Control strategy and methods for continuous direct compression processes.

We presented a control strategy for tablet manufacturing processes based on continuous direct compression. The work was conducted by the experts of pharmaceutical companies, machine suppliers, academia, and regulatory authority in Japan. Among different items in the process, the component ratio and blended powder content were selected as the items requiring the control method specific to continuous manufacturing different from the conventional batch manufacturing. The control and management of the Loss in Weight (LIW) feeder were deemed the most important, and the Residence Time Distribution (RTD) model were regarded effective for setting the control range and for controlling of the LIW feeder. Based on these ideas, the concept of process control using RTD was summarized. The presented contents can serve as a solid fundament for adopting a new control method of continuous direct compression processes in and beyond the Japanese market.

[The role of formulation and dosage form in vaccine].

The importance of vaccination has recently been widely recognized among Japanese people with a growing interest in vaccine. On the other hand, because vaccine is administrated to healthy people, it has had a difficult history due to overreaction to adverse events. With the recent rapid increase in the rate of vaccination, however, it is essential to correct the understanding of the public as to the risk and benefit of vaccine. Life spans around the world and infectious diseases are closely related, and vaccine certainly contributes to the control of the latter. Research and Development (R&D) of novel antigens is necessary for creating a next generation vaccine, a high performance device for efficient antigen delivery, and a safe adjuvant for adequate immunological response are also a key to the future. Moreover, various initiatives involving industry, academia, and government cooperation are essential to benefit the people of Japan and appropriate vaccination could actually be viewed as national security.

Epithelial-mesenchymal interactions induce enamel matrix proteins and proteases in the epithelial cells of the rests of Malassez in vitro.

Epithelial-mesenchymal interactions influence morphogenesis and cell differentiation in periodontal tissue regeneration. The current study examined the expression of amelogenin, ameloblastin, matrix metallopeptidase-20 (MMP-20), and kallikrein-4 (KLK-4) and their effects on the interactions between the epithelial cells of Malassez and periodontal ligament fibroblasts. Explants of human periodontal ligament tissues produced outgrowths containing both the epithelial cells of Malassez and periodontal ligament fibroblasts after incubation in a modified serum-free medium. Both the epithelial cells and fibroblasts were co-cultured in the same dish. The distribution and expression of all four factors were evaluated using immunohistochemistry, in-situ hybridization and RT-PCR analysis. The epithelial cells of Malassez were cultured separately and were used as the control. Immunohistochemical analysis revealed weak expression of amelogenin, ameloblastin, MMP-20 and KLK-4 in epithelial cells of Malassez co-cultured with periodontal ligament fibroblasts. in-situ hybridization and RT-PCR confirmed significant mRNA expression of these factors in co-cultured cells compared with control cells. MMP20 mRNA was not expressed in control cells. These results suggest that the epithelial-mesenchymal interactions promote differentiation of human epithelial cells of Malassez and that the induction of enamel matrix proteases facilitates the degradation of enamel matrix proteins.

Effect of some curing methods on acrylic maxillary denture base fit.

The aim of this study was to investigate the fit of acrylic maxillary denture bases processed by the methods of microwave, quick-wet-heat, slow-wet-heat, and self curing. Forty stone-casts were obtained using a mould of an undercut-free acrylic resin master cast of an edentulous maxilla. Standard acrylic replicas patterns sealed on casts and randomized to four groups (10 in each) were used to make denture bases using different processing methods for each of the four groups. The resultant discrepancy of fit between the denture base and the casts were measured using a silicone wafer. Varying fit discrepancies both within and between denture base groups was observed. The proportional fit-loss in the palatal region was significantly greater than the sulcular areas for all materials tested (p < 0.05). The fit-loss observed was greater in microwave-cured bases than for other materials examined. Careful selection of appropriate denture base materials and processing technique is important when providing complete dentures for edentulous patients.

Determinants of the utilization of dental services in a community-dwelling elderly Japanese population.

Oral health care is not only an effective strategy for the prevention, early diagnosis, and treatment of orofacial disease and disorders, but also an essential component of general health promotion programs. The current study aimed to identify the determinants of the utilization of dental services in an elderly population in Japan. A community-based comprehensive geriatric assessment, including the measurements of physical, mental, and social functioning, was conducted among elderly people aged >or= 70 years residing in a suburban area of Sendai, Japan. Oral health status and functioning, their impact on the quality of life, and dental utilization were also surveyed. Of the 1,170 participants, 418 subjects who had specific treatment needs for dental problems and reported irregular dental attendance were recommended a dental visit, and 1 year later, their compliance with the recommendation was assessed by using questionnaire. Multiple logistic regression analysis demonstrated that a higher number of remaining teeth and the use of removable dentures were significant predictors of dental utilization within 1 year. Regular utilization was associated with a higher number of remaining teeth, younger age, presence of systemic disease, absence of depressive symptoms, and higher educational attainment. Conversely, non-compliance with the treatment recommendations was associated with fewer remaining teeth, smoking, and non-utilization of dental services during the previous year. The differences in the determinants of dental attendance behavior, which may be partially associated with the insurance coverage for dental services, suggest the need for specific strategies for oral health promotion for different behavior of dental utilization.

A new dental unit for both patients in wheelchairs and general patients.

OBJECTIVE: To develop a dental unit to accommodate both patients in wheelchairs and general patients, and to evaluate the acceptability of the new chair for patients and dentists. DESIGN: To integrate a unit for patients in wheelchairs and a unit for general patients into a single dental unit. RESULTS: (1) The newly developed dental unit could be used for both patients in wheelchairs and general patients and could be installed in nearly the same space as occupied by a conventional dental unit. (2) The dentists could take the home position because of the height-adjusting and tilting mechanisms. (3) The patients could be treated with a sense of assurance because of the wheelchair immobilizer and the safety devices. (4) The dentists could perform patient treatment safely. (5) As patients did not need to be transferred from their wheelchairs, assistance was unnecessary. (6) From the questionnaires, both patients and dentists rated the newly developed dental unit favourable. CONCLUSIONS: The new dental unit for patients in wheelchairs and general patients permitted dentists to perform and patients to receive dental treatment safely and in a comfortable position. Also, as a single unit could be used for treatment of both types of patients, it required no extra space. Therefore, it has the potential to be installed in the clinics of general dental practitioners to treat both groups of patients.

Effect of P-glycoprotein modulator, cyclosporin A, on the gastrointestinal excretion of irinotecan and its metabolite SN-38 in rats.

PURPOSE: The purpose of this work was to investigate the role of the hepatic and intestinal P-glycoprotein (P-gp) and canalicular multispecific organic anion transporter/multidrug resistance-associated protein 2 (cMOAT/MRP2) on both biliary excretion and intestinal exsorption of irinotecan hydrochloride (CPT-11) and its metabolite, SN-38, in the lactone and carboxylate forms. Cyclosporin A (CsA) was used to modulate P-gp and cMOAT/MRP2. METHODS: The transcellular transport of CPT-11 and SN-38 was examined by using LLC-PK1 derivative cell lines transfected with murine mdrla both in the absence or in the presence of CsA. The excretions of the compounds through the biliary and intestinal membrane routes were investigated by in situ perfusion technique. RESULTS: Basolateral-to-apical transport of CPT-11 lactone in L-mdr1a cells was significantly decreased by CsA (10 microM). The transcellular transport of SN-38 lactone showed similar behaviors as those of CPT-11 lactone. The biliary excretion and the intestinal exsorption of both forms of CPT-11 and SN-38 were significantly inhibited when the drug was co-administered with CsA. CONCLUSIONS: The transports of CPT-11 and SN-38 via the biliary route seem to be essentially related with cMOAT/MRP2, whereas those of both compounds via the intestinal membrane seem to be related with P-gp.