Development of a child-friendly oral drug formulation using liposomal multilamellar vesicle technology.

Many medicines are only available in solid dosage forms suitable for adults, and extemporaneous compounding is required to prepare formulations for children. However, this common practice often results in inaccurate dosing and unpleasant taste, reducing the medication adherence. Here, we report the development of a new method to prepare and compound child-friendly oral formulations based on a liposomal multilamellar vesicle (MLV) platform. MLVs composed of a phospholipid (DSPC) and cholesterol (55/45, molar ratio) were prepared using the standard thin film hydration method with 300 mM citric acid (pH 2), followed by an addition of aqueous sodium carbonate to adjust the exterior pH to 8-10 for creating a transmembrane pH gradient. Weak-base drugs, such as chloroquine (CQ) and hydroxychloroquine (HCQ), could be actively and completely loaded into the MLVs at a drug-to-lipid ratio of 15-20 wt%. This technique formulated weak-base drugs from the powder or tablet form into a liquid preparation, and the complete drug encapsulation would prevent contact between the drug molecules and the taste buds. The gradient MLV formulation could be preserved by lyophilization and stored at room temperature for at least 8 weeks. Upon reconstitution with water, the MLV formulation could completely encapsulate CQ at 20 wt%, which was comparable to the freshly prepared MLVs. The CQ-loaded MLV formulation could be stored at 4 °C for 2 weeks without drug leakage. In vitro release studies indicated that MLV could retain CQ in the simulated saliva, but released up to 50% and 30% of the drug in the simulated gastric and intestinal fluids, respectively. The orally delivered MLV-CQ formulation displayed higher CQ absorption in mice, with a 2-fold increase in the area under the curve (AUC) of the plasma profile compared to CQ solution. Our data suggest that the new MLV method could serve as a platform to prepare child-friendly oral formulation for weak-base drugs.

A case of cardiac tamponade following esophageal resection.

We report a rare case of cardiac tamponade after esophageal resection for esophageal cancer. A 69-year-old man underwent subtotal esophagectomy and reconstruction of the gastric tube with cervical anastomosis via the poststernal route and three-field lymphadectomy via a median sternotomy. On postoperative day 4, the patient developed dyspnea, chest oppression, and hemodynamic instability due to cardiac tamponade. Emergency percutaneous catheter drainage was performed to manage the cardiac tamponade. Acute pericarditis due to the original surgical procedure was suspected to be the cause of the tamponade. Although rare, cardiac tamponade should be considered as a cause of hemodynamic instability after esophageal resection.