Assessing compatibility of excipients selected for a sustained release formulation of bilberry leaf extract

Abstract The study is aimed to assess the compatibility of bilberry leaf powder extract (BLPE) with six excipients selected for sustained-release (SR) tablet formulation. The BLPE was obtained with the addition of L-arginine and Myo-inositol as the carriers. Thermogravimetric (TG-DTG) analysis and Fourier-transform infrared spectroscopy (FTIR), supported by Pearson correlation analysis, were applied to detect possible interactions in the binary mixtures (1:1) of the BLPE with each excipient. The TG-DTG showed some deviations in the thermal behavior of the BLPE / excipient mixtures. However, only the thermal behavior of magnesium stearate in the mixture significantly differed from individual samples, which suggested chemical interaction for this excipient. The FTIR analysis confirmed that the BLPE is compatible with Eudragit L100, Methocel K4M, Methocel K100LV, Avicel PH-101, and Plasdone S-630. Whereas it undergoes solid-state chemical interaction in the binary mixture with magnesium stearate. According to the FTIR-spectra, it is suggested that this interaction results in the formation of stearic acid and alkalization of the medium. These findings evidence for the possibility of using TG-DTG analysis as an independent thermal technique for compatibility studies and also confirm the earlier reported interaction of basic lubricants, e.g., stearic salts, with active ingredients containing amino groups.

Impact of Compression Force on Mechanical, Textural, Release and Chewing Perception Properties of Compressible Medicated Chewing Gums.

Medicated chewing gums (MCGs) represent a beneficial platform for realizing drugs intended for dental prophylaxis and treatment. The present study aimed to investigate the impact of compression force on the mechanical, textural, release, and chewing perception characteristics of compressible MCGs with the combination of lysozyme hydrochloride (LH) and ascorbic acid (AsA). Four batches of MCGs were obtained on a laboratory single-punch tablet machine applying different forces, i.e., 5, 7, 10, and 15 kN, and evaluated by their geometrical parameters, mechanical resistance, surface and internal structure characteristics, texture profile, release behavior, and perception attributes during mastication. It was found that increasing compression force slightly affected resistance to crushing and friability of MCGs, but resulted in surface smoothing and formation of a thicker layer with highly compacted particle arrangement. According to the texture analysis, increasing compression force led to harder and more adhesive gums, indicating possible difficulties in chewing and, therefore, impairment of their consumer properties. Lower compression forces were also found to be preferable in terms of better drug release from the obtained chewing gums. The volunteers' assessment showed that an increase of compression force led to significantly raising the initial hardness and crumbliness as well as to decreasing the rate of the integral gum mass formation during mastication, which may negatively affect perceptive sensations when using MCGs. Based on the results obtained, the optimal compressing force was selected to be 7 kN, which allows obtaining MCGs with good organoleptic, mechanical, textural, and release properties.

Formulation development of anti-stress compressed lozenges using a fractional factorial Latin cube design and ANOVA approach.

The aim of this work was to develop anti-stress compressed lozenges containing 100 mg of glycine and 250 mg of magnesium citrate obtained by the direct compression method. To choose optimal excipient composition providing the sufficient pharmaco-technical properties of the tablet blend, mechanical strength of tablets and non-disintegrating, slow-dissolving behavior of compressed lozenges during sucking, 27 experimental formulations according to fractional factorial Latin cube design were prepared and tested. The excipients used in the study were: Mannogem® EZ, Cellactose® 80 and GalenIQ 721 (fillers); Plasdone S-630, Kollidon® 90 F and Avicel® PH-101 (dry binders); Metolose® 90SH-4000SR and guar gum (gel-forming binders); PRUV®, Neusilin® US2, and Compritol® 888 CG ATO (antifriction excipients). The following parameters were investigated as responses: bulk density, Carrs index, friability, resistance to crushing, and in vitro disintegration time. ANOVA approach was applied for statistical processing, which allowed to reveal the individual effects of each excipient and several interaction effects observed for the excipient amounts used in this study. Isomalt (GalenIQ 721), copovidone (Plasdone S-630), and glyceryl behenate (Compritol® 888 CG ATO) were selected to be incorporated in the final formulation of compressed lozenges.

Development and uniformity evaluation of low-dose medicated chewing gums prepared by compression method.

The aim of this work was to develop medicated chewing gums (MCGs) containing 10 mg of lysozyme hydrochloride (LH) and 20 mg of ascorbic acid (AsA) obtained by the compression method with Health in Gum® (HiG®) PWD 01 as a compressible gum base. Because of a low content of active ingredients, it was essential to choose the way of adding them to the tableting mass and evaluate their distribution homogeneity in the dosage units. The blends for compression were prepared by two methods: the first one was simple mixing of all components; the second one included the step of wet granulation of a three-component mixture - LH, sucralose and a taste additive. Flow properties of LH, AsA, HiG®, LH granules and blends for compression were studied. MCGs were evaluated according to Ph.Eur. 9.0 Chapters 2.9.5, 2.9.6 and 2.9.40. AsA and HiG® were characterized as free flowing, while LH had insufficient flow properties. Compared with a simple mixed blend, the granulation step allowed significantly improving flow properties of the final blend for compression. Unlike MCGs compressed from the simple mixed blend, MCGs prepared through the granulation step met Ph.Eur. 9.0 Chapter 2.9.40 requirements. The propriety of MCG preparation method involving the step of wet granulation also has been confirmed by mass and drug content uniformity tests.

Evaluation of anti-obesity and lipid-lowering properties of Vaccinium myrtillus leaves powder extract in a hamster model.

Background Vaccinium myrtillus leaves are known to be rich in phenols and have been used in traditional medicine as an antidiabetic remedy. This study evaluated the powder extract of V. myrtillus leaves obtained with the use of L-arginine and myo-inositol for anti-obesity and lipid-lowering potential in hamsters. Methods Standard phytochemical methods were used to determine the total phenolic and total flavonoid contents of the extract. The obesity condition was induced in Syrian hamsters by feeding them with highly palatable fat- and sugar-rich diet (40.3 kcal% fat) for 12 weeks. From the 10th week of diet feeding, the obese hamsters were treated with the powder extract of V. myrtillus leaves (15, 25 and 35 mg/kg/day, respectively) and "Styfimol" (6.2 mg/kg/day of hydroxycitric acid) as a positive control drug. At the end of the treatment period, the biochemical parameters as well as visceral fat mass were determined. Results Vaccinium myrtillus leaves powder extract at 25 and 35 mg/kg/day caused a significant reduction in body weight gain and visceral fat mass in obese hamsters. Serum triacylglycerols, free fatty acids, total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels were also significantly lower. Besides, the hamsters treated with powder extract at 25 and 35 mg/kg/day had the closest intact value ratio of high-density lipoprotein cholesterol and LDL-C compared with positive control animals. Conclusions The results showed that V. myrtillus leaves powder extract is a promising therapeutic agent for the treatment of obesity and obesity-induced diseases.