Current methods for nasal spray formulations have been elementary evaluating the dripping characteristics of a formulation and have not assessed the behavior of the nasal formulation in the presence of varying types o...Current methods for nasal spray formulations have been elementary evaluating the dripping characteristics of a formulation and have not assessed the behavior of the nasal formulation in the presence of varying types of mucus depending on the indication or diseased state. This research investigated the effects of nasal mucus on the dripping behavior of nasal formulations and focused on developing an improved in vitro analytical test method that is more physiologically relevant in characterizing nasal formulation dripping behavior. Method development was performed using simulated nasal mucus preparations for both healthy and diseased states as coatings for the dripping experiment representing a wide range of viscosity. Factors evaluated during development of this in vitro test method included amount of mucus, application of mucus, drying times, and compatibility of the mucus on a C18 Thin Layer Chromatography(TLC) substrate. The dripping behavior of nasal formulations containing a range of 1%Avicel to 3.5% Avicel was assessed by actuating the nasal spray on a perpendicular TLC plate coated with either healthy or diseased simulated nasal mucus. After actuation of the nasal spray, the dripping of the formulation on the coated TLC plate was measured after the plate was repositioned vertically. The method that was developed generated reproducible results on the dripping behavior of nasal formulations and provided critical information about the compatibility of the formulation with the nasal mucus for different diseased states, aiding in nasal spray formulation development and physical characterization of the nasal spray.展开更多
This study prospectively examined the intranasal distribution of nasal spray after nasal septal correction and decongestant administration. A cohort of 20 patients was assessed for the distribution of nasal spray befo...This study prospectively examined the intranasal distribution of nasal spray after nasal septal correction and decongestant administration. A cohort of 20 patients was assessed for the distribution of nasal spray before and after nasal septum surgery. Sprays were dyed and administered one puff per nostril when patients hold their head up in an upright position. Before and after decongestant admini-stration, the intranasal distribution was semi-quantitatively determined by nasal endoscopy. The results showed that the dyed drug was preferentially sprayed onto the nasal vestibule, the head of the inferior turbinate, the anterior part of septum and nasal floor. As far as the anterior-inferior segment of the nasal cavity was concerned, the distribution was found to be influenced neither by the decongestant nor by the surgery （P〉0.05）. However, both the decongestant and surgery expanded the distribution to the anatomical structures in the superior and posterior nasal cavity such as olfactory fissure, middle turbinate head and middle nasal meatus. No distribution was observed in the sphenoethmoidal recess, posterior septum, tail of inferior turbinate and nasopharynx. It was concluded that nasal septum surgery and decongestant administration significantly improves nasal spray distribution in the nasal cavity.展开更多
BACKGROUND： In localized brain proton magnetic resonance spectroscopy （^1H-MRS）, metabolite levels are often expressed as ratios, rather than absolute concentrations. Frequently, the denominator is creatine, which ...BACKGROUND： In localized brain proton magnetic resonance spectroscopy （^1H-MRS）, metabolite levels are often expressed as ratios, rather than absolute concentrations. Frequently, the denominator is creatine, which is assumed to be stable in normal, as well as many pathological, states. However, in vivo creatine levels do not remain constant. Therefore, absolute metabolite measurements, which provide the precise concentrations of certain chemical compounds, are superior to metabolite ratios for determining pathological and evolutional changes. OBJECTIVE： To investigate the feasibility of quantification analysis of brain metabolite changes caused by central analgesics nasal spray using the ^1H-MRS and linear combination model （LCModel） methods. DESIGN, TIME AND SETTING： This neuroimaging, observational, animal study was performed at the Laboratory of the Department of Medical Imaging, Second Affiliated Hospital, Medical College, Shantou University, China from July to December 2007. MATERIALS： Butorphanol tartrate nasal spray, as a mixed agonist-antagonist opioid analgesic, was purchased from Shanghai Hengrui Pharmacy, China. A General Electric Signa 1.5T System （General Electric Medical Systems, Milwaukee, WI, USA） and LCModel software （Stephen Provencher, Oakville, Ontario, Canada） were used in this study. METHODS： MRS images were acquired in ten healthy swine aged 2 weeks using single-voxel point-resolved spectroscopic sequence. A region of interest （2 cm × 2 cm × 2 cm） was placed in the image centers of maximum brain parenchyma. Repeated MRS scanning was performed 15-20 minutes after intranasal administration of 1 mg of butorphanol tartrate. Three settings of repetition time/echo time were selected before and after nasal spray administration 3 000 ms/30 ms,1 500 ms/30 ms, and 3 000 ms/50 ms. Metabolite concentrations were estimated by LCModel software. MAIN OUTCOME MEASURES： ^1H-MRS spectra was obtained using various repetition time/echo time settings. Concentrations of glutamate compounds （glutamate ＋ glutamine）, N-acetyl aspartate, and choline were detected in swine brain prior to and following nasal spray treatment. RESULTS： The glutamate compounds curve was consistent with original spectra, when a repetition time/echo time of 3 000 ms/30 ms was adopted. Concentrations of glutamate compounds, N-acetyl aspartate, and choline decreased following administration. The most significant reduction was observed in glutamate compound concentrations from （9.28 ± 0.54） mmol/kg to （7.28 ± 0.54） mmol/kg （P 〈 0.05）. CONCLUSION： ^1H-MRS and LCModel software were effectively utilized to quantitatively analyze and measure brain metabolites. Glutamate compounds might be an important neurotransmitter in central analgesia.展开更多
Nasal application of benzodiazepines might be an alternative to intravenous administration in acute clinical situations such as seizures emergencies. However, irritation and pain as well as symptoms like teary eyes, d...Nasal application of benzodiazepines might be an alternative to intravenous administration in acute clinical situations such as seizures emergencies. However, irritation and pain as well as symptoms like teary eyes, dizziness, discomfort, nasal drainage and bad taste usually accompany subject received midazolam and diazepam via the nasal route. The purpose of this study was to evaluate the use of a new alcohol-free microemulsion system as a carrier for diazepam or midazolam given intranasally. Midazolam (base) or diazepam was solubilized in the microemulsion to obtain a high drug concentration of 25 mg/g (2.5% by weight), to provide 2.5 mg drug in 100 μl spray (d ≈ 1.00 g/ml). The nasal absorption of both drugs from the same microemulsion formulation (containing 20% aqueous phase) was found to be fairly rapid after administration of 0.4 mg/kg to rabbits. The absolute bioavailability of diazepam after intranasal administration using this formulation was 33.45% ± 12.36% and the tmax was 18.33 ± 23.09 min, which was twice longer than the tmax obtained after midazolam administration, 9.25 ± 6.75 min. The pharmacokinetic parameters of midazolam in W/O (20% water) microemulsion and their comparison with midazolam in O/W (50% water) microemulsion have shown that both formulations resulted in a relatively short time to reach the peak plasma level (tmax), that is, 9.25 ± 6.75 min and 6.75 ± 5.67 min, respectively. However, the peak plasma levels (Cmax) and the absolute bioavailability (FA) of midazolam were significantly higher after administration of the W/O formulation than those obtained after application of O/W formulation, i.e., 46.62 ± 17.38 μg/ml vs. 15.44 ± 4.00 μg/ml, and 35.19% ± 11.83% vs. 19.83% ± 16.32%, respectively. Our results suggest that the new microemulsion system may be useful for getting rapid-onset of midazolam and diazepam following intranasal administration, resulting in reasonable peak plasma levels and bioavailability, but most importantly, providing a high measure of tolerability and comfort.展开更多
Adenoid hypertrophy associated with high morbidity in children. However, in severe cases surgery recommended, some medical treatments are effective too. This study is based on effect of nasal steroid spray, mometasone...Adenoid hypertrophy associated with high morbidity in children. However, in severe cases surgery recommended, some medical treatments are effective too. This study is based on effect of nasal steroid spray, mometasone, in decreasing upper airway obstruction and other symptoms of adenoid hypertrophy. In a clinical trial study 51 children with adenoid hypertrophy divided in two groups： 2-4 years old and 5-11 years old. Each patient receive nasal momethasone （one puff each nostril twice a day） for 3 months and their symptoms evaluated before treatment, 3 months after treatment initiation and 3 months after stop it with questionnaire and lateral neck radiography. Decreasing in all symptoms score and upper airway obstruction was statistically significant in both groups 3 months after treatment and its effect maybe stable for next 3 months. Nasal momethasone spray is effective in decreasing adenoid size and severity of symptoms of adenoid hypertrophy and this response is more obvious in 2-4 years old children.展开更多
文摘Current methods for nasal spray formulations have been elementary evaluating the dripping characteristics of a formulation and have not assessed the behavior of the nasal formulation in the presence of varying types of mucus depending on the indication or diseased state. This research investigated the effects of nasal mucus on the dripping behavior of nasal formulations and focused on developing an improved in vitro analytical test method that is more physiologically relevant in characterizing nasal formulation dripping behavior. Method development was performed using simulated nasal mucus preparations for both healthy and diseased states as coatings for the dripping experiment representing a wide range of viscosity. Factors evaluated during development of this in vitro test method included amount of mucus, application of mucus, drying times, and compatibility of the mucus on a C18 Thin Layer Chromatography(TLC) substrate. The dripping behavior of nasal formulations containing a range of 1%Avicel to 3.5% Avicel was assessed by actuating the nasal spray on a perpendicular TLC plate coated with either healthy or diseased simulated nasal mucus. After actuation of the nasal spray, the dripping of the formulation on the coated TLC plate was measured after the plate was repositioned vertically. The method that was developed generated reproducible results on the dripping behavior of nasal formulations and provided critical information about the compatibility of the formulation with the nasal mucus for different diseased states, aiding in nasal spray formulation development and physical characterization of the nasal spray.
基金supported by a grant from National Natural Science Foundation of China(No.81070772)Zhuhai Medical Scientific Research Fund(No.PC20081046)
文摘This study prospectively examined the intranasal distribution of nasal spray after nasal septal correction and decongestant administration. A cohort of 20 patients was assessed for the distribution of nasal spray before and after nasal septum surgery. Sprays were dyed and administered one puff per nostril when patients hold their head up in an upright position. Before and after decongestant admini-stration, the intranasal distribution was semi-quantitatively determined by nasal endoscopy. The results showed that the dyed drug was preferentially sprayed onto the nasal vestibule, the head of the inferior turbinate, the anterior part of septum and nasal floor. As far as the anterior-inferior segment of the nasal cavity was concerned, the distribution was found to be influenced neither by the decongestant nor by the surgery （P〉0.05）. However, both the decongestant and surgery expanded the distribution to the anatomical structures in the superior and posterior nasal cavity such as olfactory fissure, middle turbinate head and middle nasal meatus. No distribution was observed in the sphenoethmoidal recess, posterior septum, tail of inferior turbinate and nasopharynx. It was concluded that nasal septum surgery and decongestant administration significantly improves nasal spray distribution in the nasal cavity.
基金the National Natural Science Foundation of China,No. 3047051530570480
文摘BACKGROUND： In localized brain proton magnetic resonance spectroscopy （^1H-MRS）, metabolite levels are often expressed as ratios, rather than absolute concentrations. Frequently, the denominator is creatine, which is assumed to be stable in normal, as well as many pathological, states. However, in vivo creatine levels do not remain constant. Therefore, absolute metabolite measurements, which provide the precise concentrations of certain chemical compounds, are superior to metabolite ratios for determining pathological and evolutional changes. OBJECTIVE： To investigate the feasibility of quantification analysis of brain metabolite changes caused by central analgesics nasal spray using the ^1H-MRS and linear combination model （LCModel） methods. DESIGN, TIME AND SETTING： This neuroimaging, observational, animal study was performed at the Laboratory of the Department of Medical Imaging, Second Affiliated Hospital, Medical College, Shantou University, China from July to December 2007. MATERIALS： Butorphanol tartrate nasal spray, as a mixed agonist-antagonist opioid analgesic, was purchased from Shanghai Hengrui Pharmacy, China. A General Electric Signa 1.5T System （General Electric Medical Systems, Milwaukee, WI, USA） and LCModel software （Stephen Provencher, Oakville, Ontario, Canada） were used in this study. METHODS： MRS images were acquired in ten healthy swine aged 2 weeks using single-voxel point-resolved spectroscopic sequence. A region of interest （2 cm × 2 cm × 2 cm） was placed in the image centers of maximum brain parenchyma. Repeated MRS scanning was performed 15-20 minutes after intranasal administration of 1 mg of butorphanol tartrate. Three settings of repetition time/echo time were selected before and after nasal spray administration 3 000 ms/30 ms,1 500 ms/30 ms, and 3 000 ms/50 ms. Metabolite concentrations were estimated by LCModel software. MAIN OUTCOME MEASURES： ^1H-MRS spectra was obtained using various repetition time/echo time settings. Concentrations of glutamate compounds （glutamate ＋ glutamine）, N-acetyl aspartate, and choline were detected in swine brain prior to and following nasal spray treatment. RESULTS： The glutamate compounds curve was consistent with original spectra, when a repetition time/echo time of 3 000 ms/30 ms was adopted. Concentrations of glutamate compounds, N-acetyl aspartate, and choline decreased following administration. The most significant reduction was observed in glutamate compound concentrations from （9.28 ± 0.54） mmol/kg to （7.28 ± 0.54） mmol/kg （P 〈 0.05）. CONCLUSION： ^1H-MRS and LCModel software were effectively utilized to quantitatively analyze and measure brain metabolites. Glutamate compounds might be an important neurotransmitter in central analgesia.
文摘Nasal application of benzodiazepines might be an alternative to intravenous administration in acute clinical situations such as seizures emergencies. However, irritation and pain as well as symptoms like teary eyes, dizziness, discomfort, nasal drainage and bad taste usually accompany subject received midazolam and diazepam via the nasal route. The purpose of this study was to evaluate the use of a new alcohol-free microemulsion system as a carrier for diazepam or midazolam given intranasally. Midazolam (base) or diazepam was solubilized in the microemulsion to obtain a high drug concentration of 25 mg/g (2.5% by weight), to provide 2.5 mg drug in 100 μl spray (d ≈ 1.00 g/ml). The nasal absorption of both drugs from the same microemulsion formulation (containing 20% aqueous phase) was found to be fairly rapid after administration of 0.4 mg/kg to rabbits. The absolute bioavailability of diazepam after intranasal administration using this formulation was 33.45% ± 12.36% and the tmax was 18.33 ± 23.09 min, which was twice longer than the tmax obtained after midazolam administration, 9.25 ± 6.75 min. The pharmacokinetic parameters of midazolam in W/O (20% water) microemulsion and their comparison with midazolam in O/W (50% water) microemulsion have shown that both formulations resulted in a relatively short time to reach the peak plasma level (tmax), that is, 9.25 ± 6.75 min and 6.75 ± 5.67 min, respectively. However, the peak plasma levels (Cmax) and the absolute bioavailability (FA) of midazolam were significantly higher after administration of the W/O formulation than those obtained after application of O/W formulation, i.e., 46.62 ± 17.38 μg/ml vs. 15.44 ± 4.00 μg/ml, and 35.19% ± 11.83% vs. 19.83% ± 16.32%, respectively. Our results suggest that the new microemulsion system may be useful for getting rapid-onset of midazolam and diazepam following intranasal administration, resulting in reasonable peak plasma levels and bioavailability, but most importantly, providing a high measure of tolerability and comfort.
文摘Adenoid hypertrophy associated with high morbidity in children. However, in severe cases surgery recommended, some medical treatments are effective too. This study is based on effect of nasal steroid spray, mometasone, in decreasing upper airway obstruction and other symptoms of adenoid hypertrophy. In a clinical trial study 51 children with adenoid hypertrophy divided in two groups： 2-4 years old and 5-11 years old. Each patient receive nasal momethasone （one puff each nostril twice a day） for 3 months and their symptoms evaluated before treatment, 3 months after treatment initiation and 3 months after stop it with questionnaire and lateral neck radiography. Decreasing in all symptoms score and upper airway obstruction was statistically significant in both groups 3 months after treatment and its effect maybe stable for next 3 months. Nasal momethasone spray is effective in decreasing adenoid size and severity of symptoms of adenoid hypertrophy and this response is more obvious in 2-4 years old children.
