Latest Articles from Folia Medica Latest 23 Articles from Folia Medica https://foliamedica.bg/ Fri, 29 Mar 2024 08:29:34 +0200 Pensoft FeedCreator https://foliamedica.bg/i/logo.jpg Latest Articles from Folia Medica https://foliamedica.bg/ In vitro antiviral activities of fruit extract from Lycium barbarum and methylxanthines extracted from Pu-erh and Bancha tea leaves https://foliamedica.bg/article/68987/ Folia Medica 64(5): 817-823

DOI: 10.3897/folmed.64.e68987

Authors: Neli Vilhelmova, Ivanka Nikolova, Kaloyan D. Georgiev, Iliya J. Slavov

Abstract: Introduction: Based on traditional medicine, many countries use various plant products (fruits, leaves and other plant parts) as food supplements or in the form of tea. The use of these plant sources has been established through the years of use and the proven benefits of their ingredients to improve human health. Aim: In the present study, we have focused on the effect of Lycium barbarum fruit extract and methylxanthines isolated from Pu-erh (MXP) and Bancha (MXB) tea leaves on Herpes simplex virus type 1 (HSV-1), poliovirus 1 (PV1) and coxsackievirus B1 (CVB1) virus in vitro. Materials and methods: We used in vitro antiviral and virus attachment assays to determine the effects of the three extracts we studied. Results: None of the extracts showed significant inhibition of replication of the three treated viruses but a remarkable inhibitory effect on extracellular virions of HSV-1 was exhibited 30 minutes after exposure, especially by the Lycium barbarum extract. The inhibitory effect of the three extracts on the level of adsorption of the HSV-1 to sensitive cells (MDBK) was also significant, with the most pronounced effect of the MXP. The protective effect of the extracts against herpes infection on healthy cells was also determined, the MXP showing the most notable effect. Conclusions: The three studied extracts can be used effectively in the treatment of herpes infections, as well as in infections with other enveloped viruses.

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Original Article Mon, 31 Oct 2022 19:59:00 +0200
Stability study of extemporaneously compounded nitrofurantoin oral suspensions for pediatric patients https://foliamedica.bg/article/72334/ Folia Medica 64(5): 807-816

DOI: 10.3897/folmed.64.e72334

Authors: Ivaylo Pehlivanov, Stanila Stoeva, Apostol Simitchiev, Stanislav Stefanov, Velichka Andonova

Abstract: Aim: To evaluate the stability of nitrofurantoin suspended in different extemporaneously compounded vehicles after storage at 4°C and at 25°C. To formulate an effective, readily available vehicle that can guarantee extended stability and precise dosing. Materials and methods: Nitrofurantoin was suspended at a concentration of 10 mg/mL in seven different vehicles compounded of different blends of Syrupus simplex, sorbitol 70%, methylcellulose 1%, gummi arabici 1%, gummi xanthani 1%, and sodium carboxymethylcellulose (NaCMC) 1%. Samples of 100 mL of every compounded suspension were stored in dark in graded glass bottles at 4°C and at 25°C. Samples were analyzed at the beginning and every 10 days up to day 30 and every 30 days after. Variations of physical properties such as sedimentation, ease of resuspension, color and odor were evaluated visually and organoleptically. Rheological analysis was also performed in order to determine suspensions’ behavior during storage and dosing. Variations in nitrofurantoin concentration and pH were evaluated with suitable analytical procedure (UV-Vis; HPLC; pH/ORP). Microbiological stability was evaluated via incubation on suitable culture media. Results: To the 30th day, only three of the compounded suspensions exhibited significant physical stability and slight change in taste and odor stored at both temperatures. Two samples stored at 25°C exhibited nitrofurantoin concentration greater than 95% and 4 samples stored at 4°C – concentration greater than 95%. All models showed no microbial growth up to day 30. At 120 days, only three of the compounded suspensions, stored at 4°C, exhibited relatively high nitrofurantoin concentrations: 88.2%, 92%, and 81.1%, respectively. Only one model suspension showed chemical and physical stability (≥95% of the initial concentration) for 102 days. No model suspension remained sterile after 30 days. Conclusions: The suspensions compounded with vehicles of blends of syrups, xanthan, croscarmellose (NaCMC), and sorbitol exhibited low to none sedimentation, good uniformity of content and are suitable organoleptically for pediatric administration. The model suspension stored at 4°C (NTF VII 4°C – with major excipients: sucrose 16%, sorbitol 17%, xanthan gum 0.25%, NaCMC 0.25%) stands out with nitrofurantoin concentration higher than 95% along with no or little signs of sedimentation. After adding a suitable preservative agent or system, a formulation with these characteristics might have an expiration date of at least 90 days.

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Original Article Mon, 31 Oct 2022 19:59:00 +0200
Gestational diabetes mellitus: a growing economic concern https://foliamedica.bg/article/65693/ Folia Medica 64(5): 725-732

DOI: 10.3897/folmed.64.e65693

Authors: Radiana Staynova, Emanuela Vasileva, Vesselina Yanachkova

Abstract: Gestational diabetes mellitus (GDM) is a common pregnancy complication. Recent epidemiological data have shown that GDM prevalence has been on the increase worldwide. GDM could lead to adverse pregnancy outcomes and is usually associated with higher costs for its treatment and management. Pharmacoeconomics has become a crucial component of the healthcare systems in recent years because of the steadily rising costs. Despite this, there are few pharmacoeconomic studies evaluating the expenses of pregnancies impacted by GDM. This article presents a brief introduction to pharmacoeconomics and provides awareness of the economic impact of GDM. Studies associated with health care costs of GDM were reviewed and an attempt was made to determine its global economic burden.

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Review Mon, 31 Oct 2022 16:19:00 +0200
A recent solidification approach for nanosuspension: formulation, optimisation and evaluation of canagliflozin immediate release pellets https://foliamedica.bg/article/68866/ Folia Medica 64(3): 488-500

DOI: 10.3897/folmed.64.e68866

Authors: Nisha C. Patel, Hitesh A. Patel

Abstract: Abstract Introduction: Canagliflozin is a BCS class IV drug. Nanosuspension is known to enhance the saturation solubility and dissolution rate of poorly soluble drugs owing to the increased surface area of nanosized particles. Aim: In the present study, we aimed to improve the dissolution characteristics of a poorly water-soluble drug canagliflozin by nanosuspension formulation and stability of this solubility enhancing system - nanosuspension can be improved by converting them into solidified forms as immediate release pellets. Materials and methods: Canagliflozin nanosuspension was formulated using the media milling method. Poloxamer 407 was used to stabilise nanosuspension. Prepared nanosuspensions were subjected to the characterisation of particle size, polydispersity index (PDI), and drug content. Optimised nanosuspension (NS1) was solidified by converting into immediate release pellets: as improved stability, where canagliflozin nanosuspension was used as a binder. Pellets were prepared by +extrusion-spheronization technique using microcrystalline cellulose (MCC) as pelletizing aid and sodium starch glycolate as super disintegrant. Different important process parameters e.g. concentration of sodium starch glycolate (A), spheronization speed (B) and spheronization time (C) were investigated by 23 factorial design to accomplish desired disintegration time (R1) and drug release at 10 min (R2). Results: The optimised nanosuspension had 120.5 nm particle size, 99.14% drug content and the optimised immediate release pellets (PF5) disintegrated within 23.29 second, and had 99.11% drug content. In vitro dissolution studies showed 89.59% drug release within 10 min in 0.75% w/v SLS. Scanning electron microscopy (SEM) confirmed uniform and spherically shaped pellets. Fourier transform infrared spectrometry (FTIR) and differential scanning calorimetry (DSC) analysis reveal no significant interaction between drug and excipients. Conclusions: It can be concluded from the findings of this study that the formulation of nanosuspension and its use as a binder in the formulation of immediate release pellets should be investigated further in order to improve the dissolution rate and formulation stability.

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Original Article Thu, 30 Jun 2022 20:00:16 +0300
Pharmaceutical care for patients with headache https://foliamedica.bg/article/63095/ Folia Medica 64(3): 373-379

DOI: 10.3897/folmed.64.e63095

Authors: Evelina Z. Gavazova, Daniela D. Grekova-Kafalova

Abstract: Introduction: Headache cephalalgia is the condition in which individuals feel pain in different parts of the head. It is one of the most common disorders believed to be amenable to self-treatment. The pharmacist can provide significant support to patients. Aim: The aim of this study was to present the role of pharmacists in the prevention of headaches. Materials and methods: We reviewed the available information in the biggest databases on the problem. Results: Drug therapy is only part of an effective approach to the management of headaches. In many cases headache triggers can be identified and lifestyle changes instituted that reduce the frequency of attacks. Rest, sleep, and adequate hydration are often important components of successful management regimes. Patient education and detailed information for their disease can play an active role in the treatment. The reviewed literature shows the importance of the involvement of community pharmacists of the treatment of headache disorders. As the most easily approachable healthcare providers pharmacists can assist patients in finding appropriate relief of headaches and ensure rational and safe headache treatment. Conclusions: Pharmacists have a crucial role in optimizing the results of the medical therapy.

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Review Thu, 30 Jun 2022 20:00:01 +0300
Lead content in weight loss food supplements https://foliamedica.bg/article/62123/ Folia Medica 64(2): 296-301

DOI: 10.3897/folmed.64.e62123

Authors: Stanislava D Ivanova, Velislava Todorova, Kalin V. Ivanov

Abstract: Introduction: The control and prevention of lead exposure are widely discussed topics that seem to be current health concerns for the next decades. Ingestion of lead into the human body can cause toxicity which can be acute or chronic. Possible sources of lead exposure can be, among others, water, food, drugs, and food supplements. The lead content in drugs is a strictly controlled parameter worldwide. The different Pharmacopoeias (European, British, USA) provide information about the limits for lead in every drug substance and also about the tests that should be performed. Regulation of food supplements does not require obligatory analytical control. Often, these products are not monitored to ensure the quality. At the same time, during the last two decades, the global use of dietary supplements has increased manifold. Aim: This study aimed to analyse the presence of lead in food supplements used for weight control. Materials and methods: We have analysed 30 different samples of food supplements for lead content. These supplements are all sold as weight loss products. The method of analysis consists of determination the lead concentration in food supplements using inductively coupled plasma mass spectrometry. Results: We found that 4 of the analysed samples provide a lead intake of between 2.339 and 2.88 μg per day. The lead content in the other 26 samples was not significant. Conclusions: The regulation of food supplements is rather liberal and loose. Often the exact amount of the main ingredients is not properly labeled and the purity of these products is not controlled. Food supplements are used by consumers of different ages and with different medical conditions. Our recommendation is that the lead content should be obligatorily monitored and indicated on the label of every food supplement. This would be especially useful for the prevention and control of lead exposure worldwide.

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Original Article Sat, 30 Apr 2022 13:41:00 +0300
RP-HPLC method development and validation for simultaneous estimation of telmisartan, rosuvastatin calcium, and amlodipine besylate in combination https://foliamedica.bg/article/64339/ Folia Medica 64(1): 103-109

DOI: 10.3897/folmed.64.e64339

Authors: Rujuta P. Mistry, Chainesh Shah, Rakesh Jat

Abstract: Introduction: Dyslipidemia-hypertension proves to be a major risk factor for cardiovascular diseases. In order to achieve better adherence and cost-effectiveness than free equivalent combination therapies, a fixed-dose combination therapy with telmisartan (TEL), rosuvastatin calcium (ROS) and amlodipine besylate (AML) is required in this type of patients. Aim: A simple, selective and reproducible reverse phase high performance liquid chromatography (RP-HPLC) method has been developed and validated for estimation of telmisartan, rosuvastatin calcium, and amlodipine besylate in synthetic mixture. Materials and methods: Chromatographic separation was performed on a reversed-phase Luna C18 100Å column (250 mm × 4.6 mm i.d., particle size 5 μ) using an isocratic elution of mobile phase consisting of methanol and acetonitrile (pH 3.5 adjusted by ortho-phosphoric acid) (60:40 v/v) at a flow rate of 1.0 ml/min. Results: Ultraviolet (UV) detection was performed at 242 nm and retention time of telmisartan, rosuvastatin calcium and amlodipine besylate was found to be 2.67, 4.70, and 7.44 min, respectively. The calibration curve was linear (correlation coefficient >0.999) in the selected range of analyte. Conclusions: The method was validated for accuracy, precision, linearity, limit of detection, limit of quantitation and ruggedness. The system suitability parameter, such as theoretical plate, asymmetry, and resolution between standard five replicate were well within the limits.

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Original Article Mon, 28 Feb 2022 10:16:00 +0200
Neuropharmacological evaluation and HPTLC fingerprint profile of phytocompound-enriched chloroform fraction of methanolic extract of Lagenaria siceraria (Molina) Standley fruits – a potent Asian ethno-medicinal vegetable plant https://foliamedica.bg/article/59492/ Folia Medica 64(1): 84-95

DOI: 10.3897/folmed.64.e59492

Authors: Sachin Parmar, Rakesh Prajapati, Manisha Kalarias

Abstract: Introduction: Lagenaria siceraria (Molina) Standley (Cucurbitaceae) is a traditional vegetable plant, popularly known as bottle gourd (English) and lauki (Hindi). It is a climbing herb characterized with a number of therapeutic properties. Traditionally Lagenaria siceraria (LS) fruits were used for their cardioprotective, hepatoprotective, diuretic, and purgative effects, but there is very little scientific data available on its neuroprotective potential. Aims: The present study aimed to assess the neuropharmacological profile of the sterol-enriched chloroform fraction of methanolic extract of Lagenaria siceraria fruits in animal experimental models. Materials and methods: Neuropharmacological screening was conducted in specific reported animal models. Adult Wistar albino rats were subjected to behaviour despair test and elevated plus maze test. Thiopental-induced sedation, locomotor activity, and rota rod test were conducted on Swiss albino mice. Similarly, pentylenetetrazole-induced convulsions and maximal electroshock-induced seizures in Swiss albino mice were performed to evaluate the anti-epileptic potential. Results: The results of the study demonstrated that the anxiolytic activity of phytocompound-enriched chloroform fraction of methanolic extract of Lagenaria siceraria fruits (100, 200, and 400 mg/kg per os) was characterized by increased time spent in and increased number of entries into the open arms of the elevated plus maze prototype as compared to the control group (p<0.001). Chloroform fraction (100-400 mg/kg, p.o.) showed the dose-dependent significant reduction in duration of immobility (p<0.001) in the behaviour despair test. Similarly, the chloroform fraction was found to exert a significant reduction in motor co-ordination (p<0.001) and prolongation of thiopental-induced sleeping time (p<0.001) during the animal studies. Moreover, the test fraction significantly increased (p<0.001) the onset of myoclonic seizures in pentylenetetrazole-induced convulsions model as well as in the maximal electroshock-induced seizures model at all three dose levels selected. Interestingly, the chloroform fraction neither produced any overt motor dysfunction nor any kind of extra pyramidal symptoms in any of the animal models during pharmacological screening. Preliminary phytochemical screening of the fraction showed presence of saponins, phytosterols, terpenoids, fats, and trace amount of polyphenolic compounds. HPTLC fingerprinting analysis was also carried out. Conclusions: This is the first study exploring the neuroprotective potential of Lagenaria siceraria fruits by showing the anxiolytic, anti-depressant, sedative, and anti-epileptic-like activities, confirming the traditional claims. Future prospectus and investigations will give emphasis on isolation of the bioactive phytocompounds and their precise mechanisms involved in the neuroprotective activities.

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Original Article Mon, 28 Feb 2022 09:56:00 +0200
Association between Dyslipidemia and Vitamin D Deficiency: a Cross-Sectional Study https://foliamedica.bg/article/62417/ Folia Medica 63(6): 965-969

DOI: 10.3897/folmed.63.e62417

Authors: Zahrah Fathi Sharba, Rawaa Hadi Shareef, Basim A. Abd, Evan Noori Hameed

Abstract: Introduction: Dyslipidemia is one of the most common metabolic disorders. Vitamin D is one of the essential fat soluble vitamins which has many functions in the human body.Aim: The aim of this study was to evaluate the association between dyslipidemia and vitamin D deficiency.Materials and methods: This is a cross-sectional study which included 130 participants (58 males and 72 females) aged between 20-70 years and conducted between June 1 and October 30, 2020. The level of vitamin D was determined for each participant; we also measured the serum levels of cholesterol, triglyceride, high density lipoprotein, and low density lipoprotein.Results: There were 79 persons with vitamin D deficiency, 21 persons were vitamin D insufficient, and 10 - vitamin D sufficient. There were significant differences in the level of cholesterol, triglycerides, high-density and low-density lipoproteins according to the level of vitamin D.Conclusions: Deficiency of vitamin D has a negative impact on the levels of cholesterol, triglycerides, high-density and low-density lipoproteins.

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Original Article Fri, 31 Dec 2021 10:30:00 +0200
Dosage of Lipid Emulsions as an Antidote to Lipid-Soluble Substances https://foliamedica.bg/article/59216/ Folia Medica 63(6): 913-918

DOI: 10.3897/folmed.63.e59216

Authors: Gabriela Kehayova, Snezha Zlateva, Petko Marinov

Abstract: Introduction: Lipid emulsions are increasingly used as an antidote to lipophilic drug intoxications. The dose recommended by the American Society of Regional Anesthesia is used primarily for the treatment of local anesthetic systemic toxicity. There is insufficient information about what the dose of lipid emulsions (LE) should be in other intoxications depending on their severity.Aim: To determine the LE dose in a shock or haemodynamic instability in patients with acute exogenous intoxications treated with LE.Materials and methods: Forty-nine patients with acute lipophilic drug intoxications were treated with LE in the Clinic of Toxicology at the Naval Hospital in Varna.Statistical analysis was performed using the statistical functions of Excel 2016 and the Statistica 7.0 software package.Results: The percentage of patients receiving a low dose of LE of 0.3 ml/kg (93.87%) was significantly higher than the percentage of patients treated with a medium (2.04%) and a high dose (4.08%) of LF. The high dose of LE of 1.5 ml/kg recommended by the American Society of Regional Anesthesia was administered to two patients (4.08%). In severe intoxications with exotoxic shock, the rate of LE administration varies from 20 ml/h to 40 ml/h.Conclusions: In severe intoxications with cardiotoxic syndrome and haemodynamic instability, LE should be used in the dose as suggested by the American Society of Regional Anesthesia. It is possible to use lower doses of LE in the range of 0.3–0.6 ml/kg in all moderate poisonings administered by continuous intravenous infusion for 12-24-48 hours. No side effects were observed at these doses.

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Original Article Fri, 31 Dec 2021 10:30:00 +0200
Application of Plackett-Burman design for screening of factors affecting pitavastatin nanoparticle formulation development https://foliamedica.bg/article/58174/ Folia Medica 63(5): 775-785

DOI: 10.3897/folmed.63.e58174

Authors: Vinodkumar D. Ramani, Girish K. Jani, Girish U. Sailor

Abstract: Introduction: Nanoparticle formulation of pitavastatin calcium is a potential alternative to solve the solubility related problem. However, the formulation of nanoparticle involves various parameters that affect product quality. Plackett-Burman design could facilitate an economical experimental plan that focuses on determining the relative significance of many.Aim: The objective of this study was to screen the variables which could significantly affect the pitavastatin nanoparticle formulation.Materials and methods: The pitavastatin nanoparticles were formulated by preparing nanosuspension using the emulsion solvent evaporation technique followed by freeze-drying. A Plackett-Burman screening design methodology was employed in which seven factors at two levels were tested at 12 runs to study the effect of formulation and process variables on particle size and polydispersity index of nanoparticles. The surface morphology and crystalline nature of nanoparticle were also evaluated.Results: The particle size and polydispersity index of nanosuspension was found in the range of 113.1 to 768.5 nm and 0.068 to 0.508, respectively. Statistical analysis of various variables revealed that stabilizer concentration, injection flow rate, and stirring rate were the most influential factors affecting the particle size and polydispersity index of the formulation. X-ray diffraction (XRD) and scanning electron microscopy (SEM) study suggested the amorphous nature of nanoparticles.Conclusions: This study concluded that the Plackett-Burman design was an efficient tool for screening the process and formulation variables affecting the properties of pitavastatin nanoparticles and also for the identification of the most prominent factor.

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Original Article Sun, 31 Oct 2021 17:00:19 +0200
In silico analysis, synthesis and biological evaluation of DHFR inhibitors https://foliamedica.bg/article/56786/ Folia Medica 63(5): 745-759

DOI: 10.3897/folmed.63.e56786

Authors: Chaitali Lad, Ishan Panchal, Ashish Patel, Afzal Nagani, Vruti Parikh, Harnisha Patel, Bhargav Bhimani

Abstract: Introduction: Malaria is one of the varieties of fatal diseases caused by a protozoan parasite that is now considered to be the greatest global health challenge. A parasite of Plasmodium species triggers it transmitting the disease to humans by the bites of female Anopheles mosquitoes.Aim: To screen out designed molecules by molecular docking analysis and assess their pharmacokinetic properties using SwissADME. To synthesize the designed compounds. To characterize the synthesized compounds by TLC, melting point, IR spectroscopy, mass spectrometry, 1H NMR, and 13C NMR. To evaluate the synthesized compounds for antimalarial activity.Materials and methods: In silico analysis was performed with SWISSADME, and molecular docking was performed by AutoDock Vina version 4.2. In vitro antimalarial activity study was performed.Results: In-vitro studies of synthesized molecules showed that compounds C2 (IC50 1.23), C6 (IC50 0.48), C10 (IC50 0.79), and C14 (IC50 0.19) possess good antimalarial activity.Conclusions: 7-chloroquinoline-piperazine derivatives exhibited potential antimalarial compounds for pf-DHFR inhibitors.

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Original Article Sun, 31 Oct 2021 17:00:16 +0200
A contemporary chemical entities infiltrating in the antimalarial therapy era: a comprehensive review https://foliamedica.bg/article/58995/ Folia Medica 63(5): 637-646

DOI: 10.3897/folmed.63.e58995

Authors: Sandip N. Badeliya, Pankaj P. Kapupara, Navneet F. Chauhan, Ishan I. Panchal

Abstract: Malaria, a life-threatening disease, is caused by parasitic single-celled microorganisms. It is specifically transmitted by the anopheles female mosquito of the Plasmodium family. There are a lot of drugs available in the market to treat this life-challenging disease. Chloroquine, a cheaper molecule that is available worldwide, is one of them. Drug resistance has been observed with chloroquine as well as with some other quinine derivatives and with artemisinin derivatives in the southeast region of Asia in countries like Cambodia, Thailand, Myanmar, and Vietnam country since 1957. After 1970, the drug resistance has been further increased and it has been expanded in several localities of India. Also, antimalarial agents, particularly chloroquine, have so many side effects such as nausea, vomiting, blurred vision, abdominal cramps, diarrhea, headache, appetite loss, deprivation of hearing, skin color change, baldness, reduced body weight, and seizures. Furthermore, this drug cannot be given to pregnant women. Hence, it is the right time to design and develop newer antimalarial agents so that this kind of drug resistance, as well as side effects of the drugs, can be overcome.

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Review Sun, 31 Oct 2021 17:00:02 +0200
Optimization of amorphous solid dispersion techniques to enhance solubility of febuxostat https://foliamedica.bg/article/55838/ Folia Medica 63(4): 557-568

DOI: 10.3897/folmed.63.e55838

Authors: Vaishali P. Patel, Anita P. Patel, Ashish Shah

Abstract: Febuxostat is a selective inhibitor of xanthine oxidase and belongs to BCS class II drugs having low solubility and high permeability. Solubility is the most important parameter which directly affects dissolution, absorption and bioavailability of the drugs. There are different techniques by which we can improve solubility and dissolution rate of poorly soluble drug. Amorphous solid dispersion is one of the methods which can improve solubility as well as powder characteristics. The aim of the present study was to formulate and optimize various methods of formulating solid dispersion by using various drug-to-polymer ratios and identifying the batch which gives higher solubility as well as amorphous powder of the drug febuxostat. Different techniques like hot melt method, solvent evaporation method and spray drying techniques were selected for optimization. Attempts were made to improve solubility of febuxostat by employing Kolliphor P 188, Kolliphor P 237, Eudragit RLPO in different drug-to-polymer ratios (1:1, 1:1.5, 1:2) as carrier. The prepared solid dispersion was characterized for the saturation solubility, percentage yield, using differential scanning calorimetry (DSC), scanning electron microscopy (SEM), powdered X-ray diffraction studies (PXRD), and residual solvent determination. Solid state characterization indicated that febuxostat was present in the amorphous form after mixing with polymeric carrier. In contrast to the pure form of drug, solid dispersion of the drug showed better solubility and amorphous characteristics which can be attributed to decreased crystallinity due to hydrotrophy. Thus, amorphous solid dispersion approach can be used successfully to enhance solubility, dissolution rate and bioavailability of febuxostat.

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Research Note Tue, 31 Aug 2021 18:00:00 +0300
An experimental study on phytochemical composition and memory enhancing effect of Ginkgo biloba seed extract https://foliamedica.bg/article/53060/ Folia Medica 63(2): 203-212

DOI: 10.3897/folmed.63.e53060

Authors: Teodora Tomova, Nina Doncheva, Anita Mihaylova, Ilia Kostadinov, Lyudmil Peychev, Mariana Argirova

Abstract: Introduction: The Ginkgo biloba L. tree is considered as one of the oldest species on Earth. It is known as a “living fossil” dating back approximately 200 million years. Both the leaves and seeds of this tree have been used for millennia in traditional Chinese medicine.Aim: To study the phytochemical profile of Gingko biloba seed extract (GBSE) and its memory enhancing effects.Materials and methods: Liquid chromatography with mass detection (LC-MS) was performed for phytochemical analyses of the extracts. For the in vivo experiments, male Wistar rats were divided randomly into 5 groups (n=8): saline; piracetam; GBSE 50; 100, and 200 mg/kg b.w. Y-maze, T-maze, step-down passive avoidance and novel object recognition test (NORT) were performed. The observed parameters were: percentage of spontaneous alternations (% SA), working memory index, latency of reaction and recognition index, respectively. Statistical analysis was done using SPSS 19.Results: LC-MS analysis showed the presence of the flavonoids quercetin, kaempferol and isorhamnetin (as aglycones), the ginkgolides A, B, C, J, and bilobalide. In Y-maze task, the groups treated with 50 and 100 mg/kg of GBSE significantly increased the % SA during the memory test compared to saline (p<0.05). In T-maze test, the three experimental groups with GBSE significantly increased the working memory index in comparison with that of the control group (p<0.05). In step-down test, the animals receiving 100 mg/kg b.w. GBSE, notably increased the latency during both retention tests (p<0.05 and p<0.01, respectively). In NORT, only the animals with the middle dose of GBSE ameliorated the recognition index when compared to saline (p<0.05).Conclusions: GBSE enhances spatial working memory, recognition memory, and short- and long-term recall in naïve rats due to the synergic effects of detected flavonoids and terpene lactones on brain functions. The brain structures involved are probably the hippocampus and prefrontal cortex.

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Original Article Fri, 30 Apr 2021 10:00:07 +0300
Construction of metronidazole capped in gold nanoparticles against Helicobacter pylori: antimicrobial activity improvement https://foliamedica.bg/article/53479/ Folia Medica 63(2): 197-202

DOI: 10.3897/folmed.63.e53479

Authors: Roohollah Fateh, Ali Javadi, Jalil Kardan-Yamch, Hossein Ali Rahdar, Masumeh Amini, Fatemeh Ghasemi, Akram Azimi, Masoumeh Davarpanah, Razieh Mohammadzadeh

Abstract: Introduction: Helicobacter pylori is considered a major agent causing gastritis and peptic ulcer disease. Unfortunately, the occurrence of increasing drug resistance to this bacterium would result in some difficulties in its treatment. Therefore, the application of nanotechnology has been suggested to resolve such problems. Nanoparticles usage in medical research has been expanded in recent years. Among nanometals, gold nanoparticles have exclusive features that can be used in such applications. Using nanotechnology in medical science could help mankind to solve this problem in the future.Aim: Our aim in this research was to investigate the antimicrobial effect of gold nanoparticles on H. pylori strains.Materials and methods: Gold nanoparticles were synthesized by the Turkevich method. Then, their size and dispersion were investigated using spectrophotometry, DLS, and TEM microscopy. Subsequently, the combination of metronidazole and gold nanoparticles was obtained by mixing method, and then the anti-helicobacter effects of the two were evaluated according to CLSI.Results: The highest size of gold nanoparticles was between 12 and 9 nm, and the maximum absorbance was 522 nm; however, in conjugated state, the maximum absorbance was 540 nm, which indicated the accumulation of drug-conjugated nanoparticles in the conjugate state. Some changes indicated the binding of metronidazole to gold nanoparticles. Antimicrobial testing of gold nanoparticles and metronidazole did not affect the Helicobacter pylori. Therefore, the combination of gold nanoparticles and metronidazole had a 17-mm growth inhibition zone.Conclusions: The anti-helicobacter effects of metronidazole significantly increased in conjugation with gold nanoparticles.

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Original Article Fri, 30 Apr 2021 10:00:06 +0300
Efficacy and safety of Aviron Rapid® in 18-60-year-old patients with clinical diagnosis of acute respiratory viral infection: a multicenter, randomized, double-blind, placebo-controlled clinical trial https://foliamedica.bg/article/64415/ Folia Medica 63(1): 129-137

DOI: 10.3897/folmed.63.e64415

Authors: Georgi Popov, Margarita Gospodinova-Bliznakova, Zlatko Kalvatchev, Andrey Tchorbanov

Abstract: Aim: Prevention and treatment of upper respiratory tract infections are given the highest priority because of the tremendous health and economic impact of these diseases. Development of novel effective and safe options for treatment can contribute considerably to decrease the burden of disease.Materials and methods: We designed a multicenter, randomized, double-blind, placebo-controlled study in ambulatory-treated adult patients with a clinical diagnosis of acute upper respiratory tract viral infection. The patients (18-60 years old) were randomized into two groups and followed-up for 5 days. Group 1 received the standard symptomatic therapy + Aviron Rapid®, and Group 2 received the standard symptomatic therapy + placebo. The primary endpoint of the study was defined as the duration of disease measured by the percentages of disease-free patients for every 12-hour period of the study. Results: Treating clinically relevant patients with the natural product Aviron Rapid® for 5 days decreases the duration of disease, the intake of antipyretics and the severity of symptoms. Significant difference between the tested groups for most of studied parameters was found as soon as 12 or 24 hours after initiation of administration in favour of active arm and was the most prominent on days 3 and 4. Significant decrease in the total score of symptoms severity was achieved on day 4 and extended to the end of study. There were no dif-ferences in the adverse events between the groups and the tested product demonstrated excellent safety profile. Conclusions: This study is a clinical confirmation of well documented antiviral activity of the product targeting multiple points in viral replication and covering broad spectrum viral pathogens.

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Original Article Sun, 28 Feb 2021 21:16:00 +0200
Microwave and Conventional Study of Coumarin-Oxadiazole Adducts and their Anti-Microbial Evaluation https://foliamedica.bg/article/52655/ Folia Medica 63(1): 105-112

DOI: 10.3897/folmed.63.e52655

Authors: Khushal Kapadiya, Piyush Dholaria

Abstract: Introduction: Nowadays, researchers are progressively concentrated to generate economical, affordable and also greener synthesis approach for the synthesis of various heterocycles. On look at the beauty of coumarin molecules and oxazoles, it seems to be lead molecules in the anti-microbial area. Aim: With the target to identify efficient molecules, we studied 2-oxo-2H-chromen-4-yl-2-((5-substituted aryl-1,3,4-oxadiazol-2-yl) thio)acetate derivatives using two synthetic protocol/methods, i.e. conventional synthesis and microwave-based synthesis.Materials and methods: Two simultaneous methods, i.e. conventional and microwave synthesis have been used for the synthe-sis of 2-oxo-2H-chromen-4-yl-2-((5-substituted aryl-1,3,4-oxadiazol-2-yl)thio)acetate (6a-l) derivatives. The desired molecules were synthesized by conventional and microwave synthesis and a comparative study was carried out to identify an easy route for industrial applications. The confirmations of the compounds were carried out by spectroscopic techniques such as IR, 1H NMR, 13C NMR, mass spectra and elemental analysis. Results: All synthesized compounds were evaluated for their in-vitro antibacterial activity against gram-positive bacteria (Staphylococcus aureus, Staphylococcus pyogenes), gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa), and antifungal activity (Candida albicans, Aspergillus niger). Conclusions: All conventional synthesis of final coumarin derivatives were completed within 4-6 h. While that of microwave-based reaction took comparatively more reaction time. Surprisingly, the compounds 6f and 6g could not be synthesized by microwave radiation even after 32 minutes of irradiation. As to the medicinal application part, microbial evaluation of synthesized analogues showed that the compounds 6b, 6e, 6d, and 6j were found more potent in comparison to the reference drug.

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Original Article Sun, 28 Feb 2021 20:35:00 +0200
Taste Masking of Granulated Acetaminophen by Water Insoluble Ethylcellulose Coating https://foliamedica.bg/article/56052/ Folia Medica 63(1): 97-104

DOI: 10.3897/folmed.63.e56052

Authors: Amit Bansal, Brian Krieg, Navneet Sharma, James McGinnis, Inderdeep Bhatia, Carlos Paz

Abstract: Introduction: Bitter tasting of drugs leads to non-compliance especially in the case of pediatric patients due to their inability to swal-low medication. Aim: In this study, we aimed to mask the bitter taste of acetaminophen (APAP) particles through coating. Materials and methods: A pH independent water insoluble ethylcellulose polymer was used to coat the APAP. The coating of water insoluble ethylcellulose on APAP can have a significant impact on the dissolution profile. Various grades of APAP were used for coating; fine grade, Compap L90% having wide particle size distribution (PSD), and a special granular (SG) APAP 1680 having narrow PSD. Coating was performed using top spray (Vector) for Compap L90% and SG APAP 1680 grade of APAP. Results: Bitter taste of SG APAP was masked after spraying dispersion equivalent to a weight gain of 10% compared to 35% used for Compap L90%. Using bottom spray (Wurster coater, GPCP 2.0), coating was performed on SG APAP 1680 grade of APAP by spraying aqueous dispersion of ethylcellulose (Surelease) equivalent to a weight gain of 10%. The scalability of the top spray process was also evaluated in GPCG 30 and bitter taste was masked by using Surelease dispersion equivalent to a weight gain of 6%. Coated APAP was examined for particle size (PS), particle size distribution (PSD), flowability, and drug release profile. Dissolution was performed using USP apparatus 2 and 4 in phosphate buffer and evaluated for mechanism of drug release. Particle size obtained for coated SG APAP 1680 via top and bottom spray process was 404 µm d(90) and 487 µm d(90) respectively. Conclusions: The results of the study demonstrated the potential of Surelease dispersion in taste masking. The use of SG APAP 1680 having narrow PSD allowed taste masking to achieve at low weight gain without greatly affecting the dissolution profile.

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Original Article Sun, 28 Feb 2021 20:29:00 +0200
Platelet Augmentation Potential of Polyherbal Formulation in Cyclophosphamide-Induced Thrombocytopenia in Wistar Rats https://foliamedica.bg/article/49167/ Folia Medica 63(1): 67-73

DOI: 10.3897/folmed.63.e49167

Authors: Girish Sailor, Komal Hirani, Ghanshyam Parmar, Rajesh Maheshwari, Rupa Singh, Avinash Kumar Seth

Abstract: Introduction: Thrombocytopenia is a condition characterized by abnormally low levels of thrombocytes, also known as platelets, in the blood. Several medicinal plants possess curative and protective effect against thrombocytopenia associated with diseases or drugs.Aim: In the present study, we have investigated the platelet augmentation activity of polyherbal formulation (VITA PLAT Capsule) in cyclophosphamide-induced thrombocytopenic rat model. Materials and methods: Twenty-four albino Wistar rats were divided into four groups. Thrombocytopenia was induced in the rats by administering cyclophosphamide (25 mg/kg, i.p.) for three days to all the groups except normal controls. The test groups were given orally a polyherbal formulation suspended in normal saline for 14 days. Blood was withdrawn from the retro-orbital plexus of the rats on days 1, 7, and 14 of study to determine platelet counts in all groups. Clotting time and bleeding time were determined on the last day of study. Data were collected and analyzed using GraphPad Prism 8. Results: The results showed that the polyherbal formulation treatment could significantly ameliorate platelet count in thrombocyto-penic rats in the initial as well as in the later phase. The total WBC count was also improved during later phase in test groups. However, there is no significant difference between clotting time and bleeding time in all groups. Conclusions: Our study suggests a potential role of this formulation in the augmentation of platelet counts in various thrombocyto-penic disorders including a role in ameliorating the haemorrhagic complications of dengue fever.

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Original Article Sun, 28 Feb 2021 20:03:00 +0200
Recent Advances in the Development of PI3K/mTOR-Based Anticancer Agents: A Mini Review https://foliamedica.bg/article/52791/ Folia Medica 63(1): 7-14

DOI: 10.3897/folmed.63.e52791

Authors: Ishan Panchal, Archana Navale, Ashish Shah, Sandip Badeliya, Rati Tripathi

Abstract: Cancer refers to the group of diseases characterized by uncontrolled growth of abnormal cells. It spreads throughout the body which makes this disease one of the huge global threats to mankind. Intensive research over the years has established deregulation of mam-malian target of rapamycin pathway in cancer. This has led to the development of mammalian target of rapamycin inhibitors. Several inhibitors of the mammalian target of rapamycin are under preclinical and early clinical trials. Researchers have investigated a series of furoquinoline, phenyl sulphonylureas, 4-acrylamido-quinoline, pyrazolochalcones, imidazole [4,5-b] pyridine, thienopyrimidine, aminopyrimidin scaffolds in the last three years. This review provides comprehensive information and critical discussions on designing of novel selective inhibitors of mammalian target of rapamycin with superior activity in the treatment of cancer.

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Review Sun, 28 Feb 2021 17:57:00 +0200
Compassionate Drug Use – Time Arising for a New Law in Bulgaria in the Era of COVID-19 https://foliamedica.bg/article/53742/ Folia Medica 62(3): 592-596

DOI: 10.3897/folmed.62.e53742

Authors: Nigyar Dzhafer, Jannis V. Papathanasiou

Abstract: Introduction: Despite clinical trials, there are still no approved specific therapies or any vaccine against COVID-19. The only option available is using investigational drugs for compassionate use. The update of the existing regulation regarding compassionate use is to ensure the effective and sustainable development of health policies and technologies over the COVID-19 pandemic and beyond.Aim: The present short communication aimed to highlight the need for early and expanded access to investigational drugs for compassionate use as well as a call for an update of the existing regulation in Bulgaria concerning compassionate use in the era of COVID-19.Materials and Methods: In EU and Bulgaria as well, the legal framework for compassionate use was introduced by Article 83 (1) of Regulation (EC) No 726/2004 of the European Parliament and of the Council; in principle, Regulations of the European Parliament and of the Council are mandatory for all Member States. Remdesivir appears to have a favorable clinical and safety profile, as reported in a case involving patients with severe COVID-19 through a compassionate use programme.Results: The overall probability of clinical improvement observed in 36 of 53 COVID-19 patients received intravenous remdesivir as part of a compassionate use programme was 68% (95% CI 40% to 80%). Thirty two patients (60%) demonstrated at least one adverse event, twelve 12 patients (23%) experienced serious adverse events and seven patients (13%) died.Conclusion: The global pandemic mandates Bulgarian Drug Agency for a reasonable update of the existing national regulation concerning compassionate use and off-label therapies. In the era of COVID-19, it is important for Bulgarian patients to have early and expanded access to investigational drugs for compassionate use.

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Short Communication Wed, 30 Sep 2020 17:40:00 +0300
Good Manufacturing Practice for Medicinal Products in Bulgaria: an Analysis of Regulatory Inspection Findings https://foliamedica.bg/article/49802/ Folia Medica 62(1): 165-171

DOI: 10.3897/folmed.62.e49802

Authors: Assena H. Stoimenova, Bogdan J. Kirilov, Stanislav R. Gueorguiev, Elina S. Petkova-Gueorguieva, Sava G. Ognianov

Abstract: Background: The manufacture of medicinal products for human use in the European Economic Area is governed by European Directives and Regulations stipulating the relevant principles and guidelines of Good Manufacturing Practice, describing the minimum standard to be fulfilled in the production processes. Aim: To present analysis of the deficiencies reported following Good Manufacturing Practice inspections in Bulgaria in two consecutive years (2016, 2017) and to compare them with results from similar inspections reported by other EU member states. Materials and methods: A retrospective study was carried out by reviewing the complete Good Manufacturing Practice inspection reports of all manufacturers conducted by the Bulgarian Drug Agency in 2016 and 2017, according to relevant requirements and applicable local legislation. The items reviewed were scope of inspection, type of companies, classification of deficiencies – ‘critical’, ‘major’ and ‘other significant deficiencies’, their nature and reference to EU Good Manufacturing Practice. Results: The analyzed data included 55 inspections, revealing 460 various deficiencies, of which 2 were critical and 102 – major. Twenty inspections were performed in 2016 vs. 35 inspections in 2017.The pattern of deficiencies was similar to the findings of other EU regulatory agencies, showing that equivalent requirements were applied. Our analysis showed that Bulgarian Drug Agency inspectors rarely raised deficiencies related to Computer Systems, Qualification/Validation, Personnel and Qualification of Suppliers unlike other EU regulators agents. Conclusions: Our analysis of Good Manufacturing Practice inspection findings in 2016 and 2017 showed that the Bulgarian Drug Agency demonstrated its ability to detect non-compliances and take necessary regulatory actions. Quality related issues constitute the main reasons for non-compliances with the requirements.Publishing the results from the inspections performed by the national competent authorities enhances the regulatory transparency that can be useful for industry to improve its Good Manufacturing Practice compliance.

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Original Article Tue, 31 Mar 2020 13:54:34 +0300