Wen-Ting Cheng

Eudragit E accelerated the diketopiperazine formation of enalapril maleate determined by thermal FTIR microspectroscopic technique.

AbstractPurpose. Enalapril may undergo the thermal-induced intramolecular interaction to cause an enalapril diketopiperazine (DKP) formation. It is interesting to study the influence of Eudragit E, as a coating polymer, on the stability of enalapril maleate. The reaction kinetics of the solid-state degradation process of pure enalapril maleate and Eudragit E/enalapril maleate mixture with different weight ratios were examined. The mechanism of solid-state interaction between Eudragit E and enalapril maleate was also discussed. Methods. The cast samples of pure enalapril maleate or Eudragit E/enalapril maleate mixture after evaporating the solvent were prepared on an aluminum foil and also determined by reflectance Fourier transform infrared (FTIR) microspectroscopy equipped with thermal analyzer. Results. The result indicates that the interaction might occur between enalapril maleate and Eudragit E in the solid state after evaporating the solvent. The thermal-dependent FTIR spectra show that not only the formation of DKP but also the six-membered cyclic anhydride occurred in the enalapril maleate/Eudragit E mixture in the heating process. Two pathways for solid-sate interaction were proposed. The stability of enalapril maleate was dependent on the weight ratio of enalapril maleate and Eudragit E. The activation energy (n = 3) of DKP formation for pure enalapril maleate was about 141.2 ± 0.7 kJ/mol, but it was reduced significantly to 86.7 ± 0.8 kJ/mol after interaction with Eudragit E (weight ratio: 1:1), suggesting Eudragit E might exacerbate the degradation of enalapril maleate. However, the degradation accelerated by Eudragit E was reduced in high content of Eudragit E. Conclusions. When the weight ratio of both components was 1:1, Eudragit E might interact with the carboxyl group of maleic acid to exacerbate the degradation of enalapril maleate. However, the excess amount of Eudragit E might somewhat reduce the degradation of enalapril, due to the interaction that occurred between Eudragit E and carboxyl group of enalapril.

Identification of monoclinic calcium pyrophosphate dihydrate and hydroxyapatite in human sclera using Raman microspectroscopy.

Raman microspectroscopy was first used to determine the composition of a calcified plaque located at the pterygium‐excision site of a 51‐year‐old female patient’s left nasal sclera after surgery. It was unexpectedly found that the Raman spectrum of the calcified sample at 1149, 1108, 1049, 756, 517, 376 and 352/cm was similar to the Raman spectrum of monoclinic form of calcium pyrophosphate dihydrate (CPPD) crystal, but differed from the Raman spectrum of triclinic form of CPPD. An additional peak at 958/cm was also observed in the Raman spectrum of the calcified plaque, which was identical to the characteristic peak at 958/cm of hydroxyapatite (HA). This is the first study to report the spectral biodiagnosis of both monoclinic CPPD and HA co‐deposited in the calcified plaque of a patient with sclera dystrophic calcification using Raman microspectroscopy.

Famotidine polymorphic transformation in the grinding process significantly depends on environmental humidity or water content.

The effect of environmental humidity and additional water added on the polymorphic change of famotidine in the process of grinding was investigated. The famotidine form B powder with or without additional amount of water added was respectively ground for 30 min in an oscillatory ball mill under 25+/-2 degrees C and three relative humidities (RH) (50+/-5%, 75+/-5% or 95+/-5% RH). Each ground sample was periodically isolated for analytical determinations by using differential scanning calorimetry (DSC), thermogravimetric (TG) analysis and Fourier transform infrared (FT-IR) microspectroscopy. The results indicate that the higher environmental humidity might induce and promote the polymorphic transformation of famotidine from form B to form A in the process of grinding. Moreover, the more the amount of water externally added the easier the polymorphic transformation of famotidine from form B to form A obtained. In addition, the more grinding time spent the more formation of form A obtained. This study disavowed the results of other studies in which no polymorphic change of famotidine even by grinding. The apparent evidence shows that the solid-state polymorphic transformation of famotidine from form B to form A in the grinding process significantly depended on the relative humidity of atmosphere and the additional amount of water added.

Differential scanning calorimetry with curve-fitting program used to quantitatively analyze the polymorphic transformation of famotidine in the compressed compact.

Differential scanning calorimetry (DSC) combined with a curve-fitting program was utilized to quantitatively determine the polymorphic composition of famotidine in the compacts prepared by different compression treatments. Two types of famotidine compacts (compact I or II) were prepared by compressing a conical shape or a flattened shape of powder bed of famotidine form B. The compact I was constructed by a transparent region in the center with an opaque region surrounded outside, but the compact II was formed by a whole opaque region only. A drilled disc sample was prepared and then directly determined by DSC analysis. The Raman spectral results clearly indicate that all the compacts whether in any region before DSC determination were only of famotidine form B and independent of compression pressure applied. Under DSC determination, however, the curve-fitted relative compositions of form B in the drilled disc I sample were gradually reduced to 23–24% with the increase of compression pressure, whereas the curve-fitted relative composition of form A was slowly increased up to 76–77%. A transitional phase of famotidine form B (form B*) in the transparent region of the compact I after applying >150 kg/cm2 of compression pressure was easily detected, and then transformed to famotidine form A under DSC heating process. But this transitional phase and polymorphic transformation of famotidine could not be detected by other spectroscopic methods. This suggests that the DSC heating system was a preferred method not only to quantitatively analyze the polymorphic transformation of famotidine but also to find a newly transitional phase of famotidine in the compressed compact.

Preliminary Identification of [beta]-Carotene in the Vitreous Asteroid Bodies by Micro-Raman Spectroscopy and HPLC Analysis

beta-carotene was first identified from the vitreous asteroid bodies (ABs) excised from one patient with asteroid hyalosis (AH) by confocal Raman microspectroscopy and was also verified by high performance liquid chromatography (HPLC). Two patients had been diagnosed with AH and intervened by surgical vitrectomy due to blurred vision. The morphology and components of both AB specimens were observed by optical microscopy and determined by using confocal Raman microspectroscopy and HPLC analysis, respectively. Surprisingly, two unique peaks at 1528 and 1157 cm(-1) were found in the Raman spectrum for the AB specimen of patient 1 alone, which were in close agreement with that of the Raman peaks at 1525 and 1158 cm(-1) for beta-carotene and/or lutein. However, HPLC analytical data clearly indicated that the retention time for the extracted sample from the AB specimen of patient 1 was observed at 13.685 min and just identical to that of beta-carotene (13.759 min) rather than lutein (2.978 min). In addition, the lack of any peak in the HPLC profile for the AB specimen of patient 2 also confirmed the absence of Raman peaks at 1525 and 1158 cm(-1). Thus this preliminary study strongly suggests that beta-carotene as a unique component of ABs was specifically detected from the AB specimen of one AH patient by using confocal Raman microspectroscopy and HPLC analysis.