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A dissolution test method and an analytical procedure by HPLC were developed and validated for evaluation of the dissolution behavior of dietary supplements tablets containing vitamin A in the forms of retinyl acetate or retinyl palmitate. Seven different commercially available products containing retinyl acetate or retinyl palmitate were selected...
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Context 1
... supplement tablets for this study were purchased from various stores in Rockville, MD, USA. Composition of the products according to the label claims is reported in Table 1. USP Vitamin A Reference Standard (RS) Lot W0F-126 (with a certified con- tent of 30.0 mg of vitamin A acetate in 1 g of peanut oil solution) (Rockville, MD, USA) was used as the reference material. ...
Context 2
... of the sample A (Table 1) were used as the blank samples to rule out possible interferences from the typical dietary ingredi- ents and excipients in the HPLC system. One tablet was placed in the dissolution vessel containing 900 ml of the dissolution medium at 37 ± 0.5 • C and stirred for 1 h at 75 rpm using USP Apparatus 2. An aliquot was collected, filtered through a 0.45-m Millex-HV syringe filter, and analyzed by HPLC, showing no interference at the locus of the analytes of interest. ...
Context 3
... dietary supplement products containing vitamin A in the form of retinyl acetate or retinyl palmitate with different strengths and from 7 different manufacturers were used for the dissolu- tion study (Table 1). Two different rotation speeds, 50 and 75 rpm, were evaluated using USP Apparatus 2 and 900 ml of dissolution medium. ...
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Citations
... The recoveries are also similar to the previous recovery rates of reverse phase analysis of retinyl palmitate conducted by Wang and Huang (85-96%), [33] Wielinski and Olszanowski (99.2%) [12] and Davydova et al. (98.0%). [39] A very common silica column was used for chromatographic separation (stationary phase) of retinyl palmitate with UV detector. Usually, when any lipid portion is directly injected into the HPLC system, there is always a risk of declining separation efficiency as well as the lifespan of the HPLC column. ...
... which is similar to the value reported by Wielinski and Olszanowski [12] (Intra-day: 1.34%; Intra-day: 0.82-1.1%) and Davydova et al. [39] (Intra-day: 0.6-1.2%; Intra-day: 0.4-1.5%). ...
Fortification of edible oil with retinyl palmitate (vitamin A) is a significant advancement to fulfill the nutritional deficiency of major population. The growing interest in the enrichment of foods warrants a simple and accurate method to analyze fortified products. This study developed an easy and reliable strategy based on normal-phase HPLC analysis to determine the edible oil’s retinyl palmitate. We also validated the method according to the International Conference on Harmonization (ICH) guidelines. The analysis was performed with a DB silica column (250 cm × 4.6 mm; 5 μm), with a mobile phase composed of n-heptane and isopropyl alcohol at a ratio of 75:25 v/v and a flow rate of 1.0 ml/min. The detection was performed at a wavelength of 326 nm, and the retention time of vitamin A was around 8 min, with a total run time of 10 min. The calibration plot gave a linear relationship (R² = 0.9998) over the concentration range of 3.93–63 μg/ml. The LOD and LOQ were 0.029 and 0.096 μg/ml, respectively. The accuracy of the proposed method was determined by recovery studies and was found with a mean recovery of >95%. RSD% of the determination of precision was <2%. The results of robustness and solutions stability studies were within acceptable limits. The proposed method showed excellent linearity, accuracy, precision, specificity, robustness, LOD, LOQ, and system suitability results within the acceptable criteria.
... Nadal niewiele jest badań dotyczących dostępności farmaceutycznej suplementów diety. Niezależnie przeprowadzone eksperymenty według wytycznych Farmakopei Amerykańskiej dowodzą jednak, że niektóre z przebadanych suplementów diety z witaminą A [61], luteiną [62] oraz żelazem [63] charakteryzowały się niskim uwalnianiem substancji czynnej z postaci produktu. Badane produkty w kapsułkach z luteiną uwolniły zaledwie 20% substancji w ciągu 180 min badania, podczas gdy z tabletek uwolniło się nie mniej niż 80% w tym samym czasie [62]. ...
... Ponadto w dwóch produktach nie stwierdzono obecności deklarowanego stężenia luteiny [62]. Podobne wyniki stwierdzono dla suplementów z witaminą A, które uwalniały ponad 80% substancji aktywnej w ciągu 45 min, jednak dwa produkty nie spełniły tego warunku, a w przypadku jednego w ogóle nie stwierdzono obecności witaminy A [61]. • Suplementacja żelaza (w dawce ustalonej przez lekarza) u niemowląt urodzonych przedwcześnie (z masą urodzeniową 2000-2500 g), z ciąż mnogich lub dzieci matek z niedokrwistością podczas ciąży; • U wszystkich noworodków po urodzeniu wskazane jest jednorazowe podanie witaminy K (0,5 mg domięśniowo lub 2,0 mg doustnie). ...
Abstrakt
Rynek suplementów diety rozwija się bardzo dynamicznie, co ma związek z rozpowszechnieniem tej kategorii produktów w środkach masowego przekazu, stosunkowo bezproblemową procedurą wprowadzenia na polski rynek oraz powszechną dostępnością (można je nabyć w aptece, sklepach zielarskich, spożywczych oraz w Internecie). Z definicji suplementy mają być uzupełnieniem diety, zaliczają się do żywności oraz nie mogą wykazywać działania leczniczego. Ich postać, która została ustawowo określona, może być wizualnie identyczna z postacią farmaceutyczną produktów leczniczych, co może wprowadzać konsumentów w błąd, jeżeli nie wiedzą, jak rozróżniać te dwie grupy. Polska legislacja nie uwzględnia żadnych wymogów dotyczących parametrów technologicznych czy właściwości fizycznych gotowych produktów. Na bezpieczeństwo stosowania suplementów diety, oprócz ich jakości i rzeczywistej zawartości deklarowanych składników, składa się również ewentualna obecność zanieczyszczeń i niedozwolonych substancji dodatkowych. Wybiórcza kontrola rynku oraz brak szczegółowych wytycznych dotyczących parametrów postaci suplementów daje znaczną dowolność producentom, jednocześnie umożliwia wprowadzenie na rynek produktów o wątpliwej jakości, które mogą zagrażać konsumentom, będąc całkowicie pozbawionymi działania prozdrowotnego. Ze względu na rosnące zainteresowanie tą grupą produktów przez konsumentów, przedstawiono w pracy sytuację prawną suplementów diety na polskim rynku, odnosząc się także do legislacji europejskiej i amerykańskiej. Omówiono procedurę wprowadzania na rynek, podstawowe wytyczne stawiane tej grupie produktów, wskazania do stosowania oraz aspekty związane z bezpieczeństwem i zagrożeniami wynikającymi ze stosowania suplementów diety.
... Ograniczona jest ilość informacji na temat dostępności farmaceutycznej suplementów diety. Część z nich dowodzi jednak, że suplementy diety zawierające luteinę [30], żelazo [31] czy witaminę A [32] charakteryzują się niskim uwalnianiem substancji czynnej z postaci leku. ...
Suplementy diety na przestrzeni ostatniego dziesięciolecia na stałe wpisały się w świadomość konsumentów na całym świecie. Reklamę tych produktów można znaleźć w środkach masowego przekazu, takich jak, radio, telewizja, prasa, internet. Każda apteka oferuje szeroki asortyment suplementów diety, ponadto produkty te są nabywane w internecie oraz w sklepach. Według danych zawartych w raporcie statystycznym prawie 72% Polaków deklaruje przyjmowanie suplementów diety, z czego połowa przyjmuje je regularnie. Niezwykle proste jest wprowadzenie do obrotu tego typu preparatów. Jedynym wymogiem jest złożenie w siedzibie Głównego Inspektoratu Sanitarnego stosownego oświadczenia. Sprawia to, że rynek suplementów diety w Polsce rozwija się bardzo dynamicznie. Suplementy diety klasyfikowane są jako środki spożywcze. W odróżnieniu od produktów leczniczych nie są one badane pod kątem trwałości, interakcji czy potencjalnych działań niepożądanych. Badania jakości suplementów diety potwierdzają, iż niejednokrotnie preparaty te zawierają niezadeklarowane substancje lub substancje w dawce innej niż deklarowana przez producenta bądź też substancja nie uwalnia się z postaci farmaceutycznej. Stanowi to niekiedy zagrożenie dla zdrowia osób przyjmujących suplementy diety, a jednocześnie jest uzasadnieniem konieczności poddawania ich odpowiednim badaniom jakościowym.
... Repeatability or precision, on the other hand, is measured by repeated measurements of the samples both in terms of changes in time of the assay (inter-day, between-day) or laboratories. For repeatability, six dis- [77] solution samples prepared from same dissolution apparatus are used, whereas for intermediate precision, sets of six dissolution samples prepared by employing different analysts with different instruments are used [8,27]. If the absolute mean difference after the measurements does not exceed 10% at time points with less than 85% dissolved and does not exceed 5% for time points equal to or above 85%, then the results are considered as acceptable for intermediate precision. ...
After oral administration, drug absorption from solid dosage forms depend on the release of the drug active compounds from the dosage form, the dissolution or solubilization of the drug under physiological conditions, and the permeability across the gastrointestinal tract. Dissolution testing is an essential part of designing more effective solid dosage forms in pharmaceutical industry. Moreover dissolution testing contributes to the selection of appropriate formulation excipients for improving the dosage form efficiency. This study aims to analyze in-vitro drug dissolution testing in solid dosage forms since 2010 in order to present a comprehensive outlook of recent trends. In doing that the previous studies in the literature are summarized in the form of a table to demonstrate the apparatuses used for dissolution testing, the media in which the solid dosage form is dissolved, the method preferred for analysis from dissolution media, the conditions of analyses and the results obtained.
... The amount of lutein claimed in these products ranges from 2 to 10 mg per dosage and the daily recommended dosage suggested is one pharmaceutical unit per day (Anvisa, 2016). However, the quality of an oral dosage depends on its ability to release the active substance into aqueous media to facilitate its availability for gastrointestinal absorption (Azarmi, Roa, & Lobenberg, 2007;Davydova, Stippler, Jin, & Giancaspro, 2010). ...
Lutein is a carotenoid with antioxidant activity that is present in various dosage forms. The bioavailability of carotenoid from oral dosage formulations depends on their release, dissolution and its permeability through the gastrointestinal tract. Here, a dissolution test was developed for evaluating formulations and the bioavailability was assessed. The test utilized a USP-apparatus II with rotations of 50, 75 and 100 rpm in water with P80 at 1, 2 and 5% (w/v). A non-everted rat intestinal sac model was used in conjunction to assess the intestinal permeability. The most discriminative conditions were 100 rpm in water with 2% polysorbate 80, which showed profile differences between two formulations. The intestinal permeation studies showed a lag-time and apparent permeability coefficient that were characteristic of highly permeable drugs. We suggest that a dissolution test can be an essential quality control tool for formulations containing compounds as lutein, although not mandatory by the regulation agencies.
... The need for a surfactant and its particular concentration can be justified from drug substance solubility investigations, that include all common surfactant types, anionic (i.e., sodium dodecyl sulfate (SDS)), cationic (i.e., cetyltrimethyl ammonium bromide (CTAB)) and nonionic (i.e., polysorbate 80 (Tween 80) or (octoxynol 9 (Triton X100))) [17,25,28,8,9,26]. When a suitable surfactant has been identified, different concentrations should be investigated to identify the lowest concentration needed to achieve sink conditions for the dissolution test. ...
... SDS (Spectrum s , Lot 2DH221), CTAB (MP Biomedicals, Lot MR31911), Tween 80 (Fisher s , Lot 132307) and Triton X100 (Fisher s , Lot 136597) were selected since they are the surfactants most commonly used un dissolution media [17,25,26,28,8,9]. ...
The United States Pharmacopeia (USP) General Chapters Dissolution 〈711〉 and Disintegration and Dissolution of Dietary Supplements 〈2040〉 allows the use of enzymes in dissolution media when gelatin capsules do not conform to dissolution specifications due to cross linking. Possible interactions between enzymes and surfactants when used together in dissolution media could result in loss of the enzymatic activity. Pepsin is an enzyme commonly used in dissolution media, and in this work, the activity of pepsin was determined in the presence of different surfactants as usually found in case of dissolution tests of certain gelatin capsule formulations.
Pepsin enzymatic activity was determined according to the Ninth Edition of the Food Chemicals Codex (FCC) 9 method, in dissolution conditions: simulated gastric fluid, 37 °C and 50 rpm. Sodium dodecyl sulfate (SDS), cetyltrimethyl ammonium bromide (CTAB), polysorbate 80 (Tween 80) and octoxynol 9 (Triton X100) in concentrations above and below their critical micellar concentrations were selected. Results showed a significant reduction in the activity of pepsin at all the concentrations of SDS assayed. On the contrary, CTAB, Tween 80, and Triton X100 did not alter the enzymatic activity at of pepsin any of the concentration assayed.
This data demonstrates a rational selection of the surfactant to be used when pepsin is required in dissolution test.
... Encapsulation yield was determined after vitamin extraction from beads (n = 2). Briefly, VA was extracted from 20 mg of beads ground using a mortar in 30 mL of phosphate buffer (pH 6.8) supplemented with (+)-sodium L-ascorbate and 1% of Octoxynol 9 (Davydova, Stippler, Jin, & Giancaspro, 2010). The analysis was carried out, just before in vitro dissolution studies, by UV/visible spectrophotometry (Uvikon XS Ò Secomam, Alès, France) at 325 nm. ...
... Each medium was prepared freshly (i.e. the day of use). The composition of both dissolution media was suggested by Davydova et al. (2010), where (+)-sodium L-ascorbate and Octoxynol 9 were respectively used for their antioxidant and surfactant properties. ...
... The dissolution test of drugs has been employed as an excellent tool to detect formulation problems that could change drug release in the body (6). The quality of oral solid dosage forms depends on their ability to release the active components in aqueous medium in a consistent and reproducible manner, making the active substances available for gastrointestinal absorption (7). ...
Sitagliptin phosphate is a drug used to treat diabetes mellitus type 2, and it belongs to a new therapeutic class called dipeptidyl peptidase IV inhibitors. This hypoglycemic drug is commercially available in coated tablets containing 25, 50, and 100 mg of sitagliptin base. The purpose of this study was to develop and validate the conditions for the dissolution test by investigating a possible in vivo-in vitro correlation. Several parameters were tested to develop the method, and the following conditions were considered satisfactory: pH 6.8 phosphate buffer, 900 mL of dissolution medium, temperature at 37 ± 1 °C, paddle apparatus, and rotation speed at 50 rpm. The dissolved percentage of STG was quantified by high performance liquid chromatography. The sink condition and specificity were determined in all media tested during method development. The parameters evaluated to validate the method were specificity, linearity, precision, and accuracy. The stability of the sample in phosphate buffer solutions for 24 h was also determined. The method is linear in the range of 10.0-70.0 μg/mL, precise, with RSD values less than 2%, and accurate (mean recovery 98.51%). The dissolution method as developed and validated supplied a good IVIVC when employing pH 6.8 phosphate buffer medium, which can be used in quality control of sitagliptin coated tablets since no official method has been described.
... Generic and therapeutic substitution raises concerns about whether it serves the interests of patients or the target of reducing healthcare related costs. Although the total drug costs to the NHS, in 2007, was only 10.3% of the total budget, drug substitution is highly favoured within the NHS to reduce healthcare expenditure ( Davydova et al., 2010). ...
Drug substitution is mainly economically not medically-driven; it can benefit healthcare services but does not directly benefit individual patients. Many healthcare providers have been promoting drug substitution in an attempt to contain their costs. This practice has been approved and supported on the basis of the presumption that the cheaper drug is not inferior to the more expensive one and the premise that any saving that does not compromise the quality of care is essentially appropriate. However, substitutions become problematic when the cheaper drug is known to have different effects and side effects, or even when there is just uncertainty about such effects. This thesis explores issues surrounding generic and therapeutic substitution from the ethical, patients’ and physicians’ point of view and from the potential differences in formulations between the branded and generic medicines. A series of studies such as a review of the ethical issues in drug substitution, multicentre surveys to explore patients’ and physicians’ views on drug substitution and other in-vitro and in-vivo comparisons between the actual formulations of the branded medicines and their generic counterparts were included in this thesis. The main objective was to encourage safe and effective generic and therapeutic substitution by validating the appropriateness and the potential impact of these substitutions on patients’ clinical outcomes and thus to promote high quality strategic logistic planning and effective management of drug formularies in hospitals. It was confirmed in this thesis that promoting generic and therapeutic substitution on economic grounds alone is unethical because it can be potentially harmful to patients and is incompatible with patient-centred medicine. As a consequence, multicentre surveys were conducted to assess patients’ views on generic substitution in hospital settings. A total of 163 renal transplant patients were surveyed using 36 multiple-choice questions at Barts and The London Renal Transplant Clinic, in the UK. This group of patients was specified because they may be particularly affected by drug substitution. Any small changes in the medicinal effect of this group of patients can negatively impact their clinical outcome. It was revealed in this survey that 84% of participating patients felt that generic medicines were not equivalent or only equivalent sometimes and they were uncertain that generics had the same quality as branded medicines. In addition, many patients admitted that they would refuse the generic substitution of ciclosporin when it became available in the UK. Another multicentre survey in the United Arab Emirates (UAE) using 188 renal patients revealed that 68% of participating patients felt that generics were not equivalent or only equivalent sometimes, and they were uncertain that generics had the same quality as branded medicines. Therefore, many patients admitted that they would refuse the generic substitution of ciclosporin when become available. These beliefs were highly marked in patients with less education, less communication with healthcare professionals and who suspected that the cheaper drug substitution was implemented only to save costs. In another prescription based survey in the UAE, a random sampling of 1000 written prescriptions was analysed to determine physicians’ attitudes towards generic medicines and prescribing. It was explored in this study that prescribers were not yet ready to promote appropriate generic substitution. They were still prescribing generic medicines on occasions where health complications may occur as well as increase healthcare expenditure. As a result, improving awareness and education among physicians is compulsory to implement appropriate generic prescribing and substitution. In-vitro dissolution study was also conducted in this thesis to detect any potential differences in dissolution behaviour between the branded medicines and their generic counterparts. A total of 37 medicines (13 innovator medicines and 24 generic counterparts) were collected locally and internationally and tested according to the British Pharmacopeia, European Pharmacopeia and the US Pharmacopeia with the rate of dissolution determined by ultra-violet Spectrophotometer. It was marked in this study that some generic medicines showed significant differences in dissolution rate at 60 and 120 minutes compared to their branded counterparts. Other generics violated the EMA and the FDA guidelines for industry when they failed to achieve 85% dissolution at 60 minutes and to keep the same dosage form as their branded counterparts. Moreover, a bioequivalence study was carried out in this thesis using 24 healthy volunteers under fasting conditions to compare Resclar 500 mg (Neopharma, UAE) with its branded Klacid® 500 mg (Abbott Laboratories Ltd, England), both are macrolide antibiotics contain 500 mg clarithromycin per tablet. It was confirmed in this study that Resclar 500 mg met the regulatory definition of bioequivalence with Klacid® 500 mg as the innovator product based on a single dose comparative bioavailability study under fasting conditions in the selected healthy volunteers. Therefore, Resclar 500 mg could provide an acceptable prescribable alternative to Klacic® 500 mg. In conclusion, the results presented in this thesis suggested that randomly and economically-driven drug substitution can be potentially deleterious to patients and should not be promoted. Factors such as physicians and patients education, monitoring, severity of the disease and efficacy of generic medicines are essential to promote safe and effective drug substitution. Thus, to achieve excellent strategic logistic planning and effective management of drug formularies in hospitals, generic and therapeutic substitution should be solely based on providing patients with the best possible care and quality medicines.
... The release of the aroma compounds (n-hexanal and D-limonene blend) was carried out in triplicate using the rotating paddle method (AT7 Smart., Sotax, Basel) at 25 and 37 ± 1°C and 50 rpm up to 100 and 1300 min (Davydova et al., 2010). Four hundred milligrams of each film were incorporated in the dissolution medium (1000 mL). ...
This work analyses the release of n-hexanal and d-limonene from edible films, previously encapsulated in the iota-carrageenan matrix (with and without lipid). Both volatile compounds have different physico-chemical properties. The effect of temperature (25 °C and 37 °C) and dissolution medium (water and 0.9% NaCl) on the release and retention of aroma compounds were studied. Hydrophobicity and wettability properties of active iota-carrageenan films were also studied and they were related with the internal and surface microstructure of films. Results highlight that d-limonene is encapsulated in the lipid phase of the films decreasing the release in the salt medium. d-limonene, the most hydrophobic, was more sensitive to the temperature changes than hexanal. Thus, this work gives an idea of the release of aroma compounds encapsulated in iota-carrageenan films in aqueous media.
