Biomedical subjects

Makoto Otsuka

Publications and source records attributed to Makoto Otsuka.

At least 19 recordsLinked to original sources

PubMed2006

Changes in vertebral wedging rate between supine and standing position and its association with back pain: a prospective study in patients with osteoporotic vertebral compression fractures.

STUDY DESIGN: Prospective consecutive series. OBJECTIVE: To analyze supine and standing radiographs and the association of back pain using subjective pain criteria. SUMMARY OF BACKGROUND DATA: It has been considered that there is little correlation between the degree of collapse of the vertebral body and the level of pain. In previous studies, however, measurements have only been based on supine radiographs. Although there were 2 authors who reported the results of supine lateral and standing lateral radiographs in patients with thoracolumbar vertebral fractures, as far as we know, there has not been any detailed report concerning the correlation between radiologic findings using supine and standing lateral radiographs and back pain. METHODS: We examined 100 consecutively treated patients, prospectively. Back pain and the supine and standing radiographs were assessed 1 month after injury. Changes in vertebral wedging rate (WR) from supine to standing position (Delta WR) was reported by the following equation: Delta WR = WR(standing)-WR(supine). RESULTS: The median age of the cohort was 75 years (range, 60-89 years). The median VAS of back pain at supine position, at standing position, and when standing erect was 13, 33, and 41, respectively. The median wedging rate on the supine and standing radiographs were 28% and 37%, respectively (P < 0.001). There was a significant correlation between Delta WR and back pain when standing erect (r = 0.79, P < 0.001). CONCLUSION: Changes in vertebral wedging rate between supine and standing position and its association with back pain may give a clue to the pathogenesis of pain from osteoporotic thoracolumbar vertebral compression fractures.

Aged↗

PubMed2006

Effects of solid-state reaction between paracetamol and cloperastine hydrochloride on the pharmaceutical properties of their preparations.

Tablets containing both paracetamol (PM) and cloperastine hydrochloride (CLH) in a combination formulation prepared by standard vertical granulation technology were found to have altered pharmaceutical properties. The hardness and disintegration time of tablets containing both PM and CLH gradually increased during storage, and the cross-screw did not operate smoothly during preparation of the mixed powder. The objective of the present study was to investigate the mechanism of formation of eutectic mixtures consisting of PM and CLH. Binary mixtures of PM and CLH in various proportions were prepared as physical mixtures and analyzed by DSC to study their thermal behavior. Phase diagrams obtained from the endothermic peaks due to melting of physical mixtures of PM and CLH demonstrated the formation of eutectic mixtures with eutectic temperatures of 86.9-110.2 degrees C depending on the ratio of constituents. The formation of the eutectic mixture was studied for a 50:50 mol.% ratio of PM and CLH. PXRD analysis revealed that the eutectic mixture of PM and CLH is structurally different from native PM and CLH. The most probable interaction sites between PM and CLH were demonstrated by DSC analysis of a binary mixture of PM and CLH prepared by melt quenching.

Acetaminophen↗

PubMed2006

Comparative evaluation of bioactivity change of crystalline trypsin during compression by chemoinformatics and 2-D Fourier-transform infrared spectroscopy.

The purpose of this study is to develop a method of evaluating the enzymatic activity of trypsin in a solid-state based on Fourier transform infrared (FT-IR) spectra using chemoinformatics and two-dimensional (2-D) correlation spectroscopy. Crystalline trypsin powders are compressed at 0-4000 kg cm-2 by a compression/tension tester. The enzymatic activity of trypsin is assayed by the kinetic degradation method. Spectra of 10 calibration sample sets are recorded 3 times with a FT-IR spectrometer. The maximum intensity of FT-IR spectra and enzymatic activity of trypsin decrease as the compression pressure increases. The FT-IR spectra of trypsin samples are subjected to a principal component regression (PCR). A plot of the calibration data obtained is made between the actual and predicted trypsin activity based on a two-component model with gamma2=0.909 (n=30). The regression vector is almost the same as the loading vector for PC1. On the other hand, a generalized two-dimensional (2-D) correlation spectroscopic method is applied to FT-IR spectra of compressed trypsin. The result is consistent with that of the chemoinformatics method. The FT-IR chemoinformatics method allows for solid-state quantitative analysis of the bioactivity of the bulk powder of a polypeptide drug.

Animals↗

PubMed2006

Effect of pulverization and dehydration on the pharmaceutical properties of calcium lactate pentahydrate tablets.

The effects of heat conduction and pulverization on dehydration kinetics and tablet hardness were studied by a variety of kinetic equations and physical models. The dehydration behavior of unpulverized calcium lactate pentahydrate (UCLP) and pulverized calcium lactate pentahydrate (PCLP) tablets was investigated by using differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD). The hardness of both UCLP and PCLP tablets was significantly decreased after dehydration. The relationship between the extent of dehydration and the tablet hardness of both UCLP and PCLP tablets was linear. The results suggest that the reduction in tablet hardness is dependent on the dehydration of crystal water, and the values of the slopes indicate that the bonding energy of the UCLP was stronger than that of the PCLP. The dehydration of both UCLP and PCLP tablets at 55 degrees C followed a one-dimensional diffusion mechanism, whereas dehydration at storage temperatures of 60-80 degrees C followed a three-dimensional diffusion mechanism. UCLP and PCLP tablets contracted in thickness and diameter during dehydration, but final contraction ratios showed that PCLP tablets were more affected than UCLP tablets. In contrast, the micropore radius of both UCLP and PCLP tablets increased after dehydration. Thus, the pharmaceutical properties of calcium lactate pentahydrate (CLP) tablets are affected both by pulverization and by the extent of dehydration of the bulk powder in the tablet formulation.

Calcium Compounds↗

PubMed2006

Kinetic study of the transformation of mefenamic acid polymorphs in various solvents and under high humidity conditions.

The transformation kinetics of mefenamic acid form II to form I in three kinds of solvents and under high humidity conditions were extensively investigated. Form II crystals were suspended in water, 50% ethanol and ethanol at 28, 33 and 37 degrees C, or stored at 50, 60 and 70 degrees C at 97% RH. Form II transformed to form I under all storage conditions and the rate of transformation depended on the kind of solvent. The transformation followed the three-dimensional nuclei growth mechanism, depending on temperature. The nuclei formation and growth processes were significantly accelerated in ethanol compared with water. The addition of seed crystals of the stable form I shortened the both nuclei formation and growth processes and therefore the transformation was accelerated.

Drug Stability↗

PubMed2006

An accurate quantitative analysis of polymorphs based on artificial neural networks.

Measurement precision based on homogeneous and accurate standard samples has been reported to result in significant improvement in the sensitivity and accuracy of the quantitative analysis of polymorphic mixtures. The purpose of this study was to further improve the accuracy of the quantitation based on data processing by artificial neural networks (ANNs), using such high quality standard samples. Homogeneous powder mixtures of alpha- and gamma-forms of indomethacin (IMC) at various ratios (0-50% alpha-form content) were subjected to X-ray powder diffractometry. The two diffraction peaks selected as the best combination in multiple linear regression (MLR) were used in the ANN with an extended Kalman filter as a training algorithm. The results obtained by ANN had better predictive accuracy at lower contents (0-5%) compared to those of MLR. ANNs for the diffraction data based on high quality standard samples provide an extremely precise and accurate quantification for polymorphic mixtures.

Algorithms↗

PubMed2006

The treatment of acute thoracolumbar burst fractures with transpedicular intracorporeal hydroxyapatite grafting following indirect reduction and pedicle screw fixation: a prospective study.

STUDY DESIGN: Prospective consecutive series. OBJECTIVE: To evaluate the outcomes of the treatment of acute thoracolumbar burst fractures by transpedicular hydroxyapatite grafting following indirect reduction and pedicle screw fixation. SUMMARY OF BACKGROUND DATA: In the treatment of thoracolumbar burst fractures, the major problem after posterior correction and instrumentation is failure to support the anterior spinal column, leading to the loss of correction of kyphosis and instrumentation breakage. METHODS: There were 15 consecutive patients who had thoracolumbar burst fractures and associated incomplete neurologic deficit. They underwent surgery within 4 days of admission, had their implants removed within 1 year, and were prospectively followed for at least 2 years. Following indirect reduction and pedicle screw fixation, transpedicular intracorporeal hydroxyapatite grafting to the fractured vertebrae was performed. Median operating time was 130 minutes, and median blood loss was 155 g. RESULTS: The neurologic function of all 15 patients improved by at least 1 American Spine Injury Association grade, with 9 (60%) having complete neurologic recovery. Sagittal alignment was improved from a median preoperative kyphosis of 20 degrees to -1 degrees (lordosis) by surgery but was found to have slightly deteriorated to 1 degrees at final follow-up observation. Computerized tomography showed a median spinal canal narrowing of 64%, 22%, and 11%, respectively. There were no instances of instrumentation failure. CONCLUSIONS: Posterior indirect reduction, transpedicular hydroxyapatite grafting, and pedicle screw fixation could provide reliable neurologic improvement in patients with incomplete neurologic deficit, and could prevent the development of kyphosis. This technique does not require fusion to a segment, thereby preserves thoracolumbar motion.

Adolescent↗

PubMed2006

A novel white film for pharmaceutical coating formed by interaction of calcium lactate pentahydrate with hydroxypropyl methylcellulose.

We have found that a white film forms on tablets when a coating solution consisting of hydroxypropyl methylcellulose (HPMC), polyethylene glycol (PEG 6000) and calcium lactate pentahydrate (CLP) is used. The white film has also been found in casting film consisting of HPMC and CLP, and the surface state of coated tablets has been shown to be strongly affected by addition of PEG 6000. The aim of the present study was to investigate the mechanism of formation of this white film in order to derive an appropriate film prescription. Interaction among the base ingredients of the film was investigated using differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and Fourier transform-infrared (FT-IR) spectroscopy. The casting film formed with HPMC and a large excess of PEG 6000 was found to be crystalline in form. In contrast, the amorphous film consisting of HPMC, PEG 6000 and excess CLP exhibited the crystallinity film by an excess addition of CLP. Although the crystalline film had many cracks, the amorphous film appeared to be excellent as a tablet coating. The most probable interaction sites between HPMC and CLP were demonstrated by FT-IR analysis of casting films consisting of HPMC, CLP and PVP.

Calcium Compounds↗

PubMed2006

Effect of nanostructure on biodegradation behaviors of self-setting apatite/collagen composite cements containing vitamin K2 in rats.

Apatite cement and collagen were combined by a mechanochemical method to create a new self-setting apatite/collagen composite cement, and menatetrenone (VK2) was loaded into a drug-delivery system to test biocompatibility in rats. Powder X-ray diffraction analysis (XRD), scanning electron microscopy (SEM), and electron probe microanalyzer (EPMA) were performed to characterize the physicochemical properties of apatite/collagen composite cements. The XRD results suggested that ground apatite/collagen cement was completely transformed into bone-like hydroxyapatite, but that without grinding was incomplete. The SEM and EPMA results suggested that ground apatite/collagen cement was homogeneously dispersed of nanoapatite crystals in collagen matrices, similar to that in natural bone. In contrast, the cement without grinding was heterogeneously distributed. To evaluate in-vivo cement density (CMM), microradiograms were measured for 72 days after implanting apatite/collagen composite cements in intramuscular tissue on the backs of rats, and cross sections of the cements and surrounding soft tissues were observed by microscope. The CMM results of the apatite/collagen composite cements suggested that the biodegradation rate was dependent on the cement quality and nanogeometrical structure. The CMM result of VK2-loaded apatite/collagen cements suggested that the biodegradation rates of the cements were significantly dependent on their formulation. The CMM of ground apatite/collagen cement increased until 7 days and then decreased, and bone-like cells penetrated deeply in the center. The microphotograph and CMM results of apatite/collagen without grinding indicated that a lot of bone-like cells penetrated into the cement and the cement shape was totally deformed.

Animals↗

PubMed2006

Prediction of tablet hardness based on near infrared spectra of raw mixed powders by chemometrics.

The purpose of this research is to elucidate the effect of lubricant mixing on tablet hardness by near-infrared (NIR) chemometrics as a basic study of process analytical technology. Formulation cellulose (F-C) consisted of sulpyrine (SP), microcrystalline cellulose (MC), and magnesium stearate (MgSt). Formulation lactose/starch (F-L) consisted of SP bulk drug powder, spray-dried lactose (SL), corn starch (CS), and MgSt. First, F-L and F-C without MgSt were mixed in a twin-shell mixer for 60 min. MgSt was added to the mixed powder, and was mixed for various mixing times, after which the mixed powders were compressed by 8-mm diameter punch and die. NIR spectra of raw mixed powders of F-L and F-C were taken using a reflection type of Fourier transform NIR spectra spectrometer, and chemometric analysis was performed using principal component regression (PCR). The tablet hardnesses of F-L and F-C decreased with increasing mixing time. All NIR spectra of the mixed powders of F-L and F-C fluctuated depending on mixing time. In order to predict tablet hardness before tablet compression, NIR spectra of F-L and F-C mixed powders were analyzed and evaluated for hardness by PCR. The minimum standard error of cross-validation values could be realized by using five- and six-principal component models, respectively. In the cases of F-L and F-C, the relationships between the actual and predicted tablet hardnesses showed straight lines, respectively. In the regression vectors of F-L and FC, the peaks related to hydrogen groups of SP, CS, and MC appeared as positive peaks. In contrast, the peaks related to hydrocarbon due to MgSt appeared as negative peaks in the regression vectors. The calibration models to evaluate the tablet hardness were obtained based on NIR spectra of raw mixed powders by PCR. This approach to predicting tablet hardness prior to compression could be used as a routine test to indicate the quality of the final product without spending time and energy to produce samples of questionable quality.

Cellulose↗

PubMed2006

Polymorphic transformation of indomethacin under high pressures.

To study the effect of pressure on polymorphic transformation, intact powder, and ethanol slurry of alpha, gamma, and amorphous forms of indomethacin (IMC) were compressed under high pressures. A quantifying method for the percentages of these three constituents in sample powder was established. Using this method, analysis of compressed samples revealed that alpha form, which is difficult to prepare in stable form under atmospheric pressure, was easily obtained in stable form from the ethanol slurry of the amorphous IMC, which does not include any specific crystalline forms. In the ethanol slurry of gamma form, transformation to alpha form was observed: a reciprocal phenomenon under atmospheric pressure. These results can be rationally explained as follows: alpha form is more easily crystallized than gamma form in the ethanol solution, the more closely-packed crystal structure of alpha form is thermodynamically predominant over gamma form under high pressure, and pressure-induced amorphization occurs. This study indicates that crystallization experiments from the slurry of amorphous samples under various pressures can be useful in screening polymorphic or other solid states.

Calorimetry, Differential Scanning↗

PubMed2006

International harmonization of generic drugs: in vitro dissolution tests for Japanese and American generic tablets.

Ibuprofen tablets on the market in Japan and the USA were compared by manual- and automatic-dissolution tests according to USP24 criteria. Dissolution test were performed in 900 ml of phosphate buffer of pH 7.2 at 37.0+/-0.5 degrees C at 50 rpm for 60 min, and the time required for 70% dissolution (T70%) and 5% dissolution after 60 min (A60) were evaluated. The dissolution profiles of both Japanese and American tablets by the automatic-method showed almost the same profiles as those of the manual method. T70% of the American and Japanese tablets by the manual method were not significantly different (p>0.05) from the automatic-method at various sampling positions. The A60 of the American and Japanese tablets by the manual-method was not significantly different (p>0.05) except at one position. The results indicate that the automatic-method was more reproducible than the manual-method, and also that systematic error was negligible. The T70% and A60 of the American tablets were significantly different (p<0.05) from the Japanese tablets. The American tablets were a film-coated over-the-counter drug and the Japanese tablets were a sugar-coated prescription drug. There was a difference in dissolution behavior between the dosage forms of the two countries.

Absorption↗

PubMed2005

Patients' expectations and satisfaction in lumbar spine surgery.

STUDY DESIGN: Prospective consecutive series. OBJECTIVE: To determine patient expectations in lumbar spine surgery and assess the level of fulfillment of those expectations. SUMMARY OF BACKGROUND DATA: Little has been offered in the literature in specific regards to lumbar spine surgery. METHODS: Ninety-eight patients, 49 patients who underwent discectomy for lumbar disc herniation (Group 1) and 49 patients who underwent laminotomy for lumbar spinal stenosis (Group 2), completed the self-report questionnaire. Preoperative expectations, reasons for surgery, and expected postoperative status were inquired before surgery and the satisfaction at 2 years after surgery. RESULTS: Concerning patients' expectations, half of the patients expected to become completely leg pain free, and more than three fourths of the patients expected to become unlimited in their walking ability in both groups. More than half of the patients expected to have a 90% or greater chance of complete success of surgery. With regard to satisfaction, 42 of the 49 patients (86%) in Group 1 and 35 of the 49 patients (71%) in Group 2 chose "Surgery met my expectations" at the follow-up. The remaining patients selected "I did not improve as much as I had hoped." Positive expectations were associated with better satisfaction in Group 1 only. Of the patients who had achieved the expected postoperative status with respect to their no.1 reason for surgery, 2 of 34 patients in Group 1 (6%) and 5 of the 26 patients in Group 2 (19%) nonetheless reported "unfulfilled expectations." In patients whose no. 1 concern was further progression, 3 (38%) of the 8 patients in Group 1 and 2 (40%) of the 5 patients in Group 2 demonstrated unfulfilled expectations. CONCLUSIONS: Even if the clinical expectations were met, some patients were still dissatisfied. Patients with spinal stenosis (Group 2) seem to have more unrealistic expectations than patients with disc herniation (Group 1).

Adult↗

PubMed2005

Characterization of dehydration and hydration behavior of calcium lactate pentahydrate and its anhydrate.

The use of calcium lactate pentahydrate (CLP) as an additional filler-binder for direct compaction of tablets has been reported to result in a short disintegration time and rapid drug release. The aim of this study was to understand the dehydration and hydration behavior of CLP and calcium lactate anhydrate (CLA) under various conditions of storage temperature and relative humidity. The removal and acquisition of crystal water were investigated by using differential scanning calorimetry (DSC), thermogravimetry-differential thermal analysis (TG-DTA), powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM). The PXRD results indicated that CLP exists as a crystalline solid and CLA as an amorphous solid. Dehydration of CLP resulted in aggregated particles of CLA with an increase in average particle size. The dehydration and hydration kinetics of CLP were analyzed with the Hancock-Sharp equation on the basis of the isothermal DSC data. The dehydration of CLP followed a zero-order mechanism (Polany-Winger equation). In contrast, the surface roughness of CLA was significantly decreased by hydration. The hydration of CLA followed a three-dimensional diffusion model (Ginstling-Brounshtein equation).

Calcium Compounds↗

PubMed2005

Anatomic changes in lateral spondylolisthesis associated with adult lumbar scoliosis.

STUDY DESIGN: Prospective consecutive series. OBJECTIVE: To analyze the anatomic changes in lateral spondylolisthesis. SUMMARY OF BACKGROUND DATA: Previous studies have focused on the correlation between lateral spondylolisthesis, and curve progression and pain. To our knowledge, there has not been any detailed report concerning anatomic changes in lateral spondylolisthesis. METHODS: We examined 24 consecutive patients (mean age 66 years), with lateral spondylolisthesis associated with lumbar scoliosis who had computerized tomography (CT) after myelography. Coronal reconstruction CT was used to measure the vertebral translation. Vertebral rotation was measured by the Aaro method using transaxial CT. RESULTS: The Cobb angle averaged 26 degrees (range 13 degrees-75 degrees). Lateral spondylolisthesis was found most commonly at the lower-end vertebra. The cephalad-slipped vertebra rotated toward the convex side of the main curve, whereas the caudal vertebra rotated toward the convex side of the lumbosacral hemi (or fractional) curve below. Mean lateral translation and vertebral rotation were 7 mm and 8 degrees, respectively. There was a significant correlation between lateral translation and vertebral rotation (r = 0.49; P = 0.018). The convex superior articular process of the caudal vertebra had compressed the nerve root laterally in 21 patients, of whom 10 had radicular pain. The concave, inferior articular process of the cephalad vertebra had compressed the dural sac posteriorly, and 2 patients had radicular pain. CONCLUSIONS: To our knowledge, this study has been the first attempt to analyze anatomic changes in lateral spondylolisthesis using CT. It may offer further insight into the pathogenesis of adult lumbar scoliosis.

Aged↗

PubMed2005

Effect of pulverization of the bulk powder on the hydration of creatine anhydrate tablets and their pharmaceutical properties.

The hydration behavior and expansion properties of untreated and pulverized creatine anhydrate (CRA) tablets were studied under 60 and 75%RH at 25 degrees C by using differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD). The tablet hardness of untreated and pulverized CRA tablets was significantly decreased after hydration. There was a linear relationship between the degree of hydration and the tablet hardness of untreated CRA tablets compressed at 1000 kg/cm2. In contrast, the relationship between the degree of hydration and the tablet hardness of pulverized CRA tablets was nonlinear. These results suggest that the reduction in hardness of pulverized CRA tablets does not depend solely on the hydration level of crystal water. PXRD analysis indicated that the diffraction pattern of the pulverized CRA powder was similar to that of the untreated CRA powder. However, the diffraction intensity of the pulverized CRA powder was slightly lower than that of the untreated CRA powder at high angle. The micropore radius of both untreated and pulverized CRA tablets was significantly increased after hydration, but analysis of the relationship between micropore radius and fractional hydration of crystal water showed that untreated CRA tablets were more affected than pulverized CRA tablets. Therefore, the reduction in tablet hardness depends not only on the hydration behavior but also on the crystal orientation of the CRA powder.

Calorimetry, Differential Scanning↗

PubMed2005

Effect of tablet geometrical structure on the dehydration of creatine monohydrate tablets, and their pharmaceutical properties.

The effects of compression and pulverization on the dehydration kinetics and hardness of creatine monohydrate tablets were studied using a variety of kinetic equations and physical models. The dehydration behavior of unpulverized and pulverized tablets was investigated by using differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD). The hardness of both unpulverized and pulverized monohydrate tablets was significantly decreased after dehydration. The relationship between the degree of dehydration and the tablet hardness of both unpulverized and pulverized monohydrate tablets formed a straight line. The results suggest that the reduction in tablet hardness is dependent on the dehydration of crystal water, and the values of the slopes indicate that the bonding energy of the unpulverized sample was stronger than that of the pulverized sample. The dehydration kinetics of the unpulverized and pulverized monohydrate tablets were evaluated by analyzing the fit of the isothermal DSC data using a variety of solid-state kinetic models. The dehydration of the unpulverized tablets at various levels of compression pressure followed the 3-dimensional growth of nuclei mechanism. In contrast, although the dehydration kinetics of pulverized monohydrate tablets compressed at 500 and 750 kg/cm2 followed the 3-dimensional diffusion mechanism, those compressed at 1000 kg/cm2 followed the 3-dimensional growth of nuclei mechanism. The PXRD analysis indicated that the diffraction intensity of the pulverized monohydrate powder was significantly lower than that of the unpulverized powder. The diffraction peaks of the (h00) planes and the micropore structure of the unpulverized monohydrate tablets were affected by pulverization and compression force, respectively.

Compressive Strength↗

PubMed2005

Evaluation of the microcrystallinity of a drug substance, indomethacin, in a pharmaceutical model tablet by chemometric FT-Raman spectroscopy.

PURPOSE: To establish a chemometric method for the precise evaluation of the microcrystallinity of indomethacin (IMC) in a pharmaceutical model tablet, based on FT-Raman spectroscopy. METHODS: Standard sample powders of homogeneous mixtures of amorphous and crystalline IMC were prepared in various proportions. A calibration model for the crystallinity of IMC was constructed by partial least-square (PLS) analysis based on the multiplicative scatter correction (MSC)+second-derivative transformed Raman spectra. A calibration model for the crystallinity of IMC in a model pharmaceutical product (IMC/mannitol=1:9 wt/wt) was also constructed using homogeneous standard sample powders of various degrees of crystallinity of IMC. RESULTS: This technique was validated to detect to 2% an amorphous or crystalline material in IMC contained in the model product (0.2% of the total mass of the tablet). Using this technique, not only pressure-induced amorphization but also the difference in microcrystallinity of IMC at the surface and interior of a model product tablet was elucidated after compaction of the tablet. CONCLUSIONS: The established technique is ideally suited for precise quantification of microanalysis of drug substances and drug products, particularly at the surface and interior of the tablet.

Anti-Inflammatory Agents, Non-Steroidal↗