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Objective To optimize the formulation and preparation of diphenhydramine hydrochloride and caffeine orally disintegrating tablet. Methods Melt granulation technology of steric acid and API was used to mask the unpleasant tasting of diphenhydramine hydrochloride. The tablets were prepared by direct pressing the dry powder with CCMC-Na as disintegrating agent. The formulation was optimized by orthogonal experiments to achieve the shortest disintegration time and the best taste correction. Results The optimized formula of orally disintegrating tablet was as follows： diphenhydramine hydrochloride 25 mg, caffeine 60 mg, stearic acid 25 mg, aspatan 40 mg, blueberry essence 7 mg, mannitol 45 mg, MCC 210 mg, CCMC-NA 25 mg, SDS 8 mg and magnesium stearate 5 mg. Conclusion This preparation method for orally disintegrating tablet of diphenhydramine hydrochloride and caffeine is practical and easy for quality control.
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Objective To establish the HPLC method of assay for diphenhydramine hydrochloride in compound diphenhydramine cream. Method HPLC analysis was carried on ACE5C18S/N-A66766 column (150 mm×4.6 mm, 5 µm) with the mobile phase of methanol-water-triethylamine (70:30:0.67, adjusting pH to 6.50 with phosphoric acid) at room temperature. The detection wavelength was set at 230 nm and the flow rate was 1.0 ml/min. The analyte was extracted from the cream and 20 μl of sample was injected. Results The calibration curve of diphenhydramine hydrochloride was linear in the range of 39.52-197.6 µg/ml (r=0.999 7). The average recovery of diphenhydramine hydrochloride was 100.5% (RSD=1.25%, n=9). The repeatability of the method was expressed using RSD with 0.78% (n=6). The results of assay were 101.3%, 99.83% and 99.62%. Conclusion The method is accurate, sensitive, selective and repeatable, which can be applied for improving the quality standard of compound diphenhydramine cream.
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Objective To provide the reference resource for the safe clinical use of the compound of diphenhydramine hydrochloride and caffeine by observing its effects on the nervous system, cardiovascular system and respiratory system in experimental animals. Methods Single dose of the compound of diphenhydramine hydrochloride and caffeine was given to animals orally. The effects on climbing ability of mice and blood pressure, electrocardiogram, respiration rate and amplitude in beagle dogs were observed and recorded. Results With the dosage of the compound of diphenhydramine hydrochloride and caffeine (diphenhydramine hydrochloride / caffeine ratio is 1/2.4) at 51, 102, 204 mg/kg, there was no significant effect on the climbing ability in mice. With the dosages of 14.2, 28.3, 56.6 mg/kg for male Beagle dogs and 5.66, 14.2, 28.3 mg/kg for female Beagle dogs, no significant effects were observed in systolic blood pressure, diastolic blood pressure, mean arterial pressure, heart rate, ECG（P wave, R wave , T wave, QRS time, PR interval, QT interval）, respiratory rate and amplitude. Conclusion Under the experimental conditions, single oral dose of the compound of diphenhydramine hydrochloride and caffeine has no significant effect on the nervous system, cardiovascular system and respiratory system in experimental animals. Those results suggest that the compound of diphenhydramine hydrochloride and caffeine is a safe agent for clinical use.
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Objective To establish an assay method for diphenhydramine hydrochloride and caffeine in rat plasma by UPLC-MS/MS for pharmacokinetic study. Methods The chromatographic separation was performed on an ACE 3 C18-PFP (3.0 mm×150 mm, 3 μm) by isocratic elution with the mobile phase of water containing 0.1% formic acid and acetonitrile (62:38, V/V). MS condition was optimized in the positive ion detection mode by multiple reaction monitoring (MRM), along with the Agilent JetStream electrospray source interface (AJS-ESI). The precursors to the product ion transitions were 256.2→167.0 (m/z) for diphenhydramine hydrochloride, 262.0→167.0 (m/z) for the internal standard (IS) diphenhydramine-D6, 195.0→138.0 (m/z) for caffeine and 204.0→116.2 (m/z) for the IS caffeine-D9. Results The calibration curve was linear in the range of 1-1×103 ng/ml for diphenhydramine hydrochloride in rat plasma (r=0.999 6), and in the range of 15-1.5×105 ng/ml for caffeine in rat plasma, (r=0.999 9). The intra-day and inter-day precision and accuracy were good (RSD<10%, RE<±10%). Pharmacokinetic studies showed that metabolic characteristics of diphenhydramine hydrochloride 10-30 mg/kg and caffeine 24-72 mg/kg were linear after intragastric administration. The two components were metabolized in rats with gender difference, the cmax and the AUC of diphenhydramine hydrochloride and caffeine were greater in female than those in males. Conclusion This method is accurate, rapid and sensitive. It can be used for the determination of diphenhydramine hydrochloride and caffeine in rat plasma collected for pharmacokinetic study. The results of pharmacokinetic studies in rats provide reliable data support for the clinical application of the compound preparation.
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OBJECTIVE:To establish a method for simultaneous determination of ephedrine hydrochloride,nitrofural and di-phenhydramine hydrochloride in Compound diphenhydramine nasal drop. METHODS:RP-HPLC method was adopted. The determi-nation was performed on Inertsil ODS-3 C18 column with mobile phase consisted of 0.05 mol/L potassium dihydrogen phosphate buf-fer(pH 7.0)-acetonitrile(gradient elution)with flow rate of 1.0 mL/min. The detection wavelength was set at 256 nm,and the col-umn temperature was 35 ℃. The sample size was 20 μL. RESULTS:The concentrations of phedrine hydrochloride,nitrofural and diphenhydramine hydrochloride ranged 122.1-366.3 μg/mL(r=0.9999),5.2-15.5 μg/mL(r=0.9998)and 31.5-94.5 μg/mL(r=0.9994),respectively. The limits of quantitation were 2.442,0.010,2.520 μg/mL,and the limits of detection were 0.810,0.003, 0.830 μg/mL,respectively. RSDs of precision,stability and reproducibility tests were lower than 1.0%. The recoveries of them were 99.2%-101.7%(RSD=0.9%,n=9),96.4%-102.0%%(RSD=1.7%,n=9),100.2%-101.9%(RSD=0.4%,n=9),respec-tively. CONCLUSIONS:The method is simple,accurate and reproducible,and can be used for simultaneous determination of ephedrine hydrochloride,nitrofural and diphenhydramine hydrochloride in Compound diphenhydramine nasal drop.
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OBJECTIVE:To establish a method for the determination of residual solvent of ethanol and toluene in diphenhydr-amine hydrochloride raw material. METHODS:Headspace capillary gas charmatography and butanone as internal standard were used. The column was Agilent DB-624 capillary column,inlet temperature was 200 ℃,hydrogen flame ionization detector was 250 ℃,the carried gas was high purity nitrogen,flow rate was 3.0 ml/min with temperature programmed,the splitting-ratio was 20∶1,the containers of headspace injector were in equilibrium at 80 ℃ for 30 min,and the injection time was 1 min. RESULTS:With this chromatographic condition,ethanol,toluene and internal standard peak were well separated;there was a good linear rela-tionship of ethanol and toluene in the range of 0.02-0.8 mg/ml (r=0.999 8 and r=0.999 4);RSDs of precision and stability test were lower than 3%;recoveries were 95.50%-103.50%(RSD=2.6%,n=9) and 96.91%-103.74%(RSD=2.2%,n=9). CON-CLUSIONS:The method is simple,sensitive and accurate,and can be used for the determination of residual solvent of ethanol and toluene in diphenhydramine hydrochloride raw material.
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OBJECTIVE:To establish a method for the simultaneous contents determination of chloramphenicol and diphenhydr-amine hydrochloride in Chlorobenzene alcohol solution. METHODS:HPLC was performed on the column of Diamonsil C with mo-bile phase of phosphate buffer-acetonitrile(66.5∶33.5,V/V)containing 0.01 mol/L sodium heptane,column temperature was 35 ℃, flow rate was 1 ml/min,detection wavelength was 258 nm for diphenhydramine hydrochloride and 277 nm for chloramphenicol, the injection volume was 10μl. RESULTS:The linear range was 34.8-139.4μg/ml for chloramphenicol(r=0.999 8)and 93.0-930.5μg/ml for diphenhydramine hydrochloride (r=0.999 8);RSDs of precision,stability and reproducibility tests were lower than 2.0%;recoveries were 97.70%-104.02%(RSD=2.2%,n=9)and 96.72%-101.72%(RSD=1.6%,n=9). CONCLUSIONS:The method is specific,accurate with good precision,and suitable for the quality control of Chlorobenzene alcohol solution.
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Objective:To prepare the thermosensitive nasal gel of ephedrine hydrochloride and diphenhydramine hydrochloride and establish its quality control method. Methods:The amounts of P407, P188 and PEG 6000 were optimized by an orthogonal test with the gelling temperature as the index. An HPLC method was established to determine the contents of ephedrine hydrochloride and di-phenhydramine hydrochloride. Results:The optimum amount of P407, P188 and PEG 6 000 was 19%, 2% and 1%, respectively. The linear range of ephedrine hydrochloride was 1.600 0-2.400 0 mg·ml-1(r=0.999 6), and the average recovery was 99.76%with RSD of 1. 02%(n=9). The linear range of diphenhydramine hydrochloride was 0. 160 0-0. 240 0 mg·ml-1(r=0. 999 7), and the average recovery was 101. 27% with RSD of 1. 10%(n=9). Conclusion:The formula design and preparation technology of the gel are feasible. The HPLC method is suitable for the quality control of the preparation.
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The present invention provides a new composition for treating pain-associated sleep disturbances, especially shortened sleep duration, comprising ibuprofen and diphenhydramine hydrochloride. In the present work the soft gelatin capsules were formulated comprising 25 mg diphenhydramine hydrochloride and 200 mg ibuprofen using polyethylene glycol 400, propylene glycol, potassium hydroxide and purified water. The prepared soft gelatin capsules were evaluated for weight variation test, assay, dissolution and disintegration. The capsules had a fill weight of 550 ± 5%, Disintegration time of 5-6 minutes and showed 97.00% to 99.50% of labeled amount of ibuprofen and diphenhydramine hydrochloride indicating uniformity in drug contents. The capsules containing 75 mg/capsule of propylene glycol released 99.40% of diphenhydramine hydrochloride and 99.70% of ibuprofen at the end of 60 minutes. Thus, it may be concluded that soft gelatin capsules of diphenhydramine hydrochloride and ibuprofen could be successfully prepared with existing technology and machinery which have a commercial viability and enhance patient compliance with improved bioavailability.
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glycerol,and the best penetrable concentrations for it were 0.5%,0.5% and 0.2%,respectively.No obvious penetration efficacy was noted for glycerol.CONCLUSIONS: 4 kinds of penetrations enhances can increase the percutaneous absorption of DH under the certain concentration.
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OBJECTIVE:To prepare diphenhydramine hydrochloride gel and establish its quality control.METHODS:The best formula was optimized by orthogonal design with sodium carboxymethyl cellulose and so on as the base materials,the content of diphenhydramine hydrochloride was determined by UV-spectrophotometry at the wavelength of258nm.RE?SULTS:The diphenhydramine hydrochloride gel was even,fine and which has a good dispersivity;In the concentration range of100～400?g/ml,the diphenhydramine hydrochloride had a linear relationship(r=0.9999,n=6),the average recovery was99.95%,RSD=0.95%(n=9).CONCLUSION:The preparation was stable in quality and reliable in quality control method.
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OBJECTIVE:To establish a HPLC method for simultaneously detecting the contents of ephedrine hydrochloride and diphenhydramine hydrochloride in Baichuaipeng tablets METHODS:The conditions of detection were:Diamonsil C18 (4 6mm?150mm,5?),the mobile phase consisted of acetonitrile-water-phosphoric acid (60∶40∶0 1,each 1 000ml contained 4 0g sodium lauryl sulfate),flow-rate 1ml/min,detection wavelength 254nm,external standard method RESULTS:The good linearity between peak and quantity ranged form 2 69?g～32 28?g for ephedrine hydrochloride and 2 54?g～30 48?g for diphenhydramine hydrochloride(n=5) The average recoveries(n=5) of ephedrine hydrochloride and diphenhydramine hydrochloride were 100 4%(RSD=1 1%) and 99 8%(RSD=0 9%),respectively CONCLUSION:The method is accurate,sim_ple and suitable for the quality control of Baichuaipeng tablets
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OBJECTIVE:To establish an HPLC method for determination of triamcinolone acetonide(TA), diphenhydramine hydrochloride(DH) and miconazole nitrate(MN) in compound miconazole nitrate cream(MNC). METHODS: The determination was performed on Hypersil ODS2. The mobile phase consisted of methanol-acetonitrile-0.5% ammonium acetate (45∶35∶20) at a flow rate of 1.0 mL?min-1. The UV detection wavelength was 234 nm; the column temperature was 40 ℃ and the inject volume was 20 ?L. RESULTS: The linear ranges for MN, TA and DH were 0.16～0.64 (r=0.999 8), 0.02～0.06 (r=0.999 9) and 0.08～0.24 (r=0.999 2) mg?L-1 respectively, with their average recoveries at 100.0%, 99.6% and 100.7%, RSD at 1.2%, 0.8% and 0.9%(n=3) respectively. CONCLUSION: The HPLC method can be used for the simultaneous determination of the three constituents in CMNC.
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OBJECTIVE:To establish a HPLC method for content determination of ribavirin and diphenhydramine hy-drochloride in flu nasal drops.METHODS:The chromato bar was ZORBAX SB-CN,the mobile phase was acetonitrile-wa-ter-phosphoric acid(38∶62∶0.1),with the flow rate of1.0ml/min and the detection wave at224nm,the sample size was20?l.RESULTS:A good linear relationship were obtained between the peak areas and the concentrations of ribavirin and diph_ enhydramine hydrochloride respectively in the range from0.1～1.0mg/ml(r=0.9990)and0.02～0.2mg/ml(r=0.9930),the average recoveries were100.3%(RSD=0.62%,n=9)and100.8%(RSD=0.54%,n=9),respectively.CONCLUSI_ ON:This method is convenient,rapid,accurate,and brings about good recovery,it can be used for quality control of flu nasal drops.