近红外光谱无损定量分析吡嗪酰胺片

近红外光谱;径向基神经网络;吡嗪酰胺;定量分析     

The study of the applicability of content uniformity and weight variation test--the state of commercial tablets and capsules in Japan.

This study intends to determine the rational criteria (e.g., threshold value) for applying the weight variation test and to investigate the adequacy of the acceptance value for existing commercial products in Japan. The studied products were 489 lots (3 lots x 163 products) of compressed tablets (plain, film-coated, sugar-coated) and 42 lots (3 lots x 14 products) of hard capsules marketed in Japan. The individual drug content and the weight of 10 units in a lot were determined for each product and the acceptance values were calculated according to the Japanese Pharmacopoeia thirteenth edition (JP13) Content Uniformity Test (M=100.0, k=2.2). Product-specific intra-lot relative standard deviation of content (RSDD), weight (RSDW) and concentration (RSDC) were calculated by analysis of variance (ANOVA) using three lots of data per product. The RSDD and RSDC tended to increase with the decrease of the label strength for plain tablets, but not for film-coated and sugar-coated tablets, and hard capsules. A good correlation was found between RSDD and RSDC but not between RSDD and RSDW. These findings indicate that 1) it is difficult to rationally set the threshold level for weight variation, especially regarding the dosage forms except for plain tablets, 2) the application of weight variation tests should, in principle, be decided on the mixing homogeneity that is RSDC. 3) Most (99.6%) of the tablets and all the capsules investigated met the requirement of content uniformity test of JP13. Therefore the criteria of the JP13 content uniformity test are considered acceptable from the viewpoint of manufacturing capability.     

Near-infrared determination of active substance content in intact low-dosage tablets

Near-infrared (NIR) spectroscopy can be applied to determine the active substance content of tablets. Its great advantage lies in the minimal sample preparation required, which helps to reduce the potential for error. The aim of this study is to show the feasibility of this method on low-dosage tablets. The influence of various spectral pretreatments [standard normal variate (SNV), multiplicative scatter correction (MSC), second derivative (D2), orthogonal signal correction (OSC), separately and combined] and regression methods on prediction error are compared. Partial least square (PLS) regression provided better prediction than principal component regression (PCR). SNV was applied to the first data set and SNV and a second derivative to the second set to maximise model accuracy for quantifying the active substance of intact pharmaceutical products using diffuse reflectance NIR. The models yielded standard errors of prediction (SEP) of 0.1768 and 0.0682 mg for the two products. The experiments were conducted with two low-dosage pharmaceutical forms and results of NIR predictions were comparable to currently approved methods. Diffuse reflectance NIR has the potential to become a reliable and robust quality control method for determining active tablet content.     

How to Obtain the Maximum Properties Flexibility of 3D Printed Ketoprofen Tablets Using Only One Drug-Loaded Filament?

The flexibility of dose and dosage forms makes 3D printing a very interesting tool for personalized medicine, with fused deposition modeling being the most promising and intensively developed method. In our research, we analyzed how various types of disintegrants and drug loading in poly(vinyl alcohol)-based filaments affect their mechanical properties and printability. We also assessed the effect of drug dosage and tablet spatial structure on the dissolution profiles. Given that the development of a method that allows the production of dosage forms with different properties from a single drug-loaded filament is desirable, we developed a method of printing ketoprofen tablets with different dose and dissolution profiles from a single feedstock filament. We optimized the filament preparation by hot-melt extrusion and characterized them. Then, we printed single, bi-, and tri-layer tablets varying with dose, infill density, internal structure, and composition. We analyzed the reproducibility of a spatial structure, phase, and degree of molecular order of ketoprofen in the tablets, and the dissolution profiles. We have printed tablets with immediate- and sustained-release characteristics using one drug-loaded filament, which demonstrates that a single filament can serve as a versatile source for the manufacturing of tablets exhibiting various release characteristics.     

Effects of BaF2 on Preparing Mullite with Sludge from the Aluminum Profile Factory and Pyrophyllite

In this study, sludge from the aluminum profile factory and pyrophyllite were used as major raw materials to prepare mullite. Through determining optimum formula, the optimum calcination temperature and optimum temperature retention time as well as the effects of BaF2 mineralizer on the crystal structure, microstructure and properties of mullite were studied and the optimum BaF2 mineralizer dosage was determined. With XRD and SEM methods, the crystal structure and microstructure of each sample were characterized. With Rietveld Quantification method, crystal phase content in each sample was determined and properties of each sample were tested. Based on the comprehensive analysis result, it was determined that optimum BaF2 dosage was 0.5%, the fairly good calcination temperature was 1550 ℃, and the corresponding mullite solid solution content was 95.8%.     

Mass variation tests for coating tablets and hard capsules: rational application of mass variation tests

The mass variation test is a simplified alternative test version of the content uniformity test. In the case of coating tablets and capsules, the mass variation test is principally applied to test the inner cores or fillings containing the active ingredient. However, some exceptions exist in pharmacopoeias. The effects of tablet coating and capsule shell on the results of the mass variation test were studied. The mass variation of outer crusts (coatings, capsule shells) and inner cores (core tablets, fillings) was measured separately in several products. The effects of coating on weight variability were very large for sugar-coated tablets. Relative standard deviation (RSD) of the formulation weight (RSD(W)) of sugar-coated tablets (2.73%) was larger than that of plain tablets (0.77%). The cause of the large RSD(W) is the large variation the weight of sugar-coating accounting for 44% of formulation weight. In the case of film-coated tablets, the effect of coating weight on the mass variation test was very small because the rate of coating in comparison to the whole weight was small. In the case of hard capsules, the usage of whole formulation weight resulted in underestimation of variations of filling weight. The differences between dosage forms in the applicability of the mass variation test are caused by differing weight proportions and variability of the outer coatings or shells. To avoid the underestimation of mass variation for hard capsules, a corrected acceptance value is useful. For all the dosage units, the mass variation test can principally be applied to determine which mass is expected to be proportional to the content of the active ingredient. However, some modification of acceptance values enables application of the mass variation tests to inapplicable cases, such as when the RSD of drug concentration (RSD(C)) is larger than 2%.     

Application of Transmission Raman Spectroscopy in Combination with Partial Least-Squares (PLS) for the Fast Quantification of Paracetamol

In recent years, transmission Raman spectroscopy (TRS) has emerged as a potent new tool for rapid, nondestructive quantitation in pharmaceutical manufacturing. In order to expand the applicability of TRS and enhance its use in product quality monitoring during drug production, we aimed, in the present study, to apply partial least-squares (PLS) approaches to build a model consisting of 150 handmade tablets and covering 15 levels through the use of a multifactor orthogonal design of experiment (DOE), which was used to predict concentrations of validation tablets made by hand. The difference between results according to HPLC and TRS were negligible. The model was used to predict the active pharmaceutical ingredient (API) content in four random commercial paracetamol tablets, and corrected with the spectra of the commercial tablets to obtain four corresponding models. The results show that the content relative error in the model’s predictions after correction with commercially available tablets was significantly lower than that before correction. The corrected model was used to make predictions for 20 tablets from the brand Panadol. Compared with the HPLC results, the prediction relative error was basically less than 4.00%, and the relative standard deviation (RSD) of the content was 0.86%.     

A HPLC Method for the Determination of Butaperazine in Solutions,Tablets, Plasma and Bile

Abstract

A specific HPLC method for the determination of the antipsychotic drug butaperazine (B) in solutions, tablets, plasma and bile has been developed. The instrument used was a Waters HPLC equipped with a Model 440 Spectrometer and a μ-Bondapak-NH₂ column. The mobile phase, chloroform-methanol (100:3.5) was pumped at a rate of 1.5 ml per minute. Ultraviolet absorbance at a wave length of 280 nm was used for detection. The procedure involved the extraction of the drug from the dosage forms with chloroform and from plasma and bile with hexaneisopropanol (9:1). Hydrocortisone acetate was used as the internal standard. Retention times of 2.4 and 3.9 minutes were obtained for the internal standard and B respectively. Analytical calibration yielded a linear relationship from 0.1–25 μg per ml, with r² value of 0.99. The percentage recovery of B averaged 99% from the dosage forms and 94% from the biological fluids. An improvement in the method for determining B in bile and plasma was later developed. It involved the use of a different mobile phase and detecting the drug fluorometrically.     

Determination of vitamin U and its degradation products by high- performance liquid chromatography with fluorescence detection

A high-performance liquid chromatographic method has been developed for the determination of vitamin U in tablets and capsules. Threonine was employed as the internal standard through the assay. The o-phthalaldehyde derivatives were prepared and then chromatographed isocratically on a reversed-phase C18 column. The optimum reaction time for both vitamin U and threonine at pH 10.5 is 5 min. Vitamin U and its major degradation product in the dosage forms, viz., methionine sulphoxide, were separated and quantified with a relative standard deviation of about 1%, using a fluorescence detector with excitation and emission wavelengths at 340 and 450 nm respectively. A linear relationship has been established between the peak area ratio of vitamin U/threonine and the concentration of vitamin U over the range of 2.5-50 micrograms/ml.     

Tailoring Atomoxetine Release Rate from DLP 3D-Printed Tablets Using Artificial Neural Networks: Influence of Tablet Thickness and Drug Loading

Various three-dimensional printing (3DP) technologies have been investigated so far in relation to their potential to produce customizable medicines and medical devices. The aim of this study was to examine the possibility of tailoring drug release rates from immediate to prolonged release by varying the tablet thickness and the drug loading, as well as to develop artificial neural network (ANN) predictive models for atomoxetine (ATH) release rate from DLP 3D-printed tablets. Photoreactive mixtures were comprised of poly(ethylene glycol) diacrylate (PEGDA) and poly(ethylene glycol) 400 in a constant ratio of 3:1, water, photoinitiator and ATH as a model drug whose content was varied from 5% to 20% (w/w). Designed 3D models of cylindrical shape tablets were of constant diameter, but different thickness. A series of tablets with doses ranging from 2.06 mg to 37.48 mg, exhibiting immediate- and modified-release profiles were successfully fabricated, confirming the potential of this technology in manufacturing dosage forms on demand, with the possibility to adjust the dose and release behavior by varying drug loading and dimensions of tablets. DSC (differential scanning calorimetry), XRPD (X-ray powder diffraction) and microscopic analysis showed that ATH remained in a crystalline form in tablets, while FTIR spectroscopy confirmed that no interactions occurred between ATH and polymers.     

Gas-liquid partition chromatography : Column behavior and its reproduction criteria for favorable column behavior

The distribution of a solute in a gas-liquid Chromatographic column has been discussed from the probability view point and its analogy to the Bernoulli trial system has been shown. It has been shown that the reproduction of column behavior is possible by reproducing the probability. The criterion for the optimum column temperature has also been discussed. Recommendations have been made for determining the optimum column conditions and its reproduction.     

A highly sensitive spectrofluorometric method for the determination of a new antidepressant drug, reboxetine, in tablets

A highly sensitive, selective, and rapid spectrofluorometric method has been developed for the determination of reboxetine (REB) in tablets. The method is based on derivatization with 7-chloro-4-nitrobenzofurazan. The product showed an absorption maximum at 476 nm and a fluorescence emission peak at 533 nm in ethyl acetate. The optimum conditions of the reaction were investigated, and it was found that the reaction proceeded quantitatively at pH 8.5, 70 degrees C in 5 min. The calibration graph is rectilinear over the range of 0.02-0.40 microg/mL. The relative standard deviation values for intraday and interday precision were 0.40-0.93 and 0.54-1.37%, respectively. The proposed method was applied to the assay of REB in tablets. Mean recovery of REB from the tablets ranged between 99.91-100.20%. The results were compared statistically with those obtained by a method reported in the literature. The method is sensitive, simple, and selective, and can be used for routine quality control analysis.     

High performance liquid chromatography method for determination of methyl-5-benzoyl-2-benzimidazole carbamate (mebendazole) and its main degradation product in pharmaceutical dosage forms

Methyl-5-benzoyl-2-benzimidazole carbamate (mebendazole) is a drug used as an anthelmintic. A high performance liquid chromatography method has been developed in this study to determine mebendazole and its degradation product in the pharmaceutical dosage forms (tablets and suspension). The expected major degradation product of mebendazole in the dosage forms has been prepared, and identified as 2-amino-5-benzoylbenzimidazole. The proposed HPLC assay was found to be selective, accurate (% recoveries were in the range of 99.9-100.9) for both, mebendazole and the degradation product, repeatable and reproducible (replicate measurements for short and long term measurements showed % RSD of 相似文献   

Applicability of X-ray microscopy to non-contact tablet mass estimation

The pharmaceutical tablet manufacturing process requires a tablet mass measuring step to ensure that all tablets have the prescribed dosage. The digital scales commonly used for that purpose require tens of seconds to stabilize, resulting in a substantial slow-down of the manufacturing process. The alternative visual approaches are fallible because of the potential existence of voids and cracks in the tablets. This paper uses an X-ray microscopy for mass measurement. Albeit with some constraints concerning tablet size and constituents, the approach can measure a tablet’s mass in under one second, and may constitute, in the future, a viable and practical approach.     

Correlation studies between thermal and dissolution rate constants of cimetidine drug and tablets

This work developed a methodology that can potentially be applied to the quality control of cimetidine drug substance and its tablets. The kT obtained at different temperatures (200, 190, 180, 170 and 160°C) were determined by isothermal thermogravimetric method using the classical Arrhenius equations. The dissolution profiles were obtained using USP 24 (Method 711) and rate constants (kD) were determined by Kitazawa equations. An evaluation was made to check if there was statistically significant correlation between the two variables kT and kD. Isothermal TG data were used to determine the reaction order and degradation reaction rate constants. The results showed that in all temperatures thermal order (kT) was: C<A<B tablets, while dissolution order (kD) was: C<A<B tablets. In conclusion, correlation between kT/kD seems to be a suitable method for detecting possible interactions between cimetidine and excipients in development or manufacturing changes, particularly for immediate release dosage forms and therefore could be especially useful on quality control. This revised version was published online in July 2006 with corrections to the Cover Date.     

Automated flow injection spectrophotometric determination of para- and meta-substituted phenols of pharmaceutical interest based on their oxidative condensation with 1-nitroso-2-naphthol

The reaction of para- and meta-substituted phenols with 1-nitroso-2-naphthol in the presence of either CeIV or PbIV as an oxidant has been used to develop a fast automated flow injection (Fl) method. A stopped-flow kinetic study of the reaction revealed the optimum conditions for the proposed Fl method. Acetaminophen, amoxicillin, cefadroxil, isoxsuprine, nylidrin, propylparaben, tyrosine and metaraminol can be determined in the range 1 x 10(-4)-8 x 10(-4) M, with relative standard deviations of less than 2%, and a measurement throughput of 40 measurements h-1. The method was evaluated by performing interference studies of common excipients and assaying commercial formulations of acetaminophen and isoxsuprine. The results were in good agreement with those obtained by acceptable spectrophotometric or high-performance liquid chromatographic methods (mean difference 2.1%). The high sample throughput of the Fl method was exploited by performing a content uniformity test of isoxsuprine tablets.     

Some aspects of the analysis of Validol tablets by gas-liquid chromatography

The possibility of using the pharmaceutical substance Validol as a reference sample instead of a model mixture of components was theoretically considered for the analysis of Validol tablets. It was shown that the maximum relative error appeared because the difference in the compositions of the reference sample and the substance used in production should not exceed 2.5%. A procedure was developed for the analysis of Validol tablets. The performance characteristics of the procedure and the accuracy of the results were determined in an analysis of model mixtures and commercial tablets.     

Citrus bergamia juice: phytochemical and technological studies

Fresh juice from bergamot (Citrus bergamia Risso) has been studied to evaluate the polyphenolic composition by HPLC-DAD analysis and total polyphenols content by UV method. The main constituent, Naringin, has been selected as analytical and biological marker of the juice. Juice has been loaded onto maltodextrin matrix by spray-drying. The produced maltodextrin/juice powder (BMP) showed neither significant change in total polyphenols content nor decrease in antioxidant properties with respect to fresh juice. Moreover, BMP displayed high in vitro dissolution rate of the bioactive constituents in water and in simulated biological fluids. BMP appears as promising functional raw material for food, nutraceutical and pharmaceutical products. With this aim, a formulation study to develop tablets (BMT) for oral administration has been also performed. The produced solid oral dosage form preserved high polyphenols content, showed complete disaggregation in few minutes and satisfying dissolution rate of the bioactive constituents in simulated biological fluids.     

Stability Indicating Reversed-Phase High Performance Liquid Chromatography Method for Determination of Impurities in Ofloxacin Tablet Formulations

A gradient reversed-phase high performance liquid chromatography (RP-HPLC) method was developed for separation and quantitation of impurities in pharmaceutical dosage form of ofloxacin tablets. The developed method was a stability indicating test method for estimation of related impurities generated during synthesis, formulation, and storage of ofloxacin tablets. Forced degradation studies were performed on ofloxacin tablets including acid hydrolysis (5.0 M hydrochloric acid), base hydrolysis (5.0 M sodium hydroxide), oxidation (30% hydrogen peroxide), heat (105°C) humidity degradation 25°C/92% RH/119 b & 40 min, and photolytic degradation (2600 Lux/119 h & 40 min). From the degradation study, the degradation was found between 0–15%. Limit of detection and limit of quantification were established in terms of percentage for all potential impurities. The recovery studies were conducted on finished dosage samples (tablets) for all potential impurities and the average percentage recovery was ranged from 90.8 to 104.2. Placebo interference was verified by taking the placebo (composition of excipients) equivalent to weight in portion of test preparation and no interference was observed. The method was validated and found to be linear, accurate, precise, specific, robust, and reliable. The developed method was established in accordance to ICH guidelines.     

Fe3O4磁性纳米材料萃取光度法测定苯磺酸倍他司汀

提出了基于表面活性剂磁性固相萃取光度法测定药片及血清中苯磺酸倍他司汀含量的方法。在表面活性剂十二烷基磺酸钠(SDS)的辅助下,磁性材料四氧化三铁可以高效的定量萃取苯磺酸倍他司汀。对实验条件如缓冲溶液pH及用量、磁性材料用量、表面活性剂用量、萃取时间、洗脱剂种类及用量、材料重复利用率等进行优化。在优化条件下,吸附率与洗脱率均>90%,磁性纳米材料可重复使用5次,方法的回收率为95.2%~105.9%。方法可用于测定人血清及药物中苯磺酸倍他司汀含量。