Characterization of drug-cyclodextrin formulations using Raman mapping and multivariate curve resolution

Raman chemical imaging was used in the characterization of drug-excipient interactions between a drug and different types of cyclodextrins. Detailed analysis was carried out regarding the interactions between the active ingredient (API) and the cyclodextrins and the heterogeneity of the samples was studied using multivariate curve resolution-alternating least squares algorithm. The amount of recrystallized pure API was also estimated using the same curve resolution method. The Raman mapping results were validated via scanning electron microscopy-energy dispersive X-ray spectroscopy and X-ray powder diffraction. Raman mapping was found to be suitable to detect traces of pure crystalline API below the detection limit of X-ray powder diffraction.     

Quantification of atorvastatin calcium in tablets by FT-Raman spectroscopy

The FT-Raman quantification of atorvastatin calcium in tablets was performed using the partial least squares (PLS), principal component regression (PCR) and counter-propagation artificial neural networks (CP-ANN) methods. To compare the predictive abilities of the elaborated models, the relative standard errors of prediction (RSEP) were calculated. The application of PLS, PCR and 6 × 6 CP-ANN provided models of comparable quality. RSEP error values in the range of 1.9–2.8% for calibration and validation data sets were obtained for the three procedures applied. Four commercial products containing 10, 20 or 40 mg of atorvastatin calcium per tablet were successfully quantified. Concentrations found from the Raman data analysis correlate strongly with the declared values, with a recovery of 98.5–101.3%, and with the results of reference analysis, with the recovery of 98.9–102.1%, for the different models. The proposed procedure can be a fast, precise and convenient method of atorvastatin calcium quantification in commercial tablets.     

Influence of particle size on the quantitative determination of salicylic acid in a pharmaceutical ointment using FT-Raman spectroscopy.

A second order polynomial calibration model was developed and statistically validated for the direct and non-destructive quantitative analysis - without sample preparation - of the active pharmaceutical ingredient (API) salicylic acid in a pharmaceutical ointment using FT-Raman spectroscopy. The calibration curve was modeled by plotting the peak intensity of the vector normalized spectral band between 757 and 784cm(-1) against the known salicylic acid concentrations in standards. At this band, no spectral interferences from the ointment vehiculum (white vaseline) are observed. For the validation of the polynomial model, its fit and its predictive properties were evaluated. The validated model was used for the quantification of 25 ointments, compounded by different retail pharmacists. The same standards and samples were used, both for development and validation of a regression model and for quantitative determination by HPLC - with sample preparation - as described for the related substances of salicylic acid in the Ph. Eur. IV. The quantification results obtained by the FT-Raman method corresponded with the HPLC results (p=0.22), provided that the particle size of salicylic acid in the standards is the same as in the analyzed samples. The non-destructive FT-Raman method is a reliable alternative for the destructive HPLC method, as it is faster and does not require sample pre-treatment procedures.     

HPLC法检查阿司匹林及阿司匹林片中的游离水杨酸

目的:建立HPLC法检查阿司匹林及阿司匹林片中的游离水杨酸.方法:以十八烷基硅烧键合硅胶为填充剂,甲醇-水-冰醋酸(8:4 : 1)为流动相,检测波长302nm.结果:水杨酸在0.13～5.01μg·ml-1(r=0.99996)的浓度范围内线性关系良好;阿司匹林中水杨酸的方法平均回收率为101.0%,RSD为1.64%(n=6);阿司匹林片中水杨酸的方法平均回收率为99.83%,RSD为1.75%(n=6).结论:本方法快速、准确,可用于检查阿司匹林及阿司匹林片中的游离水杨酸.     

Monitoring of multiple solid-state transformations at tablet surfaces using multi-series near-infrared hyperspectral imaging and multivariate curve resolution

The assessment of the solid-state stability of active pharmaceutical ingredient (API) and/or excipients in solid dosage forms during manufacturing and storage is mandatory for safeguarding quality of the final products. In this work, the solid-state transformations in tablets prepared as blends of piroxicam monohydrate, polyvinylpyrrolidone and the lactose forms monohydrate or anhydrate were studied when the tablets were exposed to the 23–120 °C range. Multi-series near-infrared hyperspectral images were obtained from the surface of each sample for unveiling the local evolution of the solid-state transformations. The preprocessed spectra from the images (dataset) were arranged in augmented matrices, according to the composition of the tablets, and the profile of the overlapped compounds (relative concentration) along the solid-state transformations in the pixels was resolved by using multivariate curve resolution – alternating least squares (MCR-ALS). Therefore, the dehydration of piroxicam and lactose monohydrates could be mapped separately in the samples (explained variances by the models >96%) even when both compounds were being transformed simultaneously (80–120 °C). The images reproduced the same trends obtained from thermogravimetric analysis of the tablets, with the advantage that the pixel-to-pixel heterogeneity of each compound at the surface of the tablets was highlighted.     

HPLC法同时测定阿司匹林咀嚼片中阿司匹林和水杨酸的含量

目的用高效液相色谱法同时测定阿司匹林咀嚼片中阿司匹林和水杨酸的含量。方法采用Diamonsil C18色谱柱;以甲醇．醋酸．水（45：1：54）为流动相;流速：1．0mL·min-1,检测波长为275nm。结果阿司匹林线性范围：0．54～10．85μg（r=O．9999）,平均回收率为100．9％．RSD为O．36％（n=5）;水杨酸线性范围：2．65-31．77μg·mL-1（r=1．0000）,平均回收率为102．3％,RSD为2．O％（n=5）。结论此方法简便、快速、准确。值得推广应用。     

转换曲线分光光度法测定止痒酊中水杨酸和苯酚的含量

采用转换曲线分光光度法，根据吸收度的加和性同时测定了止痒酊中水杨酸和苯酚的含量，测定波长范围为２５５～２７０ｎｍ。本方法简便，结果可靠。     

气相色谱/质谱和多维分辨法分析仙鹤草挥发性成分

目的研究不同产地仙鹤草挥发油成分。方法利用水蒸气蒸馏法提取仙鹤草挥发油,用气相色谱/质谱(GC-MS)检测。先用子窗口因子分析法(SFA)定性定量分析湖南产仙鹤草的挥发油成分,然后用光谱相关色谱法(SCC)提取浙江产仙鹤草挥发油中的共有成分。结果在湖南和浙江产仙鹤草挥发油中分别鉴定出68和65个化学成分,其中有51个共有成分,主要组分都为雪松醇、α-蒎烯、芳樟醇、1-(2-呋喃基)-己酮、α-松油醇、乙酸龙脑酯和桉油精等,但含量有一定差别。结论该方法不仅鉴定的化合物数目增加,而且提高了定性准确度,可用于不同产地仙鹤草的分析和质量控制。     

HPLC法检查小剂量阿司匹林肠溶片中的游离水杨酸

目的:建立HPLC法检查小剂量阿司匹林肠溶片中游离水杨酸的方法.方法:以十八烷基硅烷键合硅胶为填充剂,甲醇-水-冰醋酸(8:5.5:1)为流动相,检测波长302nm.结果:水杨酸在1.53～30.54μg·mL-1(r=0.9999)的浓度范围内线性关系良好;方法平均回收率为99.92%,RSD为0.77%(n=6).结论:本方法快速、准确,可用于检查小剂量阿司匹林肠溶片中的游离水杨酸.     

新水杨酸溶出度标准片的标定与评价

目的对新水杨酸溶出度标准片A样和B样进行标定和评价。方法分别采用篮法、桨法、小杯法对标准片进行溶出度试验,以紫外分光光度法对水杨酸的浓度进行测定。结果A样与B样的平均溶出度为26．81％、24．21％（篮法）;28．95％、26．56％（桨法）;22．50％、20．33％（小杯法）。A样与B样的RSD为1．1％、1．2％（篮法）;1．3％、2．1％（桨法）;3．7％、3．9％（小杯法）。结论两种水杨酸片均可作为标准片使用。     

Quantitative determination of captopril and prednisolone in tablets by FT-Raman spectroscopy

A procedure for the quantitative determination of captopril and prednisolone in commercial tablets based on partial least squares (PLS) and principal component regression (PCR) treatment of FT-Raman spectroscopic data is described. In the studied medicines active pharmaceutical ingredients (APIs) constitute 4.2–16.7% of the tablet mass. Results obtained from calibration models built using unnormalised spectra were compared with the values found when an internal standard was added to each sample and the spectra were normalised by its selected band intensity at maximum or integrated. To apprise the quality of the models the relative standard error of predictions (RSEPs) were calculated for calibration and testing data sets. For captopril determination these were 1.8–2.2% (2.1–2.3%) and 2.7–3.1% (2.7–3.6%), respectively for the different PLS (PCR) models. For prednisolone these errors amounted to 1.8–2.1% (2.6–3.5%) and 3.2–3.7% (3.7–5.9%), respectively. Three commercial preparations of captopril containing 12.5 mg and one 25 mg of API per tablet were quantified using developed models. Found captopril contents, calculated versus results of iodometric titration, was equal 99.2–101.2% (99.2–102.0%), for the different PLS (PCR) calibration models and the different preparations. Quantification of prednisolone tablets, declared content 5 mg per tablet, on the basis of PLS (PCR) models gave API amount, calculated versus results of UV–vis method, in the 99.0–101.0% (98.0–102.0%) range.     

Simultaneous spectrofluorimetric determination of (acetyl)salicylic acid, codeine and pyridoxine in pharmaceutical preparations using partial least-squares multivariate calibration

A partial least-squares calibration (PLS) method for the simultaneous spectrofluorimetric determination of salicylic acid (SA), codeine (CO) and pyridoxine (PY) is proposed. The determination of SA, CO, and PY has been carried out in mixtures of up to three components by recording the emission fluorescence spectra between 300 and 500 nm (lambda(exc) = 220 nm). Due to the fact of the strong spectral overlap among the excitation and also among the emission spectra of these compounds, a previous separation should be carried out in order to determine them by conventional spectrofluorimetric methodologies. Here, a full-spectrum multivariate calibration PLS method is developed. The experimental calibration matrix was constructed with 14 samples. The concentration ranges considered were 0.1-2.0 (SA), 0.25-3.0 (CO) and 0.10-2.0 (PY) mg x l(-1). The optimum number of factors was selected by using the cross-validation method. The method also allows the simultaneous determination of acetylsalicylic acid (ASA), CO and PY by previous alkaline hydrolysis of ASA to SA. To check the accuracy of the proposed method, it was applied to the determination of these compounds in synthetic mixtures and in pharmaceuticals.     

百日咳片中鹅去氧胆酸的高效液相色谱测定方法

目的:建立百日咳片中鹅去氧胆酸的高效液相色谱测定方法。方法:用十八烷基硅烷键合硅胶为填充剂(250mm×4．6mm,5μm),甲醇-水(80:20,用10%高氯酸调pH值3．0)为流动相,差示折光检测器。结果:鹅去氧胆酸溶液浓度在3～7mg·mL~(-1)范围内呈线性关系(r=0．9999),平均回收率为98．0%,RSD为0．51%。结论:本方法准确,重现性好,专更好地控制该药的内在质量提供了方法。     

Simultaneous resolution of a binary mixture of captopril and hydrochlorothiazide in tablets by bivariate and multivariate spectral calibrations

The multivariate spectral calibration methods, two-linear regression-calibration (bivariate calibration (BC)) and multi-linear regression-calibration (MLRC) are proposed for the simultaneous resolution of a binary mixture of hydrochlorothiazide (HCT) and captopril (CTP), which have closely overlapping spectra. The BC and MLRC calibration algorithms are described for the two-component system, HCT-CTP. Some alternative methods, classical least squares (CLS), inverse least squares (ILS), principal component regression (PCR) and principal least squares (PLS) methods, were also used to determine HCT and CTP in the mixture. Using a synthetic mixture of the two drugs, all the methods were validated and applied to tablets. The BC and MLRC methods which are very rapid, and easy to apply, yet not expensive, are powerful tools with very simple mathematical contents for the quantitative analysis. Data treatment was performed using MAPLE V, EXCEL and SPSS 10.0 Software.     

Determination of salicylic acid and aspirin in multicomponent tablets by liquid chromatography on a nonionic resin

Aspirin and free salicylic acid were determined in combinations containing caffeine, phenacetin, salicylamide, and acetaminophen by liquid chromatography on poly(methyl methacrylate) resin. Precision and accuracy were +/- 2% for salicylic acid, the latter at levels corresponding to 0.02% of the aspirin content.     

反相高效液相色谱法同时测定复方水杨酸洗剂中水杨酸和间苯二酚的含量

目的　建立测定复方水杨酸洗剂中水杨酸和间苯二酚含量的高效液相色谱法。方法　采用反相C18色谱柱,以乙腈 甲醇 水(10∶5∶85 )为流动相,流速: 1. 0mL·min-1,检测波长为 278nm。结果　水杨酸与间苯二酚的线性范围均为 300 ~900μg·mL-1,水杨酸r=0. 999 6,平均回收率为 100. 24%,RSD为 0. 83%;间苯二酚r=0. 9995,平均回收率为 99. 97%,RSD为 1. 02%.结论　该方法简便准确,可同时测定复方水杨酸洗剂中水杨酸及间苯二酚的含量。