共查询到20条相似文献,搜索用时 15 毫秒
1.
Xinyi Wang Sharadrao M. Patil David A. Keire Xiaoming Xu Kang Chen 《AAPS PharmSciTech》2018,19(4):1647-1651
Generic drug products are expected to have the same active pharmaceutical ingredient (API) (Q1) with the same content (Q2) and microstructure arrangement (Q3) as the innovator product. In complex oil-in-water emulsion drugs, the hydrophobic API is mainly formulated in oil droplets stabilized by surfactant and micelles composed of extra surfactant molecules. The API phase partition in oil and water (mainly micelle) is a critical quality attribute (CQA) of emulsion product in demonstrating physicochemical equivalence using difluprednate (DFPN) emulsion product Durezol® as a model, we developed a novel low-field benchtop NMR method to demonstrate its applicability in measuring DFPN phase partition for ophthalmic oil-in-water emulsion products. Low-field 19F spectra were collected for DFPN in formulation, in water phase and oil phase after separation from ultra-centrifugation. The NMR data showed the mass balance of DFPN before and after phase separation. The average water phase content of different Durezol® lots was 32 ± 3% with 1% variation from method reproducibility test. The partition results were 52 ± 2% for the in-house control products prepared in Q1/Q2 equivalence to Durezol® but by a different process. The significant difference in DFPN-phase partition between Durezol® and the in-house formulation demonstrated manufacture difference readily changed the API partition. The newly developed ultra-centrifugation and 19F NMR by benchtop instrument is a simple, robust, and sensitive analytical method for ophthalmic emulsion drug product development and control. 相似文献
2.
The purpose of this study was to demonstrate acoustic resonance spectrometry (ARS) as an alternative process analytical technology
to near infrared (NIR) spectroscopy for the quantification of active pharmaceutical ingradient (API) in semi-solids such as
creams, gels, ointments, and lotions. The ARS used for this research was an inexpensive instrument constructed from readily
available parts. Acoustic-resonance spectra were collected with a frequency spectrum from 0 to 22.05 KHz. NIR data were collected
from 1100 to 2500 nm. Using 1-point net analyte signal (NAS) calibration, NIR for the API (colloidal oatmeal [CO]) gave anr
2 prediction accuracy of 0.971, and a standard error of performance (SEP) of 0.517%CO. ARS for the API resulted in anr
2 of 0.983 and SEP of 0.317%CO. NAS calibration is compared with principal component regression. This research demonstrates
that ARS can sometimes outperform NIR spectrometry and can be an effective analytical method for the quantification of API
in semi-solids. ARS requires no sample preparation, provides larger penetration depths into lotions than optical techniques,
and measures API concentrations faster and more accurately. These results suggest that ARS is a useful process analytical
technology (PAT).
Published: July 14, 2006 相似文献
3.
Giroud C Augsburger M Menetrey A Mangin P 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2003,789(1):131-138
Zolpidem and zaleplon are two short-acting hypnotic agents used in Europe and in the USA. An atmospheric pressure ionisation liquid chromatography-mass spectrometry (Sciex API 150 EX) method was developed for the determination of zolpidem and zaleplon in whole blood. After single-step liquid-liquid extraction, the hypnotics were separated by gradient-elution with an ammonium formate buffer/acetonitrile eluent on an Inertsil ODS-3 column. Methaqualone was used as internal standard. The recovery was higher than 70% for both hypnotics and the internal standard. The best fit for the calibration curve was achieved, between 1 and 250 ng/ml, with 1/x quadratic regression. Coefficients of intra- and inter-assay variation calculated at 5, 25 and 100 ng/ml were less than 10%. The method was successfully applied to forensic cases. 相似文献
4.
A transmission near infrared (NIR) spectroscopic method has been developed for the nondestructive determination of drug content
in tablets with less than 1% weight of active ingredient per weight of formulation (m/m) drug content. Tablets were manufactured
with drug concentrations of ∼0.5%, 0.7%, and 1.0% (m/m) and ranging in drug content from 0.71 to 2.51 mg per tablet. Transmission
NIR spectra were obtained for 110 tablets that constituted the training set for the calibration model developed with partial
least squares regression. The reference method for the calibration model was a validated UV spectrophotometric method. Several
data preprocessing methods were used to reduce the effect of scattering on the NIR spectra and base the calibration model
on spectral changes related to the drug concentration changes. The final calibration model included the spectral range from
11 216 to 8662 cm−1 the standard normal variate (SNV), and first derivative spectral pretreatments. This model was used to predict an independent
set of 48 tablets with a root mean standard error of prediction (RMSEP) of 0.14 mg, and a bias of only −0.05 mg per tablet.
The study showed that transmission NIR spectroscopy is a viable alternative for nondestructive testing of low drug content
tablets, available for the analysis of large numbers of tablets during process development and as a tool to detect drug agglomeration
and evaluate process improvement efforts.
Published: March 24, 2006 相似文献
5.
Lihong Du Cynthia M. Miller-Stein Robert J. Valesky Ashley N. Martucci Eric J. Woolf 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2009,877(14-15):1465-1471
Telcagepant (MK-0974) is a novel oral calcitonin gene-related peptide (CGRP) receptor antagonist and is currently under clinical development. Results from phases II and III clinical trials have suggested that telcagepant is effective for migraine treatment. A reliable and high throughput protein precipitation (PPT) method for determination of telcagepant in human plasma using liquid chromatography coupled with atmospheric pressure chemical ionization (APCI) tandem mass spectrometry has been developed. Clinical samples, internal standard (IS) and acetonitrile are transferred into 96-well plates using a robotic liquid handling system. An aliquot of 10 μL supernatant is directly injected into the LC–MS/MS system where separation is performed on a FluoPhase RP (150 × 2.1 mm, 5 μm) column with an isocratic mobile phase (60% acetonitrile with 0.1% formic acid and 40% water with 0.1% formic acid) at 0.2 mL/min. The interfering 3S-diastereomer of telcagepant, which is observed in clinical samples, is chromatographically resolved from telcagepant. The PPT procedure significantly reduces the time required for sample processing and the assay is sufficiently sensitive for detection using both API 4000 and API 3000 mass spectrometers. The linear calibration range is 5–5000 nM using 200 μL of plasma. Assay intraday validation was conducted using six calibration curves derived from six lots of human control plasma. Calibration standard accuracy did not deviate by more than 3% and 6% of nominal values, and precision did not exceed 4% coefficient of variation (CV) and 10% CV, respectively on the API 4000 and API 3000. Several clinical phases IIb and III studies have been successfully supported with this assay. 相似文献
6.
In this study, a new radiostereometric analysis (RSA) calibration cage was developed with the aim of improving the accuracy and precision of RSA. This development consisted of three steps: a numerical simulation technique was first used to design the new cage; a synthetic imaging method was then implemented to predict the performance of the designed cage before it was actually fabricated; and an experimental phantom test was finally conducted to verify the actual performance of the new cage and compare with two currently widely used cages. Accuracy was calculated as the 95% prediction intervals from regression analyses between the measured and actual displacements, and precision was defined as the standard deviation of repeated measurements. The final experimental phantom tests showed that the accuracy and precision of the new calibration cage were improved by about 40% over an existing biplanar cage and by about 70% compared to a uniplanar cage design. This new cage can be used with any skeletal joints, in either static or kinematic examination, which is helpful for the standardization of the RSA application. 相似文献
7.
The purpose of this research was to demonstrate the ability of reflectance near-infrared (NIR) spectroscopy for quantitative
analysis of an active ingredient in different production steps of a solid formulation. The drug is quantified at two different
steps of a pharmaceutical process: after granulation and after tablet coating. Calibration samples were prepared by mixing
pure drug, excipients, and batch samples (75–120 mg/g active ingredient) using a simple methodology that can be easily carried
out in a laboratory. Partial least squares calibration models were calculated in second-derivative mode using the wavelength
range 1,134–1,798 nm. The error of prediction for granulated samples was 1.01% and 1.63% for tablets. The results prove that
NIR spectroscopy is a good alternative to other, more time-consuming means of analysis for pharmaceutical process monitoring. 相似文献
8.
This study describes the different stages of optimization in an original drying process for lactic acid bacteria that allows the retrieval of dried samples of Lactobacillus plantarum with maximum viability. The process involves the addition of casein powder to bacterial pellets, followed by mixing and then air-drying in a fluidized bed dryer. The effects on bacterial viability of the a(w) of the casein powder and the kinetics of a(w) variation in the fluidized bed dryer are considered. These parameters were first studied in a water-glycerol solution and the results were then applied to the drying process. Data from the study in liquid medium were reliable in the fluidized drying stage, insofar as optimal viability was achieved for similar dehydration times (16-50 min in liquid medium, and 30 min in the fluidized bed dryer). However, when the powder was mixed rapidly with bacteria, the level of destruction differed from that observed in liquid medium. Viability was up to 70% when the a(w) of water-glycerol was 0.55, whereas it was only 2.1% when the a(w) of the casein-bacterial mix was 0.64. The predictive capacity of dehydration in liquid medium is discussed with regard to the permeability of cells to external solutes. The new process allowed 100% survival of L. plantarum after complete drying (final a(w) < 0.2). However, when used for the desiccation of L. bulgaricus, these parameters achieved a viability of less than 10%. 相似文献
9.
Yan LX Guo DA 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2005,824(1-2):244-248
A simple, sensitive and specific liquid chromatography-tandem mass spectrometry method (LC-MS-MS) had been developed and validated for the quantitation of astragaloside IV (AGS-IV)-an active constituent of Radix Astragali in rat plasma. Assay method was developed by a series of operations described as below. The plasma proteins were precipitated with acetonitrile and digoxin was used as the internal standard (I.S.). The sample solution containing astragaloside IV and the I.S. were obtained and subsequently injected into a LC-MS-MS system following by a gradient elution at a slow flow rate combined with a valve diversion during the liquid chromatography. Chromatographic separation was achieved on a C4 (2.1 mmx10 mm) column with a gradient mobile phase comprised of 90% methanol in water and 10 mM ammonium acetate buffer. The analytes were detected with a PE Sciex API 3000 mass spectrometer using turbo ion spray with positive ionization. Ions monitored in the multiple reaction-monitoring (MRM) modes were m/z 785.5 (precursor ion) to m/z 143.2 (product ion) for AGS-IV and m/z 781.2 (precursor ion) to m/z 243.3 (product ion) for digoxin (I.S.). The method was validated over a linear range of 1-1000 ng/ml. The low limit of quantitation was 1.0 ng/ml. Results from a 3-day validation study demonstrated that the developed method possessed good precision (CV% values were between 5.9 and 7.6%) and accuracy (96.5-102.1%) across the calibration range. The recoveries were 91 and 90% for astragaloside IV and I.S., and no significant matrix effects were observed. QC samples were stable when kept at room temperature for 4 h, at -20 degrees C for 4 weeks, and after three freeze/thaw cycles. 相似文献
10.
Giuseppe Strazzullo Agata Gambacorta Filomena Monica Vella Barbara Immirzi Ida Romano Valeria Calandrelli Barbara Nicolaus Licia Lama 《World journal of microbiology & biotechnology》2008,24(8):1513-1519
In this study we suggest a simplified and effective method to directly recover polyhydroxyalkanoates (PHAs) from humid biomass
of Halomonas campaniensis with no pre-treatment steps. Sodium dodecyl sulphate (SDS) was directly added to dispersed biomass of cultured micro-organism
(w/w ratio: 1) in distilled water followed by shaking, heat treatment, and washing steps. The purity of the recovered PHAs
synthesized by H. campaniensis was over 95%, regardless of the cell concentrations and the best yield was 12% (w/w) of the cell wet weight when the micro-organism
was cultivated in a glucose-based medium or a glucose/propionate-based medium. MS spectroscopy and 1H, 13C-NMR analysis were used to chemically characterize the PHAs; their thermal characteristics were obtained using a differential
scanning calorimeter and the average viscosity molecular weight was assessed through specific viscosity measurements. Due
to its ease and velocity, our simplified method is suitable for the detection and recovery of PHAs from humid biomasses with
high yield and purity. The method, which is quick and at low environmental impact, is very valuable for the simultaneous testing
of cultures grown with different inducers for PHAs having particular chemical/physical characteristics. 相似文献
11.
Assessing body condition and energy budget components by scoring abdominal profiles in free-ranging pink-footed geese Anser brachyrhynchus 总被引:1,自引:0,他引:1
An abdominal profile index (API) was developed for pink-footed geese Anser brachyrhynchus as a measure of body condition. On basis of carcass analysis of 56 adult geese with known API prior to collection, we found significant linear relationships between API against body mass, abdominal fat and total energy content. Hence, changes in API reflect net energy intake rates. As an example of the applicability of the calibration, we compared APIs of individually marked geese before and after long migration episodes and estimated the cost of flight at 8.9 kJ/km. In addition we estimated gain rates at three major staging sites along the spring flyway indicating an increase in fueling rates with latitude. Calibration of APIs and energy contents offers new opportunities for field studies of waterfowl energetics. 相似文献
12.
Extractive disruption process integration using ultrasonication and an aqueous two‐phase system for protein recovery from Chlorella sorokiniana
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Win Nee Phong Cheng Foh Le Pau Loke Show Jo‐Shu Chang Tau Chuan Ling 《Engineering in Life Science》2017,17(4):357-369
Microalgae emerge as the most promising protein sources for aquaculture industry. However, the commercial proteins production at low cost remains a challenge. The process of harnessing microalgal proteins involves several steps such as cell disruption, isolation and extraction. The discrete processes are generally complicated, time‐consuming and costly. To date, the notion of integrating microalgal cell disruption and proteins recovery process into one step is yet to explore. Hence, this study aimed to investigate the feasibility of applying methanol/potassium ATPS in the integrated process for proteins recovery from Chlorella sorokiniana. Parameters such as salt types, salt concentrations, methanol concentrations, NaCl addition were optimized. The possibility of upscaling and the effectiveness of recycling the phase components were also studied. The results showed that ATPS formed by 30% (w/w) K3PO4 and 20% (w/w) methanol with 3% (w/w) NaCl addition was optimum for proteins recovery. In this system, the partition coefficient and yield were 7.28 and 84.23%, respectively. There were no significant differences in the partition coefficient and yield when the integrated process was upscaled to 100‐fold. The recovered phase components can still be recycled effectively at fifth cycle. In conclusions, this method is simple, rapid, environmental friendly and could be implemented at large scale. 相似文献
13.
Cogdill RP Anderson CA Delgado M Chisholm R Bolton R Herkert T Afnan AM Drennen JK 《AAPS PharmSciTech》2005,6(2):E273-E283
This article is the second of a series of articles detailing the development of near-infrared (NIR) methods for solid dosage-form
analysis. Experiments were conducted at the Duquesne University Center for Pharmaceutical Technology to demonstrate a method
for developing and validating NIR models for the analysis of active pharmaceutical ingredient (API) content and hardness of
a solid dosage form. Robustness and cross-validation testing were used to optimize the API content and hardness models. For
the API content calibration, the optimal model was determined as multiplicative scatter correction with Savitsky-Golay first-derivative
preprocessing followed by partial least-squares (PLS) regression including 4 latent variables. API content calibration achieved
root mean squared error (RMSE) and root mean square error of cross validation (RMSECV) of 1.48 and 1.80 mg, respectively.
PLS regression and baseline-fit calibration models were compared for the prediction of tablet hardness. Based on robustness
testing, PLS regression was selected for the final hardness model, with RMSE and RMSECV of 8.1 and 8.8 N, respectively. Validation
testing indicated that API content and hardness of production-scale tablets is predicted with root mean square error of prediction
of 1.04 mg and 8.5 N, respectively. Explicit robustness testing for high-flux noise and wavelength uncertainty demonstrated
the robustness of the API concentration calibration model with respect to normal instrument operating conditions.
Published: October 6, 2005
The views presented in this article do not necessarily reflect those of the Food and Drug Administration. 相似文献
14.
The performance of an industrial pharmaceutical process (production of an active pharmaceutical ingredient by fermentation, API) was modeled by multiblock partial least squares (MBPLS). The most important process stages are inoculum production and API production fermentation. Thirty batches (runs) were produced according to an experimental planning. Rather than merging all these data into a single block of independent variables (as in ordinary PLS), four data blocks were used separately (manipulated and quality variables for each process stage). With the multiblock approach it was possible to calculate weights and scores for each independent block. It was found that the inoculum quality variables were highly correlated with API production for nominal fermentations. For the nonnominal fermentations, the manipulations of the fermentation stage explained the amount of API obtained (especially the pH and biomass concentration). Based on the above process analysis it was possible to select a smaller set of variables with which a new model was built. The amount of variance predicted of the final API concentration (cross-validation) for this model was 82.4%. The advantage of the multiblock model over the standard PLS model is that the contributions of the two main process stages to the API volumetric productivity were determined. 相似文献
15.
The present study is an attempt to develop a neural network-based method for predicting the real value of solvent accessibility from the sequence using evolutionary information in the form of multiple sequence alignment. In this method, two feed-forward networks with a single hidden layer have been trained with standard back-propagation as a learning algorithm. The Pearson's correlation coefficient increases from 0.53 to 0.63, and mean absolute error decreases from 18.2 to 16% when multiple-sequence alignment obtained from PSI-BLAST is used as input instead of a single sequence. The performance of the method further improves from a correlation coefficient of 0.63 to 0.67 when secondary structure information predicted by PSIPRED is incorporated in the prediction. The final network yields a mean absolute error value of 15.2% between the experimental and predicted values, when tested on two different nonhomologous and nonredundant datasets of varying sizes. The method consists of two steps: (1) in the first step, a sequence-to-structure network is trained with the multiple alignment profiles in the form of PSI-BLAST-generated position-specific scoring matrices, and (2) in the second step, the output obtained from the first network and PSIPRED-predicted secondary structure information is used as an input to the second structure-to-structure network. Based on the present study, a server SARpred (http://www.imtech.res.in/raghava/sarpred/) has been developed that predicts the real value of solvent accessibility of residues for a given protein sequence. We have also evaluated the performance of SARpred on 47 proteins used in CASP6 and achieved a correlation coefficient of 0.68 and a MAE of 15.9% between predicted and observed values. 相似文献
16.
Complete dissolution of the active pharmaceutical ingredient (API) is critical in the manufacturing of liquid-filled soft-gelatin capsules (SGC). Attenuated total reflectance UV spectroscopy (ATR-UV) and Raman spectroscopy have been investigated for in-line monitoring of API dissolution during manufacturing of an SGC product. Calibration models have been developed with both techniques for in-line determination of API potency. Performance of both techniques was evaluated and compared. The ATR-UV methodology was found to be able to monitor the dissolution process and determine the endpoint, but was sensitive to temperature variations. The Raman technique was also capable of effectively monitoring the process and was more robust to the temperature variation and process perturbations by using an excipient peak for internal correction. Different data preprocessing methodologies were explored in an attempt to improve method performance. 相似文献
17.
Wunnapuk K Medley GA Liu X Grice JE Jayasinghe S Gawarammana I Buckley NA Roberts MS 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2011,879(28):3047-3052
Simple, sensitive and specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods have been developed and validated for quantification of paraquat (PQ) in plasma and urine. Plasma and urine sample preparation were carried out by one-step protein precipitation using cold acetonitrile (-20 to -10 °C). After centrifugation, an aliquot of 10 μL of supernatant was injected into a Kinetex? hydrophilic interaction chromatography (HILIC) column with a KrudKatcher? Ultra in-line filter. The chromatographic separation was achieved using the mobile phase mixture of 250 mM ammonium formate (with 0.8% aqueous formic acid) in water and acetonitrile at a flow rate of 0.3 mL/min. Detection was performed using an API2000 triple quadrupole tandem mass spectrometer in multiple reaction monitoring (MRM) mode via an electrospray ionization (ESI) source. The calibration curve was linear over the concentration range of 10-5000 ng/mL, with an LLOQ of 10 ng/mL. The inter- and intra-day precision (% R.S.D.) were <8.5% and 6.4% for plasma and urine, respectively with the accuracies (%) within the range of 95.1-102.8%. PQ in plasma and urine samples was stable when stored at -70 °C for three freeze-thaw cycles. The methods were successfully applied to determine PQ concentration in rat and human samples. 相似文献
18.
Sarkar M Khandavilli S Panchagnula R 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2006,830(2):349-354
A high-performance liquid chromatographic and an UV spectrophotometric method were developed and validated for the quantitative determination of three antiretroviral drugs viz. Lamivudine, Stavudine and Nevirapine that constitute one of the first line regimens in antiretroviral therapy. The different analytical performance parameters such as linearity, precision, accuracy, specificity, limit of detection (LOD) and limit of quantification (LOQ) were determined according to International Conference on Harmonization ICH Q2B guidelines. Chromatography was carried out by isocratic technique on a reversed-phase C-18 SYMMETRY column with mobile phase based and optimized depending on the polarity of the molecules. The UV spectrophotometric determinations were performed at 270, 265 and 313 nm for Lamivudine, Stavudine and Nevirapine, respectively. The linearity of the calibration curves for each analyte in the desired concentration range is good (r(2)>0.999) by both the HPLC and UV methods. Both the methods were accurate and precise with recoveries in the range of 97 and 103% for all the three drugs and relative standard deviation (R.S.D.) <5%. Moreover, the accuracy and precision obtained with HPLC correlated well with the UV method which implied that UV spectroscopy can be a cheap, reliable and less time consuming alternative for chromatographic analysis. The proposed methods are highly sensitive, precise and accurate and hence were successfully applied for the reliable quantification of API content in the commercial formulations of Lamivudine, Stavudine and Nevirapine. 相似文献
19.
Igarashi L Kieckbusch TG Franco TT 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2004,809(1):75-80
SCH 201781 is a direct thrombin inhibitor recently under study in clinical trials to determine its safety and efficacy for the treatment of venous and arterial thrombosis. In aqueous solution, SCH 201781 exists as three forms, a ring-opened hydrated form and two ring-closed diastereomers. An automated solid-phase extraction LC-MS/MS method that chromatographically separates and measures each form was developed and validated from 1 to 1000 ng/mL in human plasma. For calibration curve standards, within- and between-run precision (%CV) ranged from 0.6 to 13.7%, while accuracy (%bias) ranged from -4.8 to 13.1%. For quality control samples, within- and between-run %CV ranged from 1.5 to 9.9% while %bias ranged from -9.1 to 4.9%. The method requires a sample volume of 0.8 ml and utilizes 2H6-labeled SCH 201781 as the internal standard. For sample processing, an Isolute C-8 96-well solid phase extraction plate and a Tomtec Quadra 96 sample processor is employed. Separation of the three forms of SCH 201781 is achieved using a 5 microm, 2 mm x 100 mm Asahipak C8 HPLC column and gradient elution. A Sciex API 365 equipped with a turbo ionspray source is used in the selected reaction monitoring mode for detection. The validated method was used to support clinical studies. 相似文献
20.
Biodiesel production from crude Jatropha curcas L. seed oil with a high content of free fatty acids 总被引:9,自引:0,他引:9
A technique to produce biodiesel from crude Jatropha curcas seed oil (CJCO) having high free fatty acids (15%FFA) has been developed. The high FFA level of JCJO was reduced to less than 1% by a two-step pretreatment process. The first step was carried out with 0.60 w/w methanol-to-oil ratio in the presence of 1% w/w H(2)SO(4) as an acid catalyst in 1-h reaction at 50 degrees C. After the reaction, the mixture was allowed to settle for 2h and the methanol-water mixture separated at the top layer was removed. The second step was transesterified using 0.24 w/w methanol to oil and 1.4% w/w NaOH to oil as alkaline catalyst to produce biodiesel at 65 degrees C. The final yield for methyl esters of fatty acids was achieved ca. 90% in 2 h. 相似文献