of insomnia in mice

To explore the mechanism of Bailemian capsules in the treatment of insomnia. A total of 50 imprinting control region (ICR) mice were randomly divided into 5 groups of normal control, model, high, medium and low-dose Bailemian capsules. After oral administration of Bailemian capsules for 14 consecutive days, except for control group, the other four groups received an injection of chlorobenzene alanine (PCPA) for murine modeling of insomnia. Then murine behaviors were observed and the brain tissue levels of serotonin (5-HT) and γ-aminobutyric acid (GABA) were detected. Another two batches of ICR mice (n = 50 each) were randomly divided into 5 groups of normal control, diazepam, high, medium and low-dose Bailemian capsules. After 14-hour fasting, except for normal control group, an intragastric dose of Bailemian was offered. Before dosing and at 30, 60, 120, 240 min, general behaviors within 5 min were recorded. For another batch, at 30 min after an intraperitoneal injection of pentobarbital sodium 25 mg/kg, disappearance of righting reflex as sleep index was used to observe the proportion of mice within 15 min in terms of sleep, sleep latency and total sleep time. In middle and high-dose groups, insomnia symptoms improved significantly. The contents of 5-HT and GABA in brain tissue were significantly higher than those of model group ((164.6 ± 12.8), (193.2 ± 25.6) vs (147.1 ± 15.5) ng/ml and (15.4 ± 1.3), (17.0 ± 1.3) vs (12.6 ± 1.4) mol/L) (all P < 0.05). And the number of activities at 120 min was significantly less than that of normal control group ((91.3 ± 10.4), (78.5 ± 12.7) vs (150.7 ± 10.8) times) (both P < 0.05). Low, medium and high-dose Bailemian capsules could improve the proportion of mice within 15 min sleep. And sleep latency was shorter than that of normal control group ((8.9 ± 0.6), (7.3 ± 0.6), (2.1 ± 0.3) vs 0 min) and total sleep time longer than that of normal control group ((76.7 ± 7.1), (85.1 ± 7.1), (110.0 ± 22.9) vs 0 min) (all P < 0.05). The mechanism of Bailemian capsules for treating the symptoms of insomnia may be related with the elevated brain contents of 5-HT and GABA.

Pharmacokinetic Properties and Tolerability of Low-dose SoluMatrix Diclofenac

PurposeThis study compared the pharmacokinetic properties and safety profile of low-dose (18- and 35-mg) diclofenac capsules manufactured using SoluMatrix Fine Particle Technology (Trademark of iCeutica Inc. (Philadelphia, Pennsylvania), and the technology is licensed to Iroko Pharmaceuticals, LLC (Philadelphia, Pennsylvania) for exclusive use in NSAIDs), which produces submicron-sized drug particles with enhanced dissolution properties, to those of diclofenac potassium immediate-release (IR) 50-mg tablets. MethodsThis Phase 1, single-center, randomized, open-label, single-dose crossover study was conducted in 40 healthy volunteers. Subjects received, in randomized order, SoluMatrix diclofenac 18- or 35-mg capsules in the fasting condition, SoluMatrix diclofenac 35-mg capsules under fed conditions, and diclofenac potassium IR 50-mg tablets under fasting and fed conditions. Pharmacokinetic parameters (Tmax, Cmax, AUC0–t, AUC0–∞) were calculated from the concentrations of diclofenac in the plasma. Absorption, food effect, and dose proportionality were determined using a mixed-model ANOVA for Cmax, AUC0–t, and AUC0–∞. Tolerability was assessed by recording adverse events, physical examination findings, vital sign measurements: clinical laboratory test results. FindingsOverall, 35 healthy volunteers aged 18 to 52 years completed the study. The mean age of the subjects was 33.4 years, and approximately half were men (47.5%). Median Tmax values were similar between the low-dose SoluMatrix diclofenac 35-mg capsules and the diclofenac potassium IR 50-mg tablets (both, ~1.0 hour). The mean maximum plasma concentration (Cmax) after the administration of low-dose SoluMatrix diclofenac 35-mg capsules was 26% lower than that with diclofenac potassium IR 50-mg tablets under fasting conditions (868.72 vs 1194.21 ng/mL). The administration of low-dose SoluMatrix diclofenac 35-mg capsules was associated with a 23% lower overall systemic exposure compared with that of diclofenac potassium IR 50-mg tablets under fasting conditions. Food decreased the rate but not the overall extent of absorption of SoluMatrix diclofenac. No serious AEs and no clinically significant abnormalities in physical examination findings, including vital sign measurements, or clinical laboratory test results, were noted during this study. ImplicationsThe pharmacokinetic properties of low-dose SoluMatrix diclofenac capsules in the healthy volunteers in this study suggest rapid diclofenac absorption as measured by Tmax. Low-dose SoluMatrix diclofenac capsules represent a potential option for the management of acute and osteoarthritis-related pain.

Investigation of the hepatoprotective properties of “Phytovenol” capsules on the model of medicamentous hepatitis in rats

Abstract This scientific paper is an investigation of the pharmacological activity of the new medical preparation “Phytovenol” (capsules in the dose of 150 mg/kg) on the pattern of hepatitis in rats induced by paracetamol administration. The authors of the article, for the first time under experimental conditions, detected a hepatoprotective effect that was brought about by “Phytovenol” capsule administration. This is realized due to the antioxidant, antitoxic and anticytolytic activity of the examined medicine. The study found that its efficacy is not lower than the classical hepatoprotector - “Silibor” tablets. The results obtained suggest that it is possible to extend the range of available hepatoprotectors and improve the quality of treatment for liver diseases, by introducing “Phytovenol” capsules into medical practice.

Anti-stress effects of lemon balm-containing foods.

Lemon balm (Melissa officinalis) has been used historically and contemporarily as a modulator of mood and cognitive function, with anxiolytic effects following administration of capsules, coated tablets and topical application. Following a pilot study with lemon balm extract administered as a water based drink, which confirmed absorption of rosmarinic acid effects on mood and cognitive function, we conducted two similar double-blind, placebo-controlled, crossover studies. These evaluated the mood and cognitive effects of a standardised M. officinalis preparation administered in palatable forms in a beverage and in yoghurt. In each study a cohort of healthy young adults’ self-rated aspects of mood were measured before and after a multi-tasking framework (MTF) administered one hour and three hours following one of four treatments. Both active lemon balm treatments were generally associated with improvements in mood and/or cognitive performance, though there were some behavioral “costs” at other doses and these effects depended to some degree on the delivery matrix.

Establishment of an enzyme-linked immunosorbent assay and application on determination of ginsenoside Re in human saliva.

This work describes an immunochemical approach for the quality control of Panax ginseng and a pharmacological study of ginsenoside Re, a major bioactive constituent in P. ginseng, using an enzyme-linked immunosorbent assay. A hybridoma secreting monoclonal antibody against ginsenoside Re was produced by fusing splenocytes immunized with a ginsenoside Re-bovine serum albumin conjugate with the hypoxanthine-aminopterin-thymidine-sensitive mouse myeloma SP2/0 cell line. The method, at an effective measuring range of 7.8-500 ng · mL(-1) of ginsenoside Re, successfully detected ginsenoside Re in Chinese traditional herb prescriptions. The results demonstrate that we generated a novel and reliable assay system for measuring ginsenoside Re in Chinese medicines more efficiently. Futhermore, we determined the ginsenoside Re concentrations in the saliva of six healthy adults after the oral administration of a ginseng capsule to study the pharmacokinetics of ginsenoside Re in human saliva.