Promethazine Research Articles

In-Lattice Occupied Rare Earth Metal Chalcogenide Nanocomposites as Electrocatalysts for Selective Detection of Promethazine Hydrochloride

In-Lattice Occupied Rare Earth Metal Chalcogenide Nanocomposites as Electrocatalysts for Selective Detection of Promethazine Hydrochloride

Rose-like structure of calcium molybdate decorated on halloysite nanotubes as an electrocatalyst: Highly sensitive and selective electrochemical determination of promethazine hydrochloride in biological and environmental samples: Density functional theory studies

Rose-like structure of calcium molybdate decorated on halloysite nanotubes as an electrocatalyst: Highly sensitive and selective electrochemical determination of promethazine hydrochloride in biological and environmental samples: Density functional theory studies

Fluorometric Detection of Five Nitrogen-Based Pharmaceuticals Based on Ion-Pairing Association with EY: DFT Calculations

Fluorometric method for detecting of five nitrogen-based drugs concentration based on inhibition of emission Eosin Y (EY). The selection of N-drugs comprised indapamide (INDP), clomipramine hydrochloride (CMI), promethazine hydrochloride (PMH), lisinopril (LSP), and trifluoperazine hydrochloride (TFPH). The Stern–Volmer style was plotted between relative emissions of EY vs. N-drugs concentration. The standard curves were linear over the concentration range of 5–50 µg mL−1 with R2 > 0.9, and the LOD for INDP, CMI, PMH, LSP, and TFPH were 2.07, 1.36, 3.02, 3.52, and 2.09 µmol·L−1, respectively. The binding constant Kapp for LSP was greater than other N-drugs. Furthermore, the suggested method was hence applied for the routine detection of the concentration of N-drugs in bulk and tablet or syrup dosage forms. FTIR analysis and the electron-mapping density provided the chemical affinity of N-drugs towards EY.

SAHA potentiates the activity of repurposed drug promethazine loaded PLGA nanoparticles in triple-negative breast cancer cells.

Triple-negative breast cancer (TNBC) is considered the most aggressive form of breast cancer owing to the negative expression of targetable bioreceptors. Epithelial to mesenchymal transition (EMT) associated with metastatic abilities is its critical feature. As an attempt to target TNBC, nanotechnology was utilised to augment the effects of drug repurposing. Concerning that, a combination therapeutic module was structured with one of the aspects being a repurposed antihistamine, promethazine hydrochloride loaded PLGA nanoparticles. The as-synthesized nanoparticles were 217 nm in size and fluoresced at 522 nm, rendering them suitable for theranostic applications too. The second feature of the module was a common histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), used as a form of pre-treatment. Experimental studies demonstrated efficient cellular internalisation and significant innate anti-proliferative potential. The use of SAHA sensitised the cells to the drug loaded nanoparticle treatment. Mechanistic studies showed increase in ROS generation, mitochondrial dysfunction followed by apoptosis. Investigations into protein expression also revealed reduction of mesenchymal proteins like vimentin by 1.90 fold; while increase in epithelial marker like E-Cadherin by 1.42 fold, thus indicating an altered EMT dynamics. Further findings also provided better insight into the benefits of SAHA potentiated targeting of tumor spheroids that mimic solid tumors of TNBC. Thus, this study paves the avenue to a more rational translational validation of combining nanotherapeutics with drug repurposing.

Unleashing the Potential of β -cyclodextrin Inclusion Complexes in Bitter Taste Abatement: Development, Optimization and Evaluation of Taste Masked Anti-emetic Chewing Gum of Promethazine Hydrochloride.

Motion sickness also known as kinetosis is a condition in which there exists a disagreement between visually perceived movement and the vestibular system's sense of movement. Nausea, vomiting, dizziness, fatigue, and headache are the most common symptoms of motion sickness. This study mainly focuses on the taste masking of Promethazine Hydrochloride (PMZ) by inclusion complexation method, its formulation development in the chewing gum form by using directly compressible gum base HIG® and its quality and performance testing. Different molar ratios (1:1, 1:2, 1:3 and 1:4) of PMZ-cyclodextrin complexes were prepared by using β-Cyclodextrin(β-CD) as a taste masking agent. These complexes were evaluated for FTIR, DSC, % Entrapment Efficiency, % drug yield, and taste evaluation by E-Tongue. The optimized ratio was further evaluated by sophisticated analytical techniques such as Scanning Electron Microscopy (SEM) and X-Ray Diffraction (XRD). A central composite design (CCD) (3 ^2) was utilized to examine the effects of independent variables (amount of gum-X1 and amount of plasticizer-X2) on dependent variables (%CDRY1 and hardness Y2). The prepared gums were evaluated for drug content, organoleptic properties, in-vitro dissolution testing by fabricated disintegration apparatus, texture analysis, etc. The optimization statistics showed that on decreasing the amount of gum, in- vitro drug release increases and hardness decreases. The optimized batch MCG-2 of Promethazine MCG showed 92.34 ± 0.92% of drug release, whereas for marketed formulation (Phenergan®-25mg) drug release value was 86.19 ± 1.88%. Results provided evidence that PMZ MCGs could be a better alternative to conventional tablet formulations with improved drug release, palatability and texture.

Repurposing promethazine hydrochloride to inhibit biofilm formation against Burkholderia thailandensis.

Melioidosis is a severe infectious disease caused by Burkholderia pseudomallei, an intracellular pathogen with a high mortality rate and significant antibiotic resistance. The high mortality rate and resistance to antibiotics have drawn considerable attention from researchers studying melioidosis. This study evaluated the effects of various concentrations (75, 50, and 25µg/mL) of promethazine hydrochloride (PTZ), a potent antihistamine, on biofilm formation and lipase activity after 24h of exposure to B. thailandensis E264. A concentration-dependent decrease in both biofilm biomass and lipase activity was observed. RT-PCR analysis revealed that PTZ treatment not only made the biofilm structure loose but also reduced the expression of btaR1, btaR2, btaR3, and scmR. Single gene knockouts of quorum sensing (QS) receptor proteins (∆btaR1, ∆btaR2, and ∆btaR3) were successfully constructed. Deletion of btaR1 affected biofilm formation in B. thailandensis, while deletion of btaR2 and btaR3 led to reduced lipase activity. Molecular docking and biological performance results demonstrated that PTZ inhibits biofilm formation and lipase activity by suppressing the expression of QS-regulated genes. This study found that repositioning PTZ reduced biofilm formation in B. thailandensis E264, suggesting a potential new approach for combating melioidosis.

A validated stability‐indicating reversed‐phase‐UPLC method for simultaneous estimation of promethazine hydrochloride, methylparaben, propylparaben and sodium benzoate assay of cough suppressant and antihistamine liquid oral dosage forms

A quick, simple, sensitive, efficient and stability-indicating reverse-phase ultraperformance liquid chromatographic method for the estimation of propylparaben, methylparaben and sodium benzoate in a pharmaceutical liquid oral formulation was developed. A Waters Acquity UPLC BEH C18, 50 × 2.1 mm, 1.7 μm i.d. column was used to perform chromatographic separation with a 0.1% perchloric acid mobile phase used as solvent A and a mixture of 0.1 % perchloric acid and methanol in the ratio 20:80 (v/v), respectively, as solvent B. The experiments were carried out at a flow rate of 0.4 ml/min and the detection wavelength was 240 nm. The compartment temperature of the column was set at 40°C and the injection volume was set at 2 μl. The main aim of the research was to develop a single UPLC assay method for promethazine (active ingredient) and preservatives in the oral solution of promethazine HCl and dextromethorphan HBr that contains promethazine (active ingredient) and methylparaben, propylparaben and sodium benzoate (preservatives). An assay of dextromethorphan HBr was developed and validated by another HPLC method. The drug and preservatives were eluted at retention times of 19.3 min for promethazine HCl, 9.3 min for methylparaben, 18.9 min for propylparaben and 8.9 min for sodium benzoate. Validation of the developed method was carried out as stated by the International Conference on Harmonization guidelines ICH Q2B and under USP<1225>. The analytical parameters verified specificity/selectivity, linearity, accuracy, ruggedness and robustness. The linearity ranges of promethazine HCL, methylparaben, propylparaben and sodium benzoate were 10-100, 10-80, 1.0-8.0 and 10-80 μg/ml, respectively, with a correlation coefficient of active ingredients and preservatives of 1.00. Percentage recoveries of promethazine, propylparaben, methylparaben, and sodium benzoate were 100.0-100.2, 99.0-100.3, 99.5-98.0 and 99.0-100.0%. The validated analytical method proves that the method is specific, precise, linear, accurate, sensitive, rugged and stable, indicating the quantification of the active ingredient and all preservatives in liquid oral formulations.

Binding studies of promethazine and its metabolites with human serum albumin by high-performance affinity chromatography and molecular docking in the presence of codeine

“Purple Drank”, a soft drink containing promethazine (PMZ) and codeine (COD), has gained global popularity for its hallucinogenic effects. Consuming large amounts of this combination can lead to potentially fatal events. The binding of these drugs to plasma proteins can exacerbate the issue by increasing the risk of drug interactions, side effects, and/or toxicity. Herein, the binding affinity to human serum albumin (HSA) of PMZ and its primary metabolites [N-desmethyl promethazine (DMPMZ) and promethazine sulphoxide (PMZSO)], along with COD, was investigated by high-performance affinity chromatography (HPAC) though zonal approach. PMZ and its metabolites exhibited a notable binding affinity for HSA (%b values higher than 80%), while COD exhibited a %b value of 65%. To discern the specific sites of HSA to which these compounds were bound, displacement experiments were performed using warfarin and (S)-ibuprofen as probes for sites I and II, respectively, which revealed that all analytes were bound to both sites. Molecular docking studies corroborated the experimental results, reinforcing the insights gained from the empirical data. The in silico data also suggested that competition between PMZ and its metabolites with COD can occur in both sites of HSA, but mainly in site II. As the target compounds are chiral, the enantioselectivity for HSA binding was also explored, showing that the binding for these compounds was not enantioselective.

Antibiofilm activity of promethazine against ESBL-producing strains of Escherichia coli in urinary catheters

The bacterium Escherichia coli is one of the main causes of urinary tract infections. The formation of bacterial biofilms, especially associated with the use of urinary catheters, contributes to the establishment of recurrent infections and the development of resistance to treatment. Strains of E. coli that produce extended-spectrum beta-lactamases (ESBL) have a greater ability to form biofilms. In addition, there is a lack of drugs available in the market with antibiofilm activity. Promethazine (PMZ) is an antihistamine known to have antimicrobial activity against different pathogens, including in the form of biofilms, but there are still few studies of its activity against ESBL E. coli biofilms. The aim of this study was to evaluate the antimicrobial activity of PMZ against ESBL E. coli biofilms, as well as to assess the application of this drug as a biofilm prevention agent in urinary catheters. To this end, the minimum inhibitory concentration and minimum bactericidal concentration of PMZ in ESBL E. coli strains were determined using the broth microdilution assay and tolerance level measurement. The activity of PMZ against the cell viability of the in vitro biofilm formation of ESBL E. coli was analyzed by the MTT colorimetric assay and its ability to prevent biofilm formation when impregnated in a urinary catheter was investigated by counting colony-forming units (CFU) and confirmed by scanning electron microscopy (SEM). PMZ showed bactericidal activity and significantly reduced (p < 0.05) the viability of the biofilm being formed by ESBL E. coli at concentrations of 256 and 512 μg/ml, as well as preventing the formation of biofilm on urinary catheters at concentrations starting at 512 μg/ml by reducing the number of CFUs, as also observed by SEM. Thus, PMZ is a promising candidate to prevent the formation of ESBL E. coli biofilms on abiotic surfaces.

Correlation between the expression of the iNOS, caspase-3 and α-SMA genes in the parotid glands of albino rats following the administration of two antihistamines from two different generations.

Several medications, including antihistamines, can alter salivary gland function, causing dry mouth or xerostomia. Antihistamines are commonly used for treating allergic rhinitis. The aim of the present study was to compare and correlate the effects of first-generation vs. second-generation H1-antihistamines on the parotid glands of rats. Twelve adult male albino rats were used; 4 rats served as a control group (group I) and the remaining rats were divided into 2 groups: group II received promethazine hydrochloride; and group III received cetirizine dihydrochloride for 3 weeks. The parotid salivary glands were dissected, and examined histologically and analyzed histomorphometrically for the acinar area percentage. In addition, mRNA gene expression of iNOS, caspase-3 and α-SMA was assessed using quantitative realtime polymerase chain reaction (qRT-PCR). Finally, all the obtained data was statistically analyzed. Histologically, group I showed the typical architecture of the gland. In group II, degenerative changes were noticed, including acinar degeneration and shrinkage with widened connective tissue septa, intracellular vacuolization, and increased inflammatory cell infiltration. In group III, similar histological features were detected as in group II, but to a lesser extent. Histomorphometric results revealed significant differences in the acinar area percentage between various groups. In addition, qRT-PCR results showed a significant increase in iNOS expression in both groups II and III as compared to group I, caspase-3 gene expression was significantly increased in group II, while in group III, it increased non-significantly. Finally, α-SMA gene expression non-significantly decreased in both groups II and III. A significant positive correlation was observed between caspase-3 and iNOS gene expression, while an inverse correlation was noticed between caspase-3 and α-SMA gene expression. The administration of antihistamines resulted in changes in the rat salivary glands, which could be due to the induction of oxidative stress and the resultant apoptotic effect. These changes were suggested to occur mainly through action on muscarinic receptors; yet, action on histamine receptors could not be excluded. However; these effects were less marked with the second-generation antihistamine.

Enantiomeric profile of promethazine in metabolic studies in liver microsomes

Promethazine (PMZ) is metabolized in the liver giving rise to chiral metabolites, including promethazine sulfoxide (PMZSO) and desmonomethyl promethazine (DMPMZ). Other metabolites, such as dioxopromethazine (DOPMZ), hydroxy promethazine (PMZOH), N-desmethyl-promethazine sulfoxide, and promethazine N-oxide (PMZNO) can also be formed, but information about them is limited. In this work, the enantiomeric metabolic profile of PMZ in ultra-pool human liver microsomes (HLM) was evaluated. For that, a novel enantioselective analytical method, by liquid chromatography coupled with high-resolution mass spectrometry was established and employed to monitor the enantiomers of PMZ and the formation of its main metabolites PMZSO and DMPMZ in two-hours assay with HLM. The enantioseparation optimized conditions were achieved with two immobilized carbamate amylose-based (3‑chloro-5-methylphenylcarbamate) columns: Lux® 3 µm i-Amylose-3 and Chiralpak® IG-U 1.6 µm. The optimized mobile phase for enantioseparation used buffer and ethanol, a green organic solvent, in a low flow rate. The sample preparation was based only in liquid-liquid extraction. (R)-PMZ consistently exhibited higher concentrations than (S)-PMZ, indicating less extension in metabolization. Regarding the metabolites, PMZSO exhibited higher concentrations compared to DMPMZ. A higher concentration for (S)-PMZSO was found when compared to the (R)-PMZSO and (R)-DMPMZ showing higher concentration compared to (S)-DMPMZ, indicating enantioselectivity in the metabolization process. The metabolites, PMZOH or PMZNO and DOPMZ were also identified. The second enantiomer of DOPMZ also showed a higher proportion than the first eluted enantiomer. These results demonstrated enantioselectivity of liver metabolism of PMZ, as well as confirmed PMZOH, PMZNO, and DOPMZ metabolites formation.

Investigation of the interaction of promethazine hydrochloride drug with tetradecyltrimethylammonium bromide: Impacts of hydrotropes composition and temperature

Investigation of the interaction of promethazine hydrochloride drug with tetradecyltrimethylammonium bromide: Impacts of hydrotropes composition and temperature

Nonenzymatic electrochemical approaches for promethazine monitoring in aquatic media

Promethazine hydrochloride (PMH) is a phenothiazine derivative extensively utilized in healthcare settings. Its excessive consumption and continuous release into environmental water bodies can lead to adverse effects on human health and disrupt the equilibrium of aquatic ecosystems. Therefore, monitoring PMH levels is essential to maintain therapeutic efficacy and safeguard the well-being of both humans and aquatic life. This study encompasses the synthesis of samarium tungstate nanorods (SmWO) via hydrothermal method, followed by their incorporation into a composite with sulfur-doped graphitic carbon nitride (SmWO/SGCN) using ultrasonication technique. The morphology and physicochemical properties of the synthesized composite were thoroughly examined using various analytical methods. Subsequently, the electrocatalytic activity of the developed sensor was assessed for sensing PMH via voltammetry techniques. Under optimized conditions, the fabricated electrode exhibited an 8.1 nM detection limit with a wide linear range (0.02–199 µM), and high sensitivity (2.349 µA µM−1 cm−2) for PMH detection. The suggested SmWO/SGCN composite electrode shows promising practical potential for detecting PMH in environmental aquatic samples.

Milligram scale enantioresolution of promethazine and its main metabolites, determination of their absolute configuration and assessment of enantioselective effects on human SY-SY5Y cells

The misuse of pharmaceuticals has significantly increased in recent decades, becoming a major public health concern. The risks associated with medication misuse are particularly high in cases of overdose, especially when the active substances are chiral, as enantioselectivity plays an important role in toxicity. Promethazine (PMZ) is a chiral antihistamine marketed as a racemate and it is misused in "Purple Drank", a recreational drug beverage, that combines codeine and/or PMZ, with soda or alcohol leading to serious health consequences and fatalities in consumers around the world, particularly among teenagers. Information regarding the enantioselectivity in the toxicity of (R,S)-PMZ and its main metabolites, namely promethazine sulfoxide (PMZSO) and desmonomethyl promethazine (DMPMZ), is unknown. This work reported, for the first time, the enantioseparation, in milligram scale, of (R,S)-PMZ, (R,S)-DMPMZ, (R,S)- PMZSO and the determination of their absolute configurations by electronic circular dichroism (ECD). The enantioseparation of all the six enantiomers was accomplished in a homemade semi-preparative column with amylose tris-3,5-dimethylphenylcarbamate (AD) coated with aminopropyl Nucleosil silica. The enantiomeric purity was evaluated using the analytical Lux® 3 µm i-Amylose-3 column, yielding enantiomeric purity values ranging between 94.4% and 99.7%. The elution order of all the enantiomers was accomplished combining the ECD results with an optical rotation detector. The elution order of the enantiomers was influenced only by the chiral selector, rather than the mobile phase.The cytotoxicity of the racemates and the isolated enantiomers towards differentiated SH-SY5Y cells was evaluated. (R,S)-DMPMZ exhibited a significantly higher cytotoxicity than (R,S)-PMZ, suggesting the metabolic bioactivation of (R,S)-PMZ. Conversely, no significant cytotoxicity was found for (R,S)-PMZSO, underscoring a metabolic detoxification pathway. Remarkably, enantioselectivity was observed for the cytotoxicity of PMZ; (R)-PMZ was significantly more cytotoxic than (S)-PMZ.The results underscore the importance to isolate the enantiomers in their enantiomerically form and their correct identification for toxicity enantioselectivity studies, which are vital to understand the drug's behaviour and safety, especially in case of overdoses.

The identification of a novel shared therapeutic target and drug across all insulin-sensitive tissues under insulin resistance.

To identify key and shared insulin resistance (IR) molecular signatures across all insulin-sensitive tissues (ISTs), and their potential targeted drugs. Three datasets from Gene Expression Omnibus (GEO) were acquired, in which the ISTs (fat, muscle, and liver) were from the same individual with obese mice. Integrated bioinformatics analysis was performed to obtain the differentially expressed genes (DEGs). Weighted gene co-expression network analysis (WGCNA) was carried out to determine the "most significant trait-related genes" (MSTRGs). Enrichment analysis and PPI network were performed to find common features and novel hub genes in ISTs. The shared genes of DEGs and genes between DEGs and MSTRGs across four ISTs were identified as key IR therapeutic target. The Attie Lab diabetes database and obese rats were used to verify candidate genes. A medical drug-gene interaction network was conducted by using the Comparative Toxicogenomics Database (CTD) to find potential targeted drugs. The candidate drug was validated in Hepa1-6 cells. Lipid metabolic process, mitochondrion, and oxidoreductase activity as common features were enriched from ISTs under an obese context. Thirteen shared genes (Ubd, Lbp, Hp, Arntl, Cfd, Npas2, Thrsp., Tpx2, Pkp1, Sftpd, Mthfd2, Tnfaip2, and Vnn3) of DEGs across ISTs were obtained and confirmed. Among them, Ubd was the only shared gene between DEGs and MSTRGs across four ISTs. The expression of Ubd was significantly upregulated across four ISTs in obese rats, especially in the liver. The IR Hepa1-6 cell models treated with dexamethasone (Dex), palmitic acid (PA), and 2-deoxy-D-ribose (dRib) had elevated expression of Ubd. Knockdown of Ubd increased the level of p-Akt. A lowing Ubd expression drug, promethazine (PMZ) from CTD analysis rescued the decreased p-Akt level in IR Hepa1-6 cells. This study revealed Ubd, a novel and shared IR molecular signature across four ISTs, as an effective biomarker and provided new insight into the mechanisms of IR. PMZ was a candidate drug for IR which increased p-Akt level and thus improved IR by targeting Ubd and downregulation of Ubd expression. Both Ubd and PMZ merit further clinical translational investigation to improve IR.

Stronger Warnings for Promethazine Hydrochloride Injection.

Stronger Warnings for Promethazine Hydrochloride Injection.

Highly sensitive detection of promethazine hydrochloride in water and human urine using flower-like ZnO nanorods supported by GO sheets and Pt nanoparticles

In this study, we developed three-dimensional flower-like stacked zinc oxide (ZnO) nanorods as cores, which were supported by graphene oxide (GO) and decorated with platinum (Pt) nanoparticles. We explored six different combinations of these materials, specifically GO, ZnO, ZnO/GO, Pt/ZnO, (Pt/ZnO)-GO, and Pt-(ZnO/GO), as potential electrochemical sensors for detecting the first-generation antihistamine drug promethazine hydrochloride (PMTZ) in water bodies. We characterized the crystallinity, chemical composition, functional groups, surface morphology, and elemental proportions of these materials using X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), Raman spectroscopy, scanning electron microscopy (SEM), and X-ray photoelectron spectroscopy (XPS) analysis. Following this, we investigated these materials further to identify the optimal one for detecting PMTZ using electrochemical techniques. The newly developed Pt/ZnO composite material-based electrochemical sensor demonstrated exceptional performance for electrochemically detecting PMTZ. It achieved an ultra-low detection limit of 1.85 × 10−2 µM, a wide linear response range from 0.2 to 116.2 µM, and an outstanding sensitivity of 1.59 µA µM−1 cm−2. Moreover, the developed sensor showed good resistance to interference (with an effect below 13.2 %), high reproducibility (RSD = 1.14 %), repeatability (RSD = 1.18 %), and stability (with an effect below 16.2 %).The real-time practical applicability of the samples was analyzed using actual human urine samples. The sensor exhibited excellent recovery rates (99.3% to 99.6%), indicating the practicality of the newly developed Pt/ZnO composite material for the electrochemical detection of promethazine hydrochloride.

Design and Evaluation of Different Transdermal Therapeutic Systems of Promethazine Hydrochloride

Design and Evaluation of Different Transdermal Therapeutic Systems of Promethazine Hydrochloride

Assessing Abuse-Deterrent formulations utilizing Ion-Exchange resin complexation processed via Twin-Screw granulation for improved safety and effectiveness

Opioid misuse is a public health crisis in the United States. In response, the FDA has approved drug products with abuse-deterrent features to reduce the risk of prescription opioid abuse. Abuse-deterrent formulations (ADFs) typically employ physical or chemical barriers or incorporate agonist–antagonist combinations as mechanisms to deter misuse. This study aims to assess the impact of abuse-deterrent properties, specifically ion-exchange resin complexation as a chemical barrier, on a model drug, promethazine hydrochloride (PMZ) tablets. Various formulations were developed through twin-screw wet granulation (TSWG) followed by twin-screw melt granulation (TSMG). In the TSWG process, the drug interacts with the resin through an exchange reaction, forming a drug-resin complex. Additionally, the study explored factors influencing the complex formation between the drug and resin, using the drug loading status as an indicator. DSC and ATR studies were carried out to confirm the formation of the drug-resin complex. Subsequently, hot melt granulation was employed to create a matrix tablet incorporating Kollidon® SR and Kollicoat® MAE 100P, thereby enabling sustained release properties. The drug-resin complex embedded in the matrix effectively deters abuse through methods like smoking, snorting, or parenteral injection, unless the drug can be extracted. In order to assess this, solvent extraction studies were conducted using an FDA-recommended solvents, determining the potential for abuse. Further investigations involved dissolution tests in change-over media, confirming the extended-release properties of the formulation. Results from dissolution studies comparing the ground and intact tablets provided positive evidence of the formulation's effectiveness in deterring abuse. Finally, alcohol-induced dose-dumping studies were conducted in compliance with FDA guidelines, concluding that the formulation successfully mitigates dose dumping in the presence of alcohol.

Determination of Micro Amounts of Promethazine Hydrochloride in Pure and Pharmaceutical Samples Using UV- Visible Spectrophotometry

This study presents the development of a novel, facile, and overly sensitive spectrophotometric approach for quantifying promethazine hydrochloride (PRO) within its pharmaceutical formulations. The method capitalizes on an oxidative coupling reaction, achieved through the oxidation of the compound in an acidic milieu utilizing ammonium cerium (IV) sulfate dehydrate (Ce+4) solution. This process leads to the creation of a green-colored solution, which, upon conjugation with 5-aminosalicylic acid, exhibits maximum absorption at a wavelength of 598 nm. The methodology investigated several parameters, encompassing oxidation duration, temperature, quantities of oxidizing agent and coupling reagent, and determining the stoichiometric ratio between promethazine hydrochloride and 5-aminosalicylic acid. The established ratio was confirmed to be 1:1. Numerous organic solvents were evaluated, with water emerging as the optimal choice due to its pronounced absorption characteristics at the 598 nm wavelength. The applicability of Beer's law was verified over a concentration range of 2 - 28 μg/mL of promethazine hydrochloride, with a calculated molar absorption coefficient of 1.9606 x 104 L/mol∙cm. The Sandell sensitivity index was determined as 0.0164 μg/cm2, while the relative standard deviation (RSD) ranged from 0.8553- 1.2671%. Notably, recovery percentages were also within the 99.88 – 100.34% range. The efficacy of this technique was effectively demonstrated through its successful application in the analysis of pharmaceutical formulations containing promethazine hydrochloride, employing the standard method as a benchmark.