1 |
The effect of long-acting #beta#â†2-adrenoreceptor agonists on cAMP accumulation in cultured cellsMcCrea, Karen Elaine January 1995 (has links)
No description available.
|
2 |
Mechanisms of allergen-induced late phase asthmatic responses and increased bronchial responsivenessTwentyman, Orion Peter January 1992 (has links)
No description available.
|
3 |
An Evaluation of the Association Between Health Care Utilization and Use of Salmeterol Among Subjects with AsthmaWang, Meng-Ting January 2006 (has links)
OBJECTIVE: To evaluate whether the use of salmeterol is associated with an increased risk of an asthma-related hospitalization or emergency care among asthma patients. METHODS: The data for this study were extracted from the Medstat MarketScan® claims databases occurring between 01/01/00 and 12/31/01. A nested case-control study design was employed. A cohort representing asthma patients was identified in 2000. Among the study cohort, hospitalized cases were identified as those who had the firsttime asthma-related hospitalization in 2001, and were matched to select controls by age (± 5 years), sex, and the number of ambulatory visits for asthma (5:1 control to case ratio). A similar process was applied to evaluating an asthma-related emergency department (ED) visit. The odds of prior salmeterol exposure among cases compared to controls were estimated using conditional multiple logistic regressions. The covariates of interest comprised age, prior hospital admission or ED visit for asthma, number of canisters of inhaled short-acting β₂ agonists and use of other asthma medications. RESULTS: A total of 35,312 subjects were eligible to be the study cohort. In addition, 285 and 640 subjects were identified as hospitalized and ED cases, respectively. The non-significant association was found when the prior salmeterol exposure was treated as a dichotomized variable. However, it was found that one unit increase in the number of canisters of salmeterol was associated with a seven percent decrease in the risk of a hospital admission for asthma (p <0.001). Additionally, current use of salmeterol was associated with a 48 percent decrease in the risk of an asthma-related hospitalization (OR = 0.52; p <0.001). The protective effect of salmeterol did not exist for those with recent or past use of salmeterol. Similar findings were observed for the ED visit outcome. CONCLUSIONS: The use of salmeterol was not found to be associated with an increased risk of an asthma-related hospital admission or ED visit. Conversely, one unit increase in the number of canisters of salmeterol and current use of salmeterol, respectively, were found to decrease the risk in an asthma-related hospitalization or ED visit among asthma patients.
|
4 |
Charakterisierung der pulmonalen Pharmakokinetik von Salmeterol und Insulin-like Growth Factor-1 / Characterisation of the pulmonary pharmacokinetics of salmeterol and insulin-like growth factor-1Vollmers, Frederic January 2015 (has links) (PDF)
Für inhalativ applizierte Arzneimittel spielt das Ausmaß der pulmonalen Absorption eine entscheidende Rolle. Für Substanzen, die lokal in der Lunge wirken sollen, sind für eine gute Wirksamkeit hohe lokale Wirkstoffkonzentrationen, und für eine geringe Nebenwirkungsrate niedrige systemische Plasmaspiegel wichtig. Sollen allerdings Substanzen das Lungenepithel überwinden und im systemischen Kreislauf wirken, ist eine hohe systemische Verfügbarkeit für eine gute Wirkung gewünscht. Das Ziel dieser Studie war es mit in vitro und ex vivo Methoden das Absorptions- und Permeationsverhalten von pulmonal applizierten Substanzen zu studieren.
Der Transportmechanismus über das Lungenepithel des langwirksamen ß2-Agonisten Salmeterol wurde mithilfe des humanen ex vivo Lungenperfusionsmodells untersucht. Die Anwendung von L-Carnitin als Hemmstoff von organischen Kationen/Carnitin Transportern (OCT/N) bewirkte eine Verringerung der pulmonalen Absorption von Salmeterol von ca. 90 %, was auf eine Beteiligung von Transportern, möglicherweise des OCTN2 oder OTCN1, für den Transport von Salmeterol über das Lungenepithel hindeutete. Es wurde somit zum ersten Mal erfolgreich gezeigt, dass Salmeterol wahrscheinlich als Substrat der Transportproteine fungiert und der Übertritt über das Lungenepithel von organischen Kationen/Carnitin Transportern abhängig ist. Bisher wurde eine Interaktion von Salmeterol mit den OCT/N nur in in vitro Versuchen studiert und Salmeterol wurde nur als Hemmstoff und nicht als Substrat untersucht. Die Beteiligung eines Transporters für die pulmonale Absorption von Salmeterol steht außerdem im Einklang mit Untersuchungen über weitere ß2-Agonisten wie das kurzwirksame Salbutamol und das langwirksame GW597901. Somit scheinen sowohl lipophile als auch hydrophile ß2-Agonisten Substrate für die OCT/N zu sein.
Die Fähigkeit von IGF-1, nach pulmonaler Applikation in den systemischen Kreislauf zu gelangen, wurde in der vorliegenden Studie mit Hilfe des Lungenperfusionsmodells untersucht. Das IGF-1 wurde gebunden an Trehalose oder an Fibroin als Pulver verabreicht. Die Trehalose sollte eine schnelle Abgabe des IGF 1 bewirken, und das Fibroin sollte zum einen ein Trägermaterial mit schützenden Eigenschaften für das IGF 1 darstellen, und zum anderen sollte eine mögliche verzögerte Freisetzung von IGF-1 aus Fibroin in einem ex vivo Modell untersucht werden, die in vorausgegangenen in vitro Versuchen über 3 h lang vorhanden war. Das Peptid wurde nach der Applikation sowohl der Trehalosepartikel als auch der Fibroinpartikel pulmonal absorbiert und folgte einer linearen Verteilungskinetik. Dieses lineare Absorptionsverhalten des IGF-1 war vergleichbar mit der Kinetik von inhalativem Insulin, die in in vivo Studien beobachtet wurde. Somit konnte gezeigt werden, dass das IGF-1 nach pulmonaler Applikation systemisch verfügbar sein könnte und eine vergleichbare pulmonale Pharmakokinetik wie das strukturell ähnliche Insulin besitzt. Außerdem unterschied sich das Absorptionsverhalten von IGF-1, gebunden an Trehalose, nicht signifikant von dem von IGF-1/Fibroin, was im Gegensatz zu in vitro Untersuchungen stand, in denen das IGF-1 verzögert aus Fibroin freigesetzt wurde. Somit wirkte sich die kontrollierte Abgabe in vitro nicht auf die Verteilungskinetik ex vivo aus. Daraus ergibt sich, dass sowohl Trehalose als auch Fibroin als Trägermaterial für IGF-1 zur pulmonalen Applikation geeignet wären, und dass IGF-1, gebunden an Fibroin eine Formulierung wäre, die zum einen das IGF 1 schützen kann und die zum anderen eine gleiche pulmonale Kinetik wie IGF 1, gebunden an schnell auflösende Trägersubstanzen, besitzt. Außerdem wurde dadurch die Wichtigkeit betont, die Pharmakokinetik von pulmonal verabreichten Substanzen am intakten Organ mit erhaltener Komplexität und Funktionalität zu untersuchen, und dass das Lungenperfusionsmodell hierfür eine geeignete Methode darstellt. Darüber hinaus wurde belegt, dass mithilfe des Lungenperfusionsmodells erfolgreich pharmakokinetische Daten für nieder- und höhermolekulare Substanzen gesammelt werden können, die als Aerosol oder als Pulver appliziert werden.
Auch in den in der vorliegenden Arbeit durchgeführten in vitro Permeationsversuchen, die mit der Bronchialepithelzelllinie Calu-3 durchgeführt wurden, zeigte IGF-1 vergleichbare lineare Permeationseigenschaften wie das Insulin, mit einem apparenten Permeationskoeffizienten von 1,49 * 10-8 cm/sec für IGF-1 und 2,11 * 10-8 cm/sec für Insulin. Das IGF 1 schien durch die Calu-3 Zellen sowohl parazellulär als auch transzytotisch zu permeieren, wie es für Makromoleküle generell vermutet wird. Durch die Verwendung von Hemmstoffen der Transzytose bzw. bestimmter endozytotischer Mechanismen in den Permeationsstudien konnte gezeigt werden, dass, wie bereits genannt, der Transport durch die Zellen eine wichtige Rolle für den Übertritt von IGF-1 über Calu-3 Zellmonolayer spielte. Die Studien ergaben außerdem, dass die zelluläre Aufnahme des IGF-1 unabhängig von Clathrin und abhängig von Dynamin war.
Der Einsatz einer humanen bronchioalveolären Lavage in den Permeationsversuchen bewirkte zum einen eine Erhöhung des Transportes von IGF 1 durch die Calu-3 Zellen, und zum anderen war die zelluläre Aufnahme in diesem Fall unabhängig von Dynamin und unterschied sich somit von den vorherigen Untersuchungen, in denen keine Lavage eingesetzt wurde. Das bedeutet, dass Faktoren in einer bronchioalveolaren Lavage enthalten waren, die sowohl das Ausmaß der Permeation als auch den Mechanismus der zellulären Aufnahme von IGF-1 in Calu-3 Zellen beeinflussten.
Zusammenfassend konnten in der vorliegenden Arbeit erfolgreich weitere Hinweise für die Beteiligung von Transportern an der pulmonalen Absorption von ß2-Agonisten mithilfe des ex vivo Lungenperfusionsmodells gefunden werden, was somit eine wertvolle Ergänzung zu bisher vorhanden in vitro Studien darstellt. Daneben wurde zum ersten Mal gezeigt, dass das IGF-1 nach Applikation in die Lunge pulmonal absorbiert werden könnte. Das belegt den Nutzen der Lunge als Eintrittsort in den systemischen Kreislauf, was vor allem für peptidische Arzneistoffe von Bedeutung ist. / The extent of the pulmonary absorption plays an important role for drugs applied via inhalation. For substances meant to exhibit local effects within the lung, high local concentrations are crucial for maximum efficacy, and for a low rate of systemic adverse effects low plasma levels are advantageous. But if substances are meant to pass the lung epithelia and act in the systemic circulation a high systemic availability is requested for good efficacy.
The aim of this study was to investigate the absorption and permeation behavior of pulmonarily applied substances using in vitro and ex vivo methods.
The transport mechanism of the long acting ß2-agonist salmeterol through lung epithelia was studied with the help of an ex vivo lung perfusion model. The organic cation/carnitine transporter inhibitor l-carnitine caused a decrease of the pulmonary absorption of salmeterol of about 90 %, indicating an involvement of transporters, possibly OCTN2 or OCTN1, for the uptake of salmeterol through the lung epithelia. For the first time it was successfully shown that salmeterol acts as a substrate for transport proteins and that its transport through the lung epithelia is dependent on the organic cation/carnitine transporters (OCT/N). So far the interaction of salmeterol with the OCT/N had been studied only in vitro and salmeterol had been solely described as an inhibitor and not as a substrate. Furthermore the results on the pulmonary absorption of salmeterol are in accordance with studies about other ß2-agonists like the short acting salbutamol and the long acting GW597901. Apparently, lipophilic and hydrophilic ß2-agonists are substrates for the OCT/N.
The pulmonary absorption of IGF-1 was investigated in this study using the lung perfusion model. IGF-1 was applied bound to trehalose or fibroin. The trehalose was used for a fast release of IGF-1. The fibroin as a carrier was meant to provide a protection of IGF-1, and a possible sustained release that was shown in previous in vitro assays over about 3 h, was to be studied in an ex vivo model. The peptide was absorbed pulmonarily after application of the treahlose and fibroin microparticles and exhibited linear distribution kinetics. This linear absorption behavior of IGF-1 was comparable to the kinetics of inhaled insulin observed in in vivo studies. Therefore it was shown that IGF-1 might be systemically available after pulmonary application and that IGF 1 displays comparable pulmonary pharmacokinetics to the structurally similar insulin. Additionally, the absorption behavoir of IGF-1 bound to trehalose was not significantly different from IGF 1/fibroin, which was in contrast to in vitro studies showing a sustained release of IGF-1 bound to fibroin. Thus, the in vitro controlled release was not mirrored in the distribution kinetics ex vivo. This suggests that both trehalose and fibroin are suitable carriers for pulmonary application of IGF-1 and that IGF-1 bound to fibroin provides a formulation that is able to protect IGF-1 and possesses comparable pulmonary kinetics to IGF-1 bound to fast dissolving carriers. Additionally these data demonstrated the importance to study the pharmacokinetics of pulmonarily applied substances by using the intact organ with conserved complexity and functionality, and that the human isolated perfused lung is a suitable model. Furthermore it was proven, that pharmakokinetic data of low and high molecular compounds applied as aerosol or powder, can be successfully obtained using the lung perfusion model.
The in vitro permeation experiments of the present study employing Calu-3 bronchial epithelial cells also showed a linear absorption behavior of IGF-1 comparable to that of insulin, with an apparent permeability coefficient of 1,49 * 10-8 cm/sec for IGF-1 and 2,11 * 10-8 cm/sec for insulin. IGF-1 apparently passed the Calu-3 cells via a paracellular and transcytotical mechanisms, which are thought to be the major routes of macromolecules. The use of inhibitors of transcytosis and certain endocytotic pathways showed that the transport through the cells was important for the passage of IGF-1 through Calu-3 cell monolayers, as mentioned before. Furthermore the studies revealed that the cellular uptake of IGF-1 was independent of clathrin and dependent on dynamin.
Human broncheoalveolar lavage caused an increase of the IGF-1 transport through the Calu-3 cells and in contrast to former investigations without a lavage the cellular uptake was independent of dynamin in this case. That implies that the broncheoalveolar lavage contained factors influencing both the extent and the mechanism of the cellular IGF-1 uptake into Calu-3 cells.
In conclusion, this work employing an ex vivo lung perfusion model provides additional evidence for the involvement of transporters in the pulmonary absorption of ß2-agonists. These data demonstrate a valuable extension of knowledge compared to previous in vitro studies. Furthermore, for the first time it has been shown that IGF 1 might be pulmonarily absorbed after application to the lung. This shows the suitability of the lung as point of entrance into the systemic circulation, which is especially interesting for peptide drugs.
|
5 |
Avaliação da deposição pulmonar de partículas liberadas de inaladores pressurizados dosimetrados associados ou não a espaçadores valvulados. Estudo da distribuição do tamanho de partículas in vitro e do seu efeito clínico in vivo em pacientes com asma mal controladaGONÇALVES, Talita Mota 29 August 2012 (has links)
Submitted by Heitor Rapela Medeiros (heitor.rapela@ufpe.br) on 2015-03-04T13:55:29Z
No. of bitstreams: 2
license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5)
Tese_GONÇALVES_TM_2012.pdf: 2666987 bytes, checksum: 7be2c9897c4c027907097ee7d6b92407 (MD5) / Made available in DSpace on 2015-03-04T13:55:29Z (GMT). No. of bitstreams: 2
license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5)
Tese_GONÇALVES_TM_2012.pdf: 2666987 bytes, checksum: 7be2c9897c4c027907097ee7d6b92407 (MD5)
Previous issue date: 2012-08-29 / A quantidade de fármaco depositado ao nível das vias respiratórias inferiores depende,
entre outros fatores, do dispositivo utilizado e da forma como é efetuada a técnica
inalatória. Através do sistema de Inaladores Pressurizados Dosimetrados (IPDs) a deposição
pulmonar do aerossol é otimizada quando associado a espaçadores. Dois importantes
problemas inerentes ao uso dos IPDs – coordenação entre premer o dispositivo e inalar
(coordenação mão-pulmão) e o depósito da medicação na orofaringe (responsável por seus
efeitos extra-pulmonares) – são minimizados pelo acoplamento de espaçadores valvulados.
Vários tipos de espaçadores estão disponíveis comercialmente e sua escolha adequada pode
repercutir significativamente na prática clínica, pois cada combinação IPD – espaçador
apresenta comportamento único. Objetivo: O presente estudo teve como objetivo avaliar in
vitro o perfil de liberação de partículas de combinações de 3 diferentes espaçadores
valvulados (Vortex®, AeroChamber Plus® e Able Spacer®) com dois dos IPDs comercialmente
disponíveis para o tratamento da asma; Seretide® (GlaxoSmithKline - Fluticasona/Salmeterol
125/25 μg por dose) e Fostair® (Chiesi Farmacêutica - Beclometasona/Formoterol 100/6 μg
por dose) e comparar o efeito in vivo deste último inalador. Métodos: O estudo foi
conduzido em duas etapas: a primeira tratou da avaliação do perfil de distribuição do
tamanho de partículas in vitro para ambos os medicamentos com e sem os espaçadores,
usando um aparelho de impactação em cascata - Next Generation Impactor (NGI); na
segunda etapa foi conduzido um estudo clínico aberto, randomizado, paralelo (2 grupos),
com 37 pacientes de ambos os sexos, idade entre 18-65 anos, portadores de asma mal
controlada que utilizaram a associação Beclometasona/Formoterol (100/6 μg por dose
Fostair® - 2 aspirações 2 vezes ao dia) para comparação da eficácia entre as duas formas de
tratamento (com e sem o espaçador Vortex®). Os pacientes foram acompanhados durante 10 semanas. As variáveis medidas foram a pontuação no questionário Asthma Control Test
(ACT), como desfecho primário, e o Volume Expiratório Forçado no primeiro segundo (VEF1).
Resultados: No estudo in vitro foi observado que, com os dois IPDs testados, os 3
espaçadores valvulados reduziram significativamente a maior parte das partículas grosseiras
que normalmente se depositam dentro da boca e na garganta. Em relação à dose de
medicação em Finas Partículas (DFP – aquelas com diâmetro de 1 a 5 μm), o espaçador Able
Space® reduziu a DFP para ambos os medicamentos, indicando menor eficácia. O emprego
dos espaçadores Vortex® e AeroChamber® Plus resultou em médias de DFP comparáveis
àquelas obtidas quando o Fostair® e o Seretide® foram testados sem espaçador. No estudo
in vivo, os resultados sugerem que os dois grupos de tratamentos (Fostair® com e sem
espaçador Vortex®) apresentaram melhora clínica, funcional e estatisticamente significativa
no controle da asma. Não houve diferença estatisticamente significativa entre os grupos em
nenhum momento de avaliação, entretanto, em ambos os grupos, foi observada diferença
estatisticamente significativa entre os valores basais e aqueles verificados aos 30 e 60 dias
de tratamento. Conclusão: O desempenho in vitro destes dispositivos pode servir como
indicativo para sua escolha em situações clínicas específicas, mas não anula a necessidade de
estudos clínicos para confirmar as consequências terapêuticas destes resultados.
|
6 |
In vitro aerodynamic analysis of co-spray dried fluticasone propionate (FP) and salmeterol xinafoate (SX) dry powder inhalation aerosols with lactose-alternative excipientMalapit, Monica, Mallory, Evan January 2017 (has links)
Class of 2017 Abstract / Objectives: Milk protein allergy is estimated to affect 1.2% to as much as 17% of people of all ages. Advair® Diskus® (FP/SX) utilizes lactose as an excipient which limits the utility of this product for this population. Furthermore, Advair® Diskus® is formulated as an interactive physical mixture via a micronization process. Alternatively, spray dried engineering achieves narrow particle size distribution, allowing greater deposition in the targeted respiratory bronchioles. The purpose of this dry powder inhaler (DPI) study was to conduct an in vitro comparative analysis of the aerodynamic performance of a co-spray dried lactose-free formulation of FP/SX with a mannitol excipient as a molecular mixture versus the Advair® Diskus® 250/50 (FP/SX) interactive physical mixture product.
Methods: Utilizing mannitol as an excipient, a co-spray dried FP/SX powder was prepared using the Buchi Mini-Spray Dryer B-290 under closed system configuration. The resulting feed solution was spray dried at pump rates of 25%, 50%, and 100% with all other parameters remaining constant (aspiration, atomization rate, nitrogen gas rate). The primary outcome measure, aerodynamic performance, was assessed using the Copley Next-Generation Impactor (NGI). NGI data for the DPIs was used to calculate mass median aerodynamic diameter (MMAD), geometric standard deviation (GSD), and fine particle fraction (FPF) of each powder, including the Advair® Diskus®. Residual water content was quantified by Karl Fischer titration. Particle characteristics were visualized by scanning electron microscopy.
Results: FPF, MMAD, and GSD were calculated from NGI data; Wolfram Alpha software was used to calculate MMAD and GSD. T-test regression was used for comparative analysis of spray-dried and Advair® Diskus® powders. MMAD for each spray dried sample was analyzed using a t-test regression against the MMAD values from the Advair® Diskus®. Using aerodynamic analysis studies triplicated for each powder, there was no significant difference between the spray dried powder and Advair® Diskus® for MMAD and GSD (p-values >0.05). The 50% and 100% pump rate samples had similar FPF to the Advair® Diskus® (p-values >0.05). However, the 25% pump rate sample had a significantly improved FPF compared to the Advair® Diskus® (p <0.01).
Conclusions: A co-spray-dried lactose-free formulation of FP/SX with a mannitol excipient demonstrated similar aerodynamic performance to the Advair® Diskus® which consists of a physical mixture of two drugs with lactose. Of significance, 25% pump rate spray-dry conditions demonstrated an improved FPF compared to the Advair® Diskus®.
|
7 |
Wirkungen der Bronchodilatation mit Salmeterol auf das autonome Nervensystem / Effects of bronchodilatation with salmeterol on the autonomic nervous systemBornemann, Thore 15 June 2015 (has links)
No description available.
|
8 |
Vibrational spectroscopic characterisation of salmeterol xinafoate polymorphs and a preliminary investigation of their transformation using simultaneous in situ portable Raman spectroscopy and differential scanning calorimetryAli, H.R.H., Edwards, Howell G.M., Hargreaves, Michael D., Munshi, Tasnim, Scowen, Ian J., Telford, Richard 15 October 2019 (has links)
No / Knowledge and control of the polymorphic phases of chemical compounds are important aspects of drug development in the pharmaceutical industry. Salmeterol xinafoate, a long acting β-adrenergic receptor agonist, exists in two polymorphic Forms, I and II. Raman and near infrared spectra were obtained of these polymorphs at selected wavelengths in the range of 488–1064 nm; significant differences in the Raman and near-infrared spectra were apparent and key spectral marker bands have been identified for the vibrational spectro-scopic characterisation of the individual polymorphs which were also characterised with X ray diffractometry. The solid-state transition of salmeterol xinafoate polymorphs was studied using simultaneous in situ portable Raman spectroscopy and differential scanning calorimetry isothermally between transitions. This method assisted in the unambiguous characterisation of the two polymorphic forms by providing a simultaneous probe of both the thermal and vibrational data. The study demonstrates the value of a rapid in situ analysis of a drug polymorph which can be of potential value for at-line in-process control.
|
9 |
Evaluation of the Effect of Critical Process and Formulation Parameters on the Attributes of Nanoparticles Produced by Microfluidics. Design of Experiments Approach for Optimisation of Process and Formulation Parameters Affecting the Fabrication of Nanocrystals of Poorly Water-Soluble Drug Using Anti-solvent Precipitation in MicrofluidicObeed, Muthana M. January 2021 (has links)
Advanced drug delivery systems have shown immense success through
nanotechnology which overcomes the challenges posed by large sized particles
such as poor solubility, bioavailability, absorption, and target-specific delivery.
This study focuses on nano sizing by application of microreactor technology and
nanoparticles to obtain polymeric particulate with a selection of model drugs for
inhalation drug delivery routes. The development of nanoparticles of two
challenging compounds in terms of solubility and permeability, namely
Ibuprofen (IBU) and Salmeterol (SAL), was conducted using a continuous,
controlled, and scalable system offered by microfluidic reactor with the
incorporation of anti-solvent approach. The research explores the potential of
this technology to enhance absorption rate and hence bioavailability of IBU via
oral route, and SAL via inhalation.
IBU, an anti-inflammatory drug, is classified as BCS Class II drug with low
solubility and high permeability. SAL is a selective long acting β2-agonist which
is co-dispensed along with a short-acting β2-agonist for quick relief of acute
bronchoconstriction due to its long onset of action. This lack of the ‘kick’ effect
in SAL can be attributed to its relatively higher lipophilicity which causes a delay
in the diffusion to the β2 receptors on the smooth muscles. It is therefore
feasible to assume that increasing the dissolution and/or diffusion rate of SAL in the interstitial fluids would reduce the delay between administration and the
onset of action of this drug which would be beneficial to patients.
Process and formulation parameters were investigated to optimize the
production and stability of nano particles of both drugs using Y shaped microfluidic reactors.
IBU results show that the smaller the angle between the two inlets were the
smaller the particle size achieved. Moreover, the particle size increased with
increasing the concentration of IBU solution. The effect of the polymer mixture
ratio (PVP/HPMC) on the initial particle size was not clear though. The smallest
particle size (113 nm) was achieved using 10° Y shaped chip with IBU
concentration of 1 mg/mL and a polymer mixture of 0.3% w/v PVP and 0.5%
w/v HPMC. Using a polymer mixture of 0.5% w/v of each polymer though
yielded a better PDI (140nm and PDI of 0.5).
Same observations were noted when the syringe pumps were replaced with a
non-pulsatile pressure pump. Particle size though dropped significantly to
33nm. Stability data showed that all systems were practically stable regardless
of the process or formulation parameters.
In addition, a considerable 2.5 fold increase in dissolution rate was observed in
the first 20 minutes when compared to the raw material.
The optimized parameters were applied to SAL to produce nanocrystals with
best result (59 nm) were obtained using 50µg/mL Salmeterol with microfluidics
inlet angle 10° with non-pulse syringe pump. The stabilizing mixture was PVP
0.8% w/v and Tween 80 at a concentration of 0.02%. This approach offered a
basis for the generation of nano sized SAL particles with higher fine particle fraction and better deposition in NGI than currently marketed formulations, thus
providing a more efficient drug dose delivery and lung deposition.
|
10 |
Use of nanoemulsion liquid chromatography (NELC) for the analysis of inhaled drugs : investigation into the application of oil-in-water nanoemulsion as mobile phase for determination of inhaled drugs in dosage forms and in clinical samplesAlthanyan, Mohammed Saad January 2011 (has links)
There has been very little research into the bioanalytical application of Microemulsion High Performance Liquid Chromatography (MELC), a recently established technique for separating an active pharmaceutical ingredient from its related substances and for determining the quantity of active drug in a dose. Also, the technique is not good at separating hydrophilic drugs of very similar chemical structures. Different phase diagrams of oil (octane or ethyl acetate), co-surfactant (butanol), surfactant (sodium dodecyl sulphate (SDS) or Brij-35) and buffer (Phosphate pH 3) were developed and several nanoemulsion mobile phases identified. Nanoemulsion mobile phase that is, prepared with SDS, octane, butanol and a phosphate buffer, failed to separate hydrophilic compounds with a very close chemical structure, such as terbutaline and salbutamol. A nanoemulsion mobile phase containing a non-ionic surfactant (Brij-35) with ethyl acetate, butanol and a phosphate buffer, was, however, successful in achieving a base line separation, and the method was validated for simultaneous determination of terbutaline and salbutamol in aqueous and urine samples. An oil-in-water (O/W) NELC method was developed and validated for the determination of formoterol in an Oxis® Turbuhaler® using pre-column fluorescence derivatisation. Although the same mobile phase was extended for separation of formoterol in urine, the formoterol peak's overlap with endogenous peaks meant that fluorescence detection could not determine formoterol in urine samples. Solid phase extraction, concentrating the final analyte 40 times, enabled determination of a low concentration of formoterol in urine samples by UV detection. The method was validated and an acceptable assay precision %CV <4.89 inter-day and %CV <2.33 intra-day was achieved. Then after the application of O/W nanoemulsion mobile phase for HPLC was extended for the separation of lipophilic drugs. The nanoemulsion liquid chromatography (NELC) method was optimised for the determination of salmeterol and fluticasone propionate in good validation data was achieved. This thesis shows that, in general, the performance of O/W NELC is superior to that of conventional High Performance Liquid Chromatography (HPLC) for the analysis of both hydrophilic and lipophilic drugs in inhaled dosage formulations and urine samples. It has been shown that NELC uses cheaper solvents and that analysis time is faster for aqueous and urine samples. This considerable saving in both cost and time will potentially improve efficiency within quality control.
|
Page generated in 0.0946 seconds