Methamphetamine and Amphetamine Pharmacokinetics in Oral Fluid and Plasma after Controlled Oral Methamphetamine Administration to Human Volunteers

Abstract Background: Methamphetamine (METH) and amphetamine (AMP) concentrations in 200 plasma and 590 oral fluid specimens were used to evaluate METH pharmacokinetics and pharmacodynamics after oral administration of sustained-release METH. Methods: Eight participants received four oral 10-mg S-(+)-METH hydrochloride sustained-release tablets within 7 days. Three weeks later, five participants received four oral 20-mg doses. Blood samples were collected for up to 24 h and oral fluid for up to 72 h after drug administration. Results: After the first oral dose, initial plasma METH detection was within 0.25–2 h; cmax was 14.5–33.8 μg/L (10 mg) and 26.2–44.3 μg/L (20 mg) within 2–12 h. In oral fluid, METH was detected as early as 0.08–2 h; cmax was 24.7–312.2 μg/L (10 mg) and 75.3–321.7 μg/L (20 mg) and occurred at 2–12 h. The median oral fluid-plasma METH concentration ratio was 2.0 across 24 h and was highly variable. Neutral cotton swab collection yielded significantly higher METH and AMP concentrations than citric acid candy-stimulated expectoration. Mean (SD) areas under the curve for AMP were 21% ± 25% and 24% ± 11% of those observed for METH in plasma and oral fluid, respectively. After a single low or high dose, plasma METH was >2.5 μg/L for up to 24 h in 9 of 12 individuals (mean, 7.3 ± 5.5 μg/L at 24 h); in oral fluid the detection window was at least 24 h (mean, 18.8 ± 18.0 μg/L at 24 h). The plasma and oral fluid 24-h METH detection rates were 54% and 60%, respectively. After four administrations, METH was measurable for 36–72 h (mean, 58.3 ± 14.5 h). Conclusions: Perceived advantages of oral fluid for verifying METH exposure compared with urine include simpler specimen collection and reduced potential for adulteration, but urine offers higher analyte concentrations and a greater window of detection.

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Blood and Oral Fluid Cannabinoid Profiles of Frequent and Occasional Cannabis Smokers

Journal of Analytical Toxicology ◽

10.1093/jat/bkab078 ◽

2021 ◽

Author(s):

Melissa A Hoffman ◽

Jacqueline A Hubbard ◽

Philip M Sobolesky ◽

Breland E Smith ◽

Raymond T Suhandynata ◽

...

Keyword(s):

Oral Fluid ◽

Safety Concern ◽

Biological Fluid ◽

Driving Under The Influence ◽

Sample Collection ◽

Detection Rates ◽

Specimen Collection ◽

Final Sample ◽

Cannabis Consumption ◽

Per Se

Abstract Increased prevalence of cannabis consumption and impaired driving are a growing public safety concern. Some states adopted per se driving laws, making it illegal to drive with more than a specified ∆9-tetrahydrocannabinol (THC) blood concentration of THC in a biological fluid (typically blood). Blood THC concentrations decrease significantly (~90%) with delays in specimen collection, suggesting use of alternative matrices, such as oral fluid (OF). We characterized 10 cannabinoids’ concentrations, including THC metabolites, in blood and OF from 191 frequent and occasional users by LC–MS-MS for up to 6 h after ad libitum smoking. Subjects self-titrated when smoking placebo, 5.9 or 13.4% THC cannabis. Higher maximum blood THC concentrations (Cmax) were observed in individuals who received the 5.9% THC versus the 13.4% THC plant material. In blood, the Cmax of multiple analytes, including THC and its metabolites, were increased in frequent compared to occasional users, whereas there were no significant differences in OF Cmax. Blood THC remained detectable (≥5 ng/mL) at the final sample collection for 14% of individuals who smoked either the 5.9% or 13.4% THC cigarette, whereas 54% had detectable THC in OF when applying the same cutoff. Occasional and frequent cannabis users’ profiles were compared, THC was detectable for significantly longer in blood and OF from frequent users. Detection rates between frequent and occasional users at multiple per se cutoffs showed larger differences in blood versus OF. Understanding cannabinoid profiles of frequent and occasional users and the subsequent impact on detectability with current drug per se driving limits is important to support forensic interpretations and the development of scientifically supported driving under the influence of cannabis laws.

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Optimizing a wet granulation process to obtain high-dose sustained-release tablets with Compritol 888 ATO

Drug Development and Industrial Pharmacy ◽

10.3109/03639045.2014.1002410 ◽

2015 ◽

Vol 41 (10) ◽

pp. 1738-1744 ◽

Cited By ~ 1

Author(s):

Yvonne Rosiaux ◽

Jean-Michel Girard ◽

Florence Desvignes ◽

Cédric Miolane ◽

Delphine Marchaud

Keyword(s):

Sustained Release ◽

Wet Granulation ◽

High Dose ◽

Granulation Process ◽

Sustained Release Tablets ◽

Compritol 888 Ato

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Plasma and Oral Fluid Pharmacokinetics and Pharmacodynamics after Oral Codeine Administration

Clinical Chemistry ◽

10.1093/clinchem/48.9.1486 ◽

2002 ◽

Vol 48 (9) ◽

pp. 1486-1496 ◽

Cited By ~ 66

Author(s):

Insook Kim ◽

Allan J Barnes ◽

Jonathan M Oyler ◽

Raf Schepers ◽

Robert E Joseph ◽

...

Keyword(s):

Drug Administration ◽

Oral Fluid ◽

Drugs Of Abuse ◽

Solid Phase ◽

Subjective Effects ◽

Fluid Collection ◽

Plasma Concentrations ◽

Gas Chromatography Mass Spectrometry ◽

High Dose ◽

Detection Window

Abstract Background: The ease, noninvasiveness, and safety of oral fluid collection have increased the use of this alternative matrix for drugs-of-abuse testing; however, few controlled drug administration data are available to aid in the interpretation of oral fluid results. Methods: Single oral codeine doses (60 and 120 mg/70 kg) were administered to 19 volunteers. Oral fluid and plasma were analyzed for free codeine, norcodeine, morphine, and normorphine by solid-phase extraction combined with gas chromatography–mass spectrometry (SPE/GC-MS). Physiologic and subjective effects were examined. Results: Mean (SE) peak codeine concentrations were 214.2 ± 27.6 and 474.3 ± 77.0 μg/L in plasma and 638.4 ± 64.4 and 1599.3 ± 241.0 μg/L in oral fluid. The oral fluid-to-plasma ratio for codeine was relatively constant (∼4) from 1 to 12 h. The mean half-life (t1/2) of codeine was 2.2 ± 0.10 h in plasma and 2.2 ± 0.16 h in oral fluid. Significant dose-related miosis and increases in sedation, psychotomimetic effect, and “high” occurred after the high dose. Mean codeine oral fluid detection time was 21 h with a 2.5 μg/L cutoff, longer than that of plasma (12–16 h). Detection times with the proposed Substance Abuse and Mental Health Services Administration cutoff (40 μg/L) were only 7 h. Norcodeine, but not morphine or normorphine, was quantified in both plasma and oral fluid. Conclusions: The disposition of codeine over time was similar in plasma and oral fluid, but because of high variability, oral fluid codeine concentrations did not reliably predict concurrent plasma concentrations. Oral fluid testing is a useful alternative matrix for monitoring codeine exposure with a detection window of 7–21 h for single doses, depending on cutoff concentrations. These controlled drug administration data should aid in the interpretation of oral fluid codeine results.

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Oral Fluid Cannabinoids in Chronic, Daily Cannabis Smokers during Sustained, Monitored Abstinence

Clinical Chemistry ◽

10.1373/clinchem.2011.164822 ◽

2011 ◽

Vol 57 (8) ◽

pp. 1127-1136 ◽

Cited By ~ 58

Author(s):

Dayong Lee ◽

Garry Milman ◽

Allan J Barnes ◽

Robert S Goodwin ◽

Jussi Hirvonen ◽

...

Keyword(s):

Oral Fluid ◽

Research Unit ◽

Driving Under The Influence ◽

Institutional Review Board ◽

Test Interpretation ◽

Test Results ◽

Detection Rates ◽

Institutional Review ◽

Detection Window ◽

Written Informed Consent

BACKGROUND Oral fluid (OF) is an accepted alternative biological matrix for drug treatment, workplace, and DUID (driving under the influence of drugs) investigations, but establishing the cannabinoid OF detection window and concentration cutoff criteria are important. METHODS Cannabinoid concentrations were quantified in OF from chronic, daily cannabis smokers during monitored abstinence. Δ9-tetrahydrocannabinol (THC)3, cannabidiol (CBD), cannabinol (CBN), and 11-nor-9-carboxy-THC (THCCOOH) were determined in daily OF samples collected with the Quantisal™ device. GC-MS limits of quantification (LOQ) were 0.5 μg/L for THC and CBD, 1 μg/L for CBN, and 7.5 ng/L for THCCOOH. RESULTS After providing written informed consent for this institutional review board–approved study, 28 participants resided from 4 to 33 days on the secure research unit and provided 577 OF specimens. At the LOQ, THC was generally quantifiable for 48 h, whereas CBD and CBN were detected only at admission. Median THCCOOH detection time was 13 days (CI 6.4–19.6 days). Mean THC detection rates decreased from 89.3% at admission to 17.9% after 48 h, whereas THCCOOH gradually decreased from 89.3% to 64.3% within 4 days. Criteria of THC ≥2 μg/L and THCCOOH ≥20 ng/L reduced detection to <48 h in chronic cannabis smokers. An OF THCCOOH/THC ratio ≤4 ng/μg or presence of CBD or CBN may indicate more recent smoking. CONCLUSIONS THC, THCCOOH, CBD, and CBN quantification in confirmatory OF cannabinoid testing is recommended. Inclusion of multiple cannabinoid cutoffs accounted for residual cannabinoid excretion in OF from chronic, daily cannabis smokers and could reduce the potential for positive test results from passive cannabis smoke exposure and lead to greatly improved test interpretation.

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FORMULATION AND EVALUATION OF DILTIAZEM HCL SUSTAINED RELEASE TABLETS BY USING DIRECT COMPRESSION METHOD

INTERNATIONAL JOURNAL OF PHARMACEUTICAL RESEARCH AND BIO-SCIENCE ◽

10.32395/ijprs.v7.i6.00001 ◽

2018 ◽

Vol 7 (6) ◽

pp. 1-18

Author(s):

CHANDRA PRAKASH ◽

R. ARCHANA ◽

S. ASMA ◽

F. JABEEN ◽

S. PARVEEN

Keyword(s):

Sustained Release ◽

Direct Compression ◽

Compression Method ◽

Sustained Release Tablets ◽

Diltiazem Hcl

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Formulation and Evaluation of Sustained Release Dosage Forms of Norfloxacin

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2018.11.6.6 ◽

2018 ◽

Vol 11 (6) ◽

pp. 4331-4337

Author(s):

C Suja ◽

Sismy C

Keyword(s):

Sustained Release ◽

Guar Gum ◽

In Vitro Release ◽

Angle Of Repose ◽

Prolonged Release ◽

Weight Variation ◽

Sustained Release Tablets ◽

Release Study ◽

Vitro Release

The goal of this study was to formulate and evaluate norfloxacin sustained release tablets. Norfloxacin sustained release tablets were prepared by wet granulation method using two polymers such as HPMC K 100 M (hydrophilic polymer) and guar gum (natural polymer) and with three polymer ratios (0.5, 1.0 and 1.5). The prepared granules were evaluated to preformulation studies such as angle of repose, bulk density, tapped density, bulkiness, compressibility index and Hauser’s ratio. All the parameters shows that the granules having good flow properties. Then the formulated tablets were taken to evaluation studies such as hardness, weight variation, friability, drug content and thickness. All the parameters were within the acceptable limits. IR spectral analysis showed that there was no interaction between the drug and polymers. The in vitro release study was performed in phosphate buffer pH 7.4 at 293 nm. The in vitro release study showed that if the polymer ratio is increased, then the release of the drug is prolonged. HPMC K 100M shows a prolonged release when compared to guar gum.

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Gastroretentive Floating Capsules of Risedronate Sodium: Development, Optimization, in vitro and in vivo Evaluation in Healthy Human Volunteers

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2015.8.2.6 ◽

2015 ◽

Vol 8 (2) ◽

pp. 2835-2842

Author(s):

Bhikshapathi D. V. R. N. ◽

Arun Kumar Jarathi ◽

Suresh Gande ◽

Viswaja Medipally ◽

Ramesh Bomma

Keyword(s):

Drug Release ◽

Sustained Release ◽

Zero Order ◽

Wet Granulation ◽

Capsule Formulation ◽

In Vivo Evaluation ◽

Healthy Human ◽

X Ray ◽

Human Volunteers

Background and the purpose of the study: Risedronate sodium inhibits osteoclast bone resorption and modulates bone metabolism. Risedronate has a high affinity for hydroxyapatite crystals in bone and is a potent antiresorptive agent. In the present investigation efforts were made to improve the bioavailability of risedronate sodium by increasing the residence time of the drug through sustained-release matrix capsule formulation via gastroretentive mechanism. Capsules were prepared by wet granulation technique. The influence of gel forming agents, amount of risedronate and total weight of capsules on physical properties, in vitro buoyancy, drug release, FTIR, DSC, X-ray studies were investigated. The release mechanisms were explored and explained by applying zero order, first order, Higuchi and Korsmeyer equations. The selected formulations were subjected to stability study at 40 °C/75% RH, 25 °C/60% RH for the period of three months. For all formulations, kinetics of drug release from capsules followed Higuchi’s square root of time kinetic treatment heralding diffusion as predominant mechanism of drug release. Formulation containing 25 mg HPMC K4M and 75 mg HPMC K100 LV (F-8) showed zero order release profile. There was no significant change in the selected formulation, when subjected to accelerated stability conditions over a period of three months. X-ray imaging in six healthy human volunteers revealed a mean gastric retention period of 5.60 ± 0.77 hrs for the selected formulation. Stable, sustained release effervescent floating capsules of risedronate sodium could be prepared by wet granulation technique.

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Crystal Transition and Drug-excipient Compatibility of Clarithromycin in Sustained Release Tablets

Current Pharmaceutical Analysis ◽

10.2174/1573412915666190328234326 ◽

2020 ◽

Vol 16 (7) ◽

pp. 950-959

Author(s):

Yu Li ◽

Xiangwen Kong ◽

Fan Hu

Keyword(s):

Sustained Release ◽

Powder Diffraction ◽

Magnesium Stearate ◽

Influential Factor ◽

High Concentration ◽

Scanning Calorimetry ◽

X Ray ◽

Sustained Release Tablets ◽

Crystal Transition ◽

Excipient Compatibility

Background: Clarithromycin is widely used for infections of helicobacter pylori. Clarithromycin belongs to polymorphic drug. Crystalline state changes of clarithromycin in sustained release tablets were found. Objective: The aim of this study was to find the influential factor of the crystal transition of clarithromycin in preparation process of sustained-release tablets and to investigate the possible interactions between the clarithromycin and pharmaceutical excipients. Methods and Results: The crystal transition of active pharmaceuticals ingredients from form II to form I in portion in clarithromycin sustained release tablets were confirmed by x-ray powder diffraction. The techniques including differential scanning calorimetry and infrared spectroscopy, x-ray powder diffraction were used for assessing the compatibility between clarithromycin and several excipients as magnesium stearate, lactose, sodium carboxymethyl cellulose, polyvinyl-pyrrolidone K-30 and microcrystalline cellulose. All of these methods showed compatibilities between clarithromycin and the selected excipients. Alcohol prescription simulation was also done, which showed incompatibility between clarithromycin and concentration alcohol. Conclusion: It was confirmed that the reason for the incompatibility of clarithromycin with high concentration of alcohol was crystal transition.

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