Using containerless methods to develop amorphous pharmaceuticals.

BACKGROUND: Many pipeline drugs have low solubility in their crystalline state and require compounding in special dosage forms to increase bioavailability for oral administration. The use of amorphous formulations increases solubility and uptake of active pharmaceutical ingredients. These forms are rapidly gaining commercial importance for both pre-clinical and clinical use. METHODS: Synthesis of amorphous drugs was performed using an acoustic levitation containerless processing method and spray drying. The structure of the products was investigated using in-situ high energy X-ray diffraction. Selected solvents for processing drugs were investigated using acoustic levitation. The stability of amorphous samples was measured using X-ray diffraction. Samples processed using both spray drying and containerless synthesis were compared. RESULTS: We review methods for making amorphous pharmaceuticals and present data on materials made by containerless processing and spray drying. It was shown that containerless processing using acoustic levitation can be used to make phase-pure forms of drugs that are known to be difficult to amorphize. The stability and structure of the materials was investigated in the context of developing and making clinically useful formulations. CONCLUSIONS: Amorphous compounds are emerging as an important component of drug development and for the oral delivery of drugs with low solubility. Containerless techniques can be used to efficiently synthesize small quantities of pure amorphous forms that are potentially useful in pre-clinical trials and for use in the optimization of clinical products. GENERAL SIGNIFICANCE: Developing new pharmaceutical products is an essential enterprise to improve patient outcomes. The development and application of amorphous pharmaceuticals to increase absorption is rapidly gaining importance and it provides opportunities for breakthrough research on new drugs. There is an urgent need to solve problems associated with making formulations that are both stable and that provide high bioavailability. This article is part of a Special Issue entitled "Science for Life" Guest Editor: Dr. Austen Angell, Dr. Salvatore Magazù and Dr. Federica Migliardo.

Acoustic levitator for structure measurements on low temperature liquid droplets.

A single-axis acoustic levitator was constructed and used to levitate liquid and solid drops of 1-3 mm in diameter at temperatures in the range -40 to +40 degrees C. The levitator comprised (i) two acoustic transducers mounted on a rigid vertical support that was bolted to an optical breadboard, (ii) an acoustic power supply that controlled acoustic intensity, relative phase of the drive to the transducers, and could modulate the acoustic forces at frequencies up to 1 kHz, (iii) a video camera, and (iv) a system for providing a stream of controlled temperature gas flow over the sample. The acoustic transducers were operated at their resonant frequency of approximately 22 kHz and could produce sound pressure levels of up to 160 dB. The force applied by the acoustic field could be modulated to excite oscillations in the sample. Sample temperature was controlled using a modified Cryostream Plus and measured using thermocouples and an infrared thermal imager. The levitator was installed at x-ray beamline 11 ID-C at the Advanced Photon Source and used to investigate the structure of supercooled liquids.

Patrones de prescripción de antibióticos en atención primaria. ¿Usamos racionalmente los antibióticos en pediatría? / Antibiotic prescribing habits in primary health care. Do pediatricians use antibiotics rationally?

Objetivos: Conocer los patrones de prescripción de antibióticos en la población lactante y preescolar de un centro de salud de la Comunidad de Madrid, así como la necesidad o no de dicho tratamiento y su adecuación a la patología diagnosticada. Métodos : Se realizó un estudio retrospectivo de los procesos infecciosos y respiratorios, así como los ciclos de tratamiento antibiótico recibido, de todos los niños menores de 4 años, durante un año. Se analizó el facultativo prescriptor, así como la adecuación de las decisiones terapéuticas tanto positivas como negativas (sin tratamiento). Resultados Se evaluaron 910 niños de 0-4 años, que presentaron un total de 3.847 procesos infecciosos o respiratorios con una media de 4,55 ñ 3,6 por niño y año. El 63 por ciento de los niños recibió al menos un ciclo antibiótico al año, con una media de 1,63 ñ 1,9 ciclos por niño y año. Se consideraron adecuadas un 85,2 por ciento de las 3.847 decisiones terapéuticas. El 36 por ciento de los procesos recibieron tratamiento antibiótico, lo cual supuso un total de 1.386 ciclos antibióticos. De ellos, el 46,2 por ciento se consideró inadecuado, mayoritariamente (71,6 por ciento) porque no debieron haberse prescrito y los restantes (28,4 por ciento) porque fueron mal elegidos. Hay diferencias entre los facultativos prescriptores, siendo la prescripción más correcta cuando se evalúa al pediatra habitual responsable de la consulta frente a otros médicos fundamentalmente de servicios de urgencias (p < 0,0001). Los antibióticos más utilizados fueron amoxicilina (41,2 por ciento) y amoxicilina-clavulánico (33 por ciento). Las cefalosporinas supusieron un 6,9 por ciento del total. Conclusiones: Se detecta un uso excesivo de antibióticos en la población preescolar que debe ser corregido (AU)