Riboflavin Sodium Phosphate Research Articles

Bilinorm administration combined with Phototherapy in the management of neonatal jaundice: a hospital based clinical trial

Background: Neonatal jaundice (NJ) is a common problem worldwide and frequent in Iraq . Several reports were published on prevalence, distribution, causes and treatment of NJ.This clinical trial was carried out to demonstrate the effect of combinations of Castrol oil, riboflavin and magnesium in mechanical elimination of bilirubin after enhancing hepatic excretion by phototherapy.Patients & methods: This clinical trial included a total of 61 significantly jaundiced neonates who were admitted to the special care baby unit of Children Welfare Teaching Hospital, medical city complex, Baghdad, Iraq, during the period June 1st to Dec.31st 2007. Phototherapy was applied alone in 30 neonates (group 1) and phototherapy with Bilinorm in 31 neonates (group 2),(Bilinorm oral gel constituted of riboflavin sodium phosphate, magnesium oxide and castor oil). Student’s t test was used to examine the differences in variables between the two groups.Results: There were no significant differences between the two groups in body weight, age of onset of jaundice, age on admission, and TSB on admission (p =0.9,0.4, 0.4, 0.4, respectively). A significant difference in total decrease in TSB was noticed between group II (7.2 ± 2.4) and group I (5.9 ± 1.8)(p = 0.02). Days of hospitalization were significantly lower in group II (2.4 ± 0.8 days) than in group I (3.3 ± 1.5 days) (p = 0.009), and hours of phototherapy were significantly lower in group II (47.4 ± 19.7 hours) than in group I (66.8 ± 27.4 hours) (p= 0.002).Conclusions: There was a statistically significant difference regarding total decrease in TSB, days of hospitalization and hours of phototherapy when both Bilinorm and phototherapy were used than when phototherapy was used alone. So mechanical elimination of bilirubin from intestinal lumen may enhance the effect of phototherapy.

Management of Corneal Ectasia After LASIK with Combined, Same-Day, Topography-Guided Partial Transepithelial PRK and Collagen Cross-Linking: The Athens Protocol

To evaluate a series of patients with corneal ectasia after LASIK that underwent the Athens Protocol: combined topography-guided photorefractive keratectomy (PRK) to reduce or eliminate induced myopia and astigmatism followed by sequential, same-day ultraviolet A (UVA) corneal collagen cross-linking (CXL). Thirty-two consecutive corneal ectasia cases underwent transepithelial PRK (WaveLight ALLEGRETTO) immediately followed by CXL (3 mW/cm(2)) for 30 minutes using 0.1% topical riboflavin sodium phosphate. Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), manifest refraction spherical equivalent, keratometry, central ultrasonic pachymetry, corneal tomography (Oculus Pentacam), and endothelial cell counts were analyzed. Mean follow-up was 27 months (range: 6 to 59 months). Twenty-seven of 32 eyes had an improvement in UDVA and CDVA of 20/45 or better (2.25 logMAR) at last follow-up. Four eyes showed some topographic improvement but no improvement in CDVA. One of the treated eyes required a subsequent penetrating keratoplasty. Corneal haze grade 2 was present in 2 eyes. Combined, same-day, topography-guided PRK and CXL appeared to offer tomographic stability, even after long-term follow-up. Only 2 of 32 eyes had corneal ectasia progression after the intervention. Seventeen of 32 eyes appeared to have improvement in UDVA and CDVA with follow-up >1.5 years. This technique may offer an alternative in the management of iatrogenic corneal ectasia.

Ultrasound-assisted powder-coating technique to improve content uniformity of low-dose solid dosage forms

An ultrasound-assisted powder-coating technique was used to produce a homogeneous powder formulation of a low-dose active pharmaceutical ingredient (API). The powdered particles of microcrystalline cellulose (MCC; Avicel® PH-200) were coated with a 4% m/V aqueous solution of riboflavin sodium phosphate, producing a uniform drug layer on the particle surfaces. It was possible to regulate the amount of API in the treated powder. The thickness of the API layer on the surface of the MCC particles increased near linearly as the number of coating cycles increased, allowing a precise control of the drug content. The tablets (n = 950) prepared from the coated powder showed significantly improved weight and content uniformity in comparison with the reference tablets compressed from a physical binary powder mixture. This was due to the coated formulation remaining uniform during the entire tabletting process, whereas the physical mixture of the powders was subject to segregation. In conclusion, the ultrasound-assisted technique presented here is an effective tool for homogeneous drug coating of powders of irregular particle shape and broad particle size distribution, improving content uniformity of low-dose API in tablets, and consequently, ensuring the safe delivery of a potent active substance to patients.

In vivo evaluation of the vaginal distribution and retention of a multi-particulate pellet formulation

Non-disintegrating microcrystalline cellulose pellets (MCC) and disintegrating starch-based pellets were evaluated as new vaginal drug delivery forms and compared with a powder formulation. Pellets and powder were packed in a HPMC or hard gelatine capsule and vaginally administered to five series of five healthy volunteers. Distribution and retention of the multi-particulate formulation was monitored by colposcopy and swabbing. Capsule disintegration in the vagina was slow. MCC pellets clustered around the fornix 3h after administration, and after 24h only a few pellets were detected in the vaginal cavity. In contrast, starch-based pellets already started to disintegrate 6h after administration, resulting in a complete coverage of the vaginal mucosa after 24h in 8 out of 10 volunteers. The powder formulation had a better distribution after 6h, although after 24h almost no powder remained in the vagina. These results were confirmed by swabbing to determine the amount of riboflavin sodium phosphate (used as marker) distributed in the different vaginal regions.

Drug Release Phenomena Within a Hydrophobic Starch Acetate Matrix: FTIR Mapping of Tablets After In Vitro Dissolution Testing

The aim of this study was to assess the utility of Fourier transform infrared mapping to study the drug release phenomena within a hydrophobic matrix tablet. Starch acetate with a degree of substitution (2.7) was used as a hydrophobic matrix former. Anhydrous caffeine and riboflavin sodium phosphate were used as water soluble model drugs. The USP (XXVIII) paddle-method was selected as an in vitro dissolution test. Mapping of the diluted tablets' cross-section was performed by attenuated total reflection mode. Fourier transform infrared mapping can distinguish drug particles from the bulk matrix and it can be considered as a valuable method for obtaining both quantitative and qualitative information on drug release processes. The physicochemical properties of the drug compound strongly contribute to its release behavior when the USP paddle in vitro dissolution test is used. Mapping of the riboflavin product revealed a more homogenous matrix distribution due to its smaller particle size. Consequently, its dissolution release profile was more uniform than caffeine which possessed a wider particle size distribution and lower solubility. Mapping showed that caffeine became localized in the lower part of the tablet unlike riboflavin. The hydrodynamic conditions during the in vitro release test might contribute to this differentiation.

Porous hydroxyapatite tablets as carriers for low-dosed drugs

The present study evaluated an innovative technique for the manufacturing of low-dosed tablets. Tablets containing hydroxyapatite and a pore forming agent (50% (w/w) Avicel PH 200/20, 37.5% and 50% corn starch/37.5% sorbitol) were manufactured by direct compression followed by sintering. The influence of pore forming agent (type and concentration), sinter temperature and sinter time on tablet properties was investigated. Sintering (1250 °C) revealed tablets with an acceptable friability (<1%). Using 50% (w/w) Avicel PH 200 as pore forming agent resulted in tablets combining the highest porosity (50%) and the highest median pore diameter (5 μm). Aqueous drug solutions (metoprolol tartrate, riboflavin sodium phosphate) were spiked on the tablet surface. The maximum volume of drug solution absorbed was limited (2 × 100μl), revealing that these porous carriers were ideal for low dosed formulations. Drug release from the tablets was slow, independent of the drug. To accelerate drug release, tablets were manufactured using a modified gelcasting technique yielding tablets with a median pore size of 60 and 80 μm. Release from these tablets was drastically increased indicating that the permeability of the tablets was influenced by the pore size, shape and connectivity of the porous network. Changing and controlling these parameters made it possible to obtain drug delivery systems providing different drug delivery behaviour.

Sweet Potato Acid Phosphatase Immobilized on Glutaraldehyde-Activated Aminopropyl Controlled-Pore Glass: Activation, Repeated Use and Enzyme Fatigue

Sweet potato acid phosphatase was covalently coupled with glutaraldehyde to aminopropyl controlled-pore glass, and used as a pre-column enzyme reactor. The immobilized enzyme reactor (IMER) was continuously operated using an automated chromatographic detection system we developed. Functional evaluation of the IMER was carried out by injecting ten samples on the same day at an injection amount of 1.25 nmol (62.5 nmol per ml) using riboflavin sodium phosphate (FMNs) as a substrate, and by prolonged use for ten months. The IMER exhibited decreased activity after repeated use for a total of 3000 samples, but about 75% of its original activity remained. The conversion rate of FMNs to riboflavin by IMER was increased from 89 to 97% by adding citrate, ethylenediaminetetraacetic acid disodium salt, etc., but especially by adding citrate. The increased conversion of FMNs to riboflavin due to the addition of citrate was probably not due to the chelation of heavy metal ions by citrate. We also investigated complex formation of acid phosphatase with the substrate FMNs using surface plasmon resonance to determine the effect of citrate on the processes of association and/or dissociation between the enzyme and substrate. Enzyme fatigue was also observed during the course of prolonged and repeated use.

Simultaneous determination of ingredients in a vitamin-enriched drink by micellar electrokinetic chromatography

Micellar electrokinetic chromatography was used to simultaneously determine six active ingredients (2-aminoethanesulfonic acid, nicotinamide, pyridoxine hydrochloride, anhydrous caffeine, riboflavin sodium phosphate and thiamine nitrate) in a vitamin-enriched drink. All the active ingredients and the formulation excipients were successfully separated by micellar electrokinetic chromatography with 135 mM sodium dodecyl sulfate, and were subsequently detected using a diode-array detector operating at 210 nm. The peak shape of pyridoxine hydrochloride was improved by use of sodium tetraborate solution as sample solvent. Sample and standard solutions were stable for at least 24 h in a light-resistant container at room temperature. The established method was validated and demonstrated to be applicable to the determination of the active ingredients in a vitamin-enriched drink. Good linearities were obtained, with correlation coefficients above 0.999. Recoveries and precisions ranged from 99.0 to 101.2%, and from 0.4 to 2.5% RSD, respectively. The detection limit for ingredients ranged from 0.3 to 125 μg ml −1. These results suggest that micellar electrokinetic chromatography can be used for the determination of ingredients in vitamin-enriched drinks.

Diffusion of a freely water-soluble drug in aqueous enteric-coated pellets.

The effects of filler used in the pellet cores (ie, waxy cornstarch or lactose) and the enteric film coat thickness on the diffusion and dissolution of a freely soluble drug were studied. Two kinds of pellet cores containing riboflavin sodium phosphate as a model drug, microcrystalline cellulose (MCC) as a basic filler, and waxy cornstarch or lactose as a cofiller were film coated (theoretically weight increase 20% or 30%) with an aqueous dispersion of cellulose acetate phthalate (CAP). The diffusion of riboflavin sodium phosphate in aqueous enteric-coated pellets was investigated using noninvasive confocal laser scanning microscopy (CLSM). The in vitro release tests were performed using a USP apparatus I (basket method). Diffusion of drug from the core to the film coat was found to be greater with lactose-containing pellets than with waxy cornstarch-containing pellets. The dissolution test showed that 30% enteric-coated waxy cornstarch pellets had a good acidic resistance in 0.1 N HCl solution for at least 1 hour, while the other enteric pellet formulations failed the test. The waxy cornstarch-containing enteric pellets dissolved at SIF in less than 10 minutes. Confocal images of film-coated pellets showed that waxy cornstarch-containing pellets had less drug dissolved than respective lactose-containing pellets. The observations were further confirmed by measurement of fluorescence intensity of riboflavin sodium phosphate in the film coat. The dissolution test was consistent with the confocal microscopy results. In conclusion, waxy cornstarch as a cofiller in the pellet cores minimizes premature drug diffusion from the core into the film coat layer.

Amylopectin as a subcoating material improves the acidic resistance of enteric-coated pellets containing a freely soluble drug

The effect of an aqueous amylopectin subcoating on the acidic resistance and dissolution behaviour of enteric-coated pellets was studied. Freely water-soluble riboflavin sodium phosphate (RSP) was used as a model drug, and microcrystalline cellulose (MCC) and lactose as fillers in the pellet cores. The pellets were subcoated with 5% aqueous amylopectin solution or with 5% hydroxypropyl methylcellulose (HPMC) solution, and subsequently film-coated with aqueous dispersion of cellulose acetate phthalate (CAP). Drug release of enteric-coated pellets was investigated by confocal laser scanning microscopy (CLSM). Dissolution tests showed that amylopectin subcoating improved the acidic resistance of the enteric-coated pellets in 0.1 N hydrochloric acid (HCl) compared with HPMC subcoating. As the amylopectin subcoating load was increased to 4% and the aqueous CAP coating load to 35%, the coated pellets resisted in 0.1 N HCl solution for approximately 1 h (the amount of drug released was below 10%), and they dissolved in the SIF without enzymes in less than 10 min. Confocal microscopy images and profiles of mean fluorescence intensities of RSP (obtained in the range of the interface of the pellet core and the film and the film coating surface) showed consistent results with dissolution tests. It seems that amylopectin subcoating can prevent the influx of the dissolution medium into the pellet core, and thus decrease the premature dissolution and release of the drug from the enteric-coated pellets in 0.1 N HCl solution. The drug release mechanism appeared to be osmotically driven release, and followed by diffusion through the polymer film.

COUNTERCURRENT CHROMATOGRAPHIC SEPARATION OF WATER-SOLUBLE VITAMINS BY CROSS-AXIS COIL PLANET CENTRIFUGE USING AN ION-PAIR REAGENT WITH POLAR TWO-PHASE SOLVENT SYSTEM

Countercurrent chromatographic separation of water-soluble vitamins, such as riboflavin sodium phosphate, cyanocobalamin, riboflavin, pyridoxine hydrochloride, and thiamine nitrate was performed using the cross-axis coil planet centrifuge equipped with a pair of eccentric coil assemblies at off-center position. The solvent system used in the present studies was prepared by adding 1.5% of 1-octanesulfonic acid sodium salt, as an ion-pair reagent, to the polar two-phase solvent system composed of 1-butanol and aqueous 0.15 M monobasic potassium phosphate. The resolution was remarkably improved as compared with that obtained in our previous studies. Overall experimental results revealed that the cross-axis coil planet centrifuge is useful for the separation of extremely hydrophilic and ionic compounds, such as water-soluble vitamins, by adding a suitable ion-pair reagent to the polar two-phase solvent system.

Characterization of particle deformation during compression measured by confocal laser scanning microscopy

Direct compression of riboflavin sodium phosphate tablets was studied by confocal laser scanning microscopy (CLSM). The technique is non-invasive and generates three-dimensional (3D) images. Tablets of 1% riboflavin sodium phosphate with two grades of microcrystalline cellulose (MCC) were individually compressed at compression forces of 1.0 and 26.8 kN. The behaviour and deformation of drug particles on the upper and lower surfaces of the tablets were studied under compression forces. Even at the lower compression force, distinct recrystallized areas in the riboflavin sodium phosphate particles were observed in both Avicel PH-101 and Avicel PH-102 tablets. At the higher compression force, the recrystallization of riboflavin sodium phosphate was more extensive on the upper surface of the Avicel PH-102 tablet than the Avicel PH-101 tablet. The plastic deformation properties of both MCC grades reduced the fragmentation of riboflavin sodium phosphate particles. When compressed with MCC, riboflavin sodium phosphate behaved as a plastic material. The riboflavin sodium phosphate particles were more tightly bound on the upper surface of the tablet than on the lower surface, and this could also be clearly distinguished by CLSM. Drug deformation could not be visualized by other techniques. Confocal laser scanning microscopy provides valuable information on the internal mechanisms of direct compression of tablets.

Microencapsulation of apomorphine HCI with gelatin

Microspheres of apomorphine HCI were prepared, with gelatin as polymer coating material, using the emulsification solvent extraction method. The microencapsulation efficiency, particle size and release profile were compared to those of riboflavin sodium phosphate (RSPh). An efficiency of approximately 95% was obtained with RSPh while the quantity of acetone and ether used as preparative solvents resulted in low microencapsulation efficiency for apomorphine HCI. A reduction of the volumes of these solvents improved the efficiency by a factor of more than two but the mean particle size range became slightly higher due to agglomeration as compared to the mean particle size when more solvent was used. A faster release rate was found for RSPh than for apomorphine HCI, according their water solubilities. Crosslinking of gelatin-RSPh microspheres with formaldehyde and glutharaldehyde (10 and 20% v/v for 1, 6, and 24 h) did not extend the duration of release of RSPh and reduced the quantity of drug microencapsulated.

Formation of a Hydroxyl Radical from Riboflavin Sodium Phosphate by Photo-Illumination.

Photo-illumination of riboflavin sodium phosphate (Rp) with phenylalanine produced significant levels of o-tyrosine, m-tyrosine and p-tyrosine as hydroxylated products. The hydroxylation of Rp was pH-dependent, and the maximum rate was around pH 4.5. Replacement of air with nitrogen prevented the formation of tyrosine isomers while the addition of superoxide dismutase or catalase to this system prevented hydroxylation. The tyrosine formation by the system was significantly prevented by hydroxyl radical (HO·) scavengers such as potassium iodide, potassium bromide, thiourea and sodium formate. No free iron and cupric ions were detected in the reaction mixture by inductively-coupled plasma atomic emission spectrometry. Tha above results suggest that the formation of HO· may occur in the photochemical reactoin system in the presence of Rp under aerobic conditions, and that a superoxide radical and hydrogen peroxide may be involved in HO· formation.

High-Performance Liquid Chromatographic Determination of Riboflavin Sodium Phosphate Based on Its Conversion to Riboflavin with Acid Phosphatase.

High-Performance Liquid Chromatographic Determination of Riboflavin Sodium Phosphate Based on Its Conversion to Riboflavin with Acid Phosphatase.

Simultaneous Liquid Chromatographic Determination of Water-Soluble Vitamins, Caffeine, and Preservative in Oral Liquid Tonics

A rapid, simple, and reliable liquid chromatographic method has been developed for the simultaneous determination of nicotinamide (niacinamide), thiamine, riboflavin, riboflavin sodium phosphate, pyridoxine, caffeine, and sodium benzoate in commercial oral liquid tonics. The 7 components are separated on a reverse phase C18 column using a mobile phase of acetonitrile-0.01M potassium dihydrogen phosphate-triethylamine (8 + 91.5 + 0.5 v/v/v) containing 5mM sodium octanesulfonate and adjusted to pH 2.8 with phosphoric acid. Components are detected at 254 nm with attenuation 0.02 AUFS. Acetanilide is used as an internal standard. In addition to the 7 components mentioned, nicotinic acid (niacin), cyanocobalamin, and folic acid are also separated under the same conditions. Sample preparation involves only addition to internal standard solution and dilution with mobile phase and then filtration. Recoveries of the 7 components and cyanocobalamin from spiked preparations ranged from 97 to 104% with coefficients of variation of 0.9-4.2%.

塩酸リトドリンの輸液中での安定性

The stability of ritodrine hydrochloride (RTD) in infusion solution was studied by using highperformance liquid chromatography (HPLC) in consideration of the practical condition in hospitals. RTD was stable in the case of the single addition into infusion solution (5% glucose solution). However, the decomposition of RTD in infusion solution was promoted by the concomitant addition of the following injections: 20mg riboflavin sodium phosphate (B2), 20mg flavin adenine dinucleotide (FAD), 1M potassium chloride containing 3mg B2 (KCl), Adelavin No.9. When the solution was exposed to scatterd light (2000 lux, 6hrs), the residual rate of RTD was 37.5%, 69.4%, 60.1% and 81.4% in the presence of B2, FAD, KCl and Adelavin No.9 respectively, compared with 100.4% in the case of no addition. The decomposition of RTD, perhaps due to photooxidation sensitized by B2, was obviously suppressed by shading the light or adding the antioxidant such as vitamin C.As a main decomposed product of RTD, p-hydroxybenzaldehyde (PHA) was identified by HPLC.