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Abstract Background Anterior knee pain due to patellar maltracking following total knee arthroplasty (TKA) reduces patients’ satisfaction. This study aimed to determine the patellofemoral pressure (PFP) in patients with favorable patellar tracking (FT) and impaired patellar tracking (IT) following TKA, the factors causing patellar maltracking, and the effect of lateral retinacular release (LRR) on patients with IT. Methods Forty-four patients with varus knee osteoarthritis undergoing cruciate-retaining TKA were enrolled. After component implantation, patients with a separation of ≥ 2 mm of the patellar medial facet from the medial femoral trochlea throughout knee range of motion were classified into the IT group; meanwhile, the others were classified into the FT group. PFP was measured intraoperatively in three phases: (1) with the resurfaced patella (RP); (2) with the resurfaced patella and knee (RPK); and (3) when LRR was performed in IT (post-LRR). The PFPs at 0°, 90°, 120°, and 135° knee flexion were compared between FT and IT using the Mann–Whitney U test. Pairwise comparison of the PFP in IT between RPK and post-LRR was performed using the Wilcoxon signed-rank test. Correlations between PFP and pre- and postoperative radiographic parameters, such as hip–knee–ankle angle, lateral distal femoral angle, medial proximal tibial angle, anterior femoral offset, Insall–Salvati ratio (ISR), patellar tilt, and patellar resection angle (PRA), were evaluated using Spearman’s rank correlation coefficients. Results High lateral PFP in the knee flexion position led to patellar maltracking. Patients with IT (n = 24) had higher lateral and lower medial PFP than did patients with FT (n = 20) at 90°, 120°, and 135° knee flexion in RP and RPK. LRR in IT reduced the lateral PFP in the knee flexion position. PRA and ISR were correlated with the lateral PFP at no less than 90° in RP and RPK. Conclusions This study demonstrated that internal rotational patellar resection, which resulted in a thick medial patellar remnant and a thin lateral counterpart, and patella alta were the causative factors of high lateral PFP, which induced patellar maltracking after TKA. Surgeons should avoid internal rotational patellar resection to achieve FT and perform LRR in patients with patellar maltracking.

Mucopolysaccharidosis II (MPS II) is a lysosomal storage disease caused by a deficiency in iduronate-2-sulfatase (IDS), leading to the accumulation of dermatan sulfate and heparan sulfate in lysosomes. Traditionally, genotyping of the IDS gene has been conducted through exome sequencing, which fails to detect inversion variants. Consequently, when no pathogenic variants are detected in exons, additional PCR-based analysis is required. Herein, we introduce a rapid genotyping technique method using long-range PCR for MPS II patients. We successfully identified an inversion variant and confirmed the sequences of the inversion regions. We also confirmed that the pathogenic variant in the patient originated de novo. These findings suggest that long-range PCR genotyping can identify inversion variants more rapidly compared to the previous PCR-based methods, making it a valuable tool for newborn screening (NBS) and genetic diagnosis.

Background:. An unstable trochanteric femoral fracture is a serious injury, with a 1-year mortality rate of 5.4% to 24.9%, for which there is currently no standard treatment method. The lag screw insertion site is one of the primary contact areas between the cortical bone and an intramedullary nail. We hypothesized that a posterolateral fracture causes intramedullary nail instability when the posterolateral fracture line interferes with lag screw insertion. The purpose of the present study was to investigate the effect of posterolateral fracture line morphology on intramedullary nail stability by simulating unstable trochanteric femoral fractures with a posterolateral fracture fragment. Methods:. Eighteen custom-made synthetic osteoporotic bone samples were used in the present study. Nine samples had a posterolateral fracture line interfering with the lag screw insertion hole (Fracture A), and the other 9 had a fracture line 10 mm away from the hole (Fracture B). Cyclic loading (750 N) was applied to the femoral head 1,500 times. Movement of the end cap attached to the intramedullary nail was recorded. The amplitudes of motion in the coronal plane (coronal swing motion), sagittal plane (sagittal swing motion), and axial plane (total swing motion) were evaluated. The change in the neck-shaft angle was evaluated on photographs that were made before and after the test. Medial cortical displacement was measured before and after the test. Results:. Two Fracture-A samples were excluded because the amplitude of sagittal swing motion was too large. The mean values for coronal, sagittal, and total swing motion were 1.13 ± 0.28 mm and 0.51 ± 0.09 mm (p < 0.001), 0.50 ± 0.12 mm and 0.46 ± 0.09 mm (p = 0.46), and 1.24 ± 0.24 mm and 0.69 ± 0.11 mm (p < 0.001) for Fractures A and B, respectively. The mean neck-shaft angle change was −8.29° ± 2.69° and −3.56° ± 2.35° for Fractures A and B, respectively (p = 0.002). The mean displacement of the medial cortex was 0.38 ± 1.12 mm and 0.12 ± 0.37 mm for Fractures A and B, respectively (p = 0.57). Conclusions:. This study showed that an unstable trochanteric femoral fracture with a posterolateral fracture line that interferes with the lag screw insertion holes is a risk factor for increased intramedullary nail instability.

Bite injuries frequently occur on human hands. Human bite injuries to the hand may lead to an infection because of limited soft tissue protection and wound contamination. However, no studies have reported severe bite injuries on hands treated by flaps. We report a case of an 80-year-old woman diagnosed with a major neurocognitive disorder. The patient accidentally had a self-bite injury accompanied with an open metacarpal fracture. Debridement and fixation of the first metacarpal fracture were performed. Afterward, skin necrosis occurred gradually on the dorsum of the hand. Therefore, a reverse posterior interosseous artery (PIA) flap was used, and the postoperative course was uneventful. Given the high risk of infection, human bite injuries, particularly hand bites, should be treated immediately. Delayed treatment for such injuries may lead to extensive soft tissue defects requiring reconstruction with flaps.

Mucopolysaccharidosis II (MPS II) is an X-linked, recessive, inborn metabolic disorder caused by defects in iduronate-2-sulfatase (IDS). The age at onset, disease severity, and rate of progression vary significantly among patients. This disease is classified into severe or mild forms depending on neurological symptom involvement. The severe form is associated with progressive cognitive decline while the mild form is predominantly associated with somatic features. Newborn screening (NBS) for MPS II has been performed since December 2016, mainly in Kyushu, Japan, where 197,700 newborns were screened using a fluorescence enzyme activity assay of dried blood spots. We diagnosed one newborn with MPS II with lower IDS activity, elevated urinary glycosaminoglycans, and a novel variant of the IDS gene. In the future, NBS for MPS II is expected to be performed in many regions of Japan and will contribute to the detection of more patients with MPS II, which is crucial to the early treatment of the disorder.

Potter syndrome, first reported in 1946 by Edith Potter, refers to fatal cases of bilateral renal aplasia with pulmonary hypoplasia, peculiar facial features, and limb deformities. Presently, patients with oligohydramnios showing similar pathological manifestations due to oligohydramnios caused by conditions other than bilateral renal aplasia have been reported, and are known as the Potter sequence. There are limited studies and unclear guidelines on the safest delivery time and detailed postpartum management for patients with the Potter sequence. We experienced a case of Potter sequence, in which the patient was born by elective cesarean section at gestational age (GA) of 34 weeks. Fetal ultrasound at GA of 26 weeks 4 days showed oligohydramnios, multilocular cystic lesions in the left kidney, and an absent right kidney. Prenatal fetal MRI at GA of 33 weeks and 3 days showed pulmonary hypoplasia, and the ratio of fetal lung volume (FLV) to fetal body weight (FBW) was 0.0135 ml/g. We suspected that the fetal lung could not grow because of persistent oligohydramnios, which leads to a further decline in the ratio of FLV to FBW during pregnancy. We performed a cesarean section at GA of 34 weeks to prevent the exacerbation of the imbalance between lung volume and physique. We struggled to keep her condition stabilized with strict management of her respiratory condition, dialysis, and nutrition. She was discharged from the hospital at 169 days of age. Elective caesarean section in the term of premature birth prevented the progression of pulmonary hypoplasia and made it possible to save her life. Potter sequence is still relatively unknown, and it is necessary for more studies to be conducted in the future.

To design a controlled drug release preparation based on a safe natural material, a Konjac glucomannan (KGM) mixture containing 16.0 w/w% calcium hydroxide (Ca(OH)2) was ground in a planetary ball mill for 0–120 min. The mechanochemical effect on the physicochemical properties of the KGM ground product was investigated by Fourier-transform infrared spectroscopy (FT-IR), powder X-ray spectroscopy, scanning electron microscopy with energy-dispersive X-ray spectroscopy, and drug release testing. The FT-IR spectra of the ground KGM indicated that the deacetylation reaction of KGM was accelerated in the Ca(OH)2-containing sols by mechanochemical energy, and the degree of deacetylation of KGM was dependent on the grinding time. The time required for tablet disintegration of the KGM matrix tablets containing theophylline increased as the grinding time increased; therefore, drug release was sustained. The Higuchi plots of the matrix tablets obtained from KGM ground for 60–120 min exhibited good linearity because they maintained their gel matrix tablet shape during the release test. However, KGM tablets ground for 0–30 min exhibited nonlinear curves, which were caused by tablet disintegration. This suggests that drug release from the KGM matrix tablet can be freely controlled by the degree of mechanochemical treatment.

Abstract Background Urologists frequently encounter malignant ureteral obstruction (MUO) caused by advanced urological or non-urological malignant disease, but the treatment policy is unclear. The present study examined the risk factors for predicting ureteral stent failure in patients with MUO after ureteral stent insertion and the change in the renal function after retrograde ureteral stent insertion in cases of bilateral hydronephrosis. Methods A total of 39 patients who required ureteral stent placement for MUO at Yokohama City University Medical Center (Yokohama, Japan) between February 2007 and May 2016 were included in this study. The age, gender, type of cancer, hydronephrosis side, pre-stenting estimated glomerular filtration rate (eGFR), and eGFR increase were assessed as predictive factors for stent failure. Among these 39 patients, 25 showed bilateral hydronephrosis. Thirteen of these patients had bilateral ureteral stents placed, and the remaining 12 had a unilateral ureteral stent placed. The renal function and overall survival (OS) were analyzed between these two groups. Results Among all 39 patients, 9 (23.1%) had stent failure. A univariate analysis revealed that causative disease (gastrointestinal cancer vs. others; p = 0.045) and laterality of hydronephrosis (bilateral vs. unilateral; p = 0.05) were associated with stent failure. A multivariate analysis revealed that only age (hazard ratio, 0.938; 95% confidence interval, 0.883–0.996; p = 0.038) was associated with stent failure. A Kaplan-Meier analysis and log-rank test indicated that having a unilateral ureteral stent placed was not correlated with a lower OS rate than having bilateral ureteral stents placed (p = 0.563). Among patients with bilateral hydronephrosis, the increase in the eGFR of those who had bilateral ureteral stents placed was not significantly different from that of those who had a unilateral ureteral stent placed (p = 0.152). Conclusions We revealed that age > 60 years was helpful for predicting stent failure. MUO due to gastrointestinal cancer and bilateral hydronephrosis may be predictive of stent failure. These factors may help urologists decide the optimal time to perform early percutaneous nephrostomy. These findings suggest that patients with bilateral hydronephrosis do not necessarily need to have a ureteral stent placed into both sides of the hydronephrosis.

Abstract Background Female urethral carcinoma is a very rare disease that accounts for 0.02% of malignant diseases in female patients. Case presentation A 70-year-old Asian Japanese woman with a urethral tumor was referred to our hospital to undergo further examination. Biopsy specimens showed urethral adenocarcinoma that was positive for prostate-specific antigen. Her serum prostate-specific antigen level before surgery was 34.4 ng/ml. Urethral tumor resection with pelvic lymph node resection was performed. Her serum prostate-specific antigen level decreased to

Abstract Background Paraganglioma is an extra site of pheochromocytoma. Paraganglioma in the bladder is a very rare disease accounting for 0.06% of all bladder tumors. Case presentation A 77-year-old Japanese man was referred to our department for the further examination of a bladder tumor detected on preoperative computed tomography of his gastric cancer. Cystoscopy revealed a submucosal tumor in the upper area of his bladder, so transurethral resection of the bladder tumor was performed. During transurethral resection of the bladder tumor, his blood pressure sharply increased, and a pathological examination showed paraganglioma in his bladder. Postoperative I-123-metaiodobenzylguanidine scintigraphy detected a higher intake of his bladder tumor. Laboratory examinations showed a slightly increased noradrenaline level of 530 pg/ml and reduced platelet count at 167,000/μL. Based on the progression of his gastric cancer, no additional therapy was performed on his bladder tumor. Eight months after surgery, he died from aspiration pneumonitis. Conclusions Here we report a rare case of paraganglioma in the bladder. We discuss paraganglioma based on previous studies.

Abstract Background Recently, sarcopenia has been reported as a new predictor for patient outcomes or likelihood of post-operative complications. The purpose of this study was to evaluate the association of the psoas muscle volume with the length of hospitalization among patients undergoing radical cystectomy. Methods A total of 63 (80.8%) male patients and 15 (19.2%) female patients who underwent radical cystectomy for their bladder cancer in our institution from 2000 to 2015 were analyzed. The psoas muscle index (PMI) was calculated by normalizing the psoas muscle area calculated using axial computed tomography at the level of the umbilicus (cm2) by the square of the body height (m2). Longer hospitalization was defined as hospitalization exceeding 30 days after surgery. Results The median PMIs (mean ± standard deviation) were 391 (394 ± 92.1) and 271 (278 ± 92.6) cm2/m2 in men and women, respectively. Thus, the PMIs of male patients were significantly larger than those of females (p

Abstract Background The neutrophil-to-lymphocyte ratio (NLR) is reported as a biomarker for some solid malignant diseases. Thus far, however, no reports of the relationship between the NLR and adrenal tumors have been published. We analyzed the utility of the preoperative NLR as a biomarker for predicting the prognosis or diagnosis of malignant disease. Methods A total of 59 patients with adrenal tumors (13 cases of malignant disease and 46 with benign disease) were analyzed in this study from February 2004 to June 2015 at our institute. The NLR was obtained just before adrenalectomy. The diagnosis of adrenal tumor was confirmed by a pathological examination of surgical specimens. Results The NLR in malignant adrenal tumor specimens was significantly higher than in non-malignant specimens (p = 0.028). Adrenocortical carcinoma (ACC) showed the highest NLR among all adrenal tumors. In ACC, the higher NLR group (NLR ≥ 5) showed a significantly poorer overall survival than the lower NLR group (NLR

Abstract Background Most patients with testicular cancer are infertile; thus, the preservation of the sperm after surgery is an important factor to consider. We report two cases of bilateral testicular cancer in patients who underwent bilateral higher orchiectomy and simultaneous testicular sperm extraction. Case presentation Two Asian-Japanese men were referred to our hospital with bilateral testicular tumors. Both of the patients were preoperatively diagnosed with azoospermia and requested testicular sperm extraction at the time of higher orchiectomy. In one patient, sperm was successfully harvested and then frozen. In the other patient, sperm could not be retrieved from the patient’s testis. In both patients, the pathological diagnosis was seminoma. Testicular tumors often occur in patients of reproductive age. The preservation of sperm before chemotherapy or bilateral orchiectomy is necessary for patients with testicular tumors who wish to be fathers. Conclusions Onco-testicular sperm extraction might be an option for patients with testicular cancer and azoospermia or severe oligospermia.

The manufacturing of solid pharmaceutical dosage forms composed of cocrystals requires numerous processes during which there is risk of dissociation into parent molecules. Resonant acoustic wet granulation (RAG) was devised in an effort to complete theophylline–citric acid (THPCIT) cocrystal formation during the granulation process, thereby reducing the number of operations. In addition, the influence of granulation liquid was investigated. A mixture of anhydrous THP (drug), anhydrous CIT (coformer), and hydroxypropyl cellulose (granulating agent) was processed by RAG with water or ethanol as a granulation liquid. The purposes were to (i) form granules using RAG as a breakthrough method; (ii) accomplish the cocrystallization during the integrated unit operation; and (iii) characterize the final solid product (i.e., tablet). The RAG procedure achieved complete cocrystal formation (>99%) and adequately sized granules (d50: >250 μm). The granulation using water (GW) facilitated formation of cocrystal hydrate which were then transformed into anhydrous cocrystal after drying, while the granulation using ethanol (GE) resulted in the formation of anhydrous cocrystal before and after drying. The dissolution of the highly dense GW tablet, which was compressed from granules including fine powder due to the dehydration, was slower than that of the GE tablet.

Ductal adenocarcinoma is an unusual variant of adenocarcinoma of the prostate. A 73-year-old male was referred to our hospital for the further examination of an elevated prostate-specific antigen level of 23.4 ng/mL. Radical prostatectomy (RP) was performed based on the diagnosis obtained by a prostate needle biopsy. The RP specimen revealed ductal adenocarcinoma of the prostate with positive capsular penetration. We herein report a rare case of ductal adenocarcinoma of the prostate.

A 36-year-old male was referred to our department for further examination of asymptomatic gross hematuria emanating from a bladder tumor. Cystoscopy revealed a broad-based tumor 40 mm in diameter. Urinary cytology was negative. Preoperative magnetic resonance imaging suggested a muscle invasive tumor. Transurethral resection was performed, and the pathological findings revealed an inflammatory myofibroblastic tumor. We herein report a rare case of bladder inflammatory myofibroblastic tumor.

A 66-year-old male was referred to our hospital for further examination of a scrotal mass. Because of the risk of testicular cancer, we first clamped the vessels as a course of higher orchiectomy. Then, we approached the tumor through the scrotum and successfully resected it while preserving the testis. A histopathological diagnosis revealed an epidermal cyst. We herein report a rare case of an intrascrotal epidermal cyst successfully treated while preserving the testis.

Abstract Background In most cases, prostate cancer metastasizes to the lymph nodes, bone, and liver. In very rare cases, it metastasizes to the ureter. Due to the difficulty in making a preoperative diagnosis, ureteral metastasis from prostate cancer is typically diagnosed after nephroureterectomy. Case presentation A 77-year-old Asian Japanese man with right hydronephrosis and hydroureter was referred to our hospital to undergo further examination due to the suspicion of ureteral cancer. He had been diagnosed 2 years previously with prostate cancer with a Gleason score of 4+5=9. He received radiotherapy and androgen deprivation therapy. A nephroureterectomy was performed for suspected right ureteral cancer. On the basis of a histopathological examination, poorly differentiated adenocarcinoma was suspected, and the tumor cells were positive for prostate-specific antigen immunohistochemically. Conclusions We herein report a rare case of ureteral metastasis in castration resistant prostate cancer.

Abstract Background Due to the recent development of laparoscopic devices, laparoscopic radical nephrectomy is the standard procedure for localized renal cell carcinoma. However, some studies have reported postoperative port site metastasis in several cancers. Case presentation A 68-year-old Asian-Japanese man was referred to our hospital for a further examination of his right renal tumor in 2009. Due to a clinical suspicion of renal cell carcinoma, laparoscopic nephrectomy was performed. The histopathological diagnosis was clear cell renal cell carcinoma. Follow-up computed tomography revealed a mass between the internal oblique muscle of his abdomen and the transverse muscle of his abdomen in 2014. The tumor size gradually increased, and positron emission tomography-computed tomography revealed the accumulation of fludeoxyglucose in that tumor with maximum standardized uptake value of 2.7. Based on these findings, port site recurrence was suspected, and tumor resection was performed in 2017. The pathological diagnosis was metastatic clear cell renal cell carcinoma. Conclusions Here we report a rare case of port site metastasis that was successfully treated 7 years after laparoscopic nephrectomy.

The granulation process of pharmaceutical standard formulation in a high-speed shear wet granulation (HSWG) was measured by in-line near-infrared spectroscopy (NIRS) and agitation power consumption (APC) methods. The F-1, F-2, and F-3 formulations (500 g) contained 96% w/w α-lactose monohydrate (LA), potato starch (PS), and a LA:PS = 7:3 mixture, respectively, and all the formulations contained 4% w/w hydroxypropyl cellulose. While adding purified water at 10 mL/min, the sample powder was mixed. The calibration models to measure the amount of binding water (Wa) and APC of the HSWG formulations were established based on NIRS of the samples measured for 60 min by partial least-squares regression analysis (PLS). Molecular interaction related to APC between the particle surface and binding liquor was analyzed based on NIRS. The predicted values of Wa and APC for all formulations were superimposed with the measured values on a straight line, respectively. The regression vector (RV) of the calibration model for Wa indicated the chemical information of all the water in the samples. In contrast, the RV for APC suggested that APC changes in the processes are related to powder aggregation because of surface tension of binding water between particles.

Cocrystallisation can enhance the solubility and bioavailability of active pharmaceutical ingredients (APIs); this method may be applied to improve the availability of materials that were previously considered unsuitable. Terahertz (THz) spectroscopy provides clear, substance-specific fingerprint spectra; the transparency of the THz wave allows us to probe inside a sample to identify medicinal materials. In this study, THz and infrared (IR) spectroscopy were used to characterise cocrystallisation in solid-phase reactions between ibuprofen and nicotinamide. Multivariate curve resolution with alternating least squares (MCR-ALS) was applied to both time-dependent THz and IR spectra to identify the intermolecular interactions between these cocrystallising species. The analytical results revealed cocrystal formation through a two-step reaction, in which the steps were dominated by thermal energy and water vapour, respectively. We infer that the presence of water molecules significantly lowered the activation energy of cocrystal formation.

In this study, we established a robust feed-forward control model for the tableting process by partial least squares regression using the near-infrared (NIR) spectra and physical attributes of the granules to be compressed. The NIR spectra of granules are rich in information about chemical attributes, such as the compositions of any ingredients and moisture content. Polymorphism and pseudo-polymorphism can also be quantitatively evaluated by NIR spectra. We used the particle size distribution, flowability, and loose and tapped density as the physical attributes of the granules. The tableting process was controlled by the lower punch fill depth and the minimum distance between the upper and lower punches at compression, which were specifically related to the tablet weight and thickness, respectively. The feed-forward control of the process would be expected to provide some advantages for automated and semi-automated continuous pharmaceutical manufacturing. As a result, our model, using a combination of NIR spectra and the physical attributes of granules to control the distance between punches, resulted in respectable agreement between the predicted process parameters and actual settings to produce tablets of the desired thickness.

A 73-year-old male was referred to our department for further treatment of a right retroperitoneal tumor. Contrast CT showed a tumor mass measuring 33 × 26 mm in size with poor contrast enhancement. Because we were unable to rule out tumor malignancy, we planned an operation. The tumor was easily separated and removed without nephrectomy. Histological study revealed a schwannoma. It is rare for this kind of tumor to arise from the retroperitoneum (approximately 0.7% of all cases), in particular at the renal hilum. We herein report a rare case of retroperitoneal schwannoma arising from the renal hilum.

Introduction: Retroperitoneal tumor is often seen in urology clinical practice. To diagnose the tumor, tumor specimens must be obtained. However, in some cases, the tumor is penetrated by vessels around the ureter, and it may be difficult to detect the optimal spot for obtaining a specimen, even when performing open surgery. Case Presentation: A 53-year-old male patient was referred to our hospital for further examination of left back pain due to hydronephrosis. Enhanced computed tomography demonstrated ureter stenosis in front of the ilium, which was surrounded by a retroperitoneal tumor. The tumor was penetrated by blood vessels; therefore, we performed an open surgical biopsy on the suspicion of a retroperitoneal tumor using ureteroscopic assistance. The diagnosis of idiopathic retroperitoneal fibrosis was made according to the biopsy. Conclusion: We herein report the first case of a ureteroscopy-assisted biopsy for the pathological diagnosis of a retroperitoneal tumor.

Introduction. Xanthogranulomatous pyelonephritis (XGP) is a type of chronic renal inflammation that usually occurs in immunocompromised middle-aged women with chronic urinary tract infection or ureteral obstruction induced by the formation of ureteral stones. XGP with an incomplete double ureter is extremely rare. Case Presentation. A 76-year-old woman was referred to our department to undergo further examination for a left renal tumor that was detected by ultrasonography. Dynamic contrast computed tomography (CT) revealed an enhanced tumor in the upper renal parenchyma. Laparoscopic radical nephrectomy was performed based on a preoperative diagnosis of renal cell carcinoma. Histological sections showed the aggregation of foam cells; thus, XGP was diagnosed. Conclusion. We herein report a rare case of XGP in the upper pole of the kidney, which might have been associated with an incomplete double ureter.

A continuous-spray granulator (CTS-SGR) is a one-step granulation technology capable of using solutions or suspensions. The present research objectives were, (1) to reduce the manufacturing operations for solid dosage formulations, (2) to make amorphous solid dispersion (ASD) granules without pre-preparation of amorphous solids of active pharmaceutical ingredients (API), and (3) to characterize the obtained SGR granules by comprehensive pharmaceutical analysis. Rebamipide (RBM), a biopharmaceutical classification system class IV drug, that has low solubility or permeability in the stomach, was selected as a model compound. Five kind of granules with different concentrations of polyvinylpyrrolidone/vinyl acetate copolymer (PVP-VA) were prepared using a one-step SGR process. All of the SGR granules could be produced in amorphous or ASD form and their thermodynamic stability was very high because of high glass transition temperatures (>178 °C). They were unstable in 20 °C/75%RH; however, their stability was improved according to the proportion of polymer. The carboxy group of RBM was ionized in the granules and interactions appeared between RBM and PVP-VA, with the formation of an ASD confirmed and the solubility was enhanced compared with bulk RBM crystals. The SGR methodology has the possibility of contributing to process development in the pharmaceutical industry.

Objective: The effects of granule size of raw materials on tablet hardness (TH) and weight (TW) in the continuous tablet manufacturing process (CTMP) were investigated using near-infrared spectroscopy (NIRS). Methods: Granule materials of different sizes were prepared by extrusion granulation from a standard granule formula powder containing lactose/starch and 4.5% acetaminophen. Large-, small-, and mediumsized granules were sequentially filled in a hopper, and tablets were produced continuously using a single- shot tableting machine. After arranging approximately 500 tablets in order, the tablets were subjected to NIRS. A total of 450 NIRS datasets were divided into three groups of 150 each (calibration, validation 1, and validation 2 datasets). Results: The best fitted calibration models for predicting TH and TW were obtained, with sufficient accuracy, based on NIRS using the partial least squares regression, and comprised both physical and chemical information. The regression and loading vectors of the calibration models suggested that the models used to predict TH and TW involve physical information based on geometrical factors of the tablet and chemical information related to binder-related intermolecular interactions. Conclusions: The changes in the predicted value profiles of TH and TW using NIRS reflected the changes in the measured values depending on the raw granule size during CTMP. [ABSTRACT FROM AUTHOR]