Novel HPTLC method for simultaneous estimation from ternary mixture of chlorpheniramine maleate, dextromethorphan hydrobromide and phenylephrine hydrochloride in syrup formulations.

OBJECTIVES: A synergic antihistamine, cough suppressant, and decongestant combination of chlorpheniramine, dextromethorphan, and phenylephrine is used to treat acute respiratory infections caused by seasonal viruses. The effective qualitative and quantitative methods require the simultaneous measurement of a ternary combination in the pharmaceutical syrup dosage form. Therefore, a new, simple, fast and robust high performance thin layer chromatographic (HPTLC) method has been developed and validated for chlorpheniramine maleate (CPM), dextromethorphan hydrobromide (DEXO) and phenylephrine hydrochloride (PE). MATERIAL AND METHODS: The chromatographic separation was carried out on precoated aluminium plates with silica gel 60 F254 as the stationary phase. Mobile phase used was chloroform: methanol: ammonia (2.5:7.5:0.3, v/v/v) for proper separation. The detection was carried out at 270nm wavelength in absorbance mode. Developed method was validated as per International Council for Harmonization (ICH) Q2 (R1) guideline. RESULTS: The linearity range is 400 to 1400ng/band for CPM, 3000 to 11500ng/band for DEXO and 1000 to 3500ng/band for PE with correlation coefficient ≥ 0.995. The consistent lower values of relative standard deviation (RSD, %) for precision and robustness study indicate the method reliability. The percent recovery ranged from 97.82 to 102.03% indicates the good accuracy of the method. CONCLUSION: The proposed method was complying for the analytical method validation parameters suggested by the ICH Q2 (R1) guideline. The method was found to be simple, rapid and reliable for the simultaneous estimation of CPM, DEXO and PE from its pharmaceutical syrup dosage form. The method was successfully applied to quantify these analytes from the several pharmaceutical syrup dosage form.

Sensitive detection of dextromethorphan hydrobromide based on portable Raman spectrometer and CuO@AgNPs nano composite SERS substrate.

A highly sensitive surface-enhanced Raman spectroscopy approach was established for the detection of dextromethorphan hydrobromide (DXM) utilizing nano CuO modified silver nanoparticles (CuO@AgNPs) as substrate. Ultraviolet visible spectra (UV-vis), X-ray diffraction (XRD) and transmission electron microscopy (TEM) characterized the synthesized CuO@AgNPs. UV-vis and fourier transform infrared (FT-IR) were adopted to investigate the interaction between DXM and CuO@AgNPs. The optimal experimental conditions (the dosages of CuO@AgNPs and NaCl as well as mixing time) were explored. The enhancement factor (EF) was 1.71 × 106. The linear relationship between SERS intensity and the concentration of DXM in the range of 67 - 1000 nmol L-1 was obtained as ISERS = 25.81 c + 40398.77, and the limit of detection (LOD) was 2.12 nmol L-1 (S/N = 3). The interference of K+, Mg2+, Zn2+, Ca2+, Cu2+, Fe3+, glucose, HSA, L-tryptophan, soluble starch and ibuprofen were investigated. The method was successfully applied to test DXM in serum samples. The recovery was 99.06% - 101.51% with the relative standard deviation (RSD) of 0.74% - 3.87%.

Fast-dissolving oral films containing dextromethorphan/phenylephrine for sinusitis treatment: formulation, characterization and optimization.

This work uses optimization study to formulate a patient-friendly antitussive fast-dissolving oral film based on phenylephrine hydrochloride (Phen) and dextromethorphan hydrobromide (Dex). The designed films were based on hydroxypropylmethyl cellulose (HPMC) with two grades (E5 and E50) as a film-forming polymer by the solvent-casting method. Polyethylene glycol with two molar masses (400 and 1000) was used as a plasticizer, while aspartame was used as a sweetener and microcrystalline cellulose intended to act as a disintegrant. To find an optimum formulation, a response surface methodology and a central composite design were employed. The percentage of HPMC E50, and PEG, as a plasticizer, were considered to be the design factors. Film thickness, surface pH, disintegration time, dissolution percent, tensile strength, elongation percent and folding endurance were considered to be the responses. A film with 11.46% E50, 88.54% E5, 25% of two drugs (8.4% of Phen and 16.6% of Dex) and 18.54% plasticizer is designed and prepared as the optimum formulation for Phen/Dex fast-dissolving oral films, with 95% confidence levels.

Bromine K-Edge X-Ray Absorption Near-Edge Structure Analysis on Hydrobromide-Salt Crystals and the Solid Dispersion of Active Pharmaceutical Ingredients.

Bromine K-edge X-ray absorption near-edge structure (XANES) spectroscopy analyses were used to evaluate the crystals of the active pharmaceutical ingredients, eletriptan hydrobromide, dextromethorphan hydrobromide and scopolamine hydrobromide salts and the solid dispersion of eletriptan hydrobromide. The crystals and the solid dispersion of the active pharmaceutical ingredient (API) salts could be discriminated based on the shape of the XANES spectra. The differences in the shape of XANES spectra was ascribable to the differences in the interatomic interactions of the bromine ions based on the crystal structures. Ratio of the eletriptan hydrobromide α-form crystal in mixed powders of α-form and monohydrate crystals could be quantified by the linear-combination fitting using their XANES spectra. These results indicated that the XANES spectroscopy are a potent method for evaluating the APIs of pharmaceutical formulations even at the higher energy region around the bromine K-edge of 13470 eV.

Acute psychosis and serotonin syndrome in the setting of "Triple-C" overdose: a case report.

BACKGROUND: Over-the-counter medication overdose is a difficult diagnostic challenge for many physicians as common drug screening assays cannot detect these substances. We present a case of acute psychosis, serotonin syndrome, and anticholinergic overdose-like properties in the setting of Coricidin HBP Cough & Cold tablets, known by their street name Triple-C. This is the first case report we are aware of involving a patient presenting with these symptoms and requiring critical-care-level support. CASE PRESENTATION: A 31-year-old African American female with a past medical history of anxiety, childhood asthma, previous methamphetamine abuse, and coronavirus disease 2019 infection in August 2020 was brought to the emergency department by the local police department with altered mental status. Initial blood work, including extended drug screens, were unremarkable for a definitive diagnosis. This patient required critical-care-level support and high sedation because of her symptoms. Collateral history revealed the patient regularly consumed Triple-C daily for the 6 weeks prior to admission. A trial off sedation was attempted after 24 hours with no complications. The patient admitted to regular Triple-C consumption and auditory hallucinations since adolescence. She was discharged safely after 48 hours back into the community. She was lost to follow-up with psychiatry and internal medicine; however, she was evaluated in the emergency room 1 month later with a similar psychiatric presentation. CONCLUSION: Overdose of Triple-C should be kept in the differential diagnosis of patients presenting with a triad of psychosis, serotonin syndrome, and anticholinergic overdose, in the setting of unknown substance ingestion.

The Effect of Intrathecal Injection of Dextromethorphan on the Experimental Neuropathic Pain Model.

BACKGROUND: Peripheral glucocorticoid receptors (GRs) are altered by peripheral nerve injury and may modulate the development of neuropathic pain. Two central pathogenic mechanisms underlying neuropathic pain are neuroinflammation and N-methyl-D-aspartate receptor (NMDAR)-dependent neural plasticity in the spinal cord. OBJECTIVES: This study examined the effect of the non-competitive NMDAR antagonist dextromethorphan on partial sciatic nerve ligation (PSL)-induced neuropathic pain and the spinal expression of the glucocorticoid receptor (GR). METHODS: Male mice were randomly assigned into a sham group and two groups receiving PSL followed by intrathecal saline vehicle or dextromethorphan (iDMP). Vehicle or iDMP was administered 8 - 14 days after PSL. The hotplate paw-withdrawal latency was considered to measure thermal pain sensitivity. The spinal cord was then sectioned and immunostained for GR. RESULTS: Thermal hyperalgesia developed similarly in the vehicle and iDMP groups prior to the injections (P = 0.828 and 0.643); however, it was completely mitigated during the iDMP treatment (P < 0.001). GR expression was significantly higher in the vehicle group (55.64 ± 4.50) than in the other groups (P < 0.001). The iDMP group (9.99 ± 0.66) showed significantly higher GR expression than the sham group (6.30 ± 1.96) (P = 0.043). CONCLUSIONS: The suppression of PLS-induced thermal hyperalgesia by iDMP is associated with the downregulation of GR in the spinal cord, suggesting that this analgesic effect is mediated by inhibiting GR-regulated neuroinflammation.

A multivariate quantification of Box-Behnken design assisted method development and validation of dextromethorphan hydrobromide and desloratadine simultaneously by reverse-phase HPLC in in-house syrup formulation.

An innovative high-performance liquid chromatography assay method was developed and validated for quantification of dextromethorphan hydrobromide and desloratadine simultaneously in monophasic liquid formulation by preparing syrup containing 30 mg/5 mL of dextromethorphan hydrobromide and 1.2 mg/mL of desloratadine. The chromatographic severance was executed by gradient solution A and B. The composition of buffer solution A contained 0.05 M monobasic potassium, then 1 mL triethylamine was added to it and the pH was adjusted to 2.3 with orthophosphoric acid. Methanol was used as solution B. The gradient elution was executed with Kromasil C8 (250 mm × 4.6 mm) column having 1.5 mL/min flow rate and 20 µL injection volume with UV-estimation at 254 nm for dextromethorphan hydrobromide and DES. The present research was planned according to Box-Behnken design by utilizing design expert software, using four factors such as column temperature (A), flow rate (B), mobile phase-organic phase (C), and pH (D); correspondingly the selected response variables were resolution between A and B, that is, desloratadine and methyl paraben (Y1), tailing of dextromethorphan hydrobromide (Y2), and tailing of desloratadine (Y3). The parameters such as system suitability, linearity, accuracy, precision, robustness, limit of detection, limit of quantitation, and ruggedness were analyzed to validate the developed method in accordance with current regulatory guidelines.

Green HPTLC and stability-indicating RP-HPLC for the assay of dextromethorphan hydrobromide and menthol in their lozenges.

Two chromatographic methods were developed for the assay of the FDA approved lozenges containing dextromethorphan hydrobromide (DXT) and menthol (MNT). The first was a green HPTLC method which uses a mobile phase of methanol-ammonia (10:0.1, v/v). The densitometric measurements of the spots which were retained at 0.28±0.01 for DXT and 0.76±0.02 for MNT was done at 210nm. The other method was RP-HPLC method with stability indicating merits at which a mixture of 20mM phosphate buffer pH 3 and acetonitrile as mobile phase in isocratic mode was used. The cited drugs were resolved in RP-HPLC method using isocratic elution using 20mM phosphate buffer: acetonitrile (65:35 v/v) with retention times of 2.21 and 3.47min for MNT and DXT, respectively and quantified using 215nm. Both methods were entirely validated and both methods were successfully able to analyze both drugs in presence of lozenges inactive ingredients. HPLC method had the advantage of being stability indicating at which resolution of the drugs from their forced degradation products was successfully attained. For HPTLC method, both drugs showed reasonable RF values when compared to rapidly eluted MNT in RP-HPLC; also it was more environmentally friendly than RP-HPLC as it used solvents which are less toxic and greener.

Fabrication of a novel drug-resin combination device for controlled release of dextromethorphan hydrobromide.

The implimentation of newer technologies in drug delivery system have always been the focus of pharmaceutical scientists with advancement of technologies. In this investigation, a novel controlled-release drug-resin combination device (DRC) was designed using dental resin to control the release of dextromethorphan hydrobromide (DH). The influence of different factors on in-vitro drug release were investigated. A Box-Behnken design was used to select the optimized DRC formulation. The optimized DH loaded DRC (DH-DRC) was prepared using 59.88% of PEG400, 16 mg of dental resin and 6.64 mg of sodium chloride (NaCl). The DH releases at 2 h, 4 h and 8 h of the optimized formulation were significantly close to the predicted responses. The pharmacokinetic study in rabbits showed DH-DRC had prolonged tmax and apparently reduced Cmax compared with commercial tablets and the AUC0-24h of DH-DRC was slightly higher than commercial tablets. This study confirmed the novel DRC could control the release of drug. It concluded that DRC would be a promising and alternative approach for the development of controlled release dosage form.

Identification of pseudobulbar affect symptoms in the nursing home setting: Development and assessment of a screening tool.

Pseudobulbar Affect (PBA) is a neurologic condition characterized by involuntary outbursts of crying and/or laughing disproportionate to patient mood or social context. Although an estimated 9% of nursing home residents have symptoms suggestive of PBA, they are not routinely screened. Our goal was to develop an electronic screening tool based upon characteristics common to nursing home residents with PBA identified through medical record data. Nursing home residents with PBA treated with dextromethorphan hydrobromide/quinidine sulfate (n = 140) were compared to age-, gender-, and dementia-diagnosis-matched controls without PBA or treatment (n = 140). Comparative categories included diagnoses, medication use and symptom documentation. Using a multivariable regression and best decision rule analysis, we found PBA in nursing home residents was associated with chart documentation of uncontrollable crying, presence of a neurologic disorder (e.g., Parkinson's disease), or by the documented presence of at least 2 of the following: stroke, severe cognitive impairment, and schizophrenia. Based on these risk factors, an electronic screening tool was created.

Effect of wet mass on dextromethorphan hydrobromide matrix pellets

Dextromethorphan hydrobromide (DM) sustained release matrix pellets containing 10% w/w drug were prepared by an extrusion/spheronization technique. The effect of mixing different concentrations of ethyl cellulose (EC), hydroxypropyl methylcellulpse (HPMC K10), and Carbopol 934 with Avicel PH101 on the rheological properties of pellet wet mass was evaluated using mixer torque rheometry (MTR). The prepared pellets were characterized for size, drug content, and in-vitro DM release rate. The results showed that increasing the concentration of the hydrophobic polymer (EC) with Avicel PH101 decreased wet mass consistency, represented by mass mean line torque. Lower binder ratio was required for optimum wet massing, while mixing with swellable polymers (HPMC and Carbopol) caused a noticeable increase in both mean line torque and binder ratio. Combinations of HPMC and Carbopol at higher concentrations resulted in controlled in vitro release of DM from the prepared pellets. Furthermore, mathematical treatment of the in vitro release data of DM from the prepared pellets showed that all formulations except those containing 5% Carbopol plus 5% HPMC (F10) follow first order release. n values of these formulation were in the range of 0.09-0.40, which support an anomalous non-Fickian release.

Inducing rat brain CYP2D with nicotine increases the rate of codeine tolerance; predicting the rate of tolerance from acute analgesic response.

Repeated opioid administration produces analgesic tolerance, which may lead to dose escalation. Brain CYP2D metabolizes codeine to morphine, a bioactivation step required for codeine analgesia. Higher brain, but not liver, CYP2D is found in smokers and nicotine induces rat brain, but not liver, CYP2D expression and activity. Nicotine induction of rat brain CYP2D increases acute codeine conversion to morphine, and analgesia, however the role of brain CYP2D on the effects of repeated codeine exposure and tolerance is unknown. Rats were pretreated with nicotine (brain CYP2D inducer; 1mg/kg subcutaneously) or vehicle (saline; 1ml/kg subcutaneously). Codeine (40-60mg/kg oral-gavage) or morphine (20-30mg/kg oral-gavage) was administered daily and analgesia was assessed daily using the tail-flick reflex assay. Nicotine (versus saline) pretreatment increased acute codeine analgesia (1.32-fold change in AUC0-60min; p<0.05) and the rate of loss of peak analgesia (11.42%/day versus 4.20%; p<0.006) across the first four days of codeine administration (time to negligible analgesia). Inducing brain CYP2D with nicotine did not alter acute morphine analgesia (1.03-fold; p>0.8), or the rate of morphine tolerance (8.1%/day versus 7.6%; p>0.9). The rate of both codeine and morphine tolerance (loss in peak analgesia from day 1 to day 4) correlated with initial analgesic response on day 1 (R=0.97, p<001). Increasing brain CYP2D altered initial analgesia and subsequent rate of tolerance. Variation in an individual's initial response to analgesic (e.g. high initial dose, smoking) may affect the rate of tolerance, and thereby the risk for dose escalation and/or opioid dependence.

"Experimental study on ""dose-time-toxicity"" relationship of hepatotoxicity in mice with multiple administration of cold medicine containing acetaminophen and Chaiqin Qingning Capsules" / 药物评价研究

Objective To study the dose-time-toxicity relationship of hepatotoxicity in mice with multiple administration of Paracetamol Tablets (PT),Compound Paracetamol and Amantadine Hydrochloride Tablets (CPAH),Compound Dextromethorphan Hydrobromide Tablets (CDH),and Chaiqin Qingning capsules (CQC).Methods Mice were randomly divided into control,PT,CPAH,CDH,and CQC high,medium,and low dose groups.The acetaminophen contents of high,medium,and low doses were 266.24,425.98,and 681.57 mg/kg in PT,CPAH,and CDH groups,and the doses of CQC group were 1437.70,2300.31,and 3 680.50 mg/kg,ig administration,once daily for 5 d.General state and toxicity of mice were observed.The changes of ALT,AST,AKP,TBIL,and ALB levels in serum and organ indexes of liver,spleen,thymus,and kidney were tested on day 1,3,7,11,and 14 after multiple administration.Results CQC with the dosage range of 1 437.70-3 680.50 mg/kg to mice within 14 d,has not yet induced the increase of AST,ALT,AKP,TBIL,and ALB levels and changes of organ indexes of liver,thymus spleen,and kidney compared with normal control (P ＞ 0.05).PT,CPAH,and CDH with repeated dose of 425.98-681.57 mg/kg could induce significant increase of the levels ofALT,AST,AKP,and TBIL which reached the peak on day 1 (P ＜ 0.05),and then gradually decreased on day 3-14.The level of ALB significant decreased on day 1-11 (P ＜ 0.05),and then gradually recovered on day 11-14.The liver index significant increased on day 1-3 (P ＜ 0.05),and recovered on day 7-14.Conclusion Multiple administration of CQC could not induce liver injury in mice within 14 d,while multiple administration ofPT,CPAH,and CDH could induce hepatotocixity in mice with a certain dose,and show an obvious dose-time-toxicity relationship.

"Experimental study on ""Dosage-Time-Toxicity"" relationship of hepatotoxicity induced by cold medicine containing acetaminophen and Chaiqin Qingning Capsules with single administration in mice" / 药物评价研究

Objective To study the time-toxicity and dose-toxicity relationship of hepatotoxicity induced by Paracetamol Tablets (PT),Compound Paracetamol and Amantadine Hydrochloride Tablets (CPAH),Compound Dextromethorphan Hydrobromide Tablets (CDH),and Chaiqin Qingning Capsules (CQC) with single dose in mice.Methods In the Time-Toxicity relationship study,Kunming mice were randomly divided into control,PT,CPAH,CDH,and CQC group,and mice of.each drug administration group were randomly divided into nine subgroups according to the time (1,2,4,8,12,24,48,72 and 96 h after administration) of blood collection.The acetaminophen contents in PT,CPAH,and CDH groups were 425.98 mg/kg,and the dose of CQC group was 3 680.50 mg/kg.In the Dosage-Time relationship study,mice were randomly divided into control,PT,CPAH,CDH,and CQC high,medium and low dose group.The acetaminophen contents of high,medium,and low dose were 266.24,425.98,and 681.57 mg/kg in PT,CPAH,and CDH group,and the dose of CQC group was 1437.70,2300.31,and 3680.50 mg/kg,10 mice in each group,sex in half.Blood was collected 12 h after administration.Animal behavior was observed every day,blood and organs were collected at the corresponding time points,serum alanine aminotransferase (ALT),aspartate aminotransferase (AST),and alkaline phosphatase (ALP) level were detected,and the organs index of spleen and thymus,liver were calculated.Results There were no significant changes of ALT,AST,ALP,and organs index after once ig administration of CQC at dosage of 1437.70 mg/kg to 3680.50 mg/kg in mice.The study on time-toxicity relationship indicated that,after once administration of PT,CPAH,and CDH at 425.98 mg/kg,mice showed toxic symptom such as hypokinesia,dry hair and so on,12 h was the most obvious,24 ～ 72 h disappeared.The level of ALT,AST,and ALP in serum increased and reached to the peak at 12 h and then restored near normality after 72,24,and 24 h in PT,CPAH,and CDH group.Their organ index of liver,spleen and thymus all had no significant changes.The study on the dosage-toxicity relationship indicated that,there were no significant changes of animal behavior,ALT,AST,ALP,and organs index after once ig administration of PT,CPAH,and CDH at 266.24 mg/kg.Obvious liver injury can be induced by the three drugs with dosage of 425.98 to 681.57 mg/kg and the level of ALT,AST,and ALP increased significantly with the increase of dosage.Their liver index increased significantly with dosage of 681.57 mg/kg,but the organs index of spleen,thymus had no significant changes.Conclusion There was no hepatotoxicity after once ig administration of CQC with dosage of 3680.50 mg/kg in mice.Mice were once ig administration ofPT,CPAH,and CDH with a large dose,may induce acute liver injury and show obvious time-toxicity and dose-toxicity relationships.

Antipyretic effects of Paracetamol Tablets, Compound Paracetamol and Amantadine Hydrochloride Tablets, Compound Dextromethorphan Hydrobromide Tablets, and Chaiqin Qingning capsules on rat model with LPS and dry yeast induced fever / 药物评价研究

Objective To study the antipyretic effect of Paracetamol Tablets,Compound Paracetamol and Amantadine Hydrochloride Tablets,Compound Dextromethorphan Hydrobromide Tablets,and Chaiqin Qingning Capsules on the fever model induced by LPS and dry yeast in rats.Methods Fever was induced by ip injecting LPS (100 μg/kg) or sc injecting dry yeast (20％) in rats.We observed the changes of temperature of the rats after administration of Paracetamol Tablets,Compound Paracetamol and Amantadine Hydrochloride Tablets,Compound Dextromethorphan Hydrobromide Tablets (the acetaminophen contents were 205.67,102.83,and 51.42 mg/kg)and Chaiqin Qingning Capsules (1110.60,555.30,and 277.65 mg/kg).Maximum temperature rise height (△T) and temperature response index (TRI) were calculated,and the curve of average rise in temperature was drawn.Results Each dose group of Paracetamol Tablets,Compound Paracetamol and Amantadine Hydrochloride Tablets,Compound Dextromethorphan Hydrobromide Tablets,and Chaiqin Qingning Capsules had obvious antipyretic effect on the fever model induced by LPS and dry yeast in rats,and there was a certain dose-effect relationship.Conclusion Paracetamol Tablets,Compound Paracetamol and Amantadine Hydrochloride Tablets,Compound Dextromethorphan Hydrobromide Tablets,and Chaiqin Qingning Capsules has certain antipyretic effect on LPS and dry yeast fever model in rats,and on the whole,the Western medicine acts rapid but continue for a short time,while the traditional Chinese medicine acts slow but continues for a long time.

Determination of Two Components and Preservative in Compound Dextromethorphan Hydrobromide Syr-ups by HPLC / 中国药师

Objective:To establish an HPLC method for the determination of two components and the preservative in compound dextromethorphan hydrobromide syrups. Methods:An Agilent Zobax SB-C18 column(250 mm × 4. 6 mm,5 μm) was used with meth-anesulfonic acid solution (adding 4. 8g methanesulfonic acid and 10ml triethylamine into 750ml water,and adjusting the pH value to 3. 5 by phosphoric acid)-acetonitrile (75∶25) as the mobile phase at the flow rate of 1. 0 ml·min-1 and 280nm as the detection wave-length. Results:The calibration curve was linear within the range of 102-1 025μg·ml-1 for guaifenesin,15-619μg ·ml-1 for dextro-methorphan hydrobromide and 10-407μg·ml-1 for benzoic acid. The average recovery of guaifenesin, dextromethorphan hydrobromide and benzoic acid was 100. 0% (RSD=0. 35%), 100. 1%(RSD=0. 77%)and 100. 8%(RSD=0. 49%), respectively. Conclusion:The method is simple,rapid and accurate,and suitable for the quality assessment of compound dextromethorphan hydrobromide syrups.

Quantization of Dextromethorphan and Levocetirizine in Combined Dosage form Using a Novel Validated RP-HPLC Method.

The present study reveals a simple isocratic RP-HPLC method for the simultaneous determination of dextromethorphan hydrobromide and levocetirizine dihydrochloride in a cough syrup. The separation of these compounds was achieved within 10 min on a Phenomenex (USA) C(18) analytical column, 250×4.0 mm i.d., using an isocratic mobile phase consisting of potassium dihydrogen phosphate buffer (pH 2.5) - acetonitrile- tetrahydrofuran (70:25:5, v/v/v). The analysis was performed at a flow rate of 1.2 ml/min and at a detection wavelength of 232 nm. Percentage recovery and RSD were 100.36% and 0.05% for levocetirizine dihydrochloride, 100.35% and 0.27% for dextromethorphan hydrobromide respectively. Quantification of the components in syrup formulation was calculated against the peak areas of freshly prepared standard solutions. The method was validated as per ICH guidelines.

Normal-phase LC method for simultaneous analysis of pseudophedrine hydrochloride, dextromethorphan hydrobromide, chlorpheniramine maleate, and paracetamol in tablet formulations.

A simple, precise, and accurate method is developed and validated for the analysis of pseudophedrine hydrochloride, dextromethorphan hydrobromide, chlorpheniramine maleate, and paracetamol in tablet formulations. The method has shown adequate separation of the four ingredients from each other. Separation was achieved on a silica column (5 µm, 125 × 4.6 mm inner diameter) using a mobile phase consisting of methanol/ammonium dihydrogen phosphate buffer (90:10, v/v) at a flow rate of 1.0 ml/min and UV detection at 220 nm. This new method is validated in accordance with USP requirements for new methods for assay determination, which include accuracy, precision, selectivity, linearity and range, robustness and ruggedness. The current method demonstrates good linearity over the range of 0.15-0.45 mg/ml of pseudophedrine hydrochloride with r (2) of 0.996, and in the range of 0.075-0.225 mg/ml of dextromethorphan hydrobromide with r (2) of 0.992, and in the range of 0.01-0.03 mg/ml of chlorpheniramine maleate with r (2) of 0.994, and in the range of 0.25-0.75 mg/ml of paracetamol with r (2) of 0.991. The average recovery of the method is 99.7%, 98.6%, 98.1%, and 99.2% for pseudophedrine hydrochloride, dextromethorphan hydrobromide, chlorpheniramine maleate, and paracetamol, respectively. The degree of reproducibility of the results obtained as a result of small deliberate variations in the method parameters and by changing analytical operator has proven that the method is robust and rugged.

Optimization of the Formulation of Dextromethorphan Hydrobromide Sustained-release Tablets by Orthogonal Test / 中国药房

OBJECTIVE:To optimize the formulation of dextromethorphan hydrobromide sustained-release tablets. METHODS: The dextromethorphan hydrobromide sustained-release tablets were prepared with HPMC as sustained release matrix. Orthogonal test was performed to optimize the formulation with in vitro accumulative drug release rate as index and the amount of HPMC and lactose as well as ethylcellulose (EC) concentration as factors. Then verification test on the in vitro drug release characteristics of the optimized tablets were performed and the influencing factors (high temperature,high light,and high moisture) were investigated as well. RESULTS: The optimized formulation of dextromethorphan hydrobromide sustained-release tablets was as follows: 30 mg HPMC,50 mg lactose,and 8% EC. The accumulative drug release rate at 8 h was above 70%. In the influencing factor test,the tablets were stable under all conditions except at high moisture condition. CONCLUSION: The optimized formulation of dextromethorphan hydrobromide sustained-release tablets is feasible.

Determination of Concentration of Dextromethorphan Hydrobromide in Human Serum by HPLC / 中国药房

OBJECTIVE:To establish a HPLC method for determination of concentration of dextromethorphan hydrobro?mide in human serum.METHODS:The assay was conducted on HiQsil C 18 column(4.6mm?150mm,5?m)with acetonitrile-water-acetic acid(35∶63∶2,V/V/V)as mobile phase.The fluorescence detector measured with the excitation wavelength of280nm and the emission wavelength of320nm,and carvedilol was taken as internal standard.RESULTS:The linear range of calibration curve of dextromethorphan hydrobromide was0.27～21.90ng/ml with a regressive equation of Y=0.1197X+0.0086,r=0.9986.The recovery was high.CONCLUSION:This method is accurate,rapid and simple,and can be used for de?termining the concentration of dextromethorphan hydrobromide in human serum.