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Scientific discussion Page 3 Steps taken for assessment Page 1

Lawsuits in context

The study of Roman procedure has benefited enormously from the discovery of wooden tablets near Pompeii. They are variously referred to as 'the Murecine tablets' (after the Agro Murecine, their place of discovery), 'the Pompeian tablets' (after the ancient site near their place of discovery), 'the Puteoli tablets' (after the ancient site from which they were removed in antiquity), or 'the archive of the Sulpicii' (after the presumed owner of the archive in antiquity). Unfortunately, the tablets are sometimes misinterpreted, for the simple reason that the procedures they describe do not always match the procedures which more familiar sources have (wrongly) led us to believe existed. The tablets, in fact, give us the rare opportunity to revise our understanding of procedure, particularly when taken together with another remarkable find, the lex Irnitana. This article gives a sketch of the 'new' Roman civil procedure now available to us as a result of these exciting finds

Comparison of the determination of a low-concentration active ingredient in pharmaceutical tablets by backscatter and transmission raman spectrometry

A total of 383 tablets of a pharmaceutical product were analyzed by backscatter and transmission Raman spectrometry to determine the concentration of an active pharmaceutical ingredient (API), chlorpheniramine maleate, at the 2% m/m (4 mg) level. As the exact composition of the tablets was unknown, external calibration samples were prepared from chlorpheniramine maleate and microcrystalline cellulose (Avicel) of different particle size. The API peak at 1594 cm(-1) in the second derivative Raman spectra was used to generate linear calibration models. The API concentration predicted using backscatter Raman measurements was relatively insensitive to the particle size of Avicel. With transmission, however, particle size effects were greater and accurate prediction of the API content was only possible when the photon propagation properties of the calibration and sample tablets were matched. Good agreement was obtained with HPLC analysis when matched calibration tablets were used for both modes. When the calibration and sample tablets are not chemically matched, spectral normalization based on calculation of relative intensities cannot be used to reduce the effects of differences in physical properties. The main conclusion is that although better for whole tablet analysis, transmission Raman is more sensitive to differences in the photon propagation properties of the calibration and sample tablets

Lubricant sensitivity in function of paddle movement in the forced feeder of a high-speed tablet press

Context: The negative impact of magnesium stearate (MgSt) on the hardness of tablets is a well-known phenomenon, but the influence of paddle movement in the forced feeder on the lubricant effect during tablet compression is often neglected. Objective: The purpose of this research was to investigate the influence of paddle speed in the forced feeder on tablet tensile strength (TS).Materials and methods: Mixtures of microcrystalline cellulose (MCC) and MgSt (0.5%) were blended using different methods (low & high shear). After blending, the formulations were compressed into tablets. All parameters of the tableting cycle were kept constant except the speed of the paddles in the forced feeder. Results and discussion: The blending technique affected the sensitivity of the formulation to the paddle speed. The TS of pure MCC tablets did not change in function of paddle speed, while tablets prepared by low shear mixing became softer at higher paddle speed. The TS of tablets manufactured using the high-shear mixed blend was low and did not vary in function of paddle speed, suggesting that overlubrication already occurred during the initial blending step. Furthermore, analysis of the machine parameters allowed evaluation of the influence of the paddles on the flowability, initial packing, and compactability of the powder mixtures. Conclusion: The results elucidated that during manufacturing of tablets using MgSt-containing blends care should not only be taken during the blending step prior to tableting, but also during the tableting process itself, as paddle speed can affect tablet TS, a critical quality attribute

“Ghost tablet” husks excreted in feces in large bupropion XL overdose

Background: Extended-release medications are widely prescribed across the spectrum of medical specialties; however, there is heterogeneity in how they are formulated. Commonly, they consist of an insoluble matrix or shell from which drug elutes, which may then be observed by patients when excreted in feces. We describe the case of a patient who ingested a large amount of extended-release bupropion tablets and subsequently passed a large number of these so-called “ghost tablets” in his stool. Case Details: A 19-year-old male presented in status epilepticus following intentional overdose of an unknown substance. He had prolonged QRS and QT intervals on ECG, hypotension requiring vasopressors, and tachycardia, and progressed to cardiac arrest and respiratory failure. On hospital day 4, he passed several large bowel movements containing apparent tablets. Serum bupropion and hydroxybupropion levels performed on serum taken at time of admission were 1800 ng/mL and 4200 ng/mL, respectively. Case Discussion: “Ghost tablets,” the insoluble remnant of some extended-release dosage forms, have been previously reported to appear in patients' stool in the course of therapeutic dosing. We present the case of a considerable quantity of these ghost tablets recovered from stool following a large bupropion XL overdose. Conclusion: Healthcare providers should be aware of the potential for this phenomenon to occur in poisoned patients. It should be documented as physical evidence of overdose in addition to clinical evidence

From compressibility to structural investigation of sodium dodecyl sulphate — Part 1: Powder and tablet physico-chemical characteristics

As a part of a study on detergent tablets, investigations were carried out to elucidate the compression behavior of a powdered surfactant, sodium dodecyl sulphate (SDS), based on a comparison with the main component of the formulation, i.e. the chorine provider (DCCNa). The compacted SDS exhibited poor cohesion as well as delayed dissolution whatever the compression pressure. The microscopic observations and the mercury porosimetry measurements both demonstrated that a residual porosity existed in the tablets but the dissolution times were always long. A modification of SDS in contact with water, forming a structure like a gel, probably occurred, inducing the closing of the pores and thereby limiting the water intrusion into the tablets

Development and optimization of a novel sustained-release dextran tablet formulation for propranolol hydrochloride

A novel oral controlled delivery system for propranolol hydrochloride (PPL) was developed and optimized. The in vitro dissolution profiles of sustained-release matrix tablets of racemic PPL were determined and compared with the United States Pharmacopeia (USP) tolerance specifications for Propranolol Hydrochloride Extended-Release Capsules. The influence of matrix forming agents (native dextran, hydroxypropyl methylcellulose (HPMC), cetyl alcohol) and binary mixtures of them on PPL release in vitro was investigated. A central composite design was applied to the optimization of a sustained-release tablet formulation. The sustained-release matrix tablets with good physical, mechanical and technological properties were obtained with a matrix excipient:PPL ratio of 60:40 (w/w), with a dextran:HPMC ratio of 4:1 (w/w) and with a cetyl alcohol amount of 15% (w/w). A comparative kinetic study of the present matrix tablets and commercial SUMIAL RETARD capsules (Spain) was established. The value for the similarity factor (f2 = 69.6) suggested that the dissolution profile of the present two sustained-release oral dosage forms are similar. Higuchi (diffusion) and Hixon–Crowell (erosion) kinetic profiles were achieved and this codependent mechanism of drug release was established

Effect of low-dosage vitamin A and riboflavin on iron-folate supplementation in anaemic pregnant women

A double-blind, placebo, controlled trial was conducted in Banyudono subdistrict, Boyolali regency, Central Java province, Indonesia. The aim of the study was to determine whether adding low-dosage vitamin A and riboflavin can enhance the effect of iron-folate supplementation in anaemic pregnant women. From July to November 2000, 202 pregnant women were screened for anaemia (haemoglobin <11.0 g/dL). One hundred and three pregnant women (51%) were found to be anaemic and were then allocated alternately into four groups. Over a period of 60 days, group IF (n = 29) received iron-folate tablets (200 mg FeSO4 and 250 µg folic acid) + 5 mg glucose; group IFR (n = 22) received iron-folate tablets + 5 mg riboflavin; group IFA (n = 29) received iron-folate tablets + 2.75 mg retinyl palmitate (equal to 5000 IU vitamin A); and group IFRA (n = 23) received iron-folate tablets + 5 mg riboflavin + 2.75 mg retinyl palmitate. At the end of the study 19 pregnant women (18.4%) were excluded from the analysis because of various reasons. Statistical analysis was based on 84 women (81.5%): group IF, n = 25; group IFR, n = 22; group IFA, n = 18; and group IFRA, n = 19. Haemoglobin measurements were carried out using the Technicon H1* (cyanmethaemoglobin method). All groups showed a significant increase in haemoglobin concentration (P 0.05), with the highest increment being in group IFR. Multiple comparisons only showed significant differences between group IFR and group IFA (P < 0.05). It can be concluded that iron-folate supplementation can increase haemoglobin concentrations in anaemic pregnant women. Adding riboflavin tends to enhance the effect of iron- folate supplementation, but this is not the case with adding vitamin A. Key words: anaemic pregnant women, iron-folate, low-dosage vitamin A, riboflavin