Dry Syrup Research Articles

A Method for Estimating the Order of Influenza Infection between Adults and Children

This paper puts forward a method for determining the infection order of influenza between adults and children from the daily variations in the amount of influenza anti-viral agents treated at a pharmacy. The time series of Tamiflu Capsule for adults and Tamiflu Dry Syrup for children are compared by means of the cross-correlation function. The results from pharmacies located in Tokyo and Kanagawa show that the influenza infection period of adults is earlier than that of children, indicating the infection order: first adults and second children. However, a pharmacy in Saitama yields no clear result.

Evaluation of Bitterness Suppression of Macrolide Dry Syrups by Jellies

The purpose of this study was to evaluate the bitterness-suppressing effect of three jellies, all commercially available on the Japanese market as swallowing aids, on two dry syrups containing the macrolides clarithromycin (CAM) or azithromycin (AZM). The bitterness intensities of mixtures of the dry syrups and acidic jellies were significantly greater than those of water suspensions of the dry syrups in human gustatory sensation tests. On the other hand, the mixture with a chocolate jelly, which has a neutral pH, was less bitter than water suspensions of the dry syrups. The bitterness intensities predicted by the taste sensor output values correlated well with the observed bitterness intensities in human gustatory sensation tests. When the concentrations of CAM and AZM in solutions extracted from physical mixtures of dry syrup and jelly were determined by HPLC, concentrations in the solutions extracted from mixtures with acidic jellies were higher than those from mixtures with a neutral jelly (almost 90 times higher for CAM, and almost 7-10 times higher for AZM). Thus, bitterness suppression is correlated with the pH of the jelly. Finally, a drug dissolution test for dry syrup with and without jelly was performed using the paddle method. There was no significance difference in dissolution profile. It was concluded the appropriate choice of jelly with the right pH is essential for taste masking. Suitable jellies might be used to improve patient compliance, especially in children. The taste sensor may be used to predict the bitterness-suppressing effect of the jelly.

A Randomized Open-Label Comparative Study of Montelukast versus Theophylline Added to Inhaled Corticosteroid in Asthmatic Children

Inhaled corticosteroids (ICSs) are widely used in combination with other classes of drugs for treatment of childhood asthma. The efficacy and the safety of montelukast added to low-dose ICS therapy were compared with those of sustained-release theophylline added to low-dose ICS therapy in asthmatic children in the present study. Following the 2-week run-in period, 6-to 14-year old patients receiving treatment with ICSs were randomized to treatment for 4 weeks with either montelukast 5 mg once daily or sustained release theophylline 5-8 mg/kg (dry syrup) or 100-200 mg (tablet) twice daily. Patients also received a fixed dose of ICS throughout the run-in and treatment periods. The primary efficacy endpoint was the change from baseline in peak expiratory flow (PEF) at Week 2. A significant increase in morning PEF was observed in the add-on montelukast group as compared with the add-on theophylline group at Week 2 (change from baseline of 22.8 L/minvs. 8.7 L/min; p = 0.041 for between-group difference) and at Week 4 (31.0 L/minvs. 9.8 L/min; p = 0.012). A significant increase in evening PEF was observed in the add-on montelukast group as compared with the add-on theophylline group at Week 4 (24.7 L/minvs. 8.7 L/min; p = 0.027). There were no significant differences between the treatment groups in incidences of clinical and laboratory adverse experiences. The results indicate that montelukast added to low-dose ICS is an effective and safe option for the treatment of asthma in children.

Population Pharmacokinetics of Pranlukast Hydrate Dry Syrup in Children with Allergic Rhinitis and Bronchial Asthma

This study aimed to assess the steady-state pharmacokinetics of pranlukast, a leukotriene receptor antagonist, in children with allergic rhinitis and bronchial asthma, and to clarify factors affecting apparent clearance (CL/F). A total of 192 plasma samples were obtained from 98 children (rhinitis 64, asthma 13, complications 21), aged 3-14 years in 2 clinical trials. Plasma concentration of pranlukast was determined by liquid chromatography connected with a tandem mass spectrometer and analyzed by a population approach using NONMEM program. The plasma concentration-time course of pranlukast was described by using a one-compartment model with the first-order absorption and lag time. The robustness of the population pharmacokinetic model was evaluated by using 200 bootstrap samples. The results of population pharmacokinetic analysis showed that only age was a factor affecting the CL/F per body weight, with CL/F decreasing with increasing age. No significant variation was seen in the CL/F between rhinitis and asthma. The interindividual variability in the CL/F and the residual variability were 19.7% and 48.4%, respectively. All the parameters fell within 10% of the bootstrapped mean. In conclusion, the results show that age is the most influential factor for explaining interindividual variability in CL/F, and the difference in diseases does not affect CL/F.

Pranlukast Inhibits Exercise-Induced Bronchospasm in Asthmatic Children: A Randomized, Multicenter, Double-Blind, Placebo-Controlled Two-Period Crossover Trial

The purpose of this study was to determine whether pranlukast, a leukotriene receptor antagonist, attenuates exercise-induced bronchospasm (EIB) in children with asthma. The study was designed as a randomized, multicenter, double-blind, placebo-controlled two-period crossover trial. The subjects were 17 stable asthmatic children aged 7–14 years old (mean, 11.0 years) with a history of typical symptoms of EIB. They received dry syrup of pranlukast or placebo both after supper on the first day and after breakfast on the second day of the study in each period. All exercise challenges were performed on a bicycle ergometer and spirometry measurements of pulmonary function (FVC, FEV1.0, PEF, MMF,50 and 25) were collected pre-and post-exercise. Compared with placebo, pranlukast significantly inhibited the reduction of pulmonary function after exercise. Consequently, this study demonstrated that pranlukast, a leukotriene receptor antagonist, is a useful drug in childhood asthma management. (Pediatr Asthma Allergy Immunol 2005;18[1]:5–11.)

味覚センサを用いたマクロライド系ドライシロップの苦味評価（苦味マスキングに関する報告 第２２報）

The purpose of this study was to evaluate the degree of bitterness of commercial dry syrups preparations of three kinds of macrolide antibiotic (erythromycin dry syrup (EMD), clarithromycin dry syrup (CAMD) and azithromycin dry syrup (AZMD) when suspended in various beverages (water, tea and acidic sports drinks) by human gustatory sensation testing and taste sensor measurements.In the human gustatory sensation test, we evaluated the bitterness at three time points. First, we evaluated the bitterness immediately after the dry syrup suspension had been kept in the mouth for 5 seconds, which we termed “immediate bitterness”. The second and third time points were directly after and 5 minutes after the suspension had been ejected from the mouth and the mouth rinsed with water, which we referred to as “residual bitterness” and “residual bitterness after 5 minutes”, respectively.By this test, the ranking of the immediate bitterness of the suspensions of the dry syrups in water was AZMD >EMD= CAMD. As compared with water and tea, the bitterness of the dry syrups was greater when suspended in sports drinks when the ranking by immediate bitterness and residual bitterness was CAMD >AZMD=EMD. The bitterness enhancement was probably due to the increased dissolution of the dry syrups under acidic conditions.In the taste sensor study, the predicted degrees of bitterness correlated well with the bitterness findings from the gustatory sensation test for both direct bitterness and residual-bitterness (r2 = 0.921, 0.794, respectively).

乳幼児の散剤服用法についての検討―少量の水で練る場合の至適水分量について―

A general method of administering powdered medicines to infants is to add a spoonful of water to the powder to make a paste and then making the paste into small dumpling-sized balls. We investigated the optimal amount of water for making a paste for 35 kinds of powdered medicine which included fine granules, granules and dry syrups. The optimal water amount was expressed as an amount per gram of powder. Approximately 80% of the powders examined in this study required 0.2-0.4 mL of water per gram of powder to make a paste that would form small balls. Optimal water amounts were calculated for amounts of powder ranging between 0.1 and 1.5 grams by proportion and when the calculated amounts of water were added, small dumpling sized balls could be formed. In the same way, we also calculated amounts of water required for powdered mixtures of several medicines for 6 prescriptions often prescribed in our pharmacy from corrected standard volumes for each medicine in the mixture. The amounts of water added on this basis achieved the required paste state for all of the powder mixtures used. These results suggest that the optimal water amount for powdered medicines of various weights can be estimated from standard volumes of water by proportion. Thus, optimal water amounts determined by our method may be useful for the administration of mixed powdered medicines to infants.

Nippon Boehringer Ingelheim has received approval for 1% epinastine [Alesion] dry syrup for use in paediatric patients in Japan.

Nippon Boehringer Ingelheim has received approval for 1% epinastine [Alesion] dry syrup for use in paediatric patients in Japan.

A new, dry syrup dosage form of the bronchodilator procaterol [Meptin] has been released in Japan

A new, dry syrup dosage form of the bronchodilator procaterol [Meptin] has been released in Japan

塩酸エピナスチンドライシロップの小児アレルギー性鼻炎における臨床試験

Purpose: To investigate the efficacy and safety of Epinastine Dry Syrup (5 mg,10 mg, once daily) in children with perennial allergic rhinitis in comparison with Ketotifen Dry Syrup (1.2 mg,2.0 mg twic e daily).Methods: This was a multicenter, randomized, parallel, double-blind study in children with perennial allergic rhinitis, who were randomly allocated to receive either Epinastine (body weight<24 kg: 5 mg>24 kg: 10 mg, once daily) or Ketotifen (body weight<24 kg: 1.2 mg>24 kg: 2.0 mg, twice daily) for 2 weeks.Severity scores of each nasal symptom (sneezing, nasal discharge, nasal obstruction) were assessed by investigators at baseline and after 2 weeks of treatment.The efficacy was analyzed based on the total severity score and the safety was assessed by the frequency of adverse events reported during the study period.Results: Of the 151 children randomized,142 (Ep inastine: 74 and Ketotifen 68) were included in the efficacy analysis. After 2 weeks of treatment, the changes of the total severity score were 1.42 with E pinastine and 1.55 with Ketotifen (based on the means of least squares).Since the 95% confidence interval of the difference in leas t squares means between groups was 0.31∼0.57, the comparatively equal efficacy of Epinastine and Ketotifen was proved. Epinastine and Ketotifen were both well-tolerated. Somnolence was repor ted in 6 children treated with Epinastine and 7 treated with Ketotifen.Conclusion: The near-equivalenc e of Epinastine and Ketotifen was proved. Epinastine and Ketotifen were both well tolerated in treating children with perennial allergic rhinitis.

The bitterness intensity of clarithromycin evaluated by a taste sensor.

The purpose of this study was to evaluate the ability of a quantitative prediction method using a taste sensor to determine the bitterness of clarithromycin powder suspensions of various concentrations and of a commercial clarithromycin dry syrup product (Clarith dry syrup, Taisho Pharmaceutical Co., Ltd., Tokyo) containing aminoalkyl methacrylate polymer as a taste-masker. The bitterness of the clarithromycin dry syrup product dissolved in various beverages was also evaluated in gustatory sensation tests and using the taste sensor. In the sensor measurements, three variables were used to predict bitterness in single and multiple regression analysis: relative sensor output (R), the change of membrane potential caused by adsorption (CPA), and CPA/R ratio. The CPA values for channel 3 of the sensor predicted well the bitterness of clarithromycin powder suspensions and their filtered solutions. For Clarith dry syrup, the sensor output was small, suggesting that aminoalkyl methacrylate polymer was successful in almost complete masking of the bitter taste of the dry syrup product. When the bitterness intensities of mixtures of 1 g of Clarith dry syrup with 25 ml of water, coffee, tea, green tea, cocoa, milk, and a sports drink were examined, a good correlation was obtained between the results from human taste tests and the predicted values calculated on the basis of multiple regression analysis using CPA data from channel 4, and the CPA/R ratio from channel 3 of the taste sensor (r(2)=0.963, p<0.005). Co-administration of 1 g of Clarith dry syrup with an acidic sports drink was found to be the most bitter using either method.

Population pharmacokinetics of pranlukast hydrate dry syrup in children with bronchial asthma

This is the first report about the pharmacokinetics (PK) of pranlukast in children. The aim of the present study was to assess the PK parameters of pranlukast in children and to compare them with those in adults. Six healthy adult male volunteers and 22 children with bronchial asthma at 3–14 years of age were enrolled in the study. Both 225 and 112.5 mg pranlukast hydrate dry syrup was administered orally to adults, whereas 3.5 mg/kg pranlukast hydrate dry syrup was given to children. Blood samples were obtained at approximately 20 time points per adult (n = 121) and at two or three time points per child (n = 54). Population PK analysis was performed using NONMEM (Globomax, Hanover, MD, USA). The concentration-time-course of pranlukast was described by using a one-compartment model with first-order absorption. The robustness of the final model was evaluated using 200 bootstrap samples. Apparent clearance (CL/F) was 1.81 and 1.14 L/h per kg in children and adults, respectively. According to subgrouping of children, no significant difference was observed in CL/F between infants (3–6 years of age) and schoolchildren (7–14 years of age). The interindividual variability of CL/F accounted for 48.7%. The additive and proportional residual variability was 7.33 ng/mL and 73.8%, respectively. All fixed effect parameters fell within 10% of the bootstrapped mean. Compared with adults, children showed a higher CL/F and more rapid elimination after ingestion of pranlukast hydrate dry syrup. However, no significant variation was seen in CL/F between infants and schoolchildren.

Faropenem dry syrup for pediatric: A postmarketing surveillance review of 3, 823 cases

Faropenem dry syrup for pediatric: A postmarketing surveillance review of 3, 823 cases

Method of evaluation of the bitterness of clarithromycin dry syrup.

The degree of bitterness of clarithromycin (CAM) dry syrup was evaluated using several methods. Using the inversion method, shaking method, and paddle method, a reasonable correlation between the bitter taste and the amount dissolved was not observed. A mini-column with inner diameter of 0.76 cm and height of 5 cm packed with CAM dry syrup was used for the release test. The release rate of CAM in test solution, which passed through the mini-column, was then measured to evaluate bitterness. The release rate of CAM in the release test using the mini-column correlated well with the results of a sensory test for the bitterness of CAM dry syrup. The dissolution rate constant, defined as the percentage of CAM dissolved from the unit void surface multiplied by the void volume, was inversely proportional to the linear velocity of the test solution. The critical factors affecting evaluation of bitterness were the void volume of the column and linear velocity of the test solution. The optimum linear velocity and void volume were 0.048-0.021 cm/min and 0.27-0.12 cm3, respectively. In addition, the threshold of bitterness of CAM dry syrup was defined as the concentration at which half of the volunteers recognized bitterness in the sensory test. This threshold was found to be 135 microg/ml using the mini-column.

Faropenem dry syrup for pediatric: A postmarketing surveillance safety review of 3, 823 cases

Faropenem dry syrup for pediatric: A postmarketing surveillance safety review of 3, 823 cases

Pharmacological and clinical properties of didanosine (VIDEX), a nucleoside reverse transcriptase inhibitor

An active metabolite, ddATP, of didanosine that is an analogue of purine-nucleoside (a component of nucleic acid) was known to inhibit the activity of DNA polymerase for E. coli. In 1985, Dr. Michiya et al. of NCI reported that didanosine and ddA inhibited replication of the human immunodeficiency virus (HIV). This discovery led to the clinical application of both the compounds. Didanosine, after being uptaken into a cell, becomes an active metabolite, ddATP, to inhibit a reverse transcriptase of HIV. Compared with zidovudine, didanosine has weak cytotoxicity both in vitro and in vivo. Didanosine, which is recommended as a first-line therapy drug in the Japanese Guideline on an anti-HIV Infection Therapy, was approved as twice-daily Videx Tablet and Dry Syrup formulations for launch in June 1992. In March 2001, a once-daily Videx EC Capsule formulation was approved and launched, having expected adherence improvements in HIV/AIDS patients.

Assay for the determination of low dosage form of formoterol dry syrup by capillary electrophoresis with head-column field-amplified sample stacking

The development of a capillary zone electrophoresis method with head-column field-amplified sample stacking injection for the determination of formoterol (FMTR) in a low dosage dry syrup form was described. To obtain the highest sensitivity, the sample solution was prepared by high content of organic solvent with the presence of a small amount of H + (60–100 μM) and the capillary inlet end was dipped in water before electroinjection. This method was fully validated in terms of repeatability (RSDs for migration time, peak area of FMTR and peak area ratio between FMTR and I.S. at 1 μg/ml of FMTR was 0.76, 1.10 and 0.55% respectively), reproducibility (RSDs from different capillaries, analytes, days and instruments were 1.52%, 1.04%, 1.16% and 1.93% respectively), linearity ( y=0.827 x−0.085, r=0.9993 ( n=6) over the range of 0.25–2.0 μg/ml), limits of quantitation, ruggedness and robustness. The method was applied to the determination of the drug in commercial dry syrup preparation (recovery was 100.9%, RSD=1.5%, n=5) and proved to be fast and reliable for the quantitation analysis of FMTR in the pharmaceutical form.

Determination of L-threonate in calcium L-threonate preparations by capillary electrophoresis with indirect UV detection.

A validated capillary electrophoresis method with indirect UV detection for the determination of L-threonate in a calcium L-threonate (Ca-Th) chewable tablet and dry syrup was described. The 2,6-naphthalenedicarboxylic acid (NDC) was used as the background carrier ion and the tetradecyltrimethylammonium bromide (TTAB) was used as electroosmotic flow modifier. The running buffer contained 2 mM NDC, 6 mM disodium carbonate and 0.2 mM TTAB. The detection wavelength was set at 240 nm. A linear calibration range of 50-500 microg/mL was obtained (r = 0.9996). The limit of detection and limit of quantitation were found to be 6 microg/mL and 20 microg/mL, respectively. The recovery was 99.45% (RSD = 0.57%, n = 5) and 99.12% (RSD = 0.48%, n = 5) for the tablet and dry syrup preparation, respectively. Repeatability tests on the migration times or peak areas proved that the results were of high precision. The RSD of peak area ratio was lower than 1% (0.74%, n = 5). The factors influencing quantitation were discussed and three batches of chewable tablet and also of dry syrup were assayed by the proposed method.

市販後調査によるrokitamycin dry syrup 200の安全性, 有効性の検討

市販後調査によるrokitamycin dry syrup 200の安全性, 有効性の検討

テオフィリン徐放性ドライシロップ剤の懸濁時における放出性および溶出性に及ぼす影響

Theophylline sustained-release dry syrup (TDR·DS) is reported to be effective for treating children with bronchial asthma. In the present study, we studied the release and dissolution of TDR·DS in water using THEODUR® as well as the effects of the volume and temperature of the water, and the suspension time of TDR·DS. The suspension of TDR·DS in water accelerated the release and dissolution time of theophylline. The release and dissolution times of TDR·DS at 37°C were shorter than those at 20°C. In conclusion, it is better to administer TDR·DS without suspending it in water.