No / The Raman spectrum of terbutaline hemisulphate is reported for the first time, and molecular assignments are proposed on the basis of ab initio BLYP DFT calculations with a 6-31G* basis set and vibrational frequencies predicted within the quasi-harmonic approximation; these predictions compare favourably with the observed vibrational spectra. Comparison with previously published infrared data explains several spectral features. The results from this study provide data that can be used for the preparative process monitoring of terbutaline hemisulphate, an important ß2 agonist drug in various dosage forms and its interaction with excipients and other components.

No / Previously, dose emission below 30 L min(-1) through DPI has not been routinely determined. However, during routine use some patients do not achieve 30 L min(-1) inhalation flows. Hence, the aim of the present study was to determine dose emission characteristics for low inhalation flows from terbutaline sulphate Turbuhaler. Total emitted dose (TED), fine particle dose (FPD) and mass median aerodynamic diameter (MMAD) of terbutaline sulphate Turbuhaler were determined using inhalation flows of 10-60 L min(-1) and inhaled volume of 4 L. TED and FPD increase significantly with the increase of inhalation flows (p <0.05). Flows had more pronounced effect on FPD than TED, thus, faster inhalation increases respirable amount more than it increases emitted dose. MMAD increases with decrease of inhalation flow until flow of 20L min(-1) then it decreases. In vitro flow dependent dose emission has been demonstrated previously for Turbuhaler for flow rates above 30 L min(-1) but is more pronounced below this flow. Minimal FPD below 30 L min(-1) suggests that during routine use at this flow rate most of emitted dose will impact in mouth. Flow dependent dose emission results suggest that Pharmacopoeias should consider the use variety of inhalation flows rather than one that is equivalent to pressure drop of 4 KPa.

Hyaluronan is an important component of the lung extracellular matrix, with a high capacity for water immobilization, but information on perinatal changes in the lung hyaluronan concentration and their association with changes in the lung water content is limited. In this study, conducted both in rabbit pups and in human infants, we investigated changes in the hyaluronan concentration and distribution in the lung and in the lung water content after preterm or term birth, and changes produced by common antenatal and postnatal pathological conditions and treatments. In rabbit pups, we found a gradual decrease in lung hyaluronan concentration and in the intensity of alveolar hyaluronan staining with advancing gestational age at birth in late gestation, but no further changes during the first 7-9 days of life. The lung water content was uniformly high before birth, but decreased significantly after preterm delivery or at birth at term. Postnatal exposure of newborn preterm or term rabbit pups to hyperoxia for 4-9 days resulted in an increase in both lung hyaluronan concentration and lung water content. This was accompanied by more intense hyaluronan staining, mainly in the alveolar walls. Antenatal exposure of rabbit pups to betamethasone or terbutaline resulted in a lower lung hyaluronan concentration at preterm birth, associated with less intense hyaluronan staining in alveolar walls, without altering the lung water content. Betamethasone exposure had a maximal effect at 25 days of gestation (term = 31 days), decreasing thereafter with advancing gestation, while terbutaline exposure resulted in a gradually increasing effect during late gestation, with a maximum at 29 days. In deceased infants born at a gestational age of &lt; 32 weeks, the lung hyaluronan concentration at death was most strongly associated with the gestational age at birth. It also covaried with sex, antenatal steroid administration, intrauterine bleeding, mode of delivery, birth weight, IRDS, and surfactant treatment. In infants born at a gestational age of &gt; 33 weeks there was a weaker association between lung hyaluronan concentration and gestational age. In this group, the lung hyaluronan concentration was associated with administration of a high concentration of oxygen, and covaried with maximal ventilatory pressure, and lung water content.

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.

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.

No description available.