Biomedical subjects

Shan-Yang Lin

Publications and source records attributed to Shan-Yang Lin.

At least 19 recordsLinked to original sources

PubMed2006

Thermal behavior and thermal decarboxylation of 10-hydroxycamptothecin in the solid state.

In order to investigate the thermal-related properties and thermal stability of 10-hydroxycamptothecin (10-HCPT) in the solid state, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and Fourier transform infrared (FT-IR) microspectroscopy were used. A novel combination of FT-IR microspectroscopy with thermal analyzer was applied simultaneously to monitor the dehydration and rehydration processes of the 10-HCPT sample. The thermal-induced decomposition of the 10-HCPT sample was also determined by using electrospray-ion trap mass spectrometry (ES-ITMS). The results indicated that the 10-HCPT sample used in this study was a monohydrate in structure, this form that can dehydrate to an anhydrate form if the temperature goes beyond 90 degrees C. The 10-HCPT anhydrate was first suggested to have two polymorphs, in which the form I might transform to form II when the 110 degrees C-preheated sample was cooled to 30 degrees C. The polymorphic transformation temperature was shown within 90-120 degrees C with 10.46 kcal/mol of enthalpy. The peak at 1723 cm(-1) found in the IR spectrum of 10-HCPT monohydrate might correspond to the hydrogen-bonded CO stretching vibration of lactone, which shifted to 1750 cm(-1) assigned to a free CO group of lactone after the destruction of hydrogen bonding via dehydration. This suggests that monohydrate seems to interact intramolecularly with 10-HCPT by hydrogen bonding. However, the rehydration process of the 10-HCPT anhydrate might cause it to return to being a monohydrate, depending on the storage condition. In addition, the thermal-induced decarboxylation of the solid-state 10-HCPT when the temperature is beyond 226 degrees C was proven by the appearance of a new IR peak at 1701 cm(-1) and one major mass spectral peak at m/z 321. This unique IR spectral peak at 1701 cm(-1) was due to the conjugated carbonyl group in the degraded product of 10-HCPT. The m/z 321 assigned to the decarboxylation of 10-HCPT was equal to the molecular weight loss of 44 from mass spectra; which was consistent with the weight loss of 11.9% (molecular weight of 43.3) from TGA curve of 10-HCPT anhydrate.

Antineoplastic Agents, Phytogenic↗

PubMed2006

Thermodynamic and kinetic characterization of polymorphic transformation of famotidine during grinding.

Two polymorphs of famotidine were prepared by recrystallization from acetonitrile for form A and methanol for form B, respectively. The effect of grinding process on the polymorphic transformation of famotidine was investigated. Each famotidine sample ground for various grinding times in a ceramic mortar was determined by differential scanning calorimetry (DSC), conventional and thermal Fourier transform infrared (FT-IR) microspectroscopy. The results indicate that the raw material of famotidine was proved to be a form B. A unique IR absorption band at 3505 cm(-1) for famotidine form B gradually decreased its intensity with the grinding time, while two newer IR absorption bands at 3451 and 1671 cm(-1) for famotidine form A slowly appeared. The peak intensity ratio of 3451/350 5 cm(-1) was linearly (r=0.9901) increased with the grinding time, suggesting that the grinding process could induce the polymorphic transformation of famotidine from form B to form A by a zero-order process. The DSC endothermic peaks also confirmed this polymorphic transformation from famotidine form B (167 degrees C, DeltaH: 165J/g) to famotidine form A (174 degrees C, DeltaH: 148J/g) in which the values of enthalpy were linearly reduced with the increase of grinding time (r=0.9943). The phase transition temperature of the different ground famotidine samples could be easily and only evidenced by using thermal FT-IR microspectroscopy, rather than by DSC analysis. These phase transition temperatures of the famotidine form B ground for 5-20 min quickly reduced from 144 to 134 degrees C and maintained a constant at 134 degrees C even after 20-30 min grinding. The grinding process not only decreased the crystallinity of famotidine form B but also reduced the particle size of famotidine form B, resulting in easy induction of the polymorphic transformation of famotidine from form B to form A in ground famotidine sample.

Calorimetry, Differential Scanning↗

PubMed2005

Identification of chemical compositions of skin calcified deposit by vibrational microspectroscopies.

Calcinosis cutis is characterized by the deposition of calcium salts in the subcutaneous tissues. Both Fourier transform infrared (FTIR) and Raman microspectroscopic analysis have been applied to easily get the chemical compositions of the skin calcified deposit (SCD), which was surgically excised from a female patient. This SCD was cut into two parts for histopathological (H&E stain) examination and vibrational microspectroscopic study. The result indicates that the whole SCD in the skin lesion was found to be a well-developed, mature and hard mass. Several FTIR absorption bands at 873, 961 and 1,031 cm(-1) [the stretching modes of carbonate and phosphate of hydroxyapatite (HA)], 1,547 and 1,658 cm(-1) (the amide I and II bands of collagen) were detected in the IR spectrum of SCD. The Raman spectral bands at 1,665 and 1,450 cm(-1) (collagen); 1,519 and 1,156 cm(-1) (beta-carotene); and 1,072 and 958 cm(-1) (HA) were also obtained. To our knowledge, this is the first report using FTIR and Raman microspectroscopies to quickly identify and quantify three predominant components, collagen, beta-carotene and type B carbonated HA, in the SCD of a patient.

Adult↗

PubMed2005

Mechanical compression affecting the thermal-induced conformational stability and denaturation temperature of human fibrinogen.

Thermal-induced conformational stability and changes in denaturation temperature of human fibrinogen (FBG) after different mechanical compressions were investigated by a simultaneous Fourier transform infrared microspectroscopy equipped with thermal analyzer (thermal FTIR microscopic system). The confocal Raman microspectroscopy was also applied to determine the thermal reversibility of solid FBG. FBG powder was pressed on one KBr pellet (1 KBr method) or sealed within two KBr pellets (2 KBr method) by different mechanical compressions. The result indicates that there was no marked difference in the thermal behavior for the solid FBG samples prepared by 1 KBr method in the heating process even under different mechanical compression pressures, in which the thermal-induced denaturation temperatures from native to denatured state were maintained constant at 66-67 degrees C. However, the denaturation temperature for the solid FBG samples prepared by 2 KBr method was shifted from 55 to 62 degrees C with the increase of mechanical compression pressure. A good linear correlation was also found between the denaturation temperature and mechanical compression pressure for FBG samples prepared by 2 KBr method. The solid FBG sample, whether prepared by 1 KBr or 2 KBr method, was also found to show the thermal-irreversible property.

Bromides↗

PubMed2005

Corneal calcification: chemical composition of calcified deposit.

BACKGROUND: The aim of this study was to quickly and quantitatively detect the chemical composition of the calcified deposit on the surface of a surgically excised cornea by using vibrational microspectroscopy. METHODS: Both attenuated total reflection (ATR)/Fourier transform infrared (FTIR) and confocal Raman microspectroscopies were used to evaluate the chemical composition of the excised corneal calcified opaque deposit of a 50-year-old male patient. Hydroxyapatite (HA) was used as a reference. RESULTS: Microscopic observations indicated that a whitish-grayish opaque plaquelike deposit was observed. A peak at 1020 cm(-1) assigned to the stretching vibration of phosphate of the poorly crystalline, immature and nonstoichiometric HA was observed from the IR spectrum of the corneal calcified deposit, as compared with the peak at 1030 cm(-1) of the mature, crystalline and stoichiometric HA reference sample. Higher contents of two IR spectral peaks at 871 cm(-1) due to the type-B carbonated apatite and at 866 cm(-1) corresponded to a labile carbonate were also evidenced in the corneal calcified deposit. The predominate peak at 959 cm(-1) due to the stretching mode of phosphate was also found in the Raman spectrum of corneal calcified deposit. CONCLUSIONS: The corneal calcified deposit was evidenced to contain much poor crystalline and immature HA having higher content of the type-B carbonated apatite within the corneal collagen matrix. The process of corneal calcification still proceeds on the surface of this cornea.

Apatites↗

PubMed2005

Micro-Raman spectroscopy used to identify and grade human skin pilomatrixoma.

Raman microspectroscopy was applied to analyze the changes in structural conformation and chemical composition of the mass of human skin pilomatrixoma (PMX). The normal skin dermis, collagen type I, and hydroxyapatite (HA) were used as control. The excised specimens from two patients diagnosed as a typical PMX were detected, in which one specimen was a soft mass, but the other was a hard mass with somewhat calcified deposits via histopathological examination. The Raman spectrum of normal skin dermis was found to be similar to the Raman spectrum of collagen type I, confirming that the collagen type I was a predominant component in normal skin dermis. The differences of Raman peak intensity between normal skin dermis and soft or hard PMX mass were obvious at 1,622-1,558, 1,400-1,230, 1,128, 1,000-850, 749, and 509 cm(-1). In particular, the peak at 1,665 cm(-1) assigned to amide I band shifted to 1,655 cm(-1) and the peak at 1,246 cm(-1) corresponding to amide III band was reduced in its intensity in hard PMX mass. The significant changes in collagen content and its structural conformation, the higher content of tryptophan, and disulfide formation in PMX masses were markedly evidenced. In addition, the shoulder and weak peak at 960 cm(-1) assigned to the stretching vibration of PO(4) (3-) of HA also appeared respectively in the Raman spectra of soft and hard PMX masses, suggesting the occurrence of calcification of HA in the PMX tissue, particularly in the hard PMX mass. The result indicates that the micro-Raman spectroscopy may provide a highly sensitive and specific method for identifying normal skin dermis and how it differs in chemical composition from different PMX tissues.

Adult↗

PubMed2005

Retained antibiotic ophthalmic ointment on an intraocular lens 34 months after sutureless cataract surgery.

PURPOSE: To quickly examine the long-term retained oily-like material on the intraocular lens (IOL) of a sutureless cataract surgical patient. DESIGN: Observational case report. METHODS: Fourier transform infrared (FT-IR) and confocal Raman microspectroscopies were used to identify the deposited materials on explanted IOL. RESULTS: A 70-year-old man underwent a sutureless cataract surgery for his right eye. Garamycin ophthalmic ointment was postoperatively applied on the conjunctival fornix. His vision was improved to 20/25 after surgery but declined gradually to 20/400 half a year later. An oily-like hump on the anterior surface of IOL was found and he underwent IOL exchange after approximately 3 years. The oily-like material was identified by using FT-IR and Raman microspectroscopies to be garamycin ophthalmic ointment. CONCLUSIONS: Both FT-IR and Raman microspectroscopies can easily examine the retained antibiotic ophthalmic ointment on the IOL. Direct access of ophthalmic ointment into ocular anterior chamber through the sutureless incision is a potential risk.

Aged↗

PubMed2005

Multiple elements in the deposits of opacified Hydroview intraocular lens.

PURPOSE: To report the ultrastructural and elemental features of two opacified intraocular lenses (IOLs). DESIGN: Histopathologic case series. METHODS: Two opaque hydrophilic acrylic IOLs (Hydroview H60M, Bausch & Lomb Surgical Clearwater, Florida, USA) explanted from two Chinese patients in Taiwan. The explanted IOLs were evaluated by light microscopy, scanning electron microscopy, and energy-dispersive x-ray spectroscopy. RESULTS: Brownish granular and scattered crystal-like deposits were found in case 2, whereas only fine white granular deposits were found in case 1. Using EDX spectroscopy, the elements of deposits on IOL optics were calcium and phosphorus in case 1, but in case 2, fluorine, magnesium, and sodium were demonstrated in addition to calcium and phosphorus. CONCLUSIONS: Our study indicated a difference in morphology and elements of deposits on opaque IOL optics between these two cases. It was suggested that multiple elements may contribute to the formation of deposits.

Acrylic Resins↗

PubMed2005

pH- and thermal-dependent conformational transition of PGAIPG, a repeated hexapeptide sequence from tropoelastin.

The secondary structure of PGAIPG (Pro-Gly-Ala-IIe-Pro-Gly), a repeated hexapeptide of tropoelastin, in buffer solution of different pH was determined by using attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy. The thermal-dependent structural change of PGAIPG in aqueous solution or in solid state was also examined by thermal FTIR microspectroscopy. The conformation of PGAIPG in aqueous solution exhibited a pH-dependent structural characterization. A predominant peak at 1614 cm(-1) (aggregated beta-sheet) with a shoulder near 1560 cm(-1) (beta-sheet) appeared in pH 5.5-8.5 buffer solutions. A new broad shoulder at 1651 cm(-1) (random coil and/or alpha-helix) with 1614 cm(-1) was observed in the pH 4.5 buffer solution. However, the broad shoulder at 1651 cm(-1) was converted to a maximum peak at 1679 cm(-1) (beta-turn/antiparallel beta-sheet) when the pH shifted from 4.5 to 3.5, but the original pronounced peak at 1614 cm(-1) became a shoulder. Once the pH was lowered to 2.5, the IR spectrum of PGAIPG was dominated by major absorption at 1679 cm(-1) with a minor peak at 1552 cm(-1) (alpha-helix/random coil). The result indicates that the pH was a predominant factor to transform PGAIPG structure from aggregated beta-sheet (pH 8.5) to beta-turn/intermolecular antiparallel beta-sheet (pH 2.5). Moreover, a partial conformation of PGAIPG with minor alpha-helix/random coil structures was also explored in the lower pH buffer solution. There was no thermal-dependent structural change for solid-state PGAIPG. The thermal-induced formation of aggregated beta-sheet for PGAIPG in aqueous solution was found from 28 to 30 degrees C, however, which might be correlated with the formation of an opaque gel that turned from clear solution. The formation of aggregated beta-sheet structure for PGAIPG beyond 30 degrees C might be due to the intermolecular hydrogen bonded interaction between the hydrophobic PGAIPG fragments induced by coacervation.

Amino Acid Sequence↗

PubMed2004

Temperature effect on the structural stability, similarity, and reversibility of human serum albumin in different states.

In order to investigate the thermal stability of human serum albumin (HAS) in three different states (aqueous solution, cast film, and solid powder), Fourier transform infrared (FTIR) spectroscopy was applied to determine the protein secondary structural changes of these HSA samples under non-isothermal or isothermal condition. The structural similarity of HSA before and after thermal treatment was also studied to estimate the thermo-reversible property of the HSA in these different states. The results indicate that with the increase of temperature, the maximum peaks at 1652 and 1547 cm(-1) (alpha-helix) shifted to 1647 and 1542 cm(-1) (random coil), respectively. An additional peak at 1620 cm(-1) assigned to intermolecular beta-sheet structure clearly appeared with temperature. The alpha-helix content was found to be reduced in favor of the formation of intermolecular hydrogen-bonded antiparallel beta-sheet structure beyond 60 degrees C in the heating process. From the data of structural similarity, HSA sample whether in solid powder or cast film form exhibited a better thermo-reversible property than HSA in aqueous solution even heating to 200 degrees C.

Drug Stability↗

PubMed2004

Pressure dependence of human fibrinogen correlated to the conformational alpha-helix to beta-sheet transition: an Fourier transform infrared study microspectroscopic study.

We used Fourier transform infrared (FTIR) microspectroscopy to investigate pressure-induced conformational changes in secondary structure of fibrinogen (FBG). Solid state FBG was compressed on a KBr pellet (1KBr method) or between two KBr pellets (2KBr method). The peak positions of the original and second-derivative ir spectra of compressed FBG samples prepared by the 1KBr method were similar to FBG sample without pressure. When FBG was prepared by the 2KBr method and pressure was increased up to 400 kg/cm(2), peaks at 1625 (intermolecular beta-sheet) and 1611 (beta-sheet aggregates structure and/or the side-chain absorption of the tyrosine residues) cm(-1) were enhanced. The peaks near 1661 (beta-sheet) and 1652 (alpha-helix) cm(-1) also exhibited a marked change with pressure. A linear correlation was found between the peak intensity ratio of 1611/1652 cm(-1) (r = 0.9879) or 1625/1652 cm(-1) (r = 0.9752) and applied pressure. The curve-fitted compositional changes in secondary structure of FBG also indicate that the composition of the alpha-helix structure (1657-1659 cm(-1)) was gradually reduced with the increase in compression pressure, but the composition of the beta-sheet structure (1681, 1629, and 1609 cm(-1)) gradually increased. This indicates that pressure-induced conformational changes in FBG include not only transformations from alpha-helix to beta-sheet structure, but also unfolding and denaturation of FBG and the formation of aggregates.

Fibrinogen↗

PubMed2004

Hydrophilic excipients modulate the time lag of time-controlled disintegrating press-coated tablets.

An oral press-coated tablet was developed by means of direct compression to achieve the time-controlled disintegrating or rupturing function with a distinct predetermined lag time. This press-coated tablet containing sodium diclofenac in the inner core was formulated with an outer shell by different weight ratios of hydrophobic polymer of micronized ethylcellulose (EC) powder and hydrophilic excipients such as spray-dried lactose (SDL) or hydroxypropyl methylcellulose (HPMC). The effect of the formulation of an outer shell comprising both hydrophobic polymer and hydrophilic excipients on the time lag of drug release was investigated. The release profile of the press-coated tablet exhibited a time period without drug release (time lag) followed by a rapid and complete release phase, in which the outer shell ruptured or broke into 2 halves. The lag phase was markedly dependent on the weight ratios of EC/SDL or EC/HPMC in the outer shell. Different time lags of the press-coated tablets from 1.0 to 16.3 hours could be modulated by changing the type and amount of the excipients. A semilogarithmic plot of the time lag of the tablet against the weight ratios of EC/SDL or EC/HPMC in the outer shell demonstrated a good linear relationship, with r = 0.976 and r = 0.982, respectively. The predetermined time lag prior to the drug release from a press-coated tablet prepared by using a micronized EC as a retarding coating shell can be adequately scheduled with the addition of hydrophilic excipients according to the time or site requirements.

Compressive Strength↗

PubMed2004

Evidence of octacalcium phosphate and Type-B carbonated apatites deposited on the surface of explanted acrylic hydrogel intraocular lens.

Fourier-transform infrared (FTIR) microspectroscopy combining with attenuated total reflection (ATR) microsampling technique and micro-Raman spectrophotometer were used to detect the deposited materials on the surface of acrylic hydrogel intraocular lens (IOL) with or without ocular implantation. Surface morphology and the interface of this IOL were further examined by a confocal laser scanning microscope. The brand-new IOL exhibited a very smooth, transparent and featureless surface, but the explanted IOL had an irregular cerebriform-like opaque appearance. Both FTIR/ATR and Raman microspectroscopic analyses showed the deposits on the surface of acrylic hydrogel IOL after ocular implantation to consist of octacalcium phosphate (OCP) and Type B carbonated apatites, leading to the opalescence of acrylic hydrogel IOL. Both vibrational microspectroscopic examinations also confirmed the mineralization still in progress on the surface of acrylic hydrogel IOL after ocular implantation for 2 years.

Aged↗

PubMed2004

Formulation design of double-layer in the outer shell of dry-coated tablet to modulate lag time and time-controlled dissolution function: studies on micronized ethylcellulose for dosage form design (VII).

The dry-coated tablet with optimal lag time was designed to simulate the dosing time of drug administration according to the physiological needs. Different compositions of ethylcellulose (EC) powder with a coarse particle (167.5 microm) and several fine particles (< 6 microm), respectively, were mixed to formulate the whole layer of the outer shell of dry-coated tablets. The formulations containing different weight ratios of coarse/fine particles of EC powders or 167.5 microm EC powder/excipient in the upper layer of the outer shell to influence the release behavior of sodium diclofenac from dry-coated tablet were also explored. The results indicate that sodium diclofenac released from all the dry-coated tablets exhibited an initial lag period, followed by a stage of rapid drug release. When the mixture of the coarse/fine particles of EC powders was incorporated into the whole layer, the lag time was almost the same. The outer shell broke into 2 halves to make a rapid drug release after the lag time, which belonged to the time-controlled disruption of release mechanism. When the lower layer in the outer shell was composed of 167.5 microm EC powder and the upper layer was formulated by mixing different weight ratios of 167.5 microm and 6 microm of EC powders, the drug release also exhibited a time-controlled disruption behavior. Its lag time might be freely modulated, depending on the amount of 6 microm EC powder added. Once different excipients were respectively incorporated into the upper layer of the outer shell, different release mechanisms were observed as follows: time-controlled explosion for Explotab, disruption for Avicel and spray-dried lactose, erosion for dibasic calcium phosphate anhydrate, and sigmoidal profile for hydroxypropyl methylcellulose.

Cellulose↗

PubMed2004

Effect of ethanol or/and captopril on the secondary structure of human serum albumin before and after protein binding.

The attenuated total reflection/Fourier transform infrared technique has been utilized to characterize secondary structural changes in human serum albumin (HSA) before and after protein binding via incubation of HSA in different concentrations of ethanol, captopril or ethanol/captopril mixture. The results indicate that ethanol induced a transition from beta-sheet to an alpha-helical structure and promoted conversion of intramolecular hydrogen-bonded beta-sheet to intermolecular hydrogen-bonded beta-sheet. In contrast, captopril or captopril/ethanol mixture induced conversion of intramolecular hydrogen-bonded beta-sheet to intermolecular hydrogen-bonded beta-sheet and resulted in exposure of the aromatic side-chain groups in the unfolding conformation of HSA. Thus, protein binding between HSA and captopril or captopril/ethanol seems to play an important role in protein secondary structure.

Captopril↗

PubMed2004

Microspectroscopic FT-IR mapping system as a tool to assess blend homogeneity of drug-excipient mixtures.

In order to prepare a controlled-release tablet by direct compression, a Fourier transform infrared (FT-IR) microspectroscopic mapping system was utilized to assess the blend homogeneity of a pharmaceutical powder blend. The model powder blend was a two-component mixture consisting of captopril as a model drug and micronized ethylcellulose (EC) as a direct-compressible model excipient, which was mixed in a laboratory mill. The two-component mixture was mixed in two different weight proportions (captopril:EC, 1:1 or 10:1). By varying the mixing time, different blend mixtures sampled were determined by a reflectance FT-IR microspectroscopic mapping system to collect successively the IR spectra from the actual analysis area. The results revealed that the blend homogeneity increased gradually with increased mixing times, but the powder began to demix or segregate as mixing continued beyond the time when homogeneity was reached. In addition, the statistical results indicated that the sample mixture proportion had an effect on the uniformity of the powder blend. This study demonstrates that microspectroscopic FT-IR mapping technique can be easily used to determine the blend homogeneity in a powder blend mixture.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2004

Ethanol or/and captopril-induced precipitation and secondary conformational changes of human serum albumin.

We determined the secondary structure of solid-state native human serum albumin (HSA) and its precipitates induced by ethanol, captopril, or a captopril/ethanol mixture. A transmission Fourier transform infrared (FT-IR) microspectroscopy equipped with a thermal analyzer was used. The secondary structural composition of solid-state native HSA was 54% alpha-helices (1655 cm(-1)), 22% beta-turns (1679 cm(-1)), and 23% beta-sheets (1633 cm(-1)). After ethanol treatment, a new peak was observed at 1690 cm(-1), and the peak at 1633 cm(-1) was more apparent in the HSA precipitates. The corresponding compositions consisted of 59% alpha-helices, 17% beta-turns, and 24% beta-sheets. After treatment with captopril with or without ethanol, the percentage of alpha-helices and beta-turns decreased in both HSA precipitates, but the percentage of beta-sheets increased. The temperature-dependent structural transformation from alpha-helices/random coils to beta-sheets for the solid-state HSA samples occurred at markedly different onset temperatures. The onset temperature for native HSA was 85 degrees C, and that for HSA precipitates obtained from ethanol, captopril, or captopril/ethanol was 100, 48 or 57 degrees C, respectively. The thermal-induced structural transformation from alpha-helices/random coils to beta-sheets implies a partial unfolding structure in these HSA samples.

Captopril↗

PubMed2004

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

PURPOSE: 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.

Algorithms↗