A Review on Multi Approaches for Impurity Isolation and its Characterization

International Conference on Harmonization (ICH) has formulated different guideline regarding the control of impurities. In this review,  the impurity sources, classification, isolation, detection and characterization methods are described. The some impurities are unavoidable and will be present in trace amounts hence ICH guidelines frame the different policies and establish the specification limits, isolation and characterization is necessary for evaluation and control of impurities. The other regulatory bodies and drug development authorities look up to these guidelines for launching a quality drug into the market. Validation of analytical process for impurity identification is performed to establish the impurity profile of any drug substance. Hence the major focus of this review article is on isolation and characterization of impurities using various technics, sources and classifications, establishment of impurity profile and analytical approaches to establish its profile. We also could apply the QbD to providing statistical documentary evidences. Keywords: Impurity profile, Impurities isolation methods, chromatographic separation, Impurity Characterization, ICH, QbD

NON-DESTRUCTIVE RAMAN SPECTROSCOPIC METHOD FOR ESTIMATION OF MONTELUKAST FROM TABLET DOSAGES FORM

Objective: A rapid, non-destructive and non-solvent raman spectroscopic method for estimation of Montelukast from tablet dosages form Methods: Quantification was carried out by measuring the intensity of analyte peak at 1440 cm-1. Each Raman spectrum corresponded to an accumulation of 4 scans with an exposure time of 5 sec for each scan with a total integration time of 20 sec.Results: The method exhibited linearity between 2 mg-24 mg show well resolve quantification From MON. The linearity equation was calculated as y = 13.036x+70.819 and the correlation coefficient was found to be 0.997 for MON. LOD (limit of detection) and LOQ(limit of quantification) values were calculated using the calibration curve slope and standard deviation of the response. The LOD (limit of detection) and LOQ (limit of quantification) values were found to be 1.71 mg and 5.13 mg respectively.Conclusion: The developed method was successfully applied for assay of montelukast in the intact formulation. The method was validated according to an international conference on harmonisation guidelines. A recent study, montelukast sodium had been analysed by the raman method, but, looking into the tremendous potential of raman spectroscopic method; it can be extended as a process analysis and technology tool in various quality checks during manufacturing of pharmaceutical products

RP-HPLC METHOD FOR ESTIMATION OF TIAPRIDE RELATED SUBSTANCE IN TABLET FORMULATION

Objective: To develop a simple, precise, accurate related substance, reverse phase high-performance liquid chomatographic (RP-HPLC) method for the quantitative estimation of impurities which are present in dosage form of Tiapride Hydrochloride.Methods: The chomatographic separation was achieved with Inertsil C8 (250 × 4.6) mm, 5µ column with mobile phase containing a gradient mixture of 0.05 mM aqueous sodiumdihydrogen phosphate (KH2PO4)solution buffer: (with octanesulphonate and final pH of buffer was adjusted to 2.7 with Orthophosphoric acid): Acetonitrile: Methanol (800:150:50 v/v), flow rate of 1.5 ml/min and a detection wavelength of 240 nm.Results: The method exhibited linearity between range 0.125 to 1200 µg/ml, shows well resolved degradation products from Tiapride hydrochloride tablet with 0.063 µg/ml of LOD (limit of detection) and 0.125 µg/ml of LOQ (limit of Quantification). Forced degradation studies proved that the method is specific for Tiapride Hydrochloride and N-oxide Tiapride reported in European pharmacopeia and British pharmacopeia is one of the degradation impurity confirmed by liquid chromatography mass spectrometry (LC-MS) analysis.Conclusion: An accurate, precise, linear, robust and specific related substance RP-HPLC method was developed and validated for the quantitative estimation of impurities presented in pharmaceutical dosage form of Tiapride Hydrochloride as per ICH guidelines. The method is stability indicating used for separation of degradation products and can be used for the identification of process related impurity.Â

Beyond the imitation game: Quantifying and extrapolating the capabilities of language models

Language models demonstrate both quantitative improvement and new qualitative capabilities with increasing scale. Despite their potentially transformative impact, these new capabilities are as yet poorly characterized. In order to inform future research, prepare for disruptive new model capabilities, and ameliorate socially harmful effects, it is vital that we understand the present and near-future capabilities and limitations of language models. To address this challenge, we introduce the Beyond the Imitation Game benchmark (BIG-bench). BIG-bench currently consists of 204 tasks, contributed by 442 authors across 132 institutions. Task topics are diverse, drawing problems from linguistics, childhood development, math, common-sense reasoning, biology, physics, social bias, software development, and beyond. BIG-bench focuses on tasks that are believed to be beyond the capabilities of current language models. We evaluate the behavior of OpenAI's GPT models, Google-internal dense transformer architectures, and Switch-style sparse transformers on BIG-bench, across model sizes spanning millions to hundreds of billions of parameters. In addition, a team of human expert raters performed all tasks in order to provide a strong baseline. Findings include: model performance and calibration both improve with scale, but are poor in absolute terms (and when compared with rater performance); performance is remarkably similar across model classes, though with benefits from sparsity; tasks that improve gradually and predictably commonly involve a large knowledge or memorization component, whereas tasks that exhibit "breakthrough" behavior at a critical scale often involve multiple steps or components, or brittle metrics; social bias typically increases with scale in settings with ambiguous context, but this can be improved with prompting