scholarly journals A Randomized, Double-Blind Study of the Effects of a Sustained Release Formulation of Sodium Nitrite (SR-nitrite) on Patients with Diabetic Neuropathy

2018 ◽  
Vol 1 (21;1) ◽  
pp. 179-190 ◽  
Author(s):  
Amol Soin
Keyword(s):  
Neuropathic Pain ◽  
Diabetic Neuropathy ◽  
Sustained Release ◽  
Sodium Nitrite ◽  
Immediate Release ◽  
Double Blind ◽  
Release Formulation ◽  
Sustained Release Formulation ◽  
Pain Scores ◽  
The Mean

Background: Background: Sodium nitrite has been reported to be effective in reducing chronic peripheral pain. Objectives: To evaluate the safety and efficacy of 40 and 80 mg, BID, of an oral sustained release formulation of sodium nitrite (SR-nitrite) in patients suffering from diabetic neuropathy, and to determine whether SR-nitrite would reduce the frequency of headaches reported previously by subjects receiving the same doses of an immediate release formulation. Study Design: Phase II, single-center, randomized, double-blind, placebo controlled clinical trial. Setting: The Ohio Pain Clinic and Kettering Medical Center. Methods: Twenty-four patients were randomized to 40 mg or 80 mg SR-nitrite or placebo twice daily for 12 weeks. The primary objective was to determine whether headaches would be reduced using SR-nitrite. The primary efficacy endpoint was the mean difference in the change of the Neuropathic Pain Symptom Inventory (NPSI) pain score from baseline to that reported after 12 weeks of treatment. Secondary endpoints included changes from baseline for the Brief Pain Inventory (BPI) Scale, the RAND 36 questionnaire, Short Form McGill Questionnaire, daily patient reported score for neuropathic pain, changes in HbA1c, PulseOx and quantitative sensory testing. Results: The number of subjects reporting adverse events and the number of adverse events did not change with dose. There were no reports of treatment-related headaches. Although no significant differences were identified in patient responses to the questionnaires, a trend was observed. In the NPSI assessment, patients in the 40 mg and 80 mg dose group reported a 12.7% and 22.0% reduction in pain, respectively, compared to an 8.4% reduction by patients in the placebo group. A trend was also observed with the BPI total severity score. However, the 40 mg dosing group reported the greatest reduction in pain using the McGill Pain index and via patient logs of daily pain scores, where the mean of pain scores reported by subjects in the 40 mg group dropped by day 41 and generally stayed lower than the mean of scores reported by subjects in either of the other two groups. Patients in the 80 mg SR-nitrite group had an improvement in both Nerve Sensory Conductance and Nerve Sensory Velocity. No changes were observed in HbA1c levels or PulseOx. Limitations: Small sample size. Conclusion: Sustained release sodium nitrite prevents the prevalent reports of headaches by patients treated with an immediate release formulation of sodium nitrite. In a previous study of patients with peripheral arterial disease (PAD), 40 mg BID treatment led to a statistically significant reduction in reported pain, similar trends were observed at the end of the trial period for most of the pain questionnaires used in the study. The 80 mg BID treatment had the more pronounced affect on bioactivity (quantitative sensory testing), which was similar to the PAD study, where this dose group had the greatest improvement in FMD {AU: spell out FMD}. The ability to alleviate pain with BID treatment of SR-nitrite offers promise for a new non-addictive, non-sedating treatment of chronic pain and warrants further study. Key words: diabetes, diabetic neuropathy, neuropathic pain, peripheral neuropathy, sodium nitrite

scholarly journals Formulation and in vitro Evaluation of Glimepiride Sustained Release Tablets: Comparison with Immediate Release Tablets

2015 ◽  
Vol 18 (2) ◽  
pp. 157-162
Author(s):  
Samira Karim ◽  
Mohiuddin Ahmed Bhuiyan ◽  
Md Sohel Rana
Keyword(s):  
Sustained Release ◽  
Immediate Release ◽  
Pharmaceutical Journal ◽  
In Vitro Dissolution ◽  
Release Formulation ◽  
Sustained Release Formulation ◽  
Zero Order Kinetics ◽  
Weight Variation ◽  
Sustained Release Tablets

This work aims at the design of a sustained release formulation of glimepiride which is currently available in the treatment of type 2 diabetes mellitus and to investigate the effect of polymers on the release profile of glimepiride. Glimepiride sustained release tablets were prepared by direct compression method using different ratios of various release retarding polymers such as carbopol, ethyl cellulose, methocel K4 MCR, methocel K15 MCR, methocel K100 MCR and xanthum gum. These formulations were also compared with glimepiride immediate release tablets. The prepared tablets were subjected to various physical parameter tests including weight variation, friability, hardness, thickness, diameter, etc. In vitro dissolution studies of the formulations were done at pH 6.8 in phosphate buffer using USP apparatus 2 (paddle method) at 50 rpm. The percent releases of all the formulations (30) were 73.11%- 98.76% after 8 hours. The release pattern followed zero order kinetics and the release of the drug was hindered by the polymers used in the study. On the other hand, 100% drug was released within 1 hour from the immediate release tablet of glimepiride. The study reveals that the polymers used have the capacity to retard the release of the drug from the sustained release tablets and the more is the amount of the polymer in the formulation the less is the release of drug showing more retardation of drug release.Bangladesh Pharmaceutical Journal 18(2): 157-162, 2015

Pharmacodynamics of Orally Administered Sustained- release Hydromorphone in Humans

2001 ◽  
Vol 94 (1) ◽  
pp. 63-73 ◽  
Author(s):  
Martin S. Angst ◽  
David R. Drover ◽  
Jörn Lötsch ◽  
Bhamini Ramaswamy ◽  
Sujata Naidu ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Sustained Release ◽  
Analgesic Effect ◽  
Time Course ◽  
Plasma Concentrations ◽  
Experimental Pain ◽  
Immediate Release ◽  
Double Blind ◽  
Sustained Release Formulation ◽  
Analgesic Effects

Background The disposition kinetics of hydromorphone generally necessitates oral administration every 4 h of the conventional immediate-release tablet to provide sustained pain relief. This trial examined time course and magnitude of analgesia to experimental pain after administration of sustained-release hydromorphone as compared with that after immediate-release hydromorphone or placebo. Methods Using a 4 x 4 Latin square double-blind design, 12 subjects were randomized to receive a single dose of 8, 16, and 32 mg sustained-release hydromorphone and placebo. The same subjects had received 8 mg immediate-release hydromorphone before this study. Using an electrical experimental pain paradigm, analgesic effects were assessed for up to 30 h after administration, and venous hydromorphone plasma concentrations were measured at corresponding times. Results The hydromorphone plasma concentration peaked significantly later (12.0 h [12.0--18.0] vs. 0.8 h [0.8--1.0]; median and interquartile range) but was maintained significantly longer at greater than 50% of peak concentration (22.7 +/- 8.2 h vs. 1.1 +/- 0.7 h; mean +/- SD) after sustained-release than after immediate-release hydromorphone. Similarly, sustained-release hydromorphone produced analgesic effects that peaked significantly later (9.0 h [9.0--12.0] vs. 1.5 h [1.0--2.0]) but were maintained significantly longer at greater than 50% of peak analgesic effect (13.3 +/- 6.3 h vs. 3.6 +/- 1.7 h). A statistically significant linear relation between the hydromorphone plasma concentration and the analgesic effect on painful stimuli existed. Conclusion A single oral dose of a new sustained-release formulation of hydromorphone provided analgesia to experimental pain beyond 24 h of its administration.

scholarly journals Optimization of floating bilayered tablets of Ketorolac Tromethamine

2017 ◽  
Vol 4 (1) ◽  
pp. 14
Author(s):  
Hitesh Jain ◽  
Kinjal Patel ◽  
Neha Savant ◽  
Umesh Upadhyay
Keyword(s):  
Sustained Release ◽  
Sodium Bicarbonate ◽  
Immediate Release ◽  
Ketorolac Tromethamine ◽  
Release Formulation ◽  
Sustained Release Formulation ◽  
Sodium Starch Glycolate ◽  
Promising Tool ◽  
Weight Variation ◽  
Floating Layer

Objective: The aim of the present study was to formulate the floating bilayer tablets of Ketorolac tromethamine, first immediate release layer and second sustained release floating layer which would provide initial loading dose of drug and remain in stomach and upper part of GIT for prolonged period of time in a view to maximize solubility of drug which is necessary for its absorption.Methods: The floating bilayered tablets of Ketorolac tromethamine were prepared by using 32 factorial designs by direct compression method. For this, polymers like sodium starch glycolate and polyox WSR 303 were used in various concentrations. Sodium bicarbonate was used as a floating effervescent agent. The formulations were evaluated for hardness, friability, weight variation, swelling index, floating lag time, floating time, % CDR etcResults: From the result obtained, S3 having 23% Polyox WSR 303 and 12% sodium bicarbonate showed better results.Conclusions: The results showed that Polyox WSR is promising tool to designing of sustained release formulation.

scholarly journals Pharmacokinetics of Immediate and Sustained Release Cephalexin Administered by Different Routes to Llamas (Lama glama)

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Verónica Kreil ◽  
Luis Ambros ◽  
Ana Paula Prados ◽  
Lisa Tarragona ◽  
Agustina Monfrinotti ◽  
...  
Keyword(s):  
Sustained Release ◽  
Immediate Release ◽  
Effective Dosage ◽  
Absolute Bioavailability ◽  
Pharmacokinetic Parameters ◽  
Release Formulation ◽  
Sustained Release Formulation ◽  
E Coli ◽  
Routes Of Administration ◽  
Elimination Half

We investigate the pharmacokinetics of two different cephalexin formulations administered to llamas by the intravenous (IV), intramuscular (IM), and subcutaneous (SC) routes, the minimum inhibitory concentration (MIC) of cephalexin against someEscherichia coliand staphylococci isolated from llamas, and we apply the PK/PD modelling approach, so that effective dosage recommendations for this species could be made. Six llamas received immediate (10 mg/kg, IV, IM, and SC) and sustained (8 mg/kg IM, SC) release cephalexin. Pharmacokinetic parameters were calculated by noncompartmental approach. Immediate release SC administration produced a significantly longer elimination half-life as compared with the IV and IM administration (1.3±0.2versus0.6±0.1and0.6±0.1 h, resp.) and higher mean absorption time as compared with the IM administration (1.7±0.5versus0.6±0.4 h). Absolute bioavailability was in the range of 72–89% for both formulations and routes of administration. Cephalexin MIC90values against staphylococci andE. coliwere 1.0 and 8.0 μg/mL, respectively. Our results show that the immediate release formulation (10 mg/kg) would be effective for treating staphylococcal infections administered every 8 h (IM) or 12 h (SC), whereas the sustained release formulation (8 mg/kg) would require the IM or SC administration every 12 or 24 h, respectively.

scholarly journals Sustained Release Formulation of Primaquine for Prevention of Relapse of Plasmodium vivax Malaria: A Randomized, Double-Blind, Comparative, Multicentric Study

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Anil Pareek ◽  
Nitin Chandurkar ◽  
Nithya Gogtay ◽  
Alaka Deshpande ◽  
Arjun Kakrani ◽  
...  
Keyword(s):  
Sustained Release ◽  
Plasmodium Vivax ◽  
Standard Dose ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Clinical Trial Registration ◽  
Release Formulation ◽  
Sustained Release Formulation ◽  
Multicentric Study ◽  
Asymptomatic Patients

Background. Primaquine is used to eradicate latent Plasmodium vivax parasite from liver, with administration of standard dose daily up to 14 days. We studied efficacy, safety, and tolerability of sustained release (SR) formulation of primaquine in comparison with conventional primaquine in preventing relapse of P. vivax malaria. Methods. Microscopically confirmed cases of P. vivax malaria received chloroquine therapy for three days. Aparasitemic and asymptomatic patients were then randomized to receive either conventional primaquine 15 mg for 14 days or primaquine SR 15 mg for 14 days, or primaquine SR 30 mg for seven days. Results. Of the 360 patients, who received chloroquine therapy, 358 patients were randomized. Two-hundred eighty-eight patients completed six-month follow-up and four patients (three: conventional primaquine 15 mg (2.86%), one: primaquine SR 30 mg (0.93%)) showed relapse confirmed by PCR genotyping. Drug compliance was significantly better in primaquine SR 30 mg group (95.57%, p=0.039) without any serious adverse events. Conclusion. Primaquine SR 15 mg and primaquine SR 30 mg could be an effective alternative to conventional primaquine 15 mg due to their comparable cure rates and safety profile. Shorter treatment duration with primaquine SR 30 mg may increase patient compliance and may further reduce relapse rates. Clinical Trial Registration. This trial is registered with CTRI/2010/091/000245.

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