Diphenhydramine Research Articles

Design of a Stable Coamorphous System Using Lactose as an Antiplasticizing Agent for Diphenhydramine Hydrochloride with a Low Glass Transition Temperature.

Coamorphous systems comprising small molecules are emerging as counterparts to polymeric solid dispersions. However, the glass transition temperatures (Tgs) of coamorphous materials are relatively low because of the lack of polymeric carriers with higher Tgs. This study aimed to investigate the applicability of lactose (LAC) as an antiplasticizing coformer to a coamorphous system. Diphenhydramine hydrochloride (DPH) was selected as a model drug (Tg = 16 °C). Differential scanning calorimetry showed a comelting point in addition to a decrease in the neat melting points depending on the composition of the physical mixtures, suggesting that the mixture of DPH-LAC was eutectic. The melting point of the eutectic mixture was calculated according to the Schröder-van Laar equation. The heat of fusion of the eutectic mixture was maximized at a 70:30 molar ratio of DPH to LAC; at this point, the melting peaks of the pure components disappeared. The heat flow profiles following the melting and cooling of DPH-LAC physical mixtures at the ratios from 10:90 to 90:10 showed a single Tg, suggesting the formation of a coamorphous system. Lactose showed a Tg of over 100 °C, and the Tg of DPH increased with the molar ratio of LAC; it was 84 °C at a 10:90 molar ratio of DPH to LAC. The Raman image indicated the formation of a homogeneous dispersion of DPH and LAC in the coamorphous system. Peak shifts in the infrared spectra indicated the presence of intermolecular interactions between the amino group of DPH and the hydroxyl group of LAC. Principal component analysis of the infrared spectra revealed a significant change at the 70:30 molar ratio of DPH to LAC, which was in agreement with the results of the thermal analysis. A stability test at 40 °C revealed rapid crystallization of the supercooled liquid DPH. The coamorphous samples containing 10-50% of LAC remained in an amorphous state for 21 days, and no crystallization was observed for the samples containing >60% of LAC for 28 days. The relatively lower Tg (less than 40 °C) of the coamorphous system containing 10-50% of LAC might have caused crystallization during storage. These findings indicate that LAC, which is a safe and widely used pharmaceutical excipient, can be applied to coamorphous systems as an antiplasticizing coformer.

Sustainable liquid chromatographic determination and purity assessment of a possible add-on triple-action over-the-counter pharmaceutical combination in COVID-19

Nowadays, all researchers are focused on combating the pandemic COVID-19. According to recent statistics, most patients are managed at home. An over-the-counter (OTC) triple action formula containing paracetamol (PAR), aspirin (ASP), and diphenhydramine (DIPH) is widely prescribed for pain, fever and as night-time sleep aid. For COVID-19 patients, this combination is now suggested as part of symptomatic therapy and prophylaxis. In this work, two simple liquid chromatographic approaches were designed for simultaneous determination of PAR, ASP, and DIPH in Excedrin® PM caplets, beside three specified official toxic impurities, namely, p-aminophenol, p-nitrophenol, and salicylic acid. The first method comprised high-performance thin-layer chromatographic separation coupled with densitometric quantification, on silica gel HPTLC 60 F254 aluminium sheets as the stationary phase, ethyl acetate–methanol-aqueous ammonium hydroxide (10.0: 2.0: 0.1, by volume) as the developing system and scanning was performed at 210.0 nm. The second one is a high-performance liquid chromatography coupled with diode array detector. Successful separation of the six components was performed on XTerra C18 column with isocratic elution of mobile phase 0.1% triethylamine acidified water: methanol (70:30, v/v) adjusted with o-phosphoric acid to pH 3.0 and methanol (90:10, v/v) with flow rate programming and detection at 210.0 nm. Validation of the proposed methods was performed according to ICH guidelines. Both methods were successfully used for quality control of the cited drugs in their marketed formulation. Moreover, the in-vitro release study was monitored using the proposed HPLC-DAD method. The greenness profile of the proposed methods was assessed and comparatively evaluated through various assessment tools, specifically; the analytical eco-scale system, national environmental method index (NEMI), green analytical procedure index (GAPI) and analytical greenness (AGREE) metric.

A Case Of Diphenhydramine With Alcohol Induced Rhabdomyolysis

Rhabdomyolysis is muscle necrosis and the release of intracellular muscle components into circulation. Approximately 26,000 cases of rhabdomyolysis are reported annually in the United States. The severity varies greatly from asymptomatic individuals to individuals with life-threatening muscle enzyme elevations along with severe electrolyte abnormalities, acute other organ damage, and compartment syndrome. The mortality rates are as high as 59% in critically ill patients. There are multiple causes of rhabdomyolysis that can be classified as traumatic or non-traumatic. The traumatic cases are usually evident at presentation however, in a non-traumatic setting, the presentation may be misleading. In this specific case report, we discuss a case of rhabdomyolysis with shock liver and acute kidney injury in a 23-year-old male that presented with complaints of back pain and blood in his urine following the recreational use of alcohol and diphenhydramine. Given the frequent use and easy accessibility of both alcohol and diphenhydramine (DPH), it is crucial to be aware of the potential risk of rhabdomyolysis as early recognition and treatment can prevent life-threatening complications.

Formulation and Evaluation of Film Forming Solution of Diphenhydramine Hydrochloride for Transdermal Delivery

Abstract: Aim: The present work intends to formulate and evaluate film forming solution of diphenhydramine. Materials and Methods: Film forming solutions (FFS) for transdermal delivery of Diphenhydramine HCl were prepared using different polymers (hydroxypropyl cellulose, Eudragit L 100, polyvinylpyrollidone K30 and polyvinylpyrollidone K90), PEG 400 as plasticizer and ethyl alcohol as solvent. Results: The film forming solutions were found to display an acceptable drying time ranging from 2 to 5 min. In-vitro release studies indicated percentage drug released by the end of 8 h from FFS of HPC-EF, Eudragit L 100 and PVP K 30 was found to be 41.31 ± 2.1%, 14.81 ± 1.2 % and 25.7 ± 1.9 % respectively. FFS of HPC-EF that readily released drug were considered for further development by incorporating penetration enhancers like azone, isopropyl myristate and oleic acid. Steady state flux of drug across shed snake skin used as a barrier in vertical Franz diffusion cell was found to be 42.27 ±3.5 mg/cm2/hr, 51.18 ±4.9 mg/cm2/hr and 57.91 ± 7.2 mg/cm2/hr for FFS containing isopropyl myristate, oleic acid and azone as permeation enhancers respectively. Conclusion: Considering the plasma clearance of the drug and transdermal steady state flux, it can be inferred that FFS containing azone as enhancer needs to be spread across an application area of 0.5 cm2 to elicit a therapeutic response. Key words: Film forming solution, Diphenhydramine HCl, Antihistamine, Transdermal delivery, Shed snake skin.

Nedocromil sodium and diphenhydramine HCl ameliorate exercise-induced arterial hypoxemia in highly trained athletes.

IntroductionExercise‐induced arterial hypoxemia (EIAH) has been observed in highly trained endurance athletes during near maximal exercise, which may be influenced by a histamine‐mediated inflammatory response at the pulmonary capillary‐alveolar membrane. In order to test this hypothesis, we examined whether the mast cell stabilizer nedocromil sodium (NS) and H1‐receptor antagonist diphenhydramine HCL (DH) would ameliorate EIAH and mitigate the drop in arterial oxyhemoglobin saturation (SaO2) during intensive exercise.MethodsSeven highly trained male cross country runners (age, 21 ± 2 years; V̇O2max, 74.7 ± 3.5 ml·kg−1·min−1) participated in the study. All subjects completed a maximal exercise treadmill test to exhaustion, followed by three 5‐min constant‐load exercise bouts at 70%, 80%, and 90% V̇O2max. Prior to testing, subjects received either placebo (PL), NS, or DH.ResultsCompared to PL, there was a significant treatment effect on SaO2 (p < 0.001) for both NS and DH during both constant‐load exercise and at V̇O2max. Post hoc tests revealed SaO2 values, compared to PL, were significantly higher at V̇O2max and during DH trials and higher with NS at constant‐load intensities except at 70% (p = 0.13).ConclusionThe findings provide further evidence that histamine contributes directly or indirectly to the development of EIAH during intense exercise in highly trained athletes.

A Gas Chromatography Flame Ionization Detector Method for Rapid Simultaneous Separation and Determination of Six Active Ingredients of Anticold Drug

Aims:To establish a rapid and simultaneous determination of multiple effective ingredients in anti-cold drugs.Background:Anti-cold drugs are stock medicines at home, and most anti-cold formulations are compound preparations. Although the active ingredients of compound preparations have significant effects on the treatment of colds, the excessive dosage or long-term use can produce a series of adverse reactions, including dependence, liver and kidney function damage, digestive system reaction, blood system damage. Now, there are many mature methods for analyzing the active ingredients of anti-cold drugs. However, these methods may have shortcomings, such as a long analysis time or a small number of analysis components.Objective:Establish a gas chromatography-flame ionization detector method for the simultaneous determination of six active ingredients, including acetaminophen, dextromethorphan hydrobromide, pseudoephedrine hydrochloride, chlorpheniramine maleate, diphenhydramine hydrochloride, and caffeine in anti-cold drugs.Method:After the standard was accurately weighed, dissolved in ethanol, filtered by 0.22 μm membrane and ultrasonically degassed, the gas chromatograph was used for detection. After the actual sample was removed from the coating, ground and crushed, accurately weighed, dissolved in ethanol, filtered by 0.22 μm membrane and ultrasonically degassed, the gas chromatograph was used for detection.Result:The six components can be completely separated within 7.0min. This method has good sensitivity, precision, accuracy and recovery rate. Under the optimum testing conditions, the limit of detection was 0.360-2.50μg/mL, the limit of quantification was 1.20-8.30μg/mL. The calibration curves showed good linearity (R2≥0.9932) over the investigated concentration range between 1.20 and 400μg/mL. The recoveries were 89.2% to 109.2%. The RSD of intra-day precision was less than 1.0%. The RSD of inter-day precision was less than 3.2%. The established method was used to determine the ingredients of three anti-cold drugs on the market, and the results showed that the method can accurately determine the ingredients.Conclusion:The method can quickly and simultaneously determine multiple active ingredients in anti-cold medicines. Compared with the published methods in literature, the proposed method has the advantages of fast, the number of analysis components wide application range, convenience, low cost, etc. It provides a reference method for quality control of active ingredients of anti-cold drugs.

Ibuprofen And Diphenhydramine Citrate Related Substances In Tablet Dosage Form May Be Determined Simultaneously Using A Reversed-Phase High-Performance Liquid Chromatographic Technique

Ibuprofen and diphenhydramine citrate have been combined into one dosage form, and a novel graded reverse-phase elevated HPLC technology has been created for the simultaneous detection of related chemicals in this dosage form. This technique is also capable of detecting degradation products and impurities associated with the manufacturing process. The approach involved the utilization of a C18 column and a mobile phase composed of a gradient mixture of solvent A and B. Moreover, this method is well-suited for the determination of the assay of citrate versions of ibuprofen and diphenhydramine from pharmaceutical sources. Furthermore, the technique is stability-indicating, indicating its suitability for evaluating the shelf-life of pharmaceutical products.

The Use of Over-the-Counter Sleep Aid Containing Diphenhydramine Hydrochloride Among Saudis.

BackgroundDiphenhydramine is a first-generation H1 receptor antihistamine that is usually used for the treatment of allergy, insect bites such as mosquitos, bee stings, and some types of skin rashes. However, it possesses antiparkinsonian, antitussive, antiemetic, and most importantly hypnotic properties. This study aimed to assess the prevalence, frequency of use, and dosage of over-the-counter (OTC) sleep aid containing diphenhydramine hydrochloride used among Saudis.Material and MethodsThe study used a descriptive cross-sectional design conducted among the Saudi population. An online self-administered questionnaire was distributed among the selected Saudi nationality using social media platforms. The subjects included were Saudis aged 15 years or older, literate in using social media. The questionnaire included basic demographic characteristics, previous and current history of medication use that contains diphenhydramine hydrochloride, its side effects, and other related behavior of using, such as frequency of use and dosage.ResultsA total of 414 respondents were recruited (51% males and 49% females). Previous and current use of medications that contain diphenhydramine hydrochloride constituted 87.2% and 31.9%, respectively. The most common reason for using sleep aid was insomnia (52.1%). Dizziness or imbalance was the most commonly reported side effect. The Chi-square test revealed that the age group of ≤25 years (p = 0.044), female gender (p = 0.040), being a student (p = 0.015), current use of sleeping aid medications (p < 0.001), and the use of other medications (p < 0.001) were significantly associated with increased use of sleep aid medications.ConclusionThe excessive use of over-the-counter (OTC) sleep aid medications containing diphenhydramine hydrochloride was widely prevalent among the Saudi population. Younger female students constitute the majority of OTC sleep aid medication users.

Synthesis of aqueous media stable MIL101-OH/chitosan for diphenhydramine and metronidazole adsorption.

In this study, pristine MIL101(Cr) was modified to synthesize hydroxyl-functionalized (MIL101(Cr)-OH) and chitosan (CS)-coated (MIL101(Cr)-OH/CS) metal-organic frameworks (MOFs) to enhance adsorption capacity and reusability, respectively. The synthesized adsorbents were characterized by XRD, FTIR, and BET analyses. The kinetics behavior and the equilibrium adsorption of diphenhydramine (DPH) and metronidazole (MNZ) from aqueous solution on the synthesized adsorbents and a commercial activated carbon were compared at 25°C. The pH-dependent of the adsorption capacity and reusability of MIL101-OH/CS were investigated. The results showed that upon adding OH functional group and chitosan polymer, the adsorption capacity increased; the DPH adsorption capacity on MIL101-OH and MIL101-OH/CS was 634 and 573 mg/g, respectively. Also, the maximum adsorption capacity of MNZ on MIL101-OH/CS was 600 mg/g, which was twice the adsorption capacity of MIL101 and four times the adsorption capacity of the commercial activated carbon. The equilibrium and kinetics behavior results were in good agreement with Langmuir and the pseudo-second-order models, respectively. The DPH and MNZ adsorption mechanisms on MIL101-OH/CS were hydrogen bonding and electrostatic interactions, respectively.

Mechanical Learning for Prediction of Sepsis-Associated Encephalopathy.

Objective: The study aims to develop a mechanical learning model as a predictive model for predicting the appearance of sepsis-associated encephalopathy (SAE).Materials and Methods: The prediction model was developed in a primary cohort of 2,028 sepsis patients from June 2001 to October 2012, retrieved from the Medical Information Mart for Intensive Care (MIMIC III) database. Least absolute shrinkage and selection operator (LASSO) regression model was used for data dimension reduction and feature selection. The model was developed using multivariable logistic regression analysis. The performance of the nomogram has been evaluated in terms of calibration, discrimination, and clinical utility.Results: There were nine particular features in septic patients that were significantly associated with SAE. Predictors of individualized prediction nomograms included age, rapid sequential evaluation of organ failure (qSOFA), and drugs including carbapenem antibiotics, quinolone antibiotics, steroids, midazolam, H2-antagonist, diphenhydramine hydrochloride, and heparin sodium injection. The area under the curve (AUC) was 0.743, indicating good discrimination. The prediction model showed calibration curves with minor deviations from the ideal predictions. Decision curve analysis (DCA) suggested that the nomogram was clinically useful.Conclusion: We propose a nomogram for the individualized prediction of SAE with satisfactory performance and clinical utility, which could aid the clinician in the early detection and management of SAE.

UHPLC-MS/MS Method for Quantifying Fangchinoline, Tetrandrine and Calycosin-7-O-β-D-Glucoside of Fangji Huangqi Decoction in Rat Plasma and Its Application to a Pharmacokinetic Study.

Fangji Huangqi Decoction is composed of Stephaniae Tetrandrae Radix, Astragli Radix, Atractylodis Macrocephalae Rhizoma and Glycyrrhizae Radix Et Rhizoma. It is a classic traditional Chinese medicine formula for the treatment of chronic glomerulonephritis in China. However, its pharmacokinetic characteristics in vivo are still unclear. In this study, a method for quantifying fangchinoline, tetrandrine and calycosin-7-O-β-D-glucoside, the main active constituents of Fangji Huangqi Decoction, in rat plasma by using ultrahigh-performance liquid chromatography-tandem mass spectrometry technique was developed. Plasma samples were processed with a deproteinization procedure using acetonitrile, followed by chromatographic separation on a Shim-pack XR-ODS C18 column using gradient elution of 0.1% aqueous formic acid and acetonitrile at 0.4mL/min. The analytes and internal standard, diphenhydramine hydrochloride, were detected using positive electrospray ionization in multiple reactions monitoring mode. The optimized mass transition ion-pairs (m/z) were 609.3/367.3 for fangchinoline, 623.3/174.3 for tetrandrine, 447.2/285.1 for calycosin-7-O-β-D-glucoside and 256.2/167.1 for diphenhydramine hydrochloride, respectively. The developed method was validated for intraday and interday precision and accuracy whose values fell in the acceptable limits. Recovery efficiency of all the analytes was found to be >90.5%. Matrix effect was found to be negligible. Stability results showed that the analytes were stable under all conditions. The validated method was successfully used for studying the pharmacokinetics of the three compounds in rat plasma after oral administration of Fangji Huangqi Decoction.

Utilization of amphiphilic antihistamines drugs to enhance micellization of anionic surfactant and improve the binding and solubility of Itraconazole drug

Many salt-based medicines are used in pharmaceutical formulations as active components. Excipients performance can be improved by using these medicines. The use of amphiphilic antihistamine medications (diphenhydramine hydrochloride (DPC) and cetirizine hydrochloride (CTZ)) to improve sodium dodecylbenzene sulfonate (SDBS) micellization is demonstrated in this work. DPC/CTZ considerably lowered the critical micelle concentration (CMC) of SDBS in aqueous media by measuring conductivity. SDBS micelles demonstrated a greater electrostatic interaction with CTZ than DPC micelles, based on counterion binding (βc and B) and binding constant (Kb) values. The DPC/CTZ mean ion occupancy (i0) per SDBS micelle was also calculated using the UV spectroscopy experiment. For SDBS micelles, we observed that DPC and CTZ had i0 values of 1.700 and 2.622, respectively. The electrostatic interaction between the medication and the surfactants was shown to be controlling the i0 levels. The medicine Itraconazole (ITZ), which is poorly water-soluble, was found to be more soluble in SDBS micelles containing CTZ than in DPC combinations. At 0.002 mol L-1 in the aqueous medium, the greatest i0 values of ITZ were 185 in SDBS + DPC and 203 in SDBS + CTZ. The CMC and the binding behaviour of drug-micelles were found to be critical determinants in controlling ITZ drug solubilization. Finally, we concluded that the above formulation might be used in the pharmaceutical industry to improve multi-drug delivery systems.

AGITATED, ALTERED, AND ELONGATED: THE RISKS OF DIPHENHYDRAMINE OVERDOSE

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: Overdose has become a leading cause of injury-related death in the United States. Rapid recognition of a toxidrome is vital in determining management. CASE PRESENTATION: A young, unknown female was brought to the ED after being found agitated and combative. Evaluation was notable for tachycardia, mydriasis and diaphoresis. She received intramuscular diphenhydramine (DPH), haloperidol and lorazepam for agitation.She developed a wide QRS complex with polymorphic ventricular tachycardia (VT) concerning for Torsades de pointes, terminated by precordial thump. She was intubated for airway protection. Magnesium and sodium bicarbonate (NaHCO) pushes were administered for sustained monomorphic VT with return to sinus tachycardia. Electrocardiogram was significant for prolonged QTc of 607ms and QRS >150ms. Initial toxicology was negative for acetaminophen, salicylate and ethanol.NaHCO infusion with goal pH 7.5 to maintain a narrow QRS was started. She had persistently prolonged QT interval. Overdrive transcutaneous pacing was unsuccessful, so isoproterenol (IPN) infusion was started. NaHCO and IPN infusions were discontinued at 48 hours with no further arrhythmias. Extended toxicology screen was positive for DPH. On extubation, she endorsed consumption of >1.25g DPH. DISCUSSION: Classic anticholinergic symptoms of tachycardia, mydriasis and delirium are also the toxidrome for DPH overdose. Severe toxicity is observed after ingestion of >1.0g (1). Cardiac toxicity is exhibited as widening of QRS and QTc intervals (1-3). Similar to TCA overdose, QRS widening is manifested from blockade of the fast-closing myocardial sodium channels (2-3). Treatment for QRS widening with NaHCO is anecdotally recommended (2-3). In this case, bolus and infusion of NaHCO successfully shortened the patient's QRS duration. One case report suggested using lipid emulsion therapy(3); however, DPH intoxication was not suspected initially thereby limiting its use. Since presenting symptoms of DPH and anticholinergic toxicity overlap, physostigmine must be avoided due to QRS prolonging effects (2). This case reminds of cautious administration of the "B52" cocktail for agitated patients. The use of intravenous DPH, haloperidol and lorazepam can be used to calm acutely agitated or aggressive patients; yet, it should be avoided with unknown ingestions.Further, QT prolongation and polymorphic VT can result from DPH's ability to weakly block the delayed rectifier potassium channels (2). Traditionally resolving this includes overdrive pacing and magnesium supplementation, which were administered in this case. However, failed overdrive transcutaneous pacing led to IPN infusion to induce tachycardia-associated QTc shortening. CONCLUSIONS: High suspicion and familiarity with toxidromes can lead to early diagnosis and intervention for critically ill patients presenting with agitated altered mental status. REFERENCE #1: Radovanovic D, Meier PJ, Guirguis M, Lorent JP, Kupferschmidt H. Dose-dependent toxicity of diphenhydramine overdose. Hum Exp Toxicol. 2000 Sep;19(9):489-95. doi: 10.1191/096032700671040438 REFERENCE #2: Jang DH, Manini AF, Trueger NS, et al. Status epilepticus and wide-complex tachycardia secondary to diphenhydramine overdose. Clin Toxicol (Phila). 2010;48(9):945-948. doi:10.3109/15563650.2010.527850 REFERENCE #3: Abdi A, Rose E, Levine M. Diphenhydramine overdose with intraventricular conduction delay treated with hypertonic sodium bicarbonate and i.v. lipid emulsion. West J Emerg Med. 2014;15(7):855-858. doi:10.5811/westjem.2014.8.23407 DISCLOSURES: No relevant relationships by Joy Ayyoub, source=Web Response No relevant relationships by Lauren Catalano, source=Web Response No relevant relationships by Sydney Emerson, source=Web Response No relevant relationships by Shahrzad Zonoozi, source=Web Response

The pharmacokinetic study on compound diphenhydramine hydrochloride and caffeine in rats

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 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.

Studies on molecular interactions of l-histidine/l-serine in aqueous diphenhydramine hydrochloride solutions at various temperatures: Volumetric, ultrasonic and viscometric approach

Thermophysical properties for varying concentrations of essential (L-histidine) and non-essential (L-serine) amino acids in water and (0.05–0.15) mol kg−1 mixed aqueous diphenhydramine hydrochloride solvent system has been deliberated at different temperatures ranging (293.15−318.15) K and ambient pressure (101.3 kPa). The experimentally obtained data has been utilized to compute different volumetric, compressibility and rheological parameters such as apparent molar volume (Vϕ), partial molar volume (V0ф), partial molar expansibility (E0ϕ), apparent molar isentropic compression (Kϕ,s), partial molar isentropic compression (K0ϕ,s), hydration number (nH), transfer parameters, viscosity coefficients etc. The structure breaking ability of the solute molecules has been comprehended using Hepler′s constant (temperature derivative of partial molar expansibility at constant pressure) and dB/dT (temperature derivative of viscosity B-coefficient) values. Further, by using the co-sphere overlap model various sorts of solute-drug interactions prevailing in the systems have been discussed.

Volumetric, compressibility and viscometric properties of diphenhydramine hydrochloride in aqueous solutions of electrolytes: An insight into interactional characteristics

The density (ρ), speeds of sound (u), and viscosity (η) measurements for diphenhydramine hydrochloride (anti histaminic drug) in aqueous solutions of different electrolytes (NaCl, KCl, RbCl, MgCl2, CaCl2 and SrCl2) have been carried out. Volumetric and compressibility properties of aqueous drug solution containing electrolyte have been explained on the basis of trends observed in different enumerated parameters and information regarding various solute–solvent interactions prevailing in the ternary system have been accessed. The effect of drug concentration and temperature on the interactional behaviour of the considered system has been analyzed by carrying out the experiments at different drug content (0.03–0.17 mmol.kg−1) and temperatures (298.15–313.15) K at definite interval of 5 K. The participation of specific as well as non-specific interactions between diphenhydramine hydrochloride (DPH) and electrolytes in aqueous solution has been found to play its role in stabilization of solution mixture. Further, the structural changes induced by drug molecules in solution containing different electrolytes with same concentration have been illustrated with the help of viscosity studies. The results obtained from different employed studies have been used to elucidate solute/solvent–solvent/solute interactions in aqueous electrolytic solution. As electrolytes are integral part of biological system, hence, the study of such systems may be very useful in understanding the mechanism of drug action that ultimately facilitates the illustration of drug – electrolyte chemistry.

Formulasi dan Evaluasi Floating System Tablet Difenhidramin HCl Menggunakan Kombinasi Matriks HPMC K4M dan Na. CMC

A floating system tablet was made using HPMC K4M and Na matrices. CMC with the active substance diphenhydramine HCl, which absorption in the stomach. The research aims to determine the effect of a combination of HPMC K4M and Na. CMC matrices are optimal in a floating system formulation. This research used an experimental method with a RAL design. Tablets were made by direct compression and were evaluated. The results were then analyzed statistically using One Way ANOVA. The loss results on the drying test, the tapped density test, and the measurement of the angle of repose of all formulations met the requirements. The powder flow rates of all formulations did not meet the requirements. The resulting tablet is white, bitter, round, and smells of medicine. Tablets in all formulations have uniform weight according to requirements. The hardness test results showed that only formulation 3 met the requirements, while all formulations did not meet the requirements in the friability test. In the lag time test, the results obtained in formulation 1 and formulation 2, formulation 3, and formulation 4 are 4 seconds, 4 seconds, 3 seconds, and 1 second. In contrast, the floating time results show that all formulations can float for 24 hours. All evaluation results indicate that the optimal formulation in formulation 3.

Personalised Tasted Masked Chewable 3D Printed Fruit-Chews for Paediatric Patients.

The development of personalised paediatric dosage forms using 3D printing technologies has gained significant interest over the last few years. In the current study extruded filaments of the highly bitter Diphenhydramine Hydrochloride (DPH) were fabricated by using suitable hydrophilic carries such as hydroxypropyl cellulose (Klucel ELFTM) and a non-ionic surfactant (Gelucire 48/16TM) combined with sweetener (Sucralose) and strawberry flavour grades. The thermoplastic filaments were used to print 3D fruit-chew designs by Fused Deposition Modelling (FDM) technology. Physicochemical characterisation confirmed the formation of glass solution where DPH was molecularly dispersed within the hydrophilic carriers. DPH was released rapidly from the 3D printed fruit-chew designs with >85% within the first 30 min. Trained panellists performed a full taste and sensory evaluation of the sweetener intensity and the strawberry aroma. The evaluation showed complete taste masking of the bitter DPH and revealed a synergistic effect of the sweetener and the strawberry flavour with enhanced sweet strawberry, fruity and aftertaste perception. The findings of the study can be used for the development of paediatric dosage forms with enhanced organoleptic properties, palatability and medication adherence.

Mixed Micellization and Spectroscopic Studies of Anti-Allergic Drug and Non-Ionic Surfactant in the Presence of Ionic Liquid.

In drug delivery, surfactants are used to reduce side effects and to increase drug efficiency. The present work aimed to study the interaction of diphenhydramine hydrochloride (anti-allergic drug) with TX–45 (non-ionic surfactant) in the absence and presence of ionic liquid (1-hexyl-3-methylimidazolium chloride). The physicochemical parameters were estimated by the surface tension measurement. Various theoretical models (Clint, Rubingh, Motomura, and Maeda) were applied to determine the attractive behavior between drug and surfactant mixtures at the surface and in bulk. The drug and surfactant mixtures exhibit synergistic behavior in the absence and presence of ionic liquid. Several energetic parameters were also estimated with the assistance of regular solution approximation and pseudo phase separation model that indicate micelle formation and adsorption of surfactant at the surface is thermodynamically advantageous. The morphology of pure and mixture of amphiphiles has been estimated by the Tanford and Israelachvili theories. UV-visible spectroscopy was used to quantify the attractive behavior of the drug with surfactant with the help of a binding constant (K).

Distribution profiles of diphenhydramine and lidocaine in scalp, axillary, and pubic hairs measured by micro-segmental hair analysis: good indicator for discrimination between administration and external contamination of the drugs

PurposeDrug distribution in scalp hair can provide historical information about drug use, such as the date and frequency of drug ingestion. We previously developed micro-segmental hair analysis, which visualizes drug distribution at 0.4-mm intervals in individual hairs. The present study examines whether the distribution profiles of drugs can be markers for the administration or external contamination of the drugs using scalp, axillary, and pubic hairs.MethodsA single dose of anti-itch ointment containing diphenhydramine (DP) and lidocaine (LD) was topically applied to the axillary or pubic areas of two volunteers; DP was also orally administered; and LD was intra-gingivally injected. Scalp, axillary, and pubic hairs were assessed using our micro-segmental analysis.ResultsThe localization of DP and LD differed within individual scalp hair strands, implying DP and LD were predominantly incorporated into scalp hair via the bloodstream and via sweat/sebum, respectively, showing double-peak profiles. However, DP and LD were distributed along the shafts of axillary and pubic hairs without appearance of the double-peak profiles when the ointment had been applied to the axillary and pubic areas. The distributions of DP and LD in scalp hairs did not significantly differ according to administration routes, such as oral administration, gingival injection, and topical application.ConclusionsMicro-segmental analysis revealed differences in the distribution profiles of drugs in hairs, and distinguished hairs with and without external contamination. These findings will be useful for understanding of the mechanism of drug uptake into hair and for estimating the circumstances for a drug use.