The Journal of Croatian Pharmaceutical Society

Acta Pharmaceutica

Acta Pharmaceutica ONL

<abstract><title style='display:none'>Abstract</title> Low oral bioavailability as a consequence of low water solubility of drugs is a growing challenge to the development of new pharmaceutical products. One of the most popular approaches of oral bioavailability and solubility enhancement is the utilization of lipid-based drug delivery systems. Their use in product development is growing due to the versatility of pharmaceutical lipid excipients and drug formulations, and their compatibility with liquid, semi-solid, and solid dosage forms. Lipid formulations, such as self-emulsifying (SEDDS), self-microemulsifying SMEDDS) and self- -nanoemulsifying drug delivery systems (SNEDDS) were explored in many studies as an efficient approach for improving the bioavailability and dissolution rate of poorly water-soluble drugs. One of the greatest advantages of incorporating poorly soluble drugs into such formulations is their spontaneous emulsification and formation of an emulsion, microemulsion or nanoemulsion in aqueous media. This review article focuses on the following topics. First, it presents a classification overview of lipid-based drug delivery systems and mechanisms involved in improving the solubility and bioavailability of poorly water-soluble drugs. Second, the article reviews components of lipid-based drug delivery systems for oral use with their characteristics. Third, it brings a detailed description of SEDDS, SMEDDS and SNEDDS, which are very often misused in literature, with special emphasis on the comparison between microemulsions and nanoemulsions.</abstract>

Abstract

Krka, d.d., Novo mesto, 8501 Novo mesto, Slovenia

Fakulteta za farmacijo, 1000 Ljubljana,Slovenia

Keywords

<article-title>Lipid-based systems as a promising approach for enhancing the bioavailability of poorly water-soluble drugs</article-title>

Lipid-based systems as a promising approach for enhancing the bioavailability of poorly water-soluble drugs

<abstract><title style='display:none'>Abstract</title> Many modern drugs are poorly water soluble substances, which causes difficulties in the development of solid dosage forms with sufficient bioavailability. Preparation of liquisolid systems (LSS) is a novel technique for improving solubility, dissolution and bioavailability of such drugs. The basic principle of LSS preparation is conversion of the drug in liquid state into a free-flowing, compressible, dry powder through its absorption into suitable excipients - porous carriers (aluminometasilicates, microcrystalline cellulose), subsequently coated with material having high absorption capacity (silicon dioxide commonly known as colloidal silica). LSS exhibit advantages such as lower production costs compared to soft capsules, simple processing and enhanced drug release. The main benefit is higher bioavailability of the liquid drug, caused by a large surface area available for absorption. The article tries to clarify specific aspects connected with the formulation of LSS: properties of excipients (surface area, absorption capacity), variables related to the processing (solubility, liquid load factor) and dosage form evaluation.</abstract>

Department of Pharmaceutics, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Brno 612 42,Czech Republic

<article-title>Liquisolid systems and aspects influencing their research and development</article-title>

Liquisolid systems and aspects influencing their research and development

{"article-title":"Liquisolid systems and aspects influencing their research and development"}

<abstract><title style='display:none'>Abstract</title> In the present study, cytotoxic effects of D-Ala, D-Pro and D-Lys are demonstrated. In an effort to study the possible mechanisms of the observed cytotoxicity, catalase activity, H2O2 generation, and apoptotic activity were measured in HeLa and MCF-7 cell lines. Although D-Lys is a poor substrate for DAO and therefore low H2O2 was detected, it was shown to provoke severe impairment of cellular integrity and survival. Interestingly, a very good substrate for DAO, such as D-Pro, did not substantially reduce cell viability. On the other hand, a moderate substrate for DAO, represented by D-Ala, was shown to moderately trigger toxicity in the tested cell lines. Although a correlation between the in vitro cytotoxicity of D-amino acids and the amount of H2O2 produced was absent, there was a good agreement between the ability of D-amino acids to trigger apoptosis and to provoke toxicity. Our results indicate that the toxicity of D-amino acids does not appear to be solely mediated by H2O2. Therefore, we hypothesize that other possible contributing apoptosis-mediated pathways might cause the observed toxicity.</abstract>

Department of Pharmaceutical Sciences, Faculty of Pharmacy, The University of Jordan, Amman 11942, Jordan

Department of Biopharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, The University of Jordan, Amman 11942 Jordan

<article-title>An in vitro based investigation into the cytotoxic effects of D-amino acids</article-title>

An in vitro based investigation into the cytotoxic effects of D-amino acids

{"article-title":"An in vitro based investigation into the cytotoxic effects of D-amino acids"}

<abstract><title style='display:none'>Abstract</title> Sterile thermoreversibly gelling systems based on chitosan- glycerol phosphate were developed for intraperitoneal delivery of the antineoplastic agent 5-FU. The formulation was evaluated for gelling characteristics and in vitro drug release. Drug free gels were evaluated for in vitro cytotoxicity in L-929 mouse fibroblast cells. Drug loaded gels were subjected to acute toxicity studies in Swiss albino mice via intraperitoneal route and efficacy studies via intratumoral injections in subcutaneous colon carcinoma bearing BALB/c mice. The formulations gelled reversibly in 8 min at 37 °C and provided prolonged release of the drug. Drug free systems showed dose dependent cytotoxicity in fibroblast cells, while in vivo studies revealed a 2.8-fold increase in LD50 of 5-FU administered intraperitoneally as the developed system. Tumor volume measurements showed comparable efficacy of 5-FU administered as gel and commercial injection with a greatly improved safety profile of the former as adjudged from mortality and body weight measurements.</abstract>

Department of Pharmaceutics, Bombay College of Pharmacy, Kalina, Santacruz (E) Mumbai, India

<article-title>Preparation and evaluation of chitosan based thermoreversible gels for intraperitoneal delivery of 5-fluorouracil (5-FU)</article-title>

Preparation and evaluation of chitosan based thermoreversible gels for intraperitoneal delivery of 5-fluorouracil (5-FU)

<abstract><title style='display:none'>Abstract</title> To investigate potential prevention or attenuation of anti- cancer drug induced cardiotoxicity using anti-ischemic drugs, a rat myoblast (H9c2) cell line was used as our in vitro cardiac model. Irinotecan and doxorubicin were found to be cytotoxic for the H9c2 cell line with IC50 of 30.69 ± 6.20 and 20.94 ± 6.05 mmol L-1, respectively. 5-Flurouracil and cladribine were not cytotoxic and thus IC50 could not be calculated. When 100 mmol L-1 doxorubicin was incubated for 72 hours with 50 mmol L-1 diltiazem, 100 mmol L-1 dexrazoxane and 100 mmol L-1 losartan, respectively, there was a 58.7 ± 10.2, 52.2 ± 11.7 and 44.7 ± 5.4 % reduction in cell death. When 200 mmol L-1 irinotecan was incubated for 72 hours with 100 mmol L-1 dexrazoxane, losartan and diltiazem, respectively, a 27.7 ± 6.9, 25.6 ± 5.1, and 19.1 ± 2.3 % reduction in cell death was observed. Our data suggests that losartan and diltiazem were as effective as dexrazoxane in protecting the cells against irinotecan- and doxorubicin-induced cell toxicity. These findings offer potential uses of anti- -ischemic drugs for ablation of cytotoxicity in response to mitochondrial injury, thereby improving patient outcomes and reducing health-care costs.</abstract>

Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada B3H 4R2, Canada

Biopharmaceutics and Drug Delivery Laboratory, Dalhousie University, Halifax, NS B3H 3J5, Canada

Pharmacokinetics and Metabolism Laboratory, College of Pharmacy, Dalhousie University, Halifax NS B3H 3J5, Canada

<article-title>Cytoprotective potential of anti-ischemic drugs against chemotherapy-induced cardiotoxicity in H9c2 myoblast cell line</article-title>

Cytoprotective potential of anti-ischemic drugs against chemotherapy-induced cardiotoxicity in H9c2 myoblast cell line

<abstract><title style='display:none'>Abstract</title> Gleditsiae Fructus Abnormalis and Gleditsiae Sinensis Fructus are obtained from different developmental stages of fruits from Gleditsia sinensis Lam. (Leguminosae). The possible interchangeable usage of the two fruits, however, has long been very controversial. Here, high performance liquid chromatography coupled with diode array detection was developed to explore their chemical fingerprinting profiles. Besides, the amounts of aglycones of saponin compounds, echinocystic acid and oleanolic acid in both fruits were quantified. The results indicated that there was no significant difference in the content of aglycones from the two types of fruits. However, their chromatographic fingerprints showed distinct characteristics. Therefore, the interchangeable application of these fruits has to be taken with a specific precaution.</abstract>

Division of Life Science and Centre for Chinese Medicine, The Hong Kong University of Science and Technology, Hong Kong, China

School of Health and Pharmacy Guandong Lingnan Institute of Technology, Guangzhou, China

School of Chinese Materia Medica Guangzhou University of Chinese Medicine, Guangzhou, China

<article-title>Chemical fingerprinting and quantitative analysis of two common Gleditsia sinensis fruits using HPLC-DAD</article-title>

Chemical fingerprinting and quantitative analysis of two common Gleditsia sinensis fruits using HPLC-DAD

<abstract><title style='display:none'>Abstract</title> Coenzyme Q10 (Q10) loaded solid lipid nanoparticles (SLN) were prepared by the high speed homogenization method and incorporated into Carbopol 974P hydrogels. Compritol 888 ATO (C888) was employed as the lipid base; Poloxamer 188 (P188) and Tween 80 (Tw80) were used as surfactant and co-surfactant. Optimum particle size with narrow distribution was obtained as 152.2 nm for blank and 142.4 nm for Q10 loaded SLNs. The overall charge of loaded SLNs was -13.7 ± 1.3 mV. Q10 entrapment efficiency was 89 % and the production yield was 94 %. Transmission electron microscopy analysis provided evidence of colloidal size, spherical shape while differential scanning calorimetry analysis confirmed recrystallization of the lipid after the preparation of SLNs. Trolox equivalent antioxidant capacity (TEAC) analysis has shown that antioxidant potential of Q10 can be protected in SLNs. Rheological characteristics demonstrated that the SLN incorporating gels were shear thinning and the mechanical strength of the gels was suitable for topical application. Diffusion studies from rat abdominal skin revealed that the delivery of Q10 was doubled in SLN incorporating gels, approximately 40 μg cm-2, in comparison with gels prepared with only Q10 (not incorporated in SLNs). As a result, it can be stated that Q10-SLN loaded gels can be successful delivery systems for carrying Q10 efficiently into the skin without losing its antioxidant properties.</abstract>

Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Ege Izmir, 35100, Turkey

<article-title>Development and evaluation of coenzyme Q10 loaded solid lipid nanoparticle hydrogel for enhanced dermal delivery</article-title>

Development and evaluation of coenzyme Q10 loaded solid lipid nanoparticle hydrogel for enhanced dermal delivery

<abstract><title style='display:none'>Abstract</title> Prevention of skin aging and its treatment is an emerging field for development of new formulations in cosmetics. Accordingly, plant extracts with antioxidant properties are beneficial cosmetic ingredients for this purpose. This study was aimed at developing a stable and easily manufactured emulgel including green tea extract and rose oil that is effective on the barrier function and hydration of the skin. An emulgel formulation containing 20 % green tea extract and 5 % rose oil was designed as a result of pre-formulation studies. Physicochemical characterization, in vitro stability studies, in vivo water content of the stratum corneum and transepidermal water loss studies were carried out afterwards. In vivo studies on ten female subjects were evaluated by using non-invasive skin bioengineering techniques. Finally, a cosmetically acceptable, stable and effective emulgel formulation for skin barrier function with good hydrating properties was obtained for skin hydration, protection and anti-aging purposes.</abstract>

The Ministry of Health of Turkey, Turkish Medicines and Medical Devices Agency, Söðütözü Mahallesi, 2176, 06520 Çankaya-Ankara, Turkey

Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Ankara, 06100 Tandoðan-Ankara, Turkey

Department of Pharmaceutical Technology, Faculty of Pharmacy, Istanbul University, 34116 Beyazýt-Istanbul, Turkey

<article-title>Design and in vivo evaluation of emulgel formulations including green tea extract and rose oil</article-title>

Design and in vivo evaluation of emulgel formulations including green tea extract and rose oil

<abstract><title style='display:none'>Abstract</title> The aim of this study was to investigate the in vitro and in vivo performance of salbutamol sulfate press-coated tablets for delayed release. The in vitro release behavior of press-coated tablets with the outer layer of PEG 6000/ Eudragit S100 blends (2:1) in pH 1.2 (0.1 mol L-1 HCl) and then pH 6.8 buffer solution was examined. Morphological change of the press-coated tablet during in vitro release was recorded with a digital camera. Release of salbutamol sulfate from press-coated tablets was less than 5 % before 3 h and was completed after 8 h in pH 6.8 phosphate buffer solution. In vivo gamma scintigraphy study carried out on healthy men indicated that the designed system released the drug in lower parts of the GI tract after a lag time of 5 hours. The results showed the capability of the system of achieving delayed release of the drug in both in vitro and in vivo gamma scintigraphy studies.</abstract>

Shenyang Pharmaceutical University Shenyang 110016, Liaoning Province China

The First Hospital of China Medical University, Shenyang 110001, Liaoning Province, China

<article-title>In vitro dissolution and in vivo gamma scintigraphic evaluation of press-coated salbutamol sulfate tablets</article-title>

In vitro dissolution and in vivo gamma scintigraphic evaluation of press-coated salbutamol sulfate tablets

<abstract><title style='display:none'>Abstract</title> Dried buckwheat herb is used in medicinal products whereas fresh green plant parts, especially sprouts, are consumed as a vegetable. The herb contains fagopyrins, which cause sensitivity to light after ingestion. The aim of this study was to investigate the impact of different growing conditions and the development phase on the content of fagopyrin and phenolic compounds in buckwheat sprouts. Total flavonoid and total phenol contents, fagopyrin content and antioxidant activity were determined spectrophotometrically. Fagopyrin and flavonoids were located almost exclusively in cotyledons. Based on a comparison to hypericin toxicity, the recommendable intake of buckwheat sprouts was estimated to be less than 40 g per day.</abstract>

Faculty of Pharmacy, University of Ljubljana, SI-1000 Ljubljana, Slovenia

Department of Agronomy, Biotechnical Faculty, University of Ljubljana, SI-1000 Ljubljana, Slovenia

<article-title>The content of fagopyrin and polyphenols in common and tartary buckwheat sprouts</article-title>

The content of fagopyrin and polyphenols in common and tartary buckwheat sprouts

{"article-title":"The content of fagopyrin and polyphenols in common and tartary buckwheat sprouts"}

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Acta Pharmaceutica ist in den folgenden Services indiziert: <ul> <li> Baidu Scholar </li> <li> CABI (over 50 subsections) </li> <li> Case </li> <li> Chemical Abstracts Service (CAS) - CAplus </li> <li> Chemical Abstracts Service (CAS) - SciFinder </li> <li> CNKI Scholar (China National Knowledge Infrastructure) </li> <li> CNPIEC - cnpLINKer </li> <li> Derwent Drug File </li> <li> Dimensions </li> <li> DOAJ (Directory of Open Access Journals) </li> <li> EBSCO </li> <li> Embase </li> <li> ExLibris </li> <li> Genamics JournalSeek </li> <li> Google Scholar </li> <li> IBIDS (National Institutes of Health) </li> <li> Japan Science and Technology Agency (JST) </li> <li> J-Gate </li> <li> Journal Citation Reports/Science Edition </li> <li> JournalGuide </li> <li> JournalTOCs </li> <li> KESLI-NDSL (Korean National Discovery for Science Leaders) </li> <li> Medline </li> <li> Meta </li> <li> MyScienceWork </li> <li> Naver Academic </li> <li> Naviga (Softweco) </li> <li> ProQuest </li> <li> Publons </li> <li> PubMed </li> <li> PubsHub </li> <li> QOAM (Quality Open Access Market) </li> <li> ReadCube </li> <li> Reaxys </li> <li> Referativnyi Zhurnal (VINITI) </li> <li> SCImago (SJR) </li> <li> SCOPUS </li> <li> Semantic Scholar </li> <li> Sherpa/RoMEO </li> <li> TDNet </li> <li> Ulrich's Periodicals Directory/ulrichsweb </li> <li> WanFang Data </li> <li> Web of Science - Biological Abstracts </li> <li> Web of Science - BIOSIS Previews </li> <li> Web of Science - Science Citation Index Expanded </li> <li> WorldCat (OCLC) </li> <li> X-MOL </li> </ul>

Editor-in-Chief Svjetlana Luterotti, Zagreb, Croatia Croatian Pharmaceutical Society, Zagreb, Croatia Managing Editor Maja Jakševac Mikša, Croatian Pharmaceutical Society, Zagreb, Croatia Editorial Board Karmela Barišiæ (Faculty of Pharmacy and Biochemistry, Zagreb, Croatia) Jelena Filipoviæ-Grèiæ (Faculty of Pharmacy and Biochemistry, Zagreb, Croatia) Mojca Kerec Kos (Faculty of Pharmacy, Ljubljana, Slovenia) Jasmina Lovriæ (Faculty of Pharmacy and Biochemistry, Zagreb, Croatia) Svjetlana Luterotti (Croatian Pharmaceutical Society, Zagreb, Croatia) Željan Maleš (Faculty of Pharmacy and Biochemistry, Zagreb, Croatia) Izidor Sosiè (Faculty of Pharmacy, Ljubljana, Slovenia) Željka Vaniæ (Faculty of Pharmacy and Biochemistry, Zagreb, Croatia) Donatella Verbanac (Faculty of Pharmacy and Biochemistry, Zagreb, Croatia) Branka Zorc (Faculty of Pharmacy and Biochemistry, Zagreb, Croatia) Alenka Zvonar Pobirk ((Faculty of Pharmacy, Ljubljana, Slovenia) Technical Editor Professor Branka Zorc, PhD University of Zagreb Faculty of Pharmacy and Biochemistry, Zagreb, Croatia Contacts Professor Svjetlana Luterotti, PhD Editor-in-Chief Croatian Pharmaceutical Society, Masarykova 2, HR-10000 Zagreb, Croatia e-mail: <A href="mailto:svjetlana.luterotti@gmail.com">svjetlana.luterotti@gmail.com</A>; <A href="mailto:svjetlana.luterotti@pharma.hr">svjetlana.luterotti@pharma.hr</A> Professor Branka Zorc, PhD Technical Editor Faculty of Pharmacy and Biochemistry University of Zagreb, HR-10000 Zagreb, Ante Kovačića 1 e-mail: <A href="mailto:bzorc.AP@farmaceut.org">bzorc.AP@farmaceut.org</A> Maja Jakševac-Mikša, PhD Managing Editor Croatian Pharmaceutical Society, HR-10000 Zagreb, Masarykova 2 phone: +385 1 48 72 849 fax: +385 1 48 72 853 e-mail: <A href="mailto:maja.jaksevac-miksa@zg.t-com.hr">maja.jaksevac-miksa@zg.t-com.hr</A>; <A href="mailto:hfd-fg-ap@zg.t-com.hr">hfd-fg-ap@zg.t-com.hr</A>; <A href="mailto:info@farmaceut.org">info@farmaceut.org</A> Section Editors Professor Karmela Barišić, PhD University of Zagreb Faculty of Pharmacy and Biochemistry, Zagreb, Croatia Professor Mojca Kerec Kos, PhD University of Ljubljana Faculty of Pharmacy, Ljubljana, Slovenia Professor Željka Vanić, PhD University of Zagreb Faculty of Pharmacy and Biochemistry, Zagreb, Croatia Professor Donatella Verbanac, PhD University of Zagreb Faculty of Pharmacy and Biochemistry, Zagreb, Croatia Publisher De Gruyter Poland Bogumiła Zuga 32A Str. 01-811 Warsaw, Poland T: +48 22 701 50 15

Please submit your manuscripts to Acta Pharmaceutica via email to: <A href="mailto:svjetlana.luterotti@gmail.com">svjetlana.luterotti@gmail.com</A> or <A href="mailto:svjetlana.luterotti@pharma.hr">svjetlana.luterotti@pharma.hr</A> PUBLICATION CHARGES Because of the high cost of preparing and publishing articles in Acta Pharmaceutica payment of publication fee is mandatory for all articles accepted for publication. Current charge is 900 € per manuscript (excl. VAT). For more information please visit <A href="https://sciendo-parsed-data-feed.s3.eu-central-1.amazonaws.com/ACPH/Instrucions_for_Authors.pdf">Instructions for Authors</A>. Open Access Statement The journal is an Open Access journal that allows a free unlimited access to all its contents without any restrictions upon publication to all users. <A href="https://sciendo-parsed-data-feed.s3.eu-central-1.amazonaws.com/ACPH/Open_Access_License.doc">Open Access License</A>

Acta Pharmaceutica (AP) is an international, scientific, multidisciplinary journal, devoted to the pharmaceutical and allied sciences, which contains articles predominantly on core biomedical and health subjects. The aim of AP is to increase the impact of pharmaceutical research in academia, industry and laboratories. With a strong emphasis on quality and originality, AP publishes reports from the discovery of a drug up to clinical practice, in the form of preliminary and short communications, original research papers and reviews. Book reviews are published also. AP is a quarterly, single-blind peer-reviewed journal in biomedicine with fully open access and “early bird” platform. All articles are submitted to scrutinized evaluation and fair judgement. AP above all puts scientific honesty and integrity. To reach the highest standards in publication ethics all the parties (authors, editors, reviewers) are required to behave responsibly and ethically. This implies submittance by authors on an exclusive basis, of only their own and new data; novelty and originality are prioritized. Also, secure handling of confidential data by reviewers and editors is a must. AP is indexed in numerous world top international bibliographic bases, like Clarivate Analytics´s Web of Science® Core Collection (SCI-Expanded, JCR/Science Edition, etc.), EMBASE/Excerpta Medica, MEDLINE/PubMed, Scopus/SCImago, and others. According to SCImago JR it is a Q2 journal (pharmaceutical sciences) with a steadily increasing Clarivate JIF value reaching 2.230 in 2020 Topics covered are: <UL> <LI>drug design </LI> <LI>molecular modelling/docking studies </LI> <LI>pharmaceutical chemistry/medicinal chemistry </LI> <LI>drug metabolism </LI> <LI>analytics of drugs </LI> <LI>pharmaceutical technology/formulation studies/nanosystems/cosmetology </LI> <LI>pharmaceutical biotechnology </LI> <LI>pharmaceutics/biopharmacy (including pharmacokinetics) and pharmacodynamics </LI> <LI>drug delivery/disposition and stability </LI> <LI>pharmacognosy and　phytopharmacy </LI> <LI>pharmacology (clinical and animal) </LI> <LI>toxicology </LI> <LI>clinical pharmacy </LI> <LI>pharmacovigilance </LI> <LI>pharmaceutical and clinical biochemistry </LI> <LI>pharmaceutical biology with genetics/pharmacogenomics/cell biology </LI> <LI>pharmacoepidemiology/pharmacoeconomics/social pharmacy </LI> <LI>physical pharmacy </LI> <LI>radiopharmaceuticals </LI> <LI>medicine (including diagnostics and therapy) </LI> <LI>peptide and protein chemistry/protein design </LI></UL> Why subscribe and read <UL> <LI>To get informed on the latest research in pharmaceutical and related sciences. </LI></UL> Why submit <UL> <LI>fair and constructive peer review by the experts in the field, </LI> <LI>editorial help and language revision services, </LI> <LI>articles abstracted by online indexing services, </LI> <LI>listed in WoS MJL by Clarivate. </LI></UL> Archiving Sciendo archives the contents of this journal in <A href="https://www.portico.org/">Portico</A> - digital long-term preservation service of scholarly books, journals and collections. Plagiarism Policy The editorial board is participating in a growing community of <A href="https://www.crossref.org/services/similarity-check/">Similarity Check System's</A> users in order to ensure that the content published is original and trustworthy. Similarity Check is a medium that allows for comprehensive manuscripts screening, aimed to eliminate plagiarism and provide a high standard and quality peer-review process.

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