Design and development of multivesicular liposomal depot delivery system for controlled systemic delivery of acyclovir sodium.

The aim of the present study was to design a depot delivery system of acyclovir sodium using multivesicular liposomes (MVLs) to overcome the limitations of conventional therapies and to investigate its in vivo effectiveness for sustained delivery. MVLs of acyclovir were prepared by the reverse phase evaporation method. The loading efficiency of the MVLs (45%-82%) was found to be 3 to 6 times higher than conventional multilamellar vesicles (MLVs). The in vitro release of acyclovir from MVL formulations was found to be in a sustained manner and only 70% of drug was released in 96 hours, whereas conventional MLVs released 80% of drug in 16 hours. Following intradermal administration to Wistar rats, the MVL formulations showed effective plasma concentration for 48 hours compared with MLVs and free drug solution (12-16 hours). C(max) values of MVL formulations were significantly less (8.6-11.4 microg/mL) than MLV and free drug solution (12.5 microg/mL). The AUC(0-48) of the MVL formulations was 1.5- and 3-fold higher compared with conventional liposomes and free drug solution, respectively. Overall, formulations containing phosphatidyl glycerol as negatively charged lipid showed better results. The MVL delivery system as an intradermal depot offers the advantage of a very high loading and controlled release of acyclovir for an extended period of time. The increase in AUC and decrease in C(max) reflects that the MVL formulations could reduce the toxic complications and limitations of conventional iv and oral therapies.

Enhancement of dissolution and oral bioavailability of gliquidone with hydroxy propyl-beta-cyclodextrin.

The virtual insolubility of gliquidone in water results in poor wettability and dissolution characteristics, which may lead to a variation in bioavailability. To improve these characteristics of gliquidone, binary systems with hydroxypropyl-beta-cyclodextrin (HP-beta-CD) were prepared by classical methods such as physical mixing, kneading, co-evaporation and co-lyophilization. The solid state interaction between the drug and HP-beta-CD was assessed by evaluating the binary systems with X-ray diffraction, differential scanning calorimetry and IR- spectroscopy. The results establish the molecular encapsulation and amorphization of gliquidone. The phase solubility profile of gliquidone in aqueous HP-beta-CD vehicle resulted in an A(L) type curve with a stability constant of 1625 M(-1). The dissolution rate of binary systems was greater than that of pure drug and was significantly higher in the case of co-lyophilized and co-evaporated systems. Upon oral administration, [AUC]-alpha was significantly higher in case of co-lyophilized (2 times) and co-evaporated systems (1.5 times) compared to pure drug suspension while other binary systems showed only a marginal improvement. The study ascertained the utility of HP-beta-CD in enhancing the oral bioavailability of gliquidone, and points towards a strong influence of the preparation method on the physicochemical properties.

How residents spend their nights on call.

PURPOSE: Night call is a significant part of residents' education, but little information about their night-call activities is available. This study recorded residents' activities during night-call rotations on internal medicine and pediatrics wards. METHOD: In June and July 1997, on-call pediatrics and internal medicine residents at an urban academic medical center were accompanied by trained observers on the general wards between the hours of 7 PM and 7 AM. The types and duration of activities were recorded. RESULTS: Residents were observed for 106 nights. Internal medicine and pediatrics residents spent their time similarly. They spent 5.3 hours and 5.7 hours per night, respectively, on "basic" activities such as eating, resting, chatting, and sleeping, and an average of 2.6 hours and 2.2 hours, respectively, on chart review and documentation. In both programs, discussing the case with team members averaged 1.5 hours per night and use of the computer averaged slightly more than half an hour. Internal medicine residents spent approximately 1.5 hours on patients' history and physical examinations while pediatrics residents spent 1.3 hours. With each new patient, internal medicine residents spent an average of 19.7 minutes and pediatrics residents spent 16.5 minutes. The only significant difference between the two groups of residents was that the pediatrics residents spent more time per night on procedures than did the internal medicine residents (37 minutes versus 14 minutes, p < 0.01). CONCLUSIONS: Residents from both programs spent a surprising amount of time each night on chart review and documentation. In fact, they spent more time with charts than with patients. Whether this activity truly contributes to residents' education or improved patients' outcomes is not clear.