Partial solubility parameters of lactose, mannitol and saccharose using the modified extended Hansen method and evaporation light scattering detection

The modified extended Hansen method was tested for the first time to determine partial solubility parameters of non-polymeric pharmaceutical excipients. The method was formerly tested with drug molecules, and is based upon a regression analysis of the logarithm of the mole fraction solubility of the solute against the partial solubility parameters of a series of solvents of different chemical classes. Two monosaccharides and one disaccharide (lactose monohydrate, saccharose and mannitol) were chosen. The solubility of these compounds was determined in a series of solvents ranging from nonpolar to polar and covering a wide range of the solubility parameter scale. Sugars do not absorb at the UV-vis region, and the saturated solutions were assayed with a recent chromatographic technique coupled to an evaporative light scattering detector. This technique was suitable to determine the concentration dissolved in most solvents. The modified extended Hansen method provided better results than the original approach. The best model was the four parameter equation, which includes the dispersion delta d, dipolar delta p, acidic delta a and basic delta b partial solubility parameters. The partial solubility parameters obtained, expressed as MPa1/2, were delta d = 17.6, delta p = 28.7, delta h = 19, delta a = 14.5, delta b = 12.4, delta T = 32.8 for lactose, delta d = 16.2, delta p = 24.5, delta h = 14.6, delta a = 8.7, delta b = 12.2, delta T = 32.8 for mannitol and delta d = 17.1, delta p = 18.5, delta h = 13, delta a = 11.3, delta b = 7.6, delta T = 28.4 for saccharose. The high total solubility parameters delta T obtained agree with the polar nature of the sugars. The dispersion parameters delta d are quite similar for the three sugars indicating that the polar delta p and hydrogen bonding parameters (delta h, delta a, delta b) are responsible for the variation in the total solubility parameters delta T obtained, as also found for drugs. The results suggest that the method could be extended to determine the partial solubility parameters of other non-polymeric pharmaceutical excipients.     

Inverse Gas Chromatographic Study of the Oxidation Stability of Lubricating Base Oils via Solubility Parameter Calculations

 The Flory-Huggins interaction parameter (χ∞1,2) and solubility parameter (δ2) and its hydrogen bonding sensing component (δh) were determined using inverse gas chromatography (IGC). These parameters were successfully used in the probes of chemical changes that occur during the oxidation of naphthenic and paraffinic base oils in a GC column. Changes in χ∞1,2 values reflect the different types of intermolecular interactions (dispersive, polar, hydrogen bonding) of the given lubricating base oil during oxidation. The obtained results showed that δh component of solubility parameter is the most important parameter for probing the oxidative-chemical changes during the oxidation of given lubricating oils.     

Comprehensive Insight into Chemical Stability of Important Antidiabetic Drug Vildagliptin Using Chromatography (LC-UV and UHPLC-DAD-MS) and Spectroscopy (Mid-IR and NIR with PCA)

During forced degradation, the intrinsic stability of active pharmaceutical ingredients (APIs) could be determined and possible impurities that would occur during the shelf life of the drug substance or the drug product could be estimated. Vildagliptin belongs to relatively new oral antidiabetic drugs named gliptins, inhibiting dipeptidyl peptidase 4 (DPP-4) and prolonging the activities of the endogenous incretin hormones. At the same time, some gliptins were shown as prone to degradation under specific pH and temperature conditions, as well as in the presence of some reactive excipients. Thus, forced degradation of vildagliptin was performed at high temperature in extreme pH and oxidative conditions. Then, selective LC-UV was used for quantitative determination of non-degraded vildagliptin in the presence of its degradation products and for degradation kinetics. Finally, identification of degradation products of vildagliptin was performed using an UHPLC-DAD-MS with positive ESI. Stability of vildagliptin was also examined in the presence of pharmaceutical excipients, using mid-IR and NIR with principal component analysis (PCA). At 70 °C almost complete disintegration of vildagliptin occurred in acidic, basic, and oxidative media. What is more, high degradation of vildagliptin following the pseudo first-order kinetics was observed at room temperature with calculated k values 4.76 × 10⁻⁴ s⁻¹, 3.11 × 10⁻⁴ s⁻¹, and 1.73 × 10⁻⁴ s⁻¹ for oxidative, basic and acidic conditions, respectively. Next, new degradation products of vildagliptin were detected using UHPLC-DAD-MS and their molecular structures were proposed. Three degradants were formed under basic and acidic conditions, and were identified as [(3-hydroxytricyclo- [3.3.1.13,7]decan-1-yl)amino]acetic acid, 1-{[(3-hydroxytricyclo[3.3.1.13,7]decan-1-yl)amino]acetyl}-pyrrolidine-2-carboxylic acid and its O-methyl ester. The fourth degradant was formed in basic, acidic, and oxidative conditions, and was identified as 1-{[(3-hydroxytricyclo[3.3.1.13,7]-decan-1-yl)amino]acetyl}pyrrolidine-2-carboxamide. When stability of vildagliptin was examined in the presence of four excipients under high temperature and humidity, a visible impact of lactose, mannitol, magnesium stearate, and polyvinylpirrolidone was observed, affecting-NH- and CO groups of the drug. The obtained results (kinetic parameters, interactions with excipients) may serve pharmaceutical industry to prevent chemical changes in final pharmaceutical products containing vildagliptin. Other results (e.g., identification of new degradation products) may serve as a starting point for qualifying new degradants of vildagliptin as it is related to substances in pharmacopoeias.     

Application of chemometrically processed thermogravimetric data for identification of baclofen-excipient interactions

Studies are constantly being conducted on the elaboration of efficient methods to confirm the compatibility of active pharmaceutical ingredients (APIs) and excipients, since medicinal products, apart from their APIs, also contain numerous excipients that not only have important functions in pharmaceutical preparations but can also initiate or participate in interactions with drug substances, which eventually lead to a decline in drug quality. With this in mind, research was undertaken to evaluate two of the most often applied pattern recognition methods, hierarchical cluster analysis (HCA) and principal component analysis (PCA), as supporting techniques in the identification of potential physicochemical interactions that may occur during the preformulation of solid dosage forms. The investigation performed with the use of baclofen and selected excipients has shown that with thermogravimetric analysis, HCA and PCA fulfill their role as supporting techniques in the interpretation of the data obtained. Based on these methods, it is possible to detect incompatibilities between baclofen and excipients, and the data obtained concur strongly with the results of differential scanning calorimetry and IR spectrometry analyses.     

Principal component analysis of polarity and interaction parameters in inverse gas chromatography

Inverse gas chromatography is used in the characterization of aliphatic-aromatic and aromatic ketones, their oximes, and ketone-oxime or oxime-oxime mixtures. All these organic materials are used as liquid stationary phases in gas chromatographic columns. A series of polarity and Flory-Huggins interaction parameters are determined and used to describe the physicochemical properties of examined materials, metal extractants, and products of their degradation. Principal component analysis (PCA) is performed on a data matrix consisting of polarity and interaction parameters for ketones, their oximes, and mixtures. The calculations are carried out on the correlation matrix. It is found that seven principal components account for more than 95% of the total variance in the data, indicating that the polarity (interaction) parameters are not correlating well. Physical meanings are attributed to the principal components, the most influential ones being that the first and the second principal components account for several Flory-Huggins interaction parameters, whereas the fifth is correlated with criterion "A". The plots of component loadings show characteristic groupings of polarity indicators, whereas that of component scores show several groupings of stationary phases. Cluster analysis provides mainly the same groupings. PCA allows for the grouping of polarity and solubility parameters based on the information carried within those parameters. There is no need to use more than one parameter from each cluster. McReynolds polarity and the partial molar excess Gibbs free energy of solution per methylene group carry the same information. The groups of ketones, oximes, and their mixtures can be distinguished with the use of PCA on the basis of the measured polarity, solubility parameters, or both.     

Thermal Stability of Amorphous Solid Dispersions

Amorphous solid dispersion drug delivery systems (ASD DDS) were proved to be efficient for the enhancement of solubility and bioavailability of poorly water-soluble drugs. One of the major keys for successful preparation of ASD is the selection of appropriate excipients, mostly polymers, which have a crucial role in improving drug solubility and its physical stability. Even though, excipients should be chemically inert, there is some evidence that polymers can affect the thermal stability of active pharmaceutical ingredients (API). The thermal stability of a drug is closely related to the shelf-life of pharmaceutical products and therefore it is a matter of high pharmaceutical relevance. An overview of thermal stability of amorphous solids is provided in this paper. Evaluation of thermal stability of amorphous solid dispersion is perceived from the physicochemical perspective, from a kinetic (motions) and thermodynamic (energy) point of view, focusing on activation energy and fragility, as well all other relevant parameters for ASD design, with a glance on computational kinetic analysis of solid-state decomposition.     

Risperidone/Randomly Methylated β-Cyclodextrin Inclusion Complex—Compatibility Study with Pharmaceutical Excipients

Risperidone (RSP) is an atypical antipsychotic drug used in treating schizophrenia, behavioral, and psychological symptoms of dementia and irritability associated with autism. The drug substance is practically insoluble in water and exhibits high lipophilicity. It also presents incompatibilities with pharmaceutical excipients such as magnesium stearate, lactose, and cellulose microcrystalline. RSP encapsulation by randomly methylated β-cyclodextrin (RM-β-CD) was performed in order to enhance drug solubility and stability and improve its biopharmaceutical profile. The inclusion complex formation was evaluated using thermal methods, powder X-ray diffractometry (PXRD), universal-attenuated total reflectance Fourier transform infrared (UATR-FTIR), UV spectroscopy, and saturation solubility studies. The 1:1 stoichiometry ratio and the apparent stability constant of the inclusion complex were determined by means of the phase solubility method. The compatibility between the supramolecular adduct and pharmaceutical excipients starch, anhydrous lactose, magnesium stearate, and cellulose microcrystalline was studied employing thermoanalytical tools (TG-thermogravimetry/DTG-derivative thermogravimetry/HF-heat flow) and spectroscopic techniques (UATR-FTIR, PXRD). The compatibility study reveals that there are no interactions between the supramolecular adduct with starch, magnesium stearate, and cellulose microcrystalline, while incompatibility with anhydrous lactose is observed even under ambient conditions. The supramolecular adduct of RSP with RM-β-CD represents a valuable candidate for further research in developing new formulations with enhanced bioavailability and stability, and the results of this study allow a pertinent selection of three excipients that can be incorporated in solid dosage forms.     

Structure determination of soybean and wheat glucosylceramides by tandem mass spectrometry

Glucosylceramide (GluCer) is a major sphingolipid of plant tissue and, thus, abundant in nature and in dietary food sources. The lipid backbones of mammalian GluCer (sphingosine, d18:1(delta4), and ceramide) induce cell death (apoptosis) and inhibit colon carcinogenesis, it is critical to know the structures of GluCer present in plants as a first step toward understanding this potential link between diet and cancer. This study characterized the molecular species of GluCer from soybean and wheat by low-resolution, high-resolution and tandem mass spectrometry. Soybean GluCer was comprised primarily (>95%) of ceramide with 4,8-sphingadiene (d18:2(delta4,delta8)) and alpha-hydroxypalmitic acid (h16:0); the remainder had the same backbone with h18:0, h20:0, h22:0 and h24:0 fatty acids. Wheat GluCer had three major ceramide, d18:2(delta4,delta8) with h16:0, d18:1(delta8) with h16:0 and d18: 2(delta4,delta8) with h20:0, and smaller amounts of other homologs. These backbones differ from those of mammalian sphingolipids, which often have a delta4-double bond (but rarely a delta8-double bond), and have alpha-hydroxy fatty acids in only some cases. Previously unexplained fragmentations that were diagnostic for the type of sphingoid base backbone (i.e. by homolytic cleavage of the doubly allylic C-6-C-7 bond to yield a stable distonic allylic radical cation and an allylic radical neutral) were also identified. Hence this method should be useful in the identification of double bonds in sphingolipids, and structure-function relationships between sphingolipids and colon carcinogenesis.     

反相气相色谱法测定高密度聚乙烯溶解度参数

采用反相气相色谱(IGC)技术测定了高密度聚乙烯(HDPE)在303.15～343.15 K温度范围内的溶解度参数(δ2)及相关指标。以正己烷(n-C6)、正庚烷(n-C7)、正辛烷(n-C8)、正壬烷(n-C9)、三氯甲烷(CHCl3)及乙酸乙酯(EtAc)作为探针分子溶剂,经计算获得了探针溶剂的比保留体积(V0g)、摩尔吸收焓(ΔHS1)、无限稀释摩尔混合焓(ΔH∞l)、摩尔蒸发焓(ΔHv)、无限稀释活度系数(Ω∞1)以及探针溶剂与HDPE的Flory-Huggins相互作用参数(χ∞1,2)等指标。结果表明,上述6种探针溶剂在测定温度范围内均为HDPE的不良溶剂。此外,还推导出了HDPE在室温(298.15 K)下的溶解度参数δ2为19.00 (J/cm3)0.5。     

Error-systematics of determining simultaneously the isotopic abundance ratios of natural lithium and natural boron as Li2BO2+

Recently, we have shown how the errors delta(j) and delta(k), that occur when measuring the two different isotopic molecular abundance ratios required for analysis, are transformed into the actual errors of elemental isotopic analysis, (deltaEi/Ei)'s. With a view to gain further understanding as to how the errors (deltaEi/Ei)'s are governed, we now evaluate theoretically the effects of selecting different isotopic molecular pairs as the monitor pairs (j and k) for measurements, and of the measurement errors (delta(j) and delta(k)), on the results of analysis (the 6Li/7Li and the 10B/11B abundance ratios), by considering all the constituent elements of Li2BO2+ at their natural isotopic abundances. It is shown that the ratio of measurement errors, delta(j)/delta(k), is a more fundamental parameter than either the individual errors (delta(j) and delta(k)), or their sum, absolute value(delta(j)) + absolute value(delta(k)), in governing deltaEi/Ei. The important implication of this observation is that it reveals the possibility of achieving not only a desired level of accuracy in analysis, but even absolute accuracy (i.e. deltaEi/Ei = 0) by causing mutual cancellation of the effects of individual measurement errors delta(j) and delta(k), through proper regulation of measurement parameters. However, as the measurement errors cannot be pre-set, it is shown how selection of proper monitor pairs (j and k) can help achieve the desired accuracy in analysis. The present work sets guidelines for the more general problem of selecting monitor pairs to avoid larger errors in analysis.     

Norbornyl cations of group 14 elements

Norbornyl cations of the group 14 elements Si --> Pb have been synthesized from substituted 3-cyclopentenemethyl precursors by intramolecular addition of transient cations to the C=C double bond of the 3-cyclopentenemethyl substituent (pi-route to norbornyl cations). The norbornyl cations 4a (E = Si, R = Me), 4e (E = Si, R = Et), 4f (E = Si, R = Bu), 4g (E = Ge, R = Bu), 4h (E = Sn, R = Bu), and 4i (E = Pb, R = Et) have been identified by their characteristic NMR chemical shifts (4a,e,f, delta((29)Si) = 80-87, delta((13)C)(CH=) = 149.6-150.6; 4g, delta((13)C)(CH=) = 144.8; 4h, delta((119)Sn) = 334, delta((13)C)(CH=) = 141.5; 4i, delta((207)Pb) = 1049, delta((13)C)(CH=) = 138). The significant deshielding of the vinylic carbon atoms (Deltadelta((13)C)) relative to those of the precursor (Deltadelta((13)C) = 19.3-20.3 (4a,e,f), Deltadelta((13)C) = 14.6 (4g), Deltadelta((13)C) = 11.1 (4h), Deltadelta((13)C) approximately 8 (4i)) and the small J coupling constants between the element and the remote vinyl carbons in the case of 4h and 4i (J(CSn) = 26 Hz, J(CPb) = 16 Hz) give experimental evidence for the intramolecular interaction and the charge transfer between the positively charged element and the remote C=C double bond. The experimental results are supported by quantum mechanical calculations of structures, energies, and magnetic properties for the norbornyl cations 4a,b (E = Ge, R = Me), 4c (E = Sn, R = Me), 4d (E = Pb, R = Me), and 4e,f at the GIAO/B3LYP/6-311G(3d,p)//MP2/6-311G(d,p) (Si, Ge, C, H), SDD (Sn, Pb) level of theory. The calculated (29)Si NMR chemical shifts for the silanorbornyl cations 4a,e,f (delta((29)Si) = 77-93) agree well with experiment, and the calculated structures of the cations 4a-f reveal their bridged norbornyl cation nature and suggest also for the experimentally observed species 4a,e-i a formally 3 + 1 coordination for the element atom with the extra coordination provided by the C=C double bond. This places five carbon atoms in the close vicinity of the positively charged element atom. The group 14 element norbornyl cations 4a,e-i exhibit only negligible interactions with the aromatic solvent, and they are, depending on the nature of the element group, stable at room temperature in aromatic solvents for periods ranging from a few hours to days. In acetonitrile solution, the intramolecular interaction in the norbornyl cations 4a,e-h breaks down and nitrilium ions with the element in a tetrahedral environment are formed. In contrast, reaction of acetonitrile with the plumbyl cation 4i forms an acetonitrile complex, 10i, in which the norbornyl cation structure is preserved. The X-ray structure of 10i reveals a trigonal bipyramidal environment for the lead atom with the C=C double bond of the cyclopentenemethyl ligand and the nitrogen atom of the acetonitrile molecule in apical positions. Density functional calculations at the B3LYP/6-311G(2d,p)//(B3LYP/6-31G(d) (C, H), SDD (Si, Ge, Sn, Pb)) + DeltaZPVE level indicate that the thermodynamic stability of the group 14 norbornyl cations increases from Si to Pb. This results in a relative stabilization for the plumbanorbornyl cation 4d compared to tert-butyl cation of 52.7 kcal mol(-)(1). In contrast, the intramolecular stabilization energy E(A) of the norbornyl cations 4a-d decreases, suggesting reduced interaction between the C=C double bond and the electron-deficient element center in the plumbacation compared to the silacations. This points to a reduced electrophilicity of the plumbacation compared to its predecessors.     

Artificial neural network combined with principal component analysis for resolution of complex pharmaceutical formulations

A chemometric approach based on the combined use of the principal component analysis (PCA) and artificial neural network (ANN) was developed for the multicomponent determination of caffeine (CAF), mepyramine (MEP), phenylpropanolamine (PPA) and pheniramine (PNA) in their pharmaceutical preparations without any chemical separation. The predictive ability of the ANN method was compared with the classical linear regression method Partial Least Squares 2 (PLS2). The UV spectral data between 220 and 300 nm of a training set of sixteen quaternary mixtures were processed by PCA to reduce the dimensions of input data and eliminate the noise coming from instrumentation. Several spectral ranges and different numbers of principal components (PCs) were tested to find the PCA-ANN and PLS2 models reaching the best determination results. A two layer ANN, using the first four PCs, was used with log-sigmoid transfer function in first hidden layer and linear transfer function in output layer. Standard error of prediction (SEP) was adopted to assess the predictive accuracy of the models when subjected to external validation. PCA-ANN showed better prediction ability in the determination of PPA and PNA in synthetic samples with added excipients and pharmaceutical formulations. Since both components are characterized by low absorptivity, the better performance of PCA-ANN was ascribed to the ability in considering all non-linear information from noise or interfering excipients.     

Spectra and structure of silicon containing compounds. XXXIX. Raman and infrared spectra,conformational stability,vibrational assignment and ab initio calculations of n-propyltrifluorosilane

The infrared (3100-40 cm(-1)) spectra of gaseous and solid and Raman (3200-20 cm(-1)) spectra of liquid with qualitative depolarization values and solid n-propyltrifluorosilane, CH(3)CH(2)CH(2)SiF(3), have been recorded. Additionally the infrared spectra of the sample in nitrogen and argon matrices have been recorded. Both the anti and gauche conformers have been identified in the fluid phases but only the anti conformer remains in the solid. Variable temperature (-105 to -150 degrees C) studies of the infrared spectra of the sample dissolved in liquid krypton have been recorded and the enthalpy difference has been determined to be 135+/-14 cm(-1) (1.62+/-0.17 kJ mol(-1)) with the anti conformer the more stable form. At ambient temperature it is estimated that there is 51+/-2% of the gauche conformer present. Also the enthalpy difference in the liquid was obtained from variable temperature studies of the Raman spectra and from three conformer pairs an average value of 179+/-18 cm(-1) (2.14+/-0.22 kJ mol(-1)) was obtained again with the anti form the more stable conformer. Relatively complete vibrational assignments are proposed for both conformers based on the relative infrared and Raman spectral intensities, infrared band contours, depolarization ratios which are supported by normal coordinate calculations. The geometrical parameters, harmonic force constants, vibrational frequencies, infrared intensities, Raman activities, depolarization ratios, and energy differences have been obtained for the anti and gauche conformers from ab initio MP2/6-31G(d) calculations. Structural parameters and energy differences have also been obtained utilizing the larger 6-311+G(d, p) and 6-311+G(2d, 2p) basis sets. By utilizing the previously reported microwave rotational constants for five isotopomers of CH(3)SiF(3) along with ab initio predicted structural values, r(0) parameters have been obtained for methyltrifluorosilane. Similarly, from the ab initio predicted parameters "adjusted r(0)" parameters have been estimated for both conformers of n-propyltrifluorosilane. The results are discussed and compared with those obtained for some similar molecules.     

Dimers of and tautomerism between 2-pyrimidinethiol and 2(1H)-pyrimidinethione: a density functional theory (DFT) study

Density functional theory (BLYP, B3LYP, B3P86, B3PW91) with the 6-31+G(d,p), 6-311+G(d,p), and cc-pVTZ basis sets has been used to calculate structural parameters, relative energies, and vibrational spectra of 2-pyrimidinethiol (1) and 2(1H)-pyrimidinethione (2) and their hydrogen-bonded homodimers (C(2) 3, C(2h) [4](double dagger), C(2h) 5), monohydrates, and dihydrates and a heterodimer (6). Several transition state structures proposed for the tautomerization process have also been examined. At the B3PW91/6-311+G(d,p)//B3PW91/6-31+G(d,p) level of theory 2-pyrimidinethiol (1) is predicted to be 3.41 kcal/mol more stable (E(rel)) than 2(1H)-pyrimidinethione (2) in the gas phase and 2 is predicted to be 6.47 kcal/mol more stable than 1 in aqueous medium. An unfavorable planar intramolecular strained four center transition state (TS1) for the tautomerization of 1 and 2 in the gas-phase lies 29.07 kcal/mol higher in energy than 2-pyrimidinethiol (1). The C(2) 2-pyrimidinethiol dimer (3) is 6.84 kcal/mol lower in energy than the C(2) homodimer transition state structure ([11](double dagger)) that connects dimers 3 and 4. Transition state [11](double dagger) provides a facile pathway for tautomerization between 1 and 2 in the gas phase (monomer-dimer promoted tautomerization). The hydrogen bonded 2-pyrimidinethiol- - -H(2)O and 2-pyrimidinethiol- - -2H(2)O structures are predicted to be 1.27 and 1.55 kcal/mol, respectively, higher in energy than 2(1H)-pyrimidinethione- - -H(2)O and 2(1H)-pyrimidinethione- - -2H(2)O. Water promoted tautomerization via cyclic transition states involving one water molecule (TS- - -H(2)O, [12](double dagger)) and two water molecules (TS- - -2H(2)O, [13](double dagger)) lie 11.42 and 11.44 kcal/mol, respectively, higher in energy than 2-pyrimidinethiol- - -H(2)O and 2-pyrimidinethiol- - -2H(2)O. Thus, the hydrated transition states [12](double dagger) and [13](double dagger) are involved in the tautomerism between 1 and 2 in aqueous medium.     

聚甲基丙烯酸三烷基锡酯的溶解性能和溶度参数的订定

本文研究了聚甲基丙烯酸三丁基锡酯(PTBTM)和聚甲基丙烯酸三甲基锡酯(PTMTM)在约六十种溶剂中的溶解性能。测定了它们在不同性质溶剂中的特性粘数,订定了PTBTM和PTMTM的溶度参数。并就有机锡聚合物中锡原子上的取代基对其溶解性能的影响进行了讨论。     

FTIR, XRD, and DSC analysis of the rosemary extract effect on polyethylene structure and biodegradability

The purpose of this research study was evaluation of the utility of two common multivariate techniques, agglomerative cluster analysis (CA) and principal component analysis (PCA), as supplementary means of detecting incompatibilities, which can occur between active pharmaceutical ingredients and excipients at the preformulation stage of a solid dosage form. For the detection of incompatibilities between atenolol (beta blocker) and selected excipients (mannitol, lactose, starch, methylcellulose, β-cyclodextrin, meglumine, chitosan, polyvinylpyrrolidone and magnesium stearate), the thermogravimetry (TG), differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) were chosen. The results have shown that compatibility between atenolol and an excipient can be identified in a CA dendrogram by two large clusters, from which one groups an excipient and physical mixtures with a high concentration of the excipient. Another cluster encompasses atenolol and mixtures with a high content of the drug. In the PCA plot, all samples are located along the first principal component axis (PC1), beginning from a single component located with the most negative PC1 value, through mixtures with gradually varying concentration of both ingredients, till the second component located close to the most positive PC1 values. The results have shown that CA and PCA fulfil their role as supporting techniques in the interpretation of the data acquired from the TG curves, and the obtained data are compatible with the results of DSC and FTIR analyses.     

Determination of delta 9-tetrahydrocannabinol in pharmaceutical vehicles by high-performance liquid chromatography

A procedure for the determination of delta 9-tetrahydrocannabinol (delta 9-THC) in the presence of its degradation products in pharmaceutical vehicles by high-performance liquid chromatography (HPLC) is described. The method compares favorably with a standard gas-liquid chromatographic procedure used for the analysis of delta 9-THC in sesame oil USP. The HPLC method is suitable for quantitating delta 9-THC in the presence of several pharmaceutical vehicles and excipients including: sesame oil USP, polyvinylpyrrolidone, Emulphor EL620 and Cremophor EL. Extractions are not required and samples require little preparation. Only the addition of an internal standard in an appropriate solvent is necessary before injection. The procedure has been applied to stability studies of delta 9-THC in various pharmaceutical vehicles.     

Fourier transform infrared spectroscopy supported by multivariate statistics in compatibility study of atenolol with excipients

The objective of this study was to use Fourier transform infrared spectroscopy (FTIR) and multivariate statistics to investigate compatibility/incompatibility of atenolol as a representative of active pharmaceutical ingredients and excipients, such as β-cyclodextrin, methylcellulose, starch and chitosan, when used in solid dosage formulations. Two-component physical mixtures consisting of atenolol and selected excipients were studied by FTIR spectroscopy and two methods of multivariate statistical analysis – principal component analysis (PCA) and cluster analysis (CA), which were used as a supplementary tool for interpretation of the FTIR spectra. Taking into account variability explained by the first two principal components, the results of PCA were visualized in the form of a bi-dimensional scatterplot. A lack of interaction was confirmed by two distinct clusters created by both atenolol and a particular excipient with their mixtures. In the case of CA, lack of interaction between both ingredients was also indicated by two large clusters at a level of 33 or 66% of the maximum distance. The results of the investigations show that with the exception of β-cyclodextrin, the remaining excipients are compatible with atenolol. These findings were confirmed by complementary methods, such as differential scanning calorimetry, thermogravimetry and X-ray powder diffraction.     

Application of inverse gas chromatography to the examination of annealing processes of semi-synthetic base oils

The Flory-Huggins chi1,2infinity parameter and solubility parameter delta2 determined by means of inverse gas chromatography (IGC) were successfully used in the physicochemical characterisation of oxidation products of mineral oil-poly-alpha-olefin mixtures. Application of IGC parameters allows one to examine the changes occurring during three different oxidation procedures: classical oxidation in a stainless steel reactor, in a GC column and separate oxidation of the mixture's components. Changes in chi1,2infinity values reflect the changing affinity of mixtures to different types (dispersive, polar, hydrogen bonding) of intermolecular interactions and their potential miscibility and solubility.     

Development and validation of a stability-indicating LC method for the assay of adapalene in bulk drug and pharmaceutical formulations

A simple and sensitive reverse phase HPLC method for the determination of adapalene (ADP) in bulk drug samples and pharmaceutical formulations has been developed and validated. The separation of ADP was achieved on an Inertsil ODS-3V (5 ??m, 15 cm ± 4.6 mm i.d.) column using UV detector at 230 nm. The mobile phase consisted of ammonium acetate (25 mM, pH 3.0), methanol and tetrahydrofuran (18: 42: 40 v/v). The linear range of detection was 2?C200 ??g/mL (R = 0.9991). Intra- and inter-day assay relative standard deviation values were less than 0.5%. The method has been successfully applied to the determination of ADP in pharmaceutical preparations. The excipients commonly present in formulations did not interfere with the assay of ADP. Analytical parameters were calculated and complete statistical evaluation was performed.