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1.
Phys Rev Lett ; 123(14): 142502, 2019 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-31702191

RESUMEN

From detailed spectroscopy of ^{110}Cd and ^{112}Cd following the ß^{+}/electron-capture decay of ^{110,112}In and the ß^{-} decay of ^{112}Ag, very weak decay branches from nonyrast states are observed. The transition rates determined from the measured branching ratios and level lifetimes obtained with the Doppler-shift attenuation method following inelastic neutron scattering reveal collective enhancements that are suggestive of a series of rotational bands. In ^{110}Cd, a γ band built on the shape-coexisting intruder configuration is suggested. For ^{112}Cd, the 2^{+} and 3^{+} intruder γ-band members are suggested, the 0_{3}^{+} band is extended to spin 4^{+}, and the 0_{4}^{+} band is identified. The results are interpreted using beyond-mean-field calculations employing the symmetry conserving configuration mixing method with the Gogny D1S energy density functional and with the suggestion that the Cd isotopes exhibit multiple shape coexistence.

2.
Clin Exp Allergy ; 47(2): 200-207, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27664415

RESUMEN

BACKGROUND: Abnormal vocal cord movements can cause laryngeal extrathoracic airway obstruction (often called vocal cord dysfunction - VCD) leading to asthma-like symptoms. These aberrant movements are characteristically present during inspiration and termed paradoxical vocal cord movement (PVCM). We have reported PVCM in up to 40% of severe asthmatics, but it is not known if PVCM is detectable in all patients with asthma-like symptoms and if the condition is more often associated with abnormal lung function. OBJECTIVE: We hypothesized that PVCM is frequently associated with asthma symptoms accompanied by airflow limitation. Studies examined whether PVCM is solely linked to experiencing asthma symptoms, or if PVCM is related to airflow limitation and/or other disease characteristics. METHODS: Patients with asthma symptoms were recruited from general practice and severe asthma clinics (n = 155). Pulmonary function measurements were conducted, asthma control and Nijmegen (dysfunctional breathing) questionnaires were administered and skin prick testing was carried out. PVCM was quantified using dynamic 320-slice computerized tomography of the larynx. Groups were divided into patients with FEV1 ≥ 80% predicted or FEV1 < 80% predicted and FEV1 /FVC < 0.7. ATS/ERS definitions of severity were also applied and evaluated. Detection of PVCM in the groups was compared and analyses performed to identify features associated with PVCM. RESULTS: Overall (n = 155), PVCM was detected in 42 cases (27.1%). Patients with FEV1 < 80% predicted had PVCM more often (25/68, 36.8%) than individuals with normal spirometry (17/87, 19.5%; P = 0.016). PVCM was associated with older age (P = 0.003) and with Nijmegen scores > 20 (P = 0.04). Patients with FEV1 < 80% predicted plus Nijmegen scores > 20 were more likely to have PVCM (OR = 9.3, P = 0.02). CONCLUSIONS AND CLINICAL RELEVANCE: Paradoxical vocal cord movement is more often associated with asthma symptoms accompanied by airflow limitation and dysfunctional breathing. Further studies are needed to determine whether PVCM is induced by dysfunctional breathing practices and/or airway obstruction. How PVCM links with symptomatic asthma and VCD also requires evaluation.


Asunto(s)
Obstrucción de las Vías Aéreas/complicaciones , Obstrucción de las Vías Aéreas/fisiopatología , Asma/complicaciones , Asma/fisiopatología , Disfunción de los Pliegues Vocales/etiología , Adulto , Anciano , Obstrucción de las Vías Aéreas/diagnóstico , Asma/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas de Función Respiratoria , Pruebas Cutáneas , Evaluación de Síntomas , Tomografía Computarizada por Rayos X
3.
Phys Rev Lett ; 109(4): 042301, 2012 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-23006079

RESUMEN

We report a precise determination of the (19)Ne half-life to be T(1/2)=17.262±0.007 s. This result disagrees with the most recent precision measurements and is important for placing bounds on predicted right-handed interactions that are absent in the current standard model. We are able to identify and disentangle two competing systematic effects that influence the accuracy of such measurements. Our findings prompt a reassessment of results from previous high-precision lifetime measurements that used similar equipment and methods.

4.
Phys Rev Lett ; 106(3): 032501, 2011 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-21405268

RESUMEN

A high-precision half-life measurement for the superallowed ß+ emitter 26Al(m) was performed at the TRIUMF-ISAC radioactive ion beam facility yielding T 1/2 6346.54 ± 0.46(stat) ± 0.60 (syst) ms, consistent with, but 2.5 times more precise than, the previous world average. The 26Al(m) half-life and ft value, 3037.53(61) s, are now the most precisely determined for any superallowed ß decay. Combined with recent theoretical corrections for isospin-symmetry-breaking and radiative effects, the corrected Ft value for (26)Al(m), 3073.0(12) s, sets a new benchmark for the high-precision superallowed Fermi ß-decay studies used to test the conserved vector current hypothesis and determine the V(ud) element of the Cabibbo-Kobayashi-Maskawa quark mixing matrix.


Asunto(s)
Aluminio/química , Partículas beta , Radioisótopos/química , Semivida
5.
Intern Med J ; 36(8): 506-12, 2006 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-16866655

RESUMEN

AIM: To compare grading of chronic obstructive pulmonary disease (COPD) using Australian guidelines Confirm diagnosis, Optimize function, Prevent deterioration, Develop a self-management plan and manage eXacerbations (COPD-X) versus Global initiative for Obstructive Lung Disease (GOLD) guidelines and to assess whether this is associated with differences in other health domains affected by COPD. Adult outpatients (n = 61) with COPD were studied using lung function measurements, six-minute walk test and body composition assessments. Subjects also completed self-rated dyspnoea scores and health-related quality-of-life scales. For each patient, COPD severity was graded using both COPD-X and GOLD guidelines, and results were collectively analysed. If significant discrepancies were observed, comparisons of other health domains were carried out. After grading severity using COPD-X and GOLD guidelines, significant discrepancies were noted. Of nine subjects with no disease (normal) based on COPD-X, seven were judged to be 'mild' according to GOLD. Similarly, 11 of 12 patients with mild disease (COPD-X) had 'moderate' disease judged by GOLD, and 9 of 23 with moderate severity (COPD-X) had 'severe' COPD using GOLD. Finally, 6 of 17 patients with COPD-X-rated severe disease had 'very severe' disease using the GOLD criteria. Among patients with COPD-X severe disease, those with GOLD discordant (very severe) severity had a poorer quality of life compared with those with GOLD concordant (severe) severity (P = 0.006). Similarly, there was also a trend towards lower six-minute walk test distance and greater subjective dyspnoea in GOLD very severe patients compared with GOLD severe patients. Significant discrepancies in grading of severity exist between Australian and international COPD guidelines. Current Australian guidelines for severity grading may not fully reflect the effect COPD has on other key domains of health.


Asunto(s)
Clasificación Internacional de Enfermedades/normas , Guías de Práctica Clínica como Asunto/normas , Enfermedad Pulmonar Obstructiva Crónica/clasificación , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Índice de Severidad de la Enfermedad , Anciano , Atención Ambulatoria/normas , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad Pulmonar Obstructiva Crónica/patología , Victoria/epidemiología
6.
Cancer Res ; 46(8 Suppl): 4299s-4302s, 1986 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-3524811

RESUMEN

An estrogen receptor enzyme immunoassay kit (ER-EIA) has been evaluated in 70 human breast carcinomas against a routine cytoplasmic [3H]estradiol binding assay (ERU). A linear correlation between the ER-EIA and the ERU was observed for binding values up to 400 fmol/mg of cytosol protein. Above this value, the ERU underestimates the concentration of receptor. The ERU gave a lower number of estrogen receptor-positive tumors (50 of 70) than did the ER-EIA assay (59 of 70). In the ERU-negative ER-EIA-positive tumors, receptor values as determined by the ER-EIA assay all fell below 50 fmol/mg of protein (mean, 19.9 +/- 4.2 fmol/mg of protein). Application of an exchange procedure which estimates the total steroid binding capacity of the cytosol gave positive results in 7 of 9 ERU-negative ER-EIA-positive tumors (mean, 16.9 +/- 2.95 fmol/mg of protein). Subdivision of the binding data according to the menopausal status of the patient indicates low receptor values in premenopausal women by each assay. A correlation between the ER-EIA assay and the histological grade of tumors was observed; Grade I well-differentiated tumors were all positive, while Grade II and III tumors were 86% and 75% positive, respectively. No correlation between the ER-EIA assay and tumor lymph node stage or tumor size was observed.


Asunto(s)
Neoplasias de la Mama/análisis , Receptores de Estrógenos/análisis , Adulto , Anciano , Neoplasias de la Mama/patología , Citosol/análisis , Femenino , Humanos , Técnicas para Inmunoenzimas , Persona de Mediana Edad , Ensayo de Unión Radioligante
7.
Cancer Res ; 50(12): 3545-50, 1990 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-2187598

RESUMEN

Frozen sections of breast tumor tissue have been stained using an immunoperoxidase [estrogen receptor (ER)-immunocytochemistry] kit incorporating a monoclonal antiserum [H222] to visualize nuclear human ERs. Quantitation of specific staining has been performed by manual procedures using optical microscopy and by a computer-assisted image analysis system (CAS 100). Initial investigations with a test panel of ER-immunocytochemistry-positive tumors revealed a good qualitative agreement between CAS and manual assessments. Reduced variance was, however, observed between quantified ER-immunocytochemistry results from four experienced investigators using the CAS analysis. An extended study confirmed the relationships between CAS and manual methods of assessment. These findings were evident when studies were scored either by assessment of the percentage of positively stained cells (n = 92; r = 0.919; P less than 0.01) or by H-score calculations (n = 92; r = 0.913; P less than 0.01). A good correlation was also found between CAS quantification and the results of an ER enzyme immunoassay of 48 primary breast cancer specimens (r = 0.715; P less than 0.05). In 49 cases it was possible to relate CAS-defined ER status and levels to the subsequent response of patients to endocrine therapy. ER was assessed on specimens obtained prior to commencement of treatments for recurrent breast cancer. Presuming the presence of ER to be a prerequisite for successful therapy, very good correlations between response and both status and levels of positivity were recorded. None of 16 patients with CAS-ER-negative tumors responded to treatment, while 16 of 33 (48.4%) CAS-ER-positive patients achieved an objective response according to International Union Against Cancer criteria. A relationship between response and the degree of CAS-ER positivity was obtained when the CAS score divisions of 0, 1-100, and greater than 100 (response rates, 0, 41, and 64%, respectively) were used. These data demonstrate that automated image analysis offers a reliable, reproducible procedure for quantifying ER in immunocytochemically stained sections. It has potential advantages over manual procedures, providing less opportunity for subjective influences in scoring sections. Future advances in software design should further reduce elements of subjectivity and increase both the speed and reliability of results. We anticipate image analysis becoming a valuable tool in investigations concerning, for example, the influence of heterogeneity of steroid receptor distribution on the rate of recurrence of breast cancer after mastectomy and in the clinical course of the disease.


Asunto(s)
Neoplasias de la Mama/análisis , Mama/análisis , Técnicas para Inmunoenzimas/instrumentación , Neoplasias Hormono-Dependientes , Receptores de Estrógenos/análisis , Neoplasias de la Mama/terapia , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Neoplasias Hormono-Dependientes/análisis , Neoplasias Hormono-Dependientes/terapia
8.
Eur J Cancer ; 27(6): 711-5, 1991.
Artículo en Inglés | MEDLINE | ID: mdl-1829909

RESUMEN

Qualitative and semiquantitative assessments of oestrogen receptor and progesterone receptor positivity determined on previously immunocytochemically stained slides were performed by eight independent assessors. Concordance between assessments of steroid receptor status was good (24/25, 96%). Interassessor variations in estimates of positive immunostaining levels were high, varying by between 10 and 75% for individual slides. In 2 cases estimates for the same section ranged between 15% nuclei positive and 90% nuclei positive. Wide variations were also recorded for slides stained for progesterone receptors. Results using an assessment procedure combining staining intensity and percentage positivity estimates were also subject to marked discordance. A computerised image analysis system, also used to assess slides gave results similar to the mean manually determined percentage positivity values. It is suggested that quality control of steroid receptor immunocytochemical quantification be considered and that automated image analysis may represent an accurate and valid means of achieving this.


Asunto(s)
Neoplasias de la Mama/química , Receptores de Estrógenos/análisis , Receptores de Progesterona/análisis , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Inmunoensayo/métodos , Control de Calidad , Reproducibilidad de los Resultados
9.
Eur J Cancer ; 29A(7): 1018-23, 1993.
Artículo en Inglés | MEDLINE | ID: mdl-8098946

RESUMEN

The expression of the epidermal growth factor receptor (EGF-R), c-erbB-2 protein product and Ki67 have been evaluated in 105 breast cancers of known responsiveness to endocrine therapy using immunohistochemistry. EGF-R staining was observed in 62 of the tumours and was significantly associated with elevated rates of cell proliferation (%Ki67 positive cells) and loss of hormone sensitivity. In contrast, c-erbB-2 expression was not correlated with cell proliferation rates and was less strongly related to hormone insensitivity. Subdivision of the EGF-R data according to c-erbB-2 measurements revealed an association between c-erbB-2 immunostaining and worsened patient outlook and hormone insensitivity in moderately EGF-R-positive tumours. c-erbB-2 immunostaining in highly EGF-R-positive tumours did not further contribute to the already poor prognosis of these patients. These data confirm the prognostic importance of EGF-R measurements in breast cancer and may infer a functional interaction between this protein and the c-erbB-2 protein product in the aberrant growth of a subset of breast tumours.


Asunto(s)
Neoplasias de la Mama/metabolismo , Receptores ErbB/metabolismo , Proteínas de Neoplasias/análisis , Proteínas Nucleares/análisis , Proteínas Proto-Oncogénicas/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/mortalidad , Femenino , Goserelina/uso terapéutico , Humanos , Inmunohistoquímica , Antígeno Ki-67 , Mitosis , Pronóstico , Receptor ErbB-2 , Tamoxifeno/uso terapéutico
10.
Surg Endosc ; 16(9): 1267-70, 2002 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-12235507

RESUMEN

BACKGROUND: The role of the human camera holder during laparoscopic surgery keeps valuable personnel from other duties. EndoAssist is a robotic camera-holding device controlled by the operator's head movements. This study assesses its introduction into clinical practice. METHOD: Ninety-three patients undergoing laparoscopic cholecystectomy were randomized to have either the robotic (40) or a human (46) assistant. Seven patients converted to open operation were excluded. Six surgeons were evaluated. Operating time and subjective assessments were recorded. Learning curves were constructed. RESULTS: The mean operating time was less using the robotic assistant (66 min) than with human assistance (74 min) (p < 0.05, two-tailed t-test). The learning curves for operating time showed that within three operations surgeons were trained in using the robot. The device was safe in use. CONCLUSION: The EndoAssist operating device is a significant asset in laparoscopic surgery and a suitable substitute for a human assistant. Surgeons became competent in the use of the robot within three operations. The robot offers stability and good control of the television image in laparoscopic surgery.


Asunto(s)
Colecistectomía Laparoscópica/instrumentación , Colecistectomía Laparoscópica/métodos , Robótica/métodos , Cirugía Asistida por Computador/métodos , Interfaz Usuario-Computador , Cirugía Asistida por Video/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Capacitación en Servicio/métodos , Masculino , Persona de Mediana Edad , Robótica/instrumentación , Factores de Tiempo
11.
Br J Oral Maxillofac Surg ; 31(3): 149-53, 1993 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-8512907

RESUMEN

Anorganic bovine bone has been used in oral and maxillofacial surgery for several years. Its use has been limited to ridge augmentation. In this paper we have tried to evaluate its use in other settings within the speciality.


Asunto(s)
Aumento de la Cresta Alveolar/métodos , Materiales Biocompatibles , Trasplante Óseo , Huesos Faciales/cirugía , Minerales , Osteotomía/métodos , Adulto , Anciano , Placas Óseas , Tornillos Óseos , Niño , Huesos Faciales/anomalías , Huesos Faciales/lesiones , Femenino , Humanos , Masculino , Maloclusión/cirugía , Persona de Mediana Edad , Hueso Nasal/cirugía , Oseointegración , Titanio , Cigoma/lesiones , Cigoma/cirugía
12.
Br J Oral Maxillofac Surg ; 33(1): 9-14, 1995 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-7718535

RESUMEN

61 orthognathic surgery patients were studied (39% male, 61% female). It confirms that the group of patients we see in the West of Scotland are well adjusted psychologically and that the majority seek orthognathic surgery for aesthetic reasons. The degree of satisfaction is high (87%). Dissatisfaction is not related to sex, age or procedure. Patients who were dissatisfied tend to have higher neuroticism scores on the Eysenck Personality Inventory and those patients who had had unreal expectations of post surgical pain, numbness and swelling, were likely to express dissatisfaction with the outcome in the early stages. Several patients initially expressed some dissatisfaction with the outcome after 3 months then went on to increase their score and by 12 months became satisfied with the procedure. The authors outline the importance of adequate patient preparation prior to surgery and the use of printed literature is recommended.


Asunto(s)
Anomalías Maxilomandibulares/psicología , Anomalías Maxilomandibulares/cirugía , Satisfacción del Paciente , Cirugía Bucal/psicología , Adolescente , Adulto , Imagen Corporal , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Trastornos Neuróticos/psicología , Procedimientos Quirúrgicos Ortognáticos , Osteotomía/psicología , Evaluación de Resultado en la Atención de Salud , Educación del Paciente como Asunto , Inventario de Personalidad , Autoimagen , Encuestas y Cuestionarios
13.
Br J Oral Maxillofac Surg ; 34(1): 23-5, 1996 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-8645677

RESUMEN

Radiotherapy given during treatment of oral and pharyngeal malignancy is frequently associated with colonization of the oral mucosa by Candida species. Treatment of these infections has included topical and systemic agents. In the present study 73 patients with oropharyngeal candidosis were treated with either amphotericin B (10 mg lozenges, four times daily for 14 days, 36 patients) or fluconazole (50 mg daily for 7 days, 37 patients). The yeasts most frequently isolated were C albicans and C glabrata. Clinical signs and symptoms showed improvement at end of treatment in 72% of patients who received amphotericin B compared with 92% of patients who received fluconazole. Mycological cure at end of treatment was achieved in 31% of the amphotericin B group and 46% of patients who received fluconazole. For both treatments the cure rate was less in denture wearers than in non denture wearers.


Asunto(s)
Anfotericina B/uso terapéutico , Antifúngicos/uso terapéutico , Candidiasis Bucal/tratamiento farmacológico , Irradiación Craneana/efectos adversos , Fluconazol/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Candidiasis Bucal/etiología , Recuento de Colonia Microbiana , Dentaduras/efectos adversos , Femenino , Neoplasias de Cabeza y Cuello/radioterapia , Humanos , Persona de Mediana Edad , Enfermedades Faríngeas/tratamiento farmacológico , Enfermedades Faríngeas/etiología , Enfermedades Faríngeas/microbiología , Resultado del Tratamiento
14.
Br J Oral Maxillofac Surg ; 30(1): 14-7, 1992 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-1550799

RESUMEN

Two hundred and fifty five patients undergoing treatment for oral cancer were studied. Tumour site, classification and treatment modality were recorded and an assessment of their ability to swallow was made postoperatively. Patients were graded into one of three groups depending on dietary consistency. Pre- and postoperative dental examinations were made and patients were weighted pre- and postoperatively. Postoperative functional problems are outlined. The results indicated that 21% of the sample reported difficulty with swallowing solid foods and 46% were limited to semi-solid or liquid diets postoperatively; 16% were unable to wear upper or lower dentures postoperatively and 15% of edentulous patients were able to wear an upper denture only; 65% of the patients who had surgery and radiotherapy were unable to regain their preoperative weight after 6 months. Patients with T1 tumours who did not progress to radiotherapy faired much better postoperatively and were more likely to return to normal diet and regain their preoperative weight.


Asunto(s)
Deglución/fisiología , Neoplasias de la Boca/radioterapia , Neoplasias de la Boca/cirugía , Boca/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Peso Corporal , Trastornos de Deglución/etiología , Dentaduras , Femenino , Alimentos , Alimentos Formulados , Humanos , Arcada Edéntula/rehabilitación , Arcada Parcialmente Edéntula/rehabilitación , Masculino , Persona de Mediana Edad , Resultado del Tratamiento
16.
Br J Oral Maxillofac Surg ; 41(5): 317-22, 2003 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-14581024

RESUMEN

AIMS: To identify the prevalence of post-traumatic psychological symptoms after maxillofacial trauma and prognostic factors related to poor outcome. METHODS: Thirty-nine patients were assessed within 10 days of injury and 24 again 4-6 weeks later using five standardised self-report measures on each occasion and a short structured interview at the time of initial contact. RESULTS: Specific post-traumatic psychological symptoms were present at initial assessment in 21 patients (54%), with 9 (41%) meeting diagnostic criteria for post-traumatic stress disorder at review 4-6 weeks later. Other psychiatric problems, such as anxiety and depression, were identified by the General Health Questionnaire and the Hospital Anxiety and Depression Scale. Characteristics associated with poorer outcome included: a previous history of psychological distress; fear of the unknown, and female sex. CONCLUSION: These findings highlight the adverse psychological effect of maxillofacial trauma both immediately after the event and 4-6 weeks after injury. Proper assessment of injured patients must include psychological aspects and further research is needed to identify the most appropriate response.


Asunto(s)
Traumatismos Maxilofaciales/psicología , Adolescente , Adulto , Ansiedad/etiología , Depresión/etiología , Miedo/psicología , Femenino , Estudios de Seguimiento , Humanos , Entrevista Psicológica , Masculino , Persona de Mediana Edad , Pronóstico , Calidad de Vida , Autoevaluación (Psicología) , Factores Sexuales , Estadísticas no Paramétricas , Trastornos por Estrés Postraumático/etiología , Estrés Psicológico/psicología , Resultado del Tratamiento
17.
Long Range Plann ; 25(3): 98-107, 1992 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-10120320

RESUMEN

Considerable interest is currently being shown in the use of information technology to assist in improving group process, particularly those associated with strategic planning. Three major approaches are developing to provide this support, and these are described in this article. In general, articles about Group DSS are overwhelmingly favourable to the approaches, although research findings suggest that some forms of Group DSS can have deleterious effects on the quality of meetings. These research findings are discussed.


Asunto(s)
Toma de Decisiones en la Organización , Sistemas de Apoyo a Decisiones Administrativas , Inglaterra , Arquitectura y Construcción de Instituciones de Salud , Procesos de Grupo , Modelos Teóricos , Técnicas de Planificación
18.
Int J Pharm ; 409(1-2): 156-63, 2011 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-21356284

RESUMEN

Mechanistic models of the spray drying and particle formation processes were used to conduct a formulation study with minimal use of material and time. A model microparticle vehicle suitable for respiratory delivery of biological pharmaceutical actives was designed. L-leucine was chosen as one of the excipients, because of its ability to enhance aerosol dispersibility. Trehalose was the second excipient. The spray drying process parameters used to manufacture the particles were calculated a priori. The kinetics of the particle formation process were assessed using a constant evaporation rate model. The experimental work was focused on the effect of increasing L-leucine mass fraction in the formulation, specifically its effect on leucine crystallinity in the microparticles, on powder density, and on powder dispersibility. Particle, powder and aerosol properties were assessed using analytical methods with minimal sample requirement, namely linear Raman spectroscopy, scanning electron microscopy, time-of-flight aerodynamic diameter measurements, and a new technique to determine compressed bulk density of the powder. The crystallinity of leucine in the microparticles was found to be correlated with a change in particle morphology, reduction in powder density, and improvement in dispersibility. It was demonstrated that the use of mechanistic models in combination with selected analytical techniques allows rapid formulation of microparticles for respiratory drug delivery using batch sizes of less than 80 mg.


Asunto(s)
Sistemas de Liberación de Medicamentos , Excipientes/química , Leucina/química , Modelos Teóricos , Aerosoles , Cristalización , Pulmón/metabolismo , Microscopía Electrónica de Rastreo , Microesferas , Espectrometría Raman , Factores de Tiempo , Trehalosa/química
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