Development of Sustained Release System Based on High Water-Absorbable Gel Formation Using Croscarmellose Sodium, Alkaline Excipients and HPMC (ACSH SR System); Novel Application of Croscarmellose Sodium as a Gel Former.

PURPOSE: Croscarmellose sodium, generally used as a superdisintegrant in pharmaceutical formulations, is hydrolyzed to form the gel structure under basic pH conditions. Utilizing this property of croscarmellose sodium, we developed a novel sustained release (SR) system. METHODS: Immediate release (IR) and SR tablets containing croscarmellose sodium, alkaline excipients and/or hydroxypropyl methylcellulose (HPMC) were prepared and examined for wet strength and in vitro drug release behavior. In vivo oral drug absorption was evaluated for IR tablets, HPMC tablets and our novel SR tablets in fasted Beagle dogs. RESULTS: To form the gel structure even under the physiological condition, alkaline excipients were added into the formulation containing croscarmellose sodium. Furthermore, HPMC was used to make the gel structure strong enough against mechanical destructive forces. The novel alkalized croscarmellose sodium-HPMC (ACSH) SR tablet, consisting of croscarmellose sodium, alkaline excipients, and HPMC, successfully sustained the release of acetaminophen, ibuprofen, or nicardipine hydrochloride, compared with the IR tablets. The ACSH SR system provided a better release of acetaminophen than the HPMC tablet without croscarmellose sodium in the release study using a small volume of liquid, suggesting that substantial release and subsequent absorption would be expected in the distal intestinal segments after oral dosing. The in vivo oral absorption study revealed that the ACSH SR system successfully suppressed and prolonged the plasma concentrations of acetaminophen. CONCLUSION: This novel ACSH SR system prepared with croscarmellose sodium, alkaline excipients, and HPMC, would be a promising SR formulation for enabling substantial drug absorption in the distal intestinal segments.

Palatability Evaluation of Sulfamethoxazole/Trimethoprim with Sweetener Using the Two-Bottle Choice Test.

Drug taste, which affects palatability, influences drug adherence. Sensory masking may be used to confound bitter tastes in drugs with other tastes and flavors; however, evaluation of sensory masking is difficult because of the existence of multiple tastes. In this study, a new two-bottle choice test was performed in rats to evaluate bitterness masking and determine the drug-to-sweetener ratio that significantly improves palatability. Sulfamethoxazole and trimethoprim were used as model bitter drugs, and sucralose was used as sweetener. The addition of sucralose and trimethoprim at a 0.13 : 1 ratio resulted in the greatest improvement in preference. This method is a useful new technique for evaluating the palatability of drug formulations.

A Case of Milk-Alkali Syndrome Caused by Diuretic-Induced Alkalosis and Polypharmacy.

Milk-alkali syndrome, which is characterized by hypercalcemia, metabolic alkalosis, and renal dysfunction, typically results from the ingestion of large amounts of calcium and absorbable alkaline products. However, these symptoms can also manifest when alkalosis and calcium loading occur simultaneously, owing to other factors. We report a case of milk-alkali syndrome caused by loop-diuretic-induced alkaline load and polypharmacy in an 85-year-old Japanese woman with multiple comorbidities, including osteoporosis, hypertension, type 2 diabetes, dyslipidemia, and Parkinson's disease. The patient regularly took 14 drugs, including calcium L-aspartate, eldecalcitol, celecoxib, and a fixed-dose combination of losartan and hydrochlorothiazide. Immediately before admission, furosemide was administered for the treatment of edema. The patient presented with chest discomfort, general malaise, and clinical signs of dehydration, hypercalcemia, hypophosphatemia, hypokalemia, and hypomagnesemia, accompanied by electrocardiogram abnormalities, renal dysfunction, and chloride-resistant metabolic alkalosis. The hypercalcemia was specifically induced by calcium L-aspartate and eldecalcitol. The hypomagnesaemia and hypophosphatemia were caused by diuretics and hypercalcemia. Thus, all the oral medications were discontinued, and rehydration and electrolyte correction therapy were administered. The final diagnosis was milk-alkali syndrome caused by the concomitant use of loop diuretics and other medications, without absorbable alkaline preparation use. This case underscores the importance of considering drug-related factors, checking concomitant medications, and being aware of the benefits, harmful effects, and side effects of polypharmacy in older adults with multimorbidity.

Antimicrobial-associated encephalopathy due to ampicillin.

Because the ß-lactam ring has a molecular structure similar to that of gamma-aminobutyric acid (GABA) neurotransmitters, it binds to GABA A receptors and inhibits GABAergic transmission, causing AAE. The possibility of antimicrobial-associated encephalopathy should be considered in cases of neurological or psychiatric symptoms after initiating an antimicrobial regimen.

Dengue Fever Complicated with Hemophagocytic Lymphohistiocytosis: A Case Report of Resolution with Steroid-Sparing Supportive Care.

Dengue fever (DF) can be complicated by hemophagocytic lymphohistiocytosis (HLH). Steroid administration is markedly effective for this hematologic complication, and for other viral infections. We present a rare case of DF-associated HLH that improved with steroid-sparing supportive care. A 47-year-old Japanese male with diabetes mellitus and no history of DF traveled to the Philippines 10 days before his hospitalization. Three days before emergency admission, he experienced fever and joint pain and was referred to our hospital for suspected DF, after blood tests indicated liver damage and thrombocytopenia. Erythema of the extremities and trunk appeared on day 2, and the next day neutrophils were 550 cells/µL, platelets 29,000 cells/µL, ferritin 9840 ng/mL, and fibrinogen 141 mg/dL. Bone marrow aspirate revealed hemophagocytic lymphohistiocytosis, and he was diagnosed with HLH. On day 4, the symptoms and findings improved; only supportive care without steroids was continued. He tested positive for dengue virus antigen on admission. He was discharged on day 9 of hospitalization in good general condition with no vascular leakage or bleeding and recovery of blood cells. Although steroid administration is markedly effective in cases of DF complicated by HLH, this case suggests that such cases can resolve with steroid-sparing supportive care.

Training items for trainee residents in community medicine in rural areas.

OBJECTIVE: To examine the significant events experienced by initial trainees during community medicine training, evaluate their impact on community medicine practice, and support improvements in rural community medicine training. RESULTS: Three faculty teachers independently evaluated the reports of 25 residents who had completed a four-week community medicine training in a rural area to analyze major events. The reports were analyzed using topics from the Model Core Curriculum for Medical Education that relate to rural medicine. The most frequently reported items were identified as follows: Primary care: 9 (36.0%); integrated community care systems: 8 (32.0%); medical care in the local community: 7 (28.0%); home health care and systems, patient-physician relationship, and end-of-life medical treatment and care: 6 each (24.0%). Reports from residents describing events related to home health care and systems and end-of-life medical treatment and care were related to more than one item.