Development and in vitro evaluation of mucoadhesive microsphere carriers for intranasal delivery of betahistine dihydrochloride.

The aim of the present work was to formulate and evaluate betahistine-loaded chitosan microspheres intended for nasal delivery with focus on their mucoadhesive properties. Betahistine-loaded chitosan microspheres were obtained via W/O emulsion solvent evaporation technique and were characterized for particle size, surphace morfology and entrapment efficiency. FTIR spectroscopy was carried out to evaluate drug-polymer interaction and powder X-ray diffractometry was applied to investigate crystallinity transformations. Tensile studies were carried out using sheep nasal mucosa to evaluate in vitro mucoadhesion. Drug release into phosphate buffer saline pH 7.4 was performed and dissolution profiles of the formulations were obtained. The results showed that the microspheres were spherical in shape having smooth surface and mean particle size of 3.82 µm to 7.69 µm which is appropriate for optimum deposition in the nasal cavity. The mean particle size increased when chitosan solutions with higher viscosity were used. In vitro mucoadhesion studies indicated that chitosan microspheres had good mucoadhesive properties and could adequately adhere to nasal mucosa. It was observed that polymer concentration enhancement led to increased mucoadhesive strength. Betahistine release studies from the microspheres showed similar and slightly icreasing dissolution profiles. Acording to the obtained results, betahistine-loaded chitosan microspheres prepared by solvent evaporation method proved to be capable of sustained release and could be used via nasal route as an alternative to oral administration

BIOLOGICAL ACTIVITY OF BULGARIAN FOLIA BETULAE DRY EXTRACT

Objective: The aim of this study was to investigate the biological activity of dry Folia Betulae (FB) extract.Methods: Extracts from birch leaves were obtained by different technological methods–maceration and percolation, extraction with different concentrations of ethanol, changes in temperature regimen. The influence of the technological factors on the content of the biologically active substances (BAS) was examined. A phytochemical characterization of the extracts and their standardization were made, according to important groups of BAS–flavonoids (rutin, quercetin) and terpenes (betulin and betulinic acid), by means of HPLC methods for detection and quantitative determination. A model extract, with optimal content of BAS was chosen for subsequent in vitro investigation of its biological activity. Antimicrobial activity was studied via in vitro tests using bacterial isolates–Staphylococcus aureus, Escherichia coli and Candida albicans. The physiological activity was investigated by using in vitro test with smooth muscle strips. The antiproliferative activity of FB extract on eukaryotic cells was examined on cell cultures in vitro. Two cell cultures were used: the mouse lymphoma cell line L5178Y and the serum-free McCoy-Plovdiv cells.Results: The dry extract from FB has a dose–dependent antibacterial effect. The bactericidal effect on Staphylococcus aureus is stronger than the one on Escherichia coli. Results prove that adding the extract leads to stimulating effect on muscle contractility. It demonstrates biological activity, expressed as changes in cell morphology, proliferation and vitality as well as initiation of apoptosis.Conclusion: The results obtained largely overlap with literature data and explain some of the applications of this plant in traditional medicine.Â

Advanced spectrophotometric chemometric methods for resolving the binary mixture of doxylamine succinate and pyridoxine hydrochloride

The prediction power of partial least squares (PLS) and multivariate curve resolution-alternating least squares (MCR-ALS) methods have been studied for simultaneous quantitative analysis of the binary drug combination – doxylamine succinate and pyridoxine hydrochloride. Analysis of first-order UV overlapped spectra was performed using different PLS models – classical PLS1 and PLS2 as well as partial robust M-regression (PRM). These linear models were compared to MCR-ALS with equality and correlation constraints (MCR-ALS-CC). All techniques operated within the full spectral region and extracted maximum information for the drugs analysed. The developed chemometric methods were validated on external sample sets and were applied to the analyses of pharmaceutical formulations. The obtained statistical parameters were satisfactory for calibration and validation sets. All developed methods can be successfully applied for simultaneous spectrophotometric determination of doxylamine and pyridoxine both in laboratory-prepared mixtures and commercial dosage forms

Carbopol hydrogel/sorbitan monostearate-almond oil based organogel biphasic formulations: Preparation and characterization of the bigels

Purpose: To obtain and evaluate carbopol hydrogel/sorbitan monostearate-almond oil-based organogel biphasic formulations (bigels) as a semi-solid vehicle for medicated topical applications.Methods: Bigel formulations were obtained under mild conditions at a hydrogel/organogel ratio of 80/20, 70/30, and 60/40 (w/w). Their stability, viscosity, spreadability, microarchitecture, and acute skin toxicity were evaluated.Results: Two formulations, prepared at ratios of 80/20 and 70/30, were stable based on intermediate stability testing, and had a similar viscosity and spreadability (38.0 ± 1.0 mm and 37.3 ± 0.6 mm, p > 0.05, respectively). Both of these formulations had a bimodal droplet size distribution and very similar values for the droplet mean diameter (0.33 ± 0.05 μm and 2.35 ± 0.44; and 0.34 ± 0.04 μm and 2.59 ± 0.21 μm). The formulation obtained at a ratio of 60/40 was unstable during storage. The in vivo results did not reveal any signs of skin toxicity.Conclusion: Considering their beneficial properties, the developed bigels are a potential semi-solid vehicle for topical application and exhibit a moisturizing effect.Keywords: Almond oil, Bigels, Carbopol hydrogel, Moisturizing effect, Organogel, Sorbitan monostearat

EYE DROPSWITH NANOPARTICLES AS DRUG DELIVERY SYSTEMS

Objective: The objective of this study was to examine and characterize topical eye drops with indomethacin-loaded poly(vinyl acetate) nanoparticles (IMC-p(VAc)-NPs).Methods: IMC-p(VAc)-NPswere obtained by emulsifier-free radical homopolymerization of the monomers in the presence of indomethacin in water and in an aqueous solution of Carbopol®. Thus obtained indomethacin nanocarriers-()- were included in topical ophthalmic formulations. (Hydroxypropyl)methyl cellulose was used in different concentrations to increase the viscosity of the eye drops. Rheological characteristics, the surface tension, the ocular tolerance according to In Vitro hen's egg test–chorioallantoic membrane-, and the indomethacinrelease from the eye drops models were studied.Results: The investigation of the rheological characteristics and the surface tension of the (hydroxypropyl)methyl cellulosesolutions showed the suitable concentrations as an excipient increasing the viscosity of the eye drops with IMC-p(VAc)-NPs. In Vitro study of the indomethacinrelease from the eye drops showed that the investigated nanocarriers had a different behavior according to the releaseddrugfrom the NPs in phosphate-phosphate buffer at pH 7.4. No signs of ocular irritation were detected within 5 min according toIn Vitrohen's egg test–chorioallantoicmembrane -for the investigated IMC-p(VAc)-NPs, contrary to the indomethacinsubstance.Conclusion: The obtained results prove the possibility to prepare topical eye drops with IMC-p(VAc)-NPs as a drug delivery systems and give reasons to continue the research in this direction.Keywords: Indomethacin-loaded nanoparticles, HPMC, Carbopol coated nanoparticles, Eye drops, In Vitro HET-CAM

Taste Masking of Enalapril Maleate by the Precipitation Method

Background: Taste masking of bitter or unpleasant drugs is an important prerequisite to improve patient compliance, especially for children and elderly patients. We aimed at obtaining taste-masked microparticles intended for incorporation into orodispersible tablets (ODTs). We selected the precipitation method using enalapril maleate (ENA) as a model bitter-tasting drug and Eudragit EPO® as a pH sensitive polymer.Aim: The aim of this study was to obtain microparticles with enalapril maleate by the precipitation method in order to mask the bitter taste of the drug.Materials and methods: Nine models of enalapril maleate – Eudragit EPO® microparticles were prepared by the precipitation method at varied drug-polymer ratios. The models were characterized in terms of size, shape, production yield, drug content, encapsulation efficiency and moisture content. Fourier-transformed infrared spectroscopy, powder X-ray diffraction and differential scanning calorimetry were used to analyze possible interactions in the complex. In vitro drug release in simulated salivary fluid and in vivo taste evaluation in rats were realized to prove taste masking.Results: The particle size distribution varied from 266.9 µm to 410.9 µm. The shape of the resulting particles was irregular. The production yield varied from 23.6% to 78.2%. The drug content ranged between 2.3% to 4.8%, encapsulation efficiency increased from 1.6% to 9.0%. In vitro drug release data indicated significant taste masking.Conclusion: Some of the obtained microparticles by the precipitation method showed satisfactory taste masking efficiency, which proved the taste masking feasibility of this method

Formulation And Performance Evaluation Of Betahistine Dihydrochloride Microspheres As Sustained Release Systems

Бетагистин дигидрохлорид представляет собой гистаминовый аналог, широко применяемый для облегчения симптомов, сопутствующих синдром Мениера. По данным фармакокинетических исследований бетагистамин имеет краткую плазменную полужизнь - 3.4 ч. В таких случаях, чтобы поддерживать концентрацию плазмы во время терапевтического „окна”, приходится вводить лекарственное вещество часто, через небольшие интервалы. Это может привести к отсутствию содействия при проведении лечения со стороны пациента, как и к ухудшению его комфорта. Современный подход достижения удлиненного освобождения лекарства заключается в его включении в частицы-носители. ЦЕЛЬ: Разработать лекарство-доставляющую систему с удлиненным освобождением бетагистина, что способствовало бы уменьшению частоты приема и снижению риска появления нежелательных лекарственных реакций. МАТЕРИАЛЫ И МЕТОДЫ: Микросферы получены через W/О эмульсионную технику с испарением растворителя и охарактеризованы по отношению к их размеру, оличественному содержанию бетагистина и эффективности нагрузки. Освобождение с бетагистином, приготовленные через эмульсионную технику с испарением растворителя, показывают склонность к удлиненному освобождению и имеют потенциал лекарствено-освобождающих систем при лечении синдрома Мениер

Advanced spectrophotometric chemometric methods for resolving the binary mixture of doxylamine succinate and pyridoxine hydrochloride

The prediction power of partial least squares (PLS) and multivariate curve resolution-alternating least squares (MCR-ALS) methods have been studied for simultaneous quantitative analysis of the binary drug combination - doxylamine succinate and pyridoxine hydrochloride. Analysis of first-order UV overlapped spectra was performed using different PLS models - classical PLS1 and PLS2 as well as partial robust M-regression (PRM). These linear models were compared to MCR-ALS with equality and correlation constraints (MCR-ALS-CC). All techniques operated within the full spectral region and extracted maximum information for the drugs analysed. The developed chemometric methods were validated on external sample sets and were applied to the analyses of pharmaceutical formulations. The obtained statistical parameters were satisfactory for calibration and validation sets. All developed methods can be successfully applied for simultaneous spectrophotometric determination of doxylamine and pyridoxine both in laboratory-prepared mixtures and commercial dosage forms

Optimization of Chitosan Microspheres Spray Drying via 32 Full Factorial Design

Background: Generally, the preparation of spray-dried microspheres is strongly affected by the process parameters. Particle size and production yield are mainly influenced by the spraying solution concentration and the pump rate of the spray dryer

Analysis of the pharmacotherapeutic effectiveness of the tyrosine kinase inhibitors therapy in patients with Chronic Myeloid Leukemia in a single hematology center in Plovdiv, Bulgaria

Aim. The aim of this study is to evaluate treatment retrospectively, response to the therapy and outcomes in patients with chronic myeloid leukemia (CML) and to what extent the European recommendations of LeukemiaNET (ELN) are followed at the Hematology Clinic, University Hospital “St. Georgi”, MU Plovdiv. Methods. All patients with Ph+, BCR-ABL1+ CML who were treated and observed between 01.01.2018 and 12.31.2022 at the clinic were included in the study and were analyzed retrospectively. Results. One hundred and eighty-eight patients with a mean age of 61.26 (21–91) years were analyzed. 151 (80.3%) were in chronic phase (CP), 27 (14.4%) in accelerating one and 10 (5.3%) in blast crisis. The actual overall survival rate was 79.26%, while for CP it is very high – 86.75%, and the mortality rate is 20.74%. All patients received some form of tyrosine kinase inhibitors therapy (TKIs-therapy). The first line TKI was imatinib in 120 patients (64%), and 68 (36%) received a second-generation TKI. Treatment response was monitored with TKIs by RT-qPCR. Conclusion. CML patients treated in the hematology clinic receive standard care in accordance with ELN and BMSH recommendations. Overall survival (OS) in routine care is comparable to published data from international studies. Molecular monitoring provides a good basis for disease control in CP. There are unmet needs in the treatment of patients in advanced stages