Medicine and Media: The Ranitidine Debate.

Ranitidine has been the topic of recent media reports. Current findings, confirmed by the US Food and Drug Administration, indicate that some ranitidine products contain a substance that may be carcinogenic. Providers and patients require additional information on the risks of continuing therapy vs. the benefits of the medication. This article comments on what is currently known about the evolving situation of elevated N-nitrosodimethylamine levels in ranitidine and the limits of the existing information to assess best practices.

Understanding and Preventing (N-Nitrosodimethylamine) NDMA Contamination of Medications.

N-nitrosodimethylamine (NDMA) is a hepatotoxic agent and carcinogen contaminant in commonly used medications such as valsartan, losartan, irbesartan, and ranitidine. NDMA can be produced during manufacture, introduced from contaminated ingredients procured elsewhere, or introduced from contaminated solvents and catalysts. The Food and Drug Administration has established a maximum dose of NDMA that is permissible per tablet and guidance for manufacturers. However, many unanswered questions about NDMA contamination need rigorous investigation.

Evaluation of recombinant human parathyroid hormone by CZE method and its correlation with in vitro bioassay and LC methods.

A stability-indicating capillary zone electrophoresis (CZE) method was validated to assess the content/potency of the recombinant human parathyroid hormone (rhPTH 1-34), using ranitidine as internal standard (IS). A fused-silica capillary, (i.d. of 50µm; effective length of 40cm) was used at 25°C; the applied voltage was 20kV. The background electrolyte solution consisted of 50mmolL-1 sodium dihydrogen phosphate solution at pH 3.0. Injections were performed using a pressure mode at 50 mbar for 45s, with detection by photodiode array (PDA) detector set at 200nm. Separation was obtained with a migration time of 5.3min, and was linear over the concentration range of 0.25-250µgmL-1 (r2 =0.9992). Specificity and stability-indicating capability were established in degradation studies, which also showed that there was no interference of the excipients. The accuracy was 100.28% with bias lower than 0.85%. Analyses of the same batches showed mean differences of the estimated content/potencies of 0.61%, 1.31% higher and 0.86% lower as compared to the validated reversed-phase and size exclusion liquid chromatography methods, and to the UMR-106 cell culture bioassay, respectively, with non-significant differences (p>0.05). Degraded forms were also subjected to the in vitro cytotoxicity test. The results obtained showed the capabilities of each one of the methods, and constitute an alternative strategy to monitor stability, improve the quality control and ensure the batch-to-batch consistency of bulk and finished biotechnology-derived medicine.

[Comparative evaluation of the anionic superdisintegrant incorporation mode on the quality of ranitidine tablets]. / Evaluarea comparativa a modului de încorporare al unui superdezagregant anionic asupra calitatii comprimatelor cu ranitidina.

UNLABELLED: The present study was based on the impact of the superdisintegrants incorporation mechanism on the immediate realese of the tablets final performances. The aim was the selection of the working method to obtain Ranitidine 150 mg tablets with the desiderate quality and in reproducible conditions. MATERIAL AND METHODS: The effect of the incorporation mode of sodium starch glycolate on the aspect, granules size distribution and flowing properties of the lubricated product, and also the weight uniformity, hardness, disintegration, friability, and dissolution of the Ranitidine 150 mg tablets prepared by dry granulation was studied. The addition mode of the disintegrant was realized in three ways: intragranular, extragranular, and distributed equally between the two phases. The distribution range for the tablets weight was established. Relative standard distribution was calculed for the weight and hardness of the uncoated tablets. RESULTS: The powder flow and, implicit, the weight uniformity of the uncoated tablets was positive influenced by the extragranular incorporation of the superdisintegrant. The disintegration time was identical for all the three disintegrant addition modes, and the hardness and the friability were not significantly influenced by working method, the obtained values were similar. For the developed formulations, the percent of the ranitidine dissolution was high, but higher in the extragranular incorporation. CONCLUSIONS: For the product quality the extragranular addition mode seemed the best method to incorporate the superdisintegrant.

Ranitidine preparations on the Belgian market: a comparative study.

Ranitidine preparations formulated as tablets and granules were evaluated with different tests including in vitro dissolution and assay. Previously the analytical methods of these tests were validated according to the guidelines of the European network of Official Medicines Control Laboratories (OMCLs). All examined products complied to the requirements as described in the European, the British and the US Pharmacopoeia and consequently they can be considered as pharmaceutically equivalent.

Solid state assay of ranitidine HCl as a bulk drug and as active ingredient in tablets using DRIFT spectroscopy with artificial neural networks.

PURPOSE: A new, simple, sensitive and rapid method was developed to analyse the polymorphic purity of crystalline ranitidine-HCI as a bulk drug and from a tablet formulation. METHODS: Diffuse reflectance infrared Fourier transform (DRIFT) spectroscopy was combined with Artificial Neural Networks (ANNs) as a data modelling tool. A standard feed-forward network, with backpropagation rule and with single hidden layer architecture was chosen. Reduction and transformation of the spectral data enhanced the ANN performance and reduced the complexity of the ANNs model. Spectral intensities from 1738 wavenumbers were reduced into 173 averaged spectral values. These 173 values were used as inputs for the ANN. Following a sensitivity analysis the number of inputs was reduced to 30, or 35, these being the input windows which had most effect on the output of the ANN. RESULTS: For the bulk drug assay, the ANN model had 30 inputs selected from a sensitivity analysis, one hidden layer, and two output neurons, one for the percentage of each ranitidine hydrochloride crystal form. The model could simultaneously distinguish between crystal forms and quantify them enabling the physical purity of the bulk drug to be checked. For the tablet assay, the ANN model had 173 averaged spectral values as the inputs, one hidden layer and five output neurons, two for the percentage of the two ranitidine hydrochloride crystal forms and three more outputs for tablet excipients and additives. The ANN was able to solve the problem of overlapping peaks and it successfully identified and quantified all components in tablet formulation with reasonable accuracy. CONCLUSIONS: Some of the advantages over conventional analytical methods include simplicity, speed and good selectivity. The results from DRIFT spectral quantification study show the benefits of the neural network approach in analysing spectral data.