HPLC-Fluorescence Detection Method for Concurrent Estimation of Domperidone and Naproxen. Validation and Eco-Friendliness Appraisal Studies.

This work demonstrates a simple and reliable HPLC method with fluorimetric detection for simultaneous estimation of domperidone (DOM) and naproxen (NAP). Successful chromatographic separation was accomplished using Inertsil ODS C18 column (5 µm, 4.6 × 150 mm) with gradient elution of the mobile phase consisting of 0.01 M phosphate buffer (pH 5.5) solution and acetonitrile. The gradient elution started with 25% acetonitrile increased linearly to 65% in 5 min, then kept at this percentage till the end of the run. The mobile phase was pumped at a flow rate of 1.0 mL/min. The excitation wavelength at 284 nm was found suitable for both DOM and NAP since it corresponds to a maximum for the minor component DOM and measurable excitation for NAP, while using 316 and 355 nm as emission wavelengths for DOM and NAP, respectively. Peaks eluted with excellent resolution at retention times 4.4 and 6.3 min for DOM and NAP, respectively. Performance of the proposed method was tested according to ICH guidelines in regard to linearity, ranges, precision, accuracy, robustness, detection and quantitation limits. Calibration curves were linear in the ranges of 0.8-3.6 and 1.0-2.5 µg/mL for DOM and NAP respectively with correlation coefficients not less than 0.9996. The validated method was successfully applied to the analysis of DOM and NAP in their laboratory prepared tablets resembling the commercial dosage form, and assay results were favorably compared with a published reference HPLC method. The method's greenness was assessed using the Analytical Eco-Scale and the novel Analytical Greenness metric (AGREE).

Investigation on the Potential Application of Na-Attapulgite as an Excipient in Domperidone Sustained-Release Tablets.

In this study, Na-attapulgite was explored as an excipient to prepare domperidone sustained-release tablets and test them in accordance with United States Pharmacopoeia requirements. Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD) and differential scanning calorimetry (DSC) were employed to explore the compatibility between Na-attapulgite and domperidone. The XRD and DSC show no interaction between the drug and Na-attapulgite. The FTIR spectrum indicates a shift in the absorption of N-H in the drug molecule, which can be explained by the hydrogen bonding interaction between the N-H in the DOM molecule and the -OH on the surface of Na-ATP. The diameter, hardness, friability and drug content of the tablets were measured, and they all met the relevant requirements of the United States Pharmacopoeia. In addition, the tablets with Na-attapulgite as excipient exhibit a better release performance within the release time of 12 h. These results demonstrate that the domperidone sustained-release tablets have been successfully prepared by using Na-attapulgite as an excipient. The doping of Na-ATP in domperidone sustained-release tablets improves the cytocompatibility. Moreover, with the increase of Na-ATP content, cells proliferate remarkably and cell activity is significantly enhanced.

Design and Optimization of 3D-Printed Gastroretentive Floating Devices by Central Composite Design.

This study aimed to optimize the size of capsule-shaped 3D-printed devices (CPD) using an experimental design by the response surface methodology to provide a gastroretentive drug delivery system (GRDDS) with optimal floating time. The CPD was fabricated using a fused deposition modeling (FDM) 3D printer. The central composite design was employed for the optimization of the devices. The morphology of the CPD was observed using a digital microscope and scanning electron microscope (SEM). The in vitro floating time and drug release were evaluated using a USP dissolution apparatus II. Appropriate total floating time (TFT) of the devices (more than 3 h) was obtained with the device's body, cap, and bottom thickness of 1.2, 1.8, and 2.9 mm, respectively. The release kinetics of the drug from the devices fitted well with zero-order kinetics. In conclusion, the optimization of CPD for GRDDS using the experimental design provided the devices with desirable floating time and ideal drug release characteristics.

Position-Dependent Diffusion from Biased Simulations and Markov State Model Analysis.

A variety of enhanced statistical and numerical methods are now routinely used to extract important thermodynamic and kinetic information from the vast amount of complex, high-dimensional data obtained from molecular simulations. For the characterization of kinetic properties, Markov state models, in which the long-time statistical dynamics of a system is approximated by a Markov chain on a discrete partition of configuration space, have seen widespread use in recent years. However, obtaining kinetic properties for molecular systems with high energy barriers remains challenging as often enhanced sampling techniques are required with biased simulations to observe the relevant rare events. Particularly, the calculation of diffusion coefficients remains elusive from biased molecular simulation data. Here, we propose a novel method that can calculate multidimensional position-dependent diffusion coefficients equally from either biased or unbiased simulations using the same formalism. Our method builds on Markov state model analysis and the Kramers-Moyal expansion. We demonstrate the validity of our formalism using one- and two-dimensional analytic potentials and also apply it to data from explicit solvent molecular dynamics simulations, including the water-mediated conformations of alanine dipeptide and umbrella sampling simulations of drug transport across a lipid bilayer. Importantly, the developed algorithm presents significant improvement compared to standard methods when the transport of solute across three-dimensional heterogeneous porous media is studied, for example, the prediction of membrane permeation of drug molecules.

Pharmacoproteomics pinpoints HSP70 interaction for correction of the most frequent Wilson disease-causing mutant of ATP7B.

Pathogenic mutations in the copper transporter ATP7B have been hypothesized to affect its protein interaction landscape contributing to loss of function and, thereby, to hepatic copper toxicosis in Wilson disease. Although targeting mutant interactomes was proposed as a therapeutic strategy, druggable interactors for rescue of ATP7B mutants remain elusive. Using proteomics, we found that the frequent H1069Q substitution promotes ATP7B interaction with HSP70, thus accelerating endoplasmic reticulum (ER) degradation of the mutant protein and consequent copper accumulation in hepatic cells. This prompted us to use an HSP70 inhibitor as bait in a bioinformatics search for structurally similar Food and Drug Administration-approved drugs. Among the hits, domperidone emerged as an effective corrector that recovered trafficking and function of ATP7B-H1069Q by impairing its exposure to the HSP70 proteostatic network. Our findings suggest that HSP70-mediated degradation can be safely targeted with domperidone to rescue ER-retained ATP7B mutants and, hence, to counter the onset of Wilson disease.

Separation of Unprecedented Degradants of Domperidone by Ultra-Performance Convergence Chromatography and Their Structure Elucidation.

Domperidone, a gastroprokinetic agent, is a common drug to treat emesis. It was subjected to acid, base-mediated hydrolysis, peroxide-mediated oxidation, photolysis and thermal degradation according to ICH guidelines to observe stability of the selected drug under the stress conditions. Although the drug is resistant to base hydrolysis, photolysis and thermal stressors, two degradants (DP-ISO1 and DP-ISO2) were formed in acid mediated hydrolysis. Oxidation with hydrogen peroxide also resulted in one product (DP-OX). All three degradants were isolated from the crude reaction mixture by preparative high-performance liquid chromatography and supercritical fluid chromatography. Structures of isolated compounds were unambiguously characterized as 5-chloro-1-(1-(3-(6-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)propyl)piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (DP-ISO1), 5-chloro-1-(3-(4-(5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)propyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (DP-ISO2), 4-(5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)-1-(3-(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)propyl)piperidine 1-oxide (DP-OX) by analysis of mass spectrometry, 1D and 2D nuclear magnetic resonance spectra. To the best of our knowledge, DP-ISO1 and DP-ISO2 are new and DP-OX was previously reported as domperidone impurity.

Domperidone nanocrystals with boosted oral bioavailability: fabrication, evaluation and molecular insight into the polymer-domperidone nanocrystal interaction.

The aim of this study was to employ experimental and molecular modelling approaches to use molecular level interactions to rationalise the selection of suitable polymers for use in the production of stable domperidone (DOMP) nanocrystals with enhanced bioavailability. A low-energy antisolvent precipitation method was used for the preparation and screening of polymers for stable nanocrystals of DOMP. Ethyl cellulose was found to be very efficient in producing stable DOMP nanocrystals with particle size of 130 ± 3 nm. Moreover, the combination of hydroxypropyl methylcellulose and polyvinyl alcohol was also shown to be better in producing DOMP nanocrystals with smaller particle size (200 ± 3.5 nm). DOMP nanosuspension stored at 2-8 °C and at room temperature (25 °C) exhibited better stability compared to the samples stored at 40 °C. Crystallinity of the unprocessed and processed DOMP was monitored by differential scanning calorimetry and powder X-ray diffraction. DOMP nanocrystals gave enhanced dissolution rate compared to the unprocessed drug substance. DOMP nanocrystals at a dose of 10 mg/kg in rats showed enhanced bioavailability compared to the raw drug substance and marketed formulation. A significant increase in plasma concentration of 2.6 µg/mL with a significant decrease in time (1 h) to reach maximum plasma concentration was observed for DOMP nanocrystals compared to the raw DOMP. Molecular modelling studies provided underpinning knowledge at the molecular level of the DOMP-polymer nanocrystal interactions and substantiated the experimental studies. This included an understanding of the impact of polymers on the size of nanocrystals and their associated stability characteristics.

Calculating Kinetic Rates and Membrane Permeability from Biased Simulations.

We present a simple approach to calculate the kinetic properties of lipid membrane crossing processes from biased molecular dynamics simulations. We demonstrate that by using biased simulations, one can obtain highly accurate kinetic information with significantly reduced computational time with respect to unbiased simulations. We describe how to conveniently calculate the transition rates to enter, cross, and exit the membrane in terms of the mean first passage times. To obtain free energy barriers and relaxation times from biased simulations only, we constructed Markov models using the dynamic histogram analysis method (DHAM). The permeability coefficients that are calculated from the relaxation times are found to correlate highly with experimentally evaluated values. We show that more generally, certain calculated kinetic properties linked to the crossing of the membrane layer (e.g., barrier height and barrier crossing rates) are good indicators of ordering drugs by permeability. Extending the analysis to a 2D Markov model provides a physical description of the membrane crossing mechanism.

Development of Domperidone Solid Lipid Nanoparticles: In Vitro and In Vivo Characterization.

Domperidone (DOP) is extensively applied orally in the management of nausea and vomiting. Upon oral administration, its bioavailability is very poor due to its poor solubility in alkaline media. Therefore, the aim of this work was to investigate DOP-loaded solid lipid nanoparticles (DOP-SLNs) in order to sustain its release pattern and to enhance oral bioavailability. DOP-SLNs were prepared using four different lipids. Prepared DOP-SLNs were characterized for "polydispersity index (PDI), particle size, zeta potential, % entrapment efficiency (% EE), and drug release behavior." Differential scanning calorimetry (DSC) study was carried out to illustrate the physical form of DOP and excipients. The morphology of DOP-SLNs was confirmed by scanning electron microscopy (SEM). Pharmacokinetic study on optimized DOP-SLN in comparison to tablet was performed in rats. The "particle size, PDI, zeta potential, and % EE" of optimized formulation (F5) were recorded as 201.4 nm, 0.071, - 6.2 mV, and 66.3%, respectively. DSC thermograms suggested amorphous state of DOP in various SLNs. Surface morphology of SLNs using SEM suggested spherical shape of the nanoparticles within nanometer size range. In vitro release studies confirmed that all SLN formulations possessed a sustained release over a period of 12 h (51.3% from optimized formulation) in comparison with immediate release from conventional tablets (100% after 90 min). Pharmacokinetic study showed significant enhancement in oral absorption of DOP from optimized SLN in comparison with DOP tablet. The enhancement in relative bioavailability of DOP from optimized SLN was 2.62-fold in comparison with DOP tablet.

Simultaneous voltammetric analysis of anti-ulcer and D2-antagonist agents in binary mixture using redox sensor and their determination in human serum.

Pencil graphite electrode was successfully modified with a thin film of poly (eriochrome black T) and applied for the sensitive and selective voltammetric simultaneous determination of pantoprazole sodium and domperidone in a binary mixture. The preparation and basic electrochemical behavior of poly (eriochrome black T) film on the Pencil graphite electrode were investigated. The modified electrode has exhibited very high electro-catalytic activity towards the cited mixture. The anodic peaks of the both species were well defined with enhanced oxidation peak currents. Under the optimum conditions, the linearity ranges were 0.4-55×10-7M and 0.1-34×10-7M for pantoprazole sodium and domperidone, respectively with detection limits of 0.12×10-7M and 0.04×10-7M for pantoprazole sodium and domperidone, respectively. The proposed sensor has been successfully applied in the analysis of pantoprazole sodium and domperidone in synthetic binary mixtures and human serum.

Aplicação de resina poliuretânica derivada do óleo de mamona em formas farmacêuticas gastrorretentivas de liberação controlada / Application of polyurethane resin from castor oil in controlled release gastroretentive dosage forms

Polímeros naturais têm sido amplamente utilizados como excipientes farmacêuticos, principalmente por serem biocompatíveis e renováveis. O objetivo deste estudo foi investigar a aplicação da resina poliuretânica derivada do óleo de mamona (RPDOM) em formas farmacêuticas gastrorretentivas de liberação controlada. O trabalho aqui apresentado está dividido em quatro capítulos. O capítulo 1 trata-se de uma visão geral sobre a aplicação dos poliuretanos como sistemas de liberação de fármacos, enfatizando os estudos contendo poliuretanos do óleo de mamona. O capítulo 2 trata-se de uma revisão sistemática sobre sistemas gastrorretentivos de liberação de fármacos. O capítulo 3 trata do desenvolvimento e da caracterização da RPDOM contendo fármaco na sua matriz. Domperidona e cloridrato de verapamil foram escolhidos como fármacos modelos devido ao potencial uso desses em formulações gastrorretentivas. Os estudos físico-químicos mostraram que parte da domperidona interagiu quimicamente com a RPDOM. Visto que não é possível a quebra dessa ligação química durante o estudo de dissolução, parte do fármaco ficou indisponível para liberação. Por outro lado, o verapamil foi incorporado com sucesso na RPDOM pelo método de evaporação do solvente. O verapamil interagiu através de forças intermoleculares com o polímero e esse sistema mostrou um promissor perfil de dissolução. O capítulo 4 trata do desenvolvimento de matrizes monolíticas flutuantes, contendo verapamil como fármaco modelo, espuma de polipropileno como excipiente de baixa densidade e um blend da RPDOM e da celulose microcristalina como sistema matricial. A capacidade de flutuação in vitro das matrizes e o controle da liberação do fármaco foram demonstrados. Por fim, a RPDOM mostrou-se um polímero promissor para o uso em sistemas de liberação controlada de fármacos devido a sua hidrofobicidade e para o uso em sistemas gastrorretentivos flutuantes devido à sua baixa densidade

Natural polymers have been extensively used as pharmaceutical excipients mainly due to their biocompatibility and renewability. The aim of this study was to investigate the application of polyurethane resin from castor oil (PU) in controlled release gastroretentive dosage forms. The work presented herein is divided in four chapters. Chapter 1 is an overview of the application of polyurethanes as drug delivery systems, emphasizing studies containing castor oil-based polyurethanes. Chapter 2 is a systematic review of gastroretentive drug delivery systems. Chapter 3 is about the development and characterization of the PU containing drug in its matrix. Domperidone and verapamil hydrochloride were chosen as model drugs due to their potential use in gastroretentive formulations. Physicochemical studies showed that part of domperidone interacted chemically with PU. Since it is not possible a cleavage of the chemical bond between domperidone and the polyurethane during the dissolution study, part of the drug was not available for release. On the other hand, verapamil was successfully incorporated into PU by solvent evaporation method. Verapamil interacted by intermolecular forces with the polymer and this system showed a promising drug dissolution profile. Chapter 4 shows the development of floating monolithic matrices, containing verapamil as model drug, polypropylene foam as low-density excipient and a blend of PU and microcrystalline cellulose as matrix-forming polymers. The in vitro buoyancy capability of the matrices and the ability to control drug release were demonstrated. Finally, PU proved to be a potential polymer to be used in controlled drug delivery systems due to its hydrophobicity and in gastroretentive floating systems due to its low density

Amphiphilic Copolymers Shuttle Drugs Across the Blood-Brain Barrier.

Medical treatment of diseases of the central nervous system requires transport of drugs across the blood-brain barrier (BBB). Here, it is extended previously in vitro experiments with a model compound to show that the non-water-soluble and brain-impermeable drug domperidone (DOM) itself can be enriched in the brain by use of an amphiphilic copolymer as a carrier. This carrier consists of poly(N-(2-hydroxypropyl)-methacrylamide), statistically copolymerized with 10 mol% hydrophobic lauryl methacrylate, into whose micellar aggregates DOM is noncovalently absorbed. As tested in a BBB model efficient transport of DOM across, the BBB is achievable over a wide range of formulations, containing 0.8 to 35.5 wt% domperidone per copolymer. In neither case, the polymer itself is translocated across the BBB model. In vivo experiments in mice show that already 10 min after intraperitoneal injection of the polymer/domperidone (PolyDOM) formulation, domperidone can be detected in blood and in the brain. Highest serum and brain levels of domperidone are detected 40 min after injection. At that time point serum domperidone is increased 48-fold. Most importantly, domperidone is exclusively detectable in high amounts in the brain of PolyDOM injected mice and not in mice injected with bare domperidone.

Simultaneous determination of domperidone and Itopride in pharmaceuticals and human plasma using RP-HPLC/UV detection: Method development, validation and application of the method in in-vivo evaluation of fast dispersible tablets.

Domperidone and Itopride are pro-kinetic agents, regulating the gastric motility and are commonly prescribed as anti emetic drugs. In the present study a simple, rapid and sensitive RP-HPLC/UV method was developed for simultaneous determination of Domperidone and Itopride in pharmaceutical samples and human plasma, using Tenofavir as internal standard. Experimental conditions were optimized and method was validated according to the standard guidelines. Combination of water (pH 3.0) and acetonitrile (65:35 v/v) was used as mobile phase, pumped at the flow rate of 1.5 ml/min. Detector wavelength was set at 210 nm and column oven temperature was 40oC. Unlike conventional liquid-liquid extraction, simple precipitation technique was applied for drug extraction from human plasma using acetonitrile for deprotienation. The method showed adequate separation of both the analytes and best resolution was achieved using Hypersil BDS C8 column (150 mm × 4.6 mm, 5 µm). The method was quite linear in the range of 20-600 ng/ml. Recovery of the method was 92.31% and 89.82% for Domperidone and Itopride, respectively. Retention time of both the analytes and internal standard was below 15 min. The lower limit of detection (LLOD) and lower limit of quantification (LLOQ) for Domperidone were 5 and 10 ng/ml while for Itopride was 12 and 15 ng/ml, respectively. The developed method was successfully applied for in-vivo analysis of fast dispersible tablets of Domperidone in healthy human volunteer. The proposed method was a part of formulation development study and was efficiently applied for determination of the two drugs in various pharmaceutical products and human plasma.

Formulation and development of orodispersible sustained release tablet of domperidone.

Commercially available domperidone orodispersible tablets (ODT) are intended for immediate release of the drug, but none of them have been formulated for sustained action. The aim of the present research work was to develop and evaluate orodispersible sustained release tablet (ODT-SR) of domperidone, which has the convenience of ODT and benefits of controlled release product combined in one. The technology comprised of developing sustained release microspheres (MS) of domperidone, followed by direct compression of MS along with suitable excipients to yield ODT-SR which rapidly disperses within 30 seconds and yet the dispersed MS maintain their integrity to have a sustained drug release. The particle size of the MS was optimized to be less than 200 µm to avoid the grittiness in the mouth. The DSC thermograms of MS showed the absence of drug-polymer interaction within the microparticles, while SEM confirmed their spherical shape and porous nature. Angle of repose, compressibility and Hausner's ratio of the blend for compression showed good flowability and high percent compressibility. The optimized ODT-SR showed disintegration time of 21 seconds and matrix controlled drug release for 9 h. In-vivo pharmacokinetic studies in Wistar rats showed that the ODT-SR had a prolonged MRT of 11.16 h as compared 3.86 h of conventional tablet. The developed technology is easily scalable and holds potential for commercial exploitation.

Validation of four different spectrophotometric methods for simultaneous determination of Domperidone and Ranitidine in bulk and pharmaceutical formulation.

Four simple, specific, accurate and precise spectrophotometric methods were developed and validated for simultaneous determination of Domperidone (DP) and Ranitidine Hydrochloride (RT) in bulk powder and pharmaceutical formulation. The first method was simultaneous ratio subtraction (SRS), the second was ratio subtraction (RS) coupled with zero order spectrophotometry (D(0)), the third was first derivative of the ratio spectra ((1)DD) and the fourth method was mean centering of ratio spectra (MCR). The calibration curve is linear over the concentration range of 0.5-5 and 1-45 µg mL(-1) for DP and RT, respectively. The proposed spectrophotometric methods can analyze both drugs without any prior separation steps. The selectivity of the adopted methods was tested by analyzing synthetic mixtures of the investigated drugs, also in their pharmaceutical formulation. The suggested methods were validated according to International Conference of Harmonization (ICH) guidelines and the results revealed that; they were precise and reproducible. All the obtained results were statistically compared with those of the reported method, where there was no significant difference.

Co-processed chitin-mannitol as a new excipient for Oro-dispersible tablets.

This study describes the preparation, characterization and performance of a novel excipient for use in oro-dispersible tablets (ODT). The excipient (Cop-CM) consists of chitin and mannitol. The excipient with optimal physicochemical properties was obtained at a chitin: mannitol ratio of 2:8 (w/w) and produced by roll compaction (RC). Differential scanning calorimetry (DSC), Fourier transform-Infrared (FT-IR), X-ray powder diffraction (XRPD) and scanning electron microscope (SEM) techniques were used to characterize Cop-CM, in addition to characterization of its powder and ODT dosage form. The effect of particle size distribution of Cop-CM was investigated and found to have no significant influence on the overall tablet physical properties. The compressibility parameter (a) for Cop-CM was calculated from a Kawakita plot and found to be higher (0.661) than that of mannitol (0.576) due to the presence of the highly compressible chitin (0.818). Montelukast sodium and domperidone ODTs produced, using Cop-CM, displayed excellent physicochemical properties. The exceptional binding, fast wetting and superdisintegration properties of Cop-CM, in comparison with commercially available co-processed ODT excipients, results in a unique multifunctional base which can successfully be used in the formulation of oro-dispersible and fast immediate release tablets.

Two sites of action for PLD2 inhibitors: The enzyme catalytic center and an allosteric, phosphoinositide biding pocket.

Phospholipase D (PLD) has been implicated in many physiological functions, such as chemotaxis and phagocytosis, as well as pathological functions, such as cancer cell invasion and metastasis. New inhibitors have been described that hamper the role of PLD in those pathologies but their site of action is not known. We have characterized the biochemical and biological behavior of the PLD1/2 dual inhibitor 5-Fluoro-2-indolyl des-chlorohalopemide (FIPI), and the specific PLD2 inhibitor, N-[2-[1-(3-Fluorophenyl)-4-oxo-1,3,-8-triazaspiro[4.5]dec-8-yl]ethyl]-2-naphthalenecarboxamide (NFOT), and found that both FIPI and NFOT are mixed-kinetics inhibitors. Mutagenesis studies indicate that FIPI binds at S757 of PLD2, which is within the HKD2 catalytic site of the enzyme, whereas NFOT binds to PLD2 at two different sites, one being at S757/S648 and another to an allosteric site that is a natural site occupied by PIP2 (R210/R212). This latter site, along with F244/L245/L246, forms a hydrophobic pocket in the PH domain. The mechanism of action of FIPI is a direct effect on the catalytic site (and as such inhibits both PLD1 and PLD2 isoforms), whereas PLD2 affects both the catalytic site (orthosteric) and blocks PIP2 binding to PLD2 (allosteric), which negates the natural enhancing role of PIP2. Moreover, NFOT prevents cell invasion of cancer cells, which does not occur in cells overexpressing PLD2-F244A/L245A/L246A, or PLD2-R210A/R212A, or PLD2-S757/S648 mutants. This study provides new specific knowledge of enzyme regulation and mechanisms of activation and inhibition of PLD2 that are necessary to understand its role in cell signaling and to develop new inhibitors for cancer cell invasion and metastasis.

The ultra-performance liquid chromatography determination of domperidone and its process-related impurities.

A rapid ultra-performance liquid chromatography (UPLC) method for the determination of domperidone in the presence of its process impurities and droperidol was developed and validated. The rapid chromatographic separation was achieved using a sub 2 µm Hypersil Zorbax eXtra Densely Bonded C18 column (30 × 4.6 mm, i.d., 1.8 µm). A gradient mobile phase consisting of Solvent A: 0.06 M ammonium acetate and Solvent B: methanol, with a flow rate of 1 mL/min was employed. The column temperature was set at 40°C, and the diode-array detector was set at 280 nm. An injection volume of 3 µL was used. The currently utilized European Pharmacopeia (Eur. Pharm.) method employed by Janssen Pharmaceuticals Ltd was run on a Hypersil Base-Deactivated Silica C18 column (100 × 4.6 mm, i.d., 3 µm) with a run time of 12.5 min. The developed UPLC method, with a run time of 7.5 min was determined to be accurate, precise, specific, robust and highly sensitive according to the International Conference on Harmonization guidelines. The method herein demonstrated a reduction in analysis time of 40%, allowing for a much higher sample throughput. A solvent consumption decrease of over 58% was also observed, which results in a dramatic reduction in running costs for Janssen Pharmaceuticals Ltd.

Evaluation and comparison of different brands of domperidone tablets available in Karachi, Pakistan.

Domperidone is an anti-dopaminergic drug used for the treatment of nausea, vomiting and dyspepsia. It has also been used in Parkinson's disease. In this study, five different brands of Domeperidone tablets were selected from the local market for evaluation of their quality as the local market is occupied of many competitors for a single generic. The evaluation of Domperidone tablets was done using various pharmacopoeial and non-pharmacopoeial tests. All the test results fell within BP specified limits for all the selected brands i.e. the results for Brands A to E for weight variation, thickness and diameter were satisfactory and within limits. For Brands A to E, the results for hardness and friability were also satisfactory i.e. 4-10kg/cm2and 0.1-0.6% respectively. The results for Brands A to E for disintegration were 2-6 minutes; for dissolution and assay, the results were 89-92% and 95-99% respectively. The results of similarity factor (f2) also showed that all brands of Domperidone have comparative dissolution profiles.

Liquid chromatography coupled with fluorimetric detection and third derivative synchronous fluorescence spectroscopy as two analytical methods for the simultaneous determination of rabeprazole sodium and domperidone after derivatization with 4-chloro-7-nitrobenzofurazan.

Two simple, sensitive, rapid, economic and validated methods, namely reversed phase liquid chromatography (method Ι) and third derivative synchronous fluorescence spectroscopy (method ΙΙ) have been developed for the simultaneous determination of rabeprazole sodium and domperidone in their laboratory prepared mixture after derivatization with 4-Chloro-7-nitrobenzofurazan. Reversed phase chromatography was conducted using a Zorbax® SB-Phenyl column (250.0 mm × 4.6 mm id) combined with a guard column at ambient temperature with fluorimetric detection at 540 nm after excitation at 483 nm. A mobile phase composed of a mixture of distilled water with methanol and acetonitrile in a ratio of 50:20:30 adjusted pH to 4 has been used at a flow rate of 1 mL/min. Sharp well resolved peaks were obtained for domperidone and rabeprazole sodium with retention times of 5.5 and 6.4 min respectively. While in method ΙΙ, the third-derivative spectra were estimated at 507 and 436 nm for rabeprazole sodium and domperidone respectively. Linearity ranges for rabeprazole sodium and domperidone respectively in both methods were found to be 0.15-2.0 and 0.1-1.5 µg/mL. The proposed methods were successfully applied for the analysis of the two compounds in their binary mixtures, and laboratory prepared tablets. The obtained results were favorably compared with those obtained by the comparison method. Furthermore, detailed validation procedure was also conducted.