Stability-indicating RP-HPLC method for determination of beclomethasone dipropionate in nanocapsule suspensions

abstract A simple stability-indicating RP-HPLC/UV method was validated for determination of beclomethasone dipropionate (BD) in nanocapsule suspensions. Chromatographic conditions consisted of a RP C18column (250 mm x 4.60 mm, 5 µm, 110 Å), using methanol and water (85:15 v/v) as mobile phase at 1.0 mL/min with UV detection at 254 nm. The calibration curve was found to be linear in the concentration range of 5.0-25.0 µg/mL with a correlation coefficient > 0.999. Precision was demonstrated by a relative standard deviation lower than 2.0%. Accuracy was assessed by the recovery test of BD from nanocapsules (98.03% to 100.35%). Specificity showed no interference from the components of nanocapsules or from the degradation products derived from acid, basic and photolytic conditions. In conclusion, the method is suitable to be applied to assay BD in bulk drug and in nanocapsules, and it can be employed to study stability and degradation kinetics.

resumo Um método simples de CLAE-FR/UV indicativo de estabilidade foi validado para a determinação do dipropionato de beclometasona (BD) em suspensões de nanocápsulas. As condições cromatográficas foram: coluna C18 fase reversa (250 mm x 4,60 mm, 5 µm, 110 Å), usando como fase móvel metanol e água (85:15 v/v) a 1,0 mL/min, com detecção UV a 254 nm. A curva de calibração foi linear no intervalo de 5,0-25,0 µg/mL com coeficiente de correlação >0,999. A precisão foi demonstrada por um desvio padrão relativo menor que 2,0%. A exatidão foi avaliada pelo teste de recuperação do BD a partir das nanocápsulas (98,03% a 100,35%). O teste de especificidade não mostrou interferência dos componentes das nanocápsulas e nem dos produtos de degradação derivados de condições ácidas, básicas e fotolíticas. Em conclusão, o método é adequado para ser aplicado na avaliação do BD puro e em nanocápsulas e pode ser empregado para o estudo de estabilidade e degradação cinética.

Formulation and evaluation of CFC free inhalers for beclomethasone dipropionate

Beclomethasone dipropionate CFC free inhalation formulations were developed with a view to treat asthma prophylactically. Dry powder inhalers (DPI) for beclomethasone dipropionate were prepared with different grades of lactose monohydrate. The influence of carrier and overages on performance of DPI was studied. Metered dose inhalers (MDI) with HFA based propellants were formulated with various doses, overages and different concentrations of alcohol. Formulated DPI and MDI were evaluated for various official and unofficial quality control tests. The influence of over doses on valve delivery, effect of overages on emitted dose and influence of alcohol on spray pattern from MDI were studied. The better fine particle fraction and emitted dose were obtained from the DPI formulated with 10:90 ratio of fine lactose: coarse lactose and with 20% w/w overages. The studies on MDI revealed that the 15% of overdoses are required for effective valve delivery and 20% overages are required for 100% drug delivery. 5-10%v/v alcohol was found to be preferable to get optimum emitted dose and fine particle fraction.

Desenvolveram-se formulações por inalação de dipropionato de beclometasona, livres de CFC, com o objetivo de tratar a asma profilaticamente. Prepararam-se inaladores de pó seco (DPI) para o dipropionato de beclometasona com diferentes gradações de lactose monoidratada. Estudou-se a influência do transportador e dos excessos de fármaco em relação ao rotulado no desempenho do DPI. Inaladores de dose calibrada (MDI) com propelentes à base de hidrofluoralcanos (HFA) foram formulados com várias doses, excessos de fármaco em relação ao rotulado e diferentes concentrações de álcool. Avaliaram-se as DPI e MDI formuladas por vários métodos oficiais e não oficiais de controle de qualidade. Estudaram-se a influência da superdosagem na liberação da válvula, o efeito dos excessos na dose emitida e a influência do álcool no padrão do spray do MDI. Obtiveram-se a melhor partícula fina e a dose emitida do DPI formulado com proporção de 10:90 de lactose fina:lactose grossa e 20% p/p de excesso. Os estudos em MDI revelaram que 15% de sobredose são requeridos para a liberação efetiva da válvula e 20% de excessos, para a liberação de 100% dos fármacos. Álcool a 5-10% v/v permitiu alcançar ótima dose emitida e fração de partícula fina.

Tratamiento profiláctico del asma bronquial en dos consultorios médicos / Prophylactic treatment of Asthma in patients of two outpatients departments in Cotorro Municipality

El asma bronquial constituye un problema de salud en Cuba y en el mundo. El tratamiento profiláctico con glucocorticoides inhalados tiene una eficacia y seguridad reconocidas en muchos países. Nuestro objetivoha sido describir el tratamiento profiláctico del asma bronquial en los pacientes de dos consultorios de un área de salud del municipio Cotorro e identificar el grado de control de los síntomas en los mismos.Realizamos un Estudio de Utilización de Medicamentos de indicación–prescripción con elementos de esquema terapéutico y de consecuencias prácticas. Se entrevistaron 63 pacientes con asma bronquial dispensarizados en dos consultorios visitados (75 por ciento del total). Por un cuestionario previamente estructurado, obtuvimos información sobre los medicamentos prescriptos para el tratamiento profiláctico del asma bronquial, consumo de agonista beta-2 de corta duración y el comportamiento de los síntomas en el último año. La variable principal fue medicamentos de uso profiláctico. El 53.4 por ciento no tenía tratamiento profiláctico o recibían fármacos no adecuados para esta indicación. El 28.5 por ciento refirió consumo habitual de corticoides sistémicos, solo 2 pacientes recibían corticoides inhalados. Más de 33 por ciento consumían agonista beta-2 de corta duración a dosis superiores a las aceptadas. Existió un mal control de los síntomas en los pacientes estudiados.Encontramos dificultades en el tratamiento profiláctico, inadecuado uso de los medicamentos para dicha indicación y muy baja prescripción de corticoides inhalados. Esta situación puede explicar el mal control de los síntomas de la enfermedad en los pacientes entrevistados.

Asthma is a major health problem in Cuba and around the world. Its prophylactic treatment with inhaled glucocorticoids has a well known efficacy and safety in many countries. To describe the prophylactic drug treatment of asthma in patients of two outpatients departments in Cotorro Municipality and to identify the extent of asthma control on them. A drugs utilization study of the indication-prescription type with elements of therapeutic method and medical consequences was carried out. 75 percent of the asthmatic patients were interviewed in the two visited outpatient departments. By a questionnaire previously constructed, we got information about prophylactic drug, beta 2 agonists of short duration used, and the behavior of the symptoms during the last year. The main variable was prophylactic medications. A 53, 4 percent didn’t have a prophylactic drug treatment nor received proper drugs for this indication. A 28.5 percent received systemic corticoids; only 2 patients received inhaled corticoids. More than a 33 percent received beta 2 agonists of short duration at higher recommended dose; there was a poor control of symptoms on those patients. We found difficulties in the prophylactic drug treatment, as a non adequate use of medications used for such prescription and very low indication of inhaled corticosteroids. This situation may explain the bad prophylactic control of the patients unde.