ABSTRACT
OBJECTIVE: To prepare of a torotrope transdermal patch for in vitro consistency evaluation and explor of the impact of quality standard characteristics on industrialization. METHODS: The tulobuterol transdermal patch was prepared with polyisobutylene B50, polybutene and petroleum resin as auxiliary excipients. The drug content in the sample was determined by high-performance liquid chromatography; in vitro consistency was evaluated by microscopy, differential thermal analysis, Fourier transform infrared spectroscopy, viscosity tester, dissolution Tester, and transdermal tester. The dissolution of the patch and its relationship with transdermal permeation, drug crystallization and in vitro release mechanism of the patch were studied in order to explore the influence of quality standard characteristics on industrialization. RESULTS: The self-made patch and the reference preparation have conformity in the drug content, drug crystallization, DSC, MATR, heat resistance, cold resistance, viscosity and shape. The dissolution tests were performed in medium of water and phosphate buffer (pH 7.4, 6.8, 4.0), and the corresponding f2 were 72.516, 94.840, 90.905, and 81.760. The average transdermal permeability ratio is 1.02 and the skin retention ratio is 0.88. The drug solubility is pH dependent while the in vitro dissolution is not sensitive to pH. The correlation between transdermal and dissolution in vitro is good. The in vitro release is affected by the composition of the excipients and the crystallization of the drug. CONCLUSION: The self-adhesive and the reference preparation have good consistency in vitro evaluation; the in vitro dissolution test can effectively reflect the transdermal permeation and absorption process of the drug in vitro. The drug crystallization evaluation index in the preparation is introduced to improve the quality control detection efficiency and quality assurance in the industrialization process. Research reference is provided for the consistency evaluation research, industrialization and quality standard improvement of this product.
ABSTRACT
OBJECTIVE: To prepare the tulobuterol crystal reservoir patch, and to evaluate morphology, stability and crystallization factors of the crystal in the patch, adhesive force, dissolution, transdermal properties in vitro and the pharmacokinetics in rabbits. METHODS: The transdermal patch was prepared on the basis of drug recrystallization and characterized by morphology, stability and crystallization factors using microscope and adhesive force using initial adhesion tester, adhesion tester and peel tester. The dissolution and transdermal properties were evaluated by using the dissolution tester and transdermal tester. In addition, pharmacokinetics was studied using New Zealand rabbits as experimental animals. RESULTS: The drug crystals were evenly distributed in the form of filaments, which had average width of (4.4±1.8)μm and kept stable at 2-40 ℃. The crystallization in patches is affected by tulobuterol supersaturation and temperature. The adhesive force of patch was suitable and its dissolution matched standard which can be fitted by the Higuchi equation. In the diffusion cell in vitro, the drug penetrated through the skin in a Zero-order kinetic equation, and the cumulative penetration percentage and skin retention concentration were 92.04% and 10.36 μg·cm-2 with in 24 h. The pharmaceutic parameters showed that the tulobuterol blood concentration can be maintained within 24 h, whose tmax and ρmax were (6.67±3.06)h and (3.08±1.32) ng·mL-1, respectively. CONCLUSION: The tulobuterol crystal reservoir patch can be established by control of recrystallization conditions. The patch has good adhesive properties and sustained release characteristics in vitro and in vivo, which has the practical significance for further study.
ABSTRACT
Objective To establish a method for the determination of residual solvents in tulobuterol by GC and optimize the purified process of crude tulobuterol product by this method. Methods The analysis was performed on Agilent DB-624 capillary column (30 m×0.32 mm,1.8 μm).The carrier gas was nitrogen at 1 mL·min-1.The injector temperature was 250 ℃.Detector was FID with hydrogen at 45 mL·min-1and air at 450 mL·min-1.The detector temperature was 250 ℃.The column temperature program was used.And the flow ratio was 10:1.Dimethyl sulfoxide (DMSO) was used as solvent of reference and test solution. Results Ethanol,tert-butylamine,dichloromethane,tert-butyl-methyl ether,n-hexane and 1,4-dioxane were completely separated.The calibration curve of each solvent showed good linear correlation. The RSD of precision was less than 5.0% and the average recovery ranged from 97.0% to 104.0% (RSD<5%).By optimizing the purification process of toloterol,the residue of organic solvent in the preparation of tolobuterol was in accordance with the Chinese Pharmacopoeia ( 2015) limit. Conclusion Validated by methodology,this simple,rapid and precise method can be used for the test of residual solvents in tulobuterol.
ABSTRACT
BACKGROUND: Endotracheal intubation during anesthesia induction may increase airway resistance (R(aw)) and decrease dynamic lung compliance (Cdyn). We hypothesized that prophylactic treatment with a transdermal β2-agonist tulobuterol patch (TP) would help to reduce the risk of bronchospasm after placement of the endotracheal tube. METHODS: Eighty-two American Society of Anesthesiologists (ASA) category I or II adult patients showing obstructive patterns were divided randomly into a control and a TP group (n = 41 each). The night before surgery, a 2-mg TP was applied to patients in the TP group. Standard monitors were recorded, and target controlled infusion (TCI) with propofol and remifentanil was used for anesthesia induction and maintenance. Simultaneously, end-tidal carbon dioxide, R(aw), and Cdyn were determined at 5, 10, and 15 min intervals after endotracheal intubation. RESULTS: There was no significant difference in demographic data between the two groups. The TP group was associated with a lower R(aw) and a higher Cdyn, as compared to the control group. R(aw) was significantly lower at 10 min (P < 0.05) and 15 min (P < 0.01), and Cdyn was significantly higher at 5 min (P < 0.05) and 15 min (P < 0.01) in the TP group. A trend towards a lower R(aw) was observed showing a statistically significant difference 5 min after endotracheal intubation (P < 0.01) in each group. CONCLUSIONS: Prophylactic treatment with TP showed a bronchodilatory effect through suppressing an increase in R(aw) and a decrease in C(dyn) after anesthesia induction without severe adverse effects.
Subject(s)
Adult , Humans , Airway Resistance , Anesthesia , Bronchial Spasm , Carbon Dioxide , Intubation, Intratracheal , Lung Compliance , Propofol , Respiratory SystemABSTRACT
Objective To explore the effectiveness and safety of tiotropium bromide inhalation agent with tulobuterol patch in the treatment of C and D level of COPD in stable period .Methods According to the digital table,255 cases of C and D level in patients with stable COPD were randomly divided into the study group and control group,the patients in study group received inhalation of tiotropium bromide dry powder 18μg/times,one time every day,and give tulobuterol patch(2mg/paste),one time every day.The control group received inhalation of tiotropium bromide dry powder 18μg/times,one time every day.The changes of lung function were observed before and after treatment,the clinical symptom score and inhaled short acting beta 2 agonists used,6min walk test,times of acute exacerbation condition.Results The patients in the two groups after treatment ,pulmonary function ,clinical symptoms score,inhaled short acting beta 2 agonists used,6min walk test,times of acute exacerbation compared with statistical significance(all P0.05).Conclusion Tiotropium bromide inhalation agent with tulobuterol patch can improve clinical symptoms and pulmonary function in patients with C and D level part of the stable phase of COPD .
ABSTRACT
Objective:To observe the effects and adverse reactions of tulobuterol patches in the adjuvant treatment of capillary bronchitis to elucidate the treatment effect of tulobuterol patches in the patients with capillary bronchitis. Methods:A total of 160 chil-dren with capillary bronchitis were randomly divided into the observation group and the control group. Both groups were given conven-tional therapy:oxygen treatment, aerosol inhalation of budesonide and anti-infection, etc. The control group was given nebulized al-buterol aerosols additionally, while the observation group was received tulobuterol patches additionally. The disappearance time of clini-cal symptoms and signs, the average length of stay in hospital and the incidence of adverse reactions between the two groups were com-pared. Results:In the observation group, the symptom of cough disappeared in (5. 08 ± 2. 35) d, wheezing disappeared in (3. 26 ± 1. 87)d, and the hospitalization time was (6. 15 ± 2. 27) d. Compared with those in the control group, the above indices were all shor-ter with statistically significant difference (P<0. 05). The incidence of adverse reactions was 3. 75% in the observation group while 38. 75% in the control group, the difference was statistically significant(P<0. 05) . Conclusion:Tulobuterol patches in the adjuvant treatment of capillary bronchitis can improve the clinical curative effect with promising safety and practicability.
ABSTRACT
Objective To evaluate the therapeutic effect of tulobuterol tape on mild or moderate bronchial asthma in children less than three years old . Methods Sixty-two children with mild or moderate asthma were randomized to receive either tulobuterol tape(treatment group) or procaterol hydrochloride tablet(control group) on the basis of inhaled fluticasone propionate for 2 weeks. Symptom scores of asthma, frequencies of episode of wheeze, doses of inhaled ventolin as rescue drug and the incidence of adverse reactions were recorded. Results In the treatment group,the symptom scores during daytime in the treatment group were (2. 2 ±0. 9)/week and (0. 9 ±0. 5)/week after 1 and 2 weeks of treatment, respectively, which were significantly lower than that in the control group(3.4 ± 1. 1)/week and (1. 3 ± 0. 6)/week after 1 and 2 weeks of treatment, respectively) (P < 0. 05). The symptom scores during night in the treatment group was significantly lower than that in the control group after one week of treatment (1. 8 ± 0. 7) /week v. s. (3. 3 ± 0. 9) /week, P < 0. 05). The frequencies of episode of wheeze was significantly different between the two groups (2. 3 ±1.2 and 3. 6 ± 1.3 in the treatment and control groups, respectively (P < 0.05) .The doses of inhaled ventolin in the treatment group (2. 6 ±0.9 spray/week) was significantly lower than that in the control group (3.7 ± 0. 8) spray/week) (P < 0. 05). The incidence of adverse reactions in the treatment group was significantly lower than that in the control group (3. 12% v. s. 23. 33% ,x2 = 3. 89,P<0.05). Conclusions Tulobuterol tape is a safe and effective medication for the treatment of mild or moderate bronchial asthma in children less than three years old.
ABSTRACT
PURPOSE: We aim to compare the effectiveness and safety of fluticasone propionate (Flt) plus tulobuterol (Hk) versus high-dose Flt alone in controlling asthma in children. METHODS: Fifty three children aged 4 to 8 years, who were diagnosed with mild persistent asthma and underwent maintenance therapy with a low dose of inhaled corticosteroid (Flt) of 50-100 microgram/day were randomized to receive Flt plus Hk (Hokunalin(R) patch 1 mg, Abbott Japan, Tokyo, Japan), or Flt alone at twice the dosage. Patients underwent new treatment for 4 weeks. Asthma symptom scores, mean changes in morning and evening peak expiratory flow (PEF), the frequency of night awakenings, the use of reliever medication, caregiver's overall satisfaction and safety were evaluated and compared in each group. And they were followed-up again 4 week after treatment course for the evaluation of treatment-emergent adverse event (TEAE). RESULTS: No significant difference was found between the groups in terms of mean changes in the morning and evening PEF, the frequency of night awakening, the use of rescue medication and caregiver's overall satisfaction (P=0.83, P=0.83, P=0.17, P=0.32 and P=0.63). Furthermore, no statistically significant difference was observed between 2 groups in the incidence of any TEAE (P=1.00). CONCLUSION: This study demonstrated that a combination of Flt and Hk was as effective as a high-dose Flt therapy in the management of mild persistent asthma in children. The results of this study suggest that tulobuterol add-on therapy can be considered as a reasonable substitute to an increase in the dosage of steroid in the patients with steroid-phobia and it might be used to reduce the risk of high dose steroid therapy.