Analysis and stability of polymorphs in tablets: The case of Risperidone (original) (raw)
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Non-destructive quantitative analysis of risperidone in film-coated tablets
Journal of Pharmaceutical and Biomedical Analysis, 2008
A simple, non-destructive, methodology based on FT-Raman spectroscopy was developed for the quantitative analysis of risperidone in commercially available film-coated tablets. A simple linear regression model was constructed based on standard tablets, prepared using the same manufacturing process as the commercially available. The tablets contained 0.27, 0.54, 1.08, 1.62, 2.16, 3.24 and 4.32 wt% risperidone. The most prominent Raman vibration of the active pharmaceutical ingredient at 1533 cm −1 , recorded using a home-made rotating system, was plotted against concentration. The model was tested on commercial film-coated tablets. The results were compared against those obtained by application of HPLC on the same samples.
Applied spectroscopy, 2017
Polymorph detection is critical for ensuring pharmaceutical product quality in drug substances exhibiting polymorphism. Conventional analytical techniques such as X-ray powder diffraction and solid-state nuclear magnetic resonance are utilized primarily for characterizing the presence and identity of specific polymorphs in a sample. These techniques have encountered challenges in analyzing the constitution of polymorphs in the presence of other components commonly found in pharmaceutical dosage forms. Laborious sample preparation procedures are usually required to achieve satisfactory data interpretability. There is a need for alternative techniques capable of probing pharmaceutical dosage forms rapidly and nondestructively, which is dictated by the practical requirements of applications such as quality monitoring on production lines or when quantifying product shelf lifetime. The sensitivity of transmission Raman spectroscopy for detecting polymorphs in final tablet cores was inves...
International journal of pharmaceutics, 2008
Common analytical techniques including Raman, NIR, and XRD were evaluated for quantitative determination of three solid-state forms (amorphous, Form B and Form C) of a development compound. Raman spectroscopy was selected as the primary analytical technique with sufficient sensitivity to monitor and quantify the neat drug substance alone and in the drug product. A reliable multivariate curve resolution (MCR) method based on the second derivative Raman measurements of the three pure physical forms was developed and validated with 3.5% root mean square error of prediction (RMSEP) for Form B, which was selected as the preferred form for further development. A partial least squares (PLS) algorithm was also used for the multivariate calibration of both the NIR and Raman measurements. The long-term stability of Form B as a neat active pharmaceutical ingredient (API) and in a tablet formulation was quantitatively monitored under various stress conditions of temperature and moisture. Moistu...
Identification of drugs in pharmaceutical dosage forms by X-ray powder diffractometry
Journal of Pharmaceutical and Biomedical Analysis, 1997
A simple X-ray powder diffractometric (XRD) method was developed for the identification of the active ingredient in a variety of dosage forms. The method was successfully used to unambiguously identify the active ingredient(s) in tablet, capsule, suppository and ointment formulations. The unique feature of the method is that it provides information about the solid-state of the drug. Thus, a capsule formulation containing anhydrous ampicillin was readily distinguished from that containing ampicillin trihydrate. The USP stipulates the use of the fl-polymorphic form of anhydrous carbamazepine in carbamazepine tablets. Contamination by the c~-polymorph (down to a level of 1.4% w/w of the formulation) could be detected. In some of the multicomponent formulations, there was a pronounced overlap of the powder patterns of ingredients which made identification difficult. This problem was solved by using a pattern subtraction technique, which permitted selective subtraction of the XRD pattern of the constituents of the formulation from the overall XRD pattern. Such an approach enabled identification of the drug even when it constituted only 5% w/w of the formulation. The method also permitted simultaneous identification of the multiple active ingredients in trimethoprim-sulfamethoxazole and acetaminophen-aspirin-caffeine formulations.
International Journal of Pharmaceutics, 2010
The focus of present investigation was to assess the utility of non-destructive techniques in the evaluation of risperidone solid dispersions (SD) with methyl-β-cyclodextrin (MBCD) and subsequent incorporation of the SD into orally disintegrating tablets (ODT) for a faster release of risperidone. The SD was prepared by a solvent evaporation method and evaluated by scanning electron microscopy (SEM), Fourier transform infrared (FTIR), near infrared spectroscopy (NIR), NIR-chemical imaging (NIR-CI), powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC). DSC and XRD analysis indicated that crystallinity of SD has reduced significantly. FTIR showed no interaction between risperidone and MBCD. Partial least square (PLS) was applied to the NIR data for the construction of chemometric models to determine both components of the SD. Good correlations were obtained for calibration and prediction as indicated by correlation coefficients >0.9965. The model was more accurate and less biased in predicting the MBCD than risperidone as indicated by its lower mean accuracy and mean bias values. SD-3 (risperidone:MBCD, 1:3) was incorporated into ODT tablets containing diluent (D-mannitol, FlowLac® 100 or galenIQ™-721) and superdisintegrant (Kollidon® CL-SF, Ac-Di-Sol or sodium starch glycolate). Disintegration time, T50 and T90 were decreased in the formulations containing mannitol and Kollidon® CL-SF, but increased with galenIQ™-721 and sodium starch glycolate, respectively. NIR-CI images confirmed the homogeneity of SD and ODT formulations.
Drug Characterization in Low Dosage Pharmaceutical Tablets Using Raman Microscopic Mapping
Applied Spectroscopy, 2006
Raman micro-spectroscopic mapping is utilized to analyze pharmaceutical tablets containing a low concentration (0.5% w/w) of active pharmaceutical ingredient (API). The domain sizes and spatial distributions of the API and the major excipients are obtained. Domain size of the API is found to be dependent upon the particle size distribution of the ingoing API material, making the Raman maps good indicators of the source of API used in tablet manufacturing. Multivariate classification was performed to simultaneously check for the presence of two undesired API polymorphs within tablets. Raman mapping was demonstrated capable of detecting in the tablet matrix as little as 10% form conversion of the low-dosage (0.5% w/w) API, which is equivalent to detection of a 0.05% w/w polymorphic impurity. Overall, the information provided by Raman micro-spectroscopic mapping was found to have potential utility for manufacturing process optimization or predictive stability assessments.
Quantitative polymorph contaminant analysis in tablets using Raman and near infra-red spectroscopies
Journal of Pharmaceutical and Biomedical Analysis, 2013
The detection and quantification of alternate polymorphs of Active Pharmaceutical Ingredients (API), particularly at low concentrations is a key issue for the manufacture and analysis of solid state formulations. Each polymorph can possess unique physical and chemical properties which in turn can directly affect factors such as solubility and bioavailability. Near Infra-red (NIR) and Raman spectroscopies can be used for the rapid characterisation and quantification of polymorphs in solid samples. In this study we have generated a model tablet system with two excipients and a 10% API concentration, where the API is a mixture of the FII and FIII polymorphs of Piracetam. Using Transmission Raman Spectroscopy (TRS) and NIR spectroscopy it was possible to detect FII polymorph contamination in these model tablets with Limits of Detection (LODs) of 0.6 and 0.7% respectively with respect to the total tablet weight (or ~6-7% of the API content). The TRS method is the superior method because of the speed of analysis (~6 seconds per sample), better sampling statistics, and because the sharper, more resolved bands in the Raman spectra allowed for better interpretation of the spectral data. In addition the TRS used here provides facile access to the low frequency wavenumber region for analysis of solid-state lattice modes.
Journal of Pharmaceutical and Biomedical Analysis, 1997
Changes in the dissolution of a solid dispersion capsule formulation composed of amorphous SCH 48461 in a polyethylene glycol 8000 matrix were investigated. SCH 48461 [(3R,4S)-1,4-bis(4-methoxyphenyl)-3-(3-phenylpropyl)-2-azetidinone] is a potent cholesterol absorption inhibitor with low water solubility and low melting point. Several capsule lots placed under controlled storage conditions exhibited a slowing of dissolution as a function of time with large inter-lot and intra-lot dissolution variations. Capsule contents were analyzed by attenuated total reflectance infrared (ATR-IR) microspectroscopy and solid-state cross-polarization, magic angle spinning (CPMAS) 13 C-nuclear magnetic resonance (NMR) spectrometry. ATR-IR microspectroscopic analysis showed large IR spectral differences between the lots including the presence of a crystalline drug fraction in lots which exhibited incomplete dissolution. Solid-state CPMAS 13 C-NMR analysis confirmed the presence of a crystalline drug fraction in the problematic capsule lots. Both ATR-IR and CPMAS 13 C-NMR spectral results produced a rank ordering of the crystalline drug fraction present in the capsule lots that correspond to the dissolution results.