Nasal carriage of Staphylococcus aureus in children with grass pollen-induced allergic rhinitis and the effect of polyvalent mechanical bacterial lysate immunostimulation on carriage status: A randomized controlled trial.

BACKGROUND: Numerous studies indicate that Staphylococcus aureus (S. aureus) colonizing the nasal cavity plays a role in the pathogenesis of allergic rhinitis (AR). This bacterium is able to produce a variety of toxins with superantigenic properties that can exacerbate allergic inflammation. OBJECTIVE: The objective of the study was to evaluate the ability of polyvalent mechanical bacterial lysate (PMBL) to eliminate S. aureus nasal carriage in children with grass pollen-induced AR. METHODS: This randomized, double-blind, placebo-controlled study included 80 children aged 5-17 years with seasonal AR (SAR). At the randomization visit and after 12 weeks of the study, a swab was taken from the region of the middle nasal meatus. Standard microbiology culture and identification techniques were used to analyze the swab contents. RESULTS: Nasal colonization by S. aureus was confirmed in 29 children (42%), with Moraxella catarrhalis in three participants (4.4%). Physiological flora was detected in 37 children. No statistically significant differences were observed between the two measurement points in both the PMBL and placebo groups with respect to the number of patients whose nasal swab cultures showed a growth of S. aureus (p = 1). Both groups also showed no significant changes in the mean number of S. aureus colonies in nasal swab cultures taken at baseline and after 12 weeks of the study (PMBL group p = .41; placebo group p = .16). CONCLUSION: Almost every second child with SAR is S. aureus nasal carrier. Sublingual administration of PMBL in children with grass pollen-induced AR did not affect S. aureus nasal colonization. Therefore, PMBL should not be used for the eradication of S. aureus from the nasal cavity.

Polyvalent Mechanical Bacterial Lysate Administration Improves the Clinical Course of Grass Pollen-Induced Allergic Rhinitis in Children: A Randomized Controlled Trial.

BACKGROUND: Recent studies highlight the immunoregulatory potential of bacterial lysates, indicating their potential use in the prevention and treatment of allergic diseases. OBJECTIVE: To investigate the clinical efficacy of polyvalent mechanical bacterial lysates (PMBLs) in children with grass pollen-induced allergic rhinitis. METHODS: Seventy children with seasonal allergic rhinitis were enrolled to this study and were randomly assigned to the PMBL and placebo groups. Severity of seasonal allergic rhinitis symptoms was assessed by the total nasal symptom score, total ocular symptom score, and visual analogue scale. During 3 visits, peak nasal inspiratory flow was measured, and nasal smears for the presence of eosinophils and nasal lavage fluids for the presence of allergen-specific IgE against timothy grass pollen allergens were sampled. RESULTS: A statistically significant decrease in total nasal symptom score (P = .001), total ocular symptom score (P = .04), and visual analogue scale score for nasal and eye symptoms (P < .001 and P < .001, respectively) and an increase in peak nasal inspiratory flow (P = .04) were observed in the PMBL group versus the placebo group. During the grass pollen season, an increase and then a decrease in the number of eosinophils in nasal smears was observed in both groups; however, the number of eosinophils was significantly lower in the PMBL group versus the placebo group. No significant changes in allergen-specific IgE concentrations were observed in the PMBL group, whereas in the placebo group a statistically significant increase in allergen-specific IgE concentration was observed. CONCLUSIONS: Sublingual administration of PMBLs during the grass pollen season offers significant efficacy in alleviating seasonal allergic rhinitis symptoms in children sensitized to grass pollen allergens. PMBLs probably affect mucosal immunity, weakening the response of TH2 cells.

Bioaccessibility of phenolic compounds, lutein, and bioelements of preparations containing Chlorella vulgaris in artificial digestive juices.

Chlorella vulgaris Beijerinck is a spherical, green alga belonging to the genus Chlorella and family Chlorellaceae. It has high nutritional value and shows multiple biological effects. Dietary supplements that contain extracts of C. vulgaris are sold in the form of tablets, capsules, powders, and aqueous solutions. To the best of our knowledge, this is the first study to determine the content of bioelements (zinc, iron, and magnesium), phenolic compounds, and lutein before and after incubation with artificial digestive juices from preparations containing C. vulgaris. In this study, we used commercial preparations in the form of powder and tablets. The samples were incubated in artificial gastric juice and then in artificial intestinal juice for 30 and 90 min. The contents of bioelements were determined by using the flame atomic absorption spectrometric method. Lutein and phenolic compounds were analyzed by high-pressure liquid chromatography. We also aimed to evaluate the quality of chlorella-containing formulations by using the methods described in the European Pharmacopoeia 8th edition. According to the results, the preparations containing C. vulgaris demonstrated the presence of phenolic compounds and lutein. Therefore, daily supplementation of preparations containing C. vulgaris substantiates its usefulness for humans. The qualitative composition of the examined organic substances and bioelements was found to be in accordance with the manufacturer's declarations on the packaging containing C. vulgaris compared with the control samples; however, the contents of bioelements were found to be negligible after incubation with artificial digestive juices. This shows that the examined preparations containing C. vulgaris are not good sources of bioelements such as zinc, iron, or magnesium.

THE PROCESS OF MASS TRANSFER ON THE SOLID-LIQUID BOUNDARY LAYER DURING THE RELEASE OF DICLOFENAC SODIUM AND PAPAVERINE HYDROCHLORIDE FROM TABLETS IN A PADDLE APPARATUS.

The release study of diclofenac sodium (DIC) and papaverine hydrochloride (PAP) from two formulations of the tablets in the paddle apparatus using different rotation speeds to characterize the process of mass transfer on the solid-liquid boundary layer was carried out. The dissolution process of active substances was described by values of mass transfer coefficients, the diffusion boundary layer thickness and dimensionless numbers (Sh and Re). The values of calculated parameters showed that the release of DIC and PAP from tablets comprising potato starch proceeded faster than from tablets containing HPMC and microcrystalline cellulose. They were obtained by direct dependencies between Sh and Re in the range from 75 rpm to 125 rpm for both substances from all tablets. The description of the dissolution process with the dimensionless numbers make it possible to plan the drug with the required release profile under given in vitro conditions.

DISSOLUTION PROPERTIES AND KINETIC STUDY OF SULFADIMIDINE AND TRIMETHOPRIM TABLETS CONTAINING FOUR DIFFERENT SUPERDISINTEGRANTS.

The objective of this study was to evaluate and compare the effect of four superdisintegrants such as croscarmellose sodium (Ac-Di-Sol), crospovidone (Kollidon CL and with smaller particle sizes Kollidon CL-F), sodium starch glycolate (Explotab) in combination with ß-lactose and microcrystalline cellulose (Avicel PH-102) as base excipients exhibiting properties of directly compressed tablets and increasing the disintegration and the dissolution rate of sulfadimidine sodium (SDD-Na) and trimethoprim (TMP). All tablets were prepared by direct compression method and superdisintegrants were used at 2% for all formulations. The tablets were evaluated with regard to uniformity of weight, hardness, friability, drug content, disintegration time and dissolution properties. Dissolution properties such as t50% and t80% (time to release 50 and 80% of drug), DP3045 (percent of drug dissolved in 30 and 45 min) and the dissolution rate constant value (K) were considered in comparing the dissolution results. The results showed that crospovidone (Kollidon CL) provides the shortest disintegration time and the fastest rate of dissolution for both TMP and SDD-Na. The kinetic study of the dissolution data reveals that in vitro release profiles of TMP and SDD-Na can be best explained by first order model or by Higuchi model. The obtained data were plotted into Korsmeyer-Peppas equation to find out the confirmed diffusion mechanism. For TMP release, the values of the release exponent are beyond the limits of Korsmeyer model, so-called, power law. For SDD-Na release, exponent values are characteristic for anomalous transport (non-Fickian) or the value of the release exponent is beyond the limits of Korsmeyer model.

PHARMACOKINETICS OF DICLOFENAC SODIUM AND PAPAVERINE HYDROCHLORIDE AFTER ORAL ADMINISTRATION OF TABLETS TO RABBITS.

Non-compartmental pharmacokinetic analysis of diclofenac sodium (DIC) and papaverine hydrochloride (PAP) after oral administration of composed tablets to rabbits was developed. HPLC method for determination of DIC and PAP in rabbit plasma was developed and validated. Chromatographic separation of DIC, PAP and the IS was achieved on a Zorbax SB C18 5-µm column (150 mm x 4.6 mm) using methanol-water (55:45, v/v) as mobile phase at a flow rate of 0.8 mL/min. Pharmacokinetic analysis showed that oral administration of a tablet composed of DIC and PAP do not change the pharmacokinetic parameters such as MRT, MAT, Cl and bioavailability of the active substances compared with single administration of DIC and PAP after single dose.

The effect of excipients on the release kinetics of diclofenac sodium and papaverine hydrochloride from composed tablets.

For increased analgesic effect, new composed tablets containing diclofenac sodium (DIC) with an addition of papaverine hydrochloride (PAP) were prepared to investigate the mechanism of release of the active substances from tablets with different excipients in eight different formulations. To detect the possible interactions between active substances and excipients differential scanning calorimetry (DSC) was used. A shift of the melting point and enthalpy values of the physical mixtures of tablets components suggested a kind of interaction between components in certain formulations, however, the tabletting process was not disturbed in any of them. Kinetics of drug release from formulations was estimated by zero order, first order and Higuchi and Korsmeyer-Peppas models using results of dissolution of DIC and PAP from tablets. The study revealed that the mechanism of release of active substances was dependent on the excipients contained in tablets and the best fitted kinetics models were obtained for formulations with potentially prolonged release of DIC and PAP.

[Application of ß-cyclodextrin in the formulation of ODT tablets containing ibuprofen]. / Zastosowanie ß-cyklodekstryn w formulacji tabletek ODT zawierajacych ibuprofen.

BACKGROUND: Oral disintegrating tablet (ODT) dissolves or disintegrates in saliva and then it is swallowed. Diluent in direct compression formulation has a dual role: it increases bulk of the dosage form and it promotes binding of the constituent particles of the formulation. Hence, selection of diluent is important in tablets produced by direct compression method. OBJECTIVES: The aim of this work was to exame feasibility of preparing and optimizing oral disintegrating tablet formulation using ß-cyclodextrin as a diluent. MATERIAL AND METHODS: 400 mg round tablets were prepared by direct compression method on single punch tablet press using flat plain-face. 60% ß-CD and MCC (microcrystalline cellulose - MCC-Vivapur 102) were used at different proportions for all the formulations. 5% of Kollidon CL was added as superdisintegrant. The eight formulations prepared were assessed for weight variation, thickness, disintegration time, hardness and dissolution rate according to FP IX. A dissolution test was performed at 37ºC using the paddle method at 50 rpm with 900 mL phosphate buffer (pH 6.8) as a dissolution medium. RESULTS: The content of ibuprofen sodium was found inside the ± 5% of the theoretical value. Hardness values of presented tablets were in the range 0.11-0.15 kG/mm2. Friability of the tablets lower than 1% indicates that the developed formulations can be processed and handled without excessive care. Disintegration time was in the range of 86 to 161 s. CONCLUSIONS: The results confirm the good mechanical properties of tablets containing ß-CD. A composition with 20% ß-CD and 40% MCC fulfilled a maximum requisite of an optimum formulation. These properties were similar to Ludiflash, the formulation used for comparison purposes. In the present study, higher concentration of ß cyclodextrin was found to improve the hardness of tablets without increasing the disintegration time.

[Production and assessing release of imipramine and magnesium from tablets]. / Technologia otrzymywania i ocena uwalniania imipraminy i magnezu z tabletek.

BACKGROUND: In the pharmaceutical technology there is a trend to produce tablets composed of several medicinal substances to increase therapeutic effect and reduce the frequency of drug administration. In the literature there are reports concerning pharmacological studies in which a potentiation of the effects has been observed after a co-administration of antidepressant imipramine and magnesium. Currently, there is no formulation on the market comprising imipramine and magnesium, therefore, it was decided to produce uncoated tablets. In order to prepare the tablets by direct compression, it was necessary to select suitable excipients. OBJECTIVES: The aim of the study was to elaborate the composition and to prepare the tablets with imipramine and magnesium, as well as to assess the quality of the tablets by physical characteristics and by the release study of the active substances. MATERIAL AND METHODS: In order to prepare the tablets, compositions of different polymers and other excipients were added. The tablets were produced by direct compression method in a tablet press. Physical properties of the obtained tablets and the release of the active substances into an acidic medium in a paddle apparatus were tested. The contents of imipramine and magnesium were determined by different methods: spectrophotometrically and atomic absorption spectrometry, respectively. RESULTS: The composition of excipients necessary to produce tablets comprising imipramine and magnesium was established. All of prepared tablets were in compliance with the pharmacopoeial requirements. The release tests showed that above 80% of imipramine was released within 20-35 min and 80-76% of magnesium up to 45 min from the composed tablets and one-ingredient tablets, respectively. CONCLUSIONS: The compositions of excipients for tablets consisting of imipramine and magnesium were presented. The active substances were released within 45 min in the acidic medium, and the administration of these substances in the composed tablets did not affect pharmaceutical availability.

[Modern polymers in matrix tablets technology]. / Nowoczesne polimery w technologii tabletek matrycowych.

Matrix tablets are the most popular method of oral drug administration, and polymeric materials have been used broadly in matrix formulations to modify and modulate drug release rate. The main goal of the system is to extend drug release profiles to maintain a constant in vivo plasma drug concentration and a consistent pharmacological effect. Polymeric matrix tablets offer a great potential as oral controlled drug delivery systems. Cellulose derivatives, like hydroxypropyl methylcellulose (HPMC) are often used as matrix formers. However, also other types of polymers can be used for this purpose including: Kollidon SR, acrylic acid polymers such as Eudragits and Carbopols. Nevertheless, polymers of natural origin like: carragens, chitosan and alginates widely used in the food and cosmetics industry are now coming to the fore of pharmaceutical research and are used in matrix tablets technology. Modern polymers allow to obtain matrix tablets by 3D printing, which enables to develop new formulation types. In this paper, the polymers used in matrix tablets technology and examples of their applications were described.

Release kinetics of papaverine hydrochloride from tablets with different excipients.

The influence of excipients on the disintegration times of tablets and the release of papaverine hydrochloride (PAP) from tablets were studied. Ten different formulations of tablets with PAP were prepared by direct powder compression. Different binders, disintegrants, fillers, and lubricants were used as excipients. The release of PAP was carried out in the paddle apparatus using 0.1 N HCl as a dissolution medium. The results of the disintegration times of tablets showed that six formulations can be classified as fast dissolving tablets (FDT). FDT formulations contained Avicel PH 101, Avicel PH 102, mannitol, (3-lactose, PVP K 10, gelatinized starch (CPharmGel), Prosolv Easy Tab, Prosolv SMCC 90, magnesium stearate, and the addition of disintegrants such as AcDiSol and Kollidon CL. Drug release kinetics were estimated by the zero- and first-order, Higuchi release rate, and Korsmeyer-Peppas models. Two formulations of the tablets containing PVP (K10) (10%), CPharmGel (10% and 25%), and Prosolv Easy Tab (44% and 60%) without the addition of a disintegrant were well-fitted to the kinetics models such as the Higuchi and zero-order, which are suitable for controlled- or sustained-release.

Polysaccharide formulation for improvement of racemic vitamin E bioavailability.

The relative bioavailability of polysaccharide--racemic vitamin E preparation in comparison with a commercial product was assessed in a kinetic study of plasma alpha-tocopherol in rabbits. Six male rabbits were used in a cross-over design. Alpha-Tocopherol levels were determined by the fluorometric method. A secondary peak in alpha-Tocopherol plasma concentration--time profiles was observed in connection with enterohepatic circulation of vitamin E. A simple one-compartment pharmacokinetic model was proposed to explain enterohepatic circulation of alpha-tocopherol in rabbits. On the basis of the results obtained, it is apparent that polysaccharide--vitamin E preparation achieved a higher rate and extent of absorption. The total AUC of experimental preparation was 1.78-fold greater than that of a commercial capsule preparation, suggesting an increase of bioavailability by 78%.