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Article ; Online: Preparation and evaluation of a lipid-based drug delivery system to ımprove valsartan oral bioavailability: pharmacokinetic and pharmacodynamic analysis.

Gülmezoğlu, Eda / Yıldız Türkyılmaz, Gülbeyaz / Karasulu, H Yeşim

Drug development and industrial pharmacy

2023 Volume 48, Issue 12, Page(s) 727–736

Abstract: Antihypertensive treatment reduces the risk of cardiovascular complications in patients with high mortality with hypertension. Valsartan is highly selective antihypertensive that is rapidly absorbed after oral administration, but its oral bioavailability ...

Abstract	Antihypertensive treatment reduces the risk of cardiovascular complications in patients with high mortality with hypertension. Valsartan is highly selective antihypertensive that is rapidly absorbed after oral administration, but its oral bioavailability is only 25%. It is absorbed from the upper part of the gastrointestinal tract but is less soluble in this acidic environment. We aimed to develop a lipid-based formulation to produce a self-emulsifying drug delivery system (SEDDS) for valsartan. Solubility studies were performed to identify the components of the SEDDS that provided the best dissolution of valsartan. Ternary phase diagrams were drawn using the titration method with oil, surfactants and co-surfactants in which valsartan was highly soluble, and microemulsion formulations with the highest area were determined. Characterization and
MeSH term(s)	Rats ; Animals ; Valsartan/chemistry ; Antihypertensive Agents ; Emulsions/chemistry ; Chemistry, Pharmaceutical/methods ; Drug Delivery Systems/methods ; Surface-Active Agents/chemistry ; Solubility ; Biological Availability ; Lipids/chemistry ; Administration, Oral
Chemical Substances	Valsartan (80M03YXJ7I) ; Antihypertensive Agents ; Emulsions ; Surface-Active Agents ; Lipids
Language	English
Publishing date	2023-01-12
Publishing country	England
Document type	Journal Article
ZDB-ID	751874-2
ISSN	1520-5762 ; 0363-9045
ISSN (online)	1520-5762
ISSN	0363-9045
DOI	10.1080/03639045.2022.2164588
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Article ; Online: In vitro

Diril, Mine / Özdokur, Kemal Volkan / Yıldırım, Yeliz / Karasulu, H Yeşim

Pharmaceutical development and technology

2023 Volume 28, Issue 10, Page(s) 915–927

Abstract: Hepatocellular carcinoma (HCC), more than 800 000 cases reported annually, is the most common primary liver cancer globally. Doxorubicin hydrochloride (Dox-HCl) is a widely used chemotherapy drug for HCC, but efficacy and tolerability are limited, thus ... ...

Abstract	Hepatocellular carcinoma (HCC), more than 800 000 cases reported annually, is the most common primary liver cancer globally. Doxorubicin hydrochloride (Dox-HCl) is a widely used chemotherapy drug for HCC, but efficacy and tolerability are limited, thus critical to develop delivery systems that can target Dox-HCl to the tumour site. In this study, liver-targeting ligand glycyrrhetinic acid (Gly) was conjugated to polyethylene glycol (PEG)
MeSH term(s)	Animals ; Mice ; Carcinoma, Hepatocellular/drug therapy ; Carcinoma, Hepatocellular/pathology ; Liver Neoplasms/drug therapy ; Liver Neoplasms/pathology ; Doxorubicin/pharmacology ; Doxorubicin/therapeutic use ; Polyethylene Glycols ; Drug Delivery Systems ; Cell Line, Tumor
Chemical Substances	liposomal doxorubicin ; Doxorubicin (80168379AG) ; Polyethylene Glycols (3WJQ0SDW1A)
Language	English
Publishing date	2023-12-18
Publishing country	England
Document type	Journal Article
ZDB-ID	1331774-x
ISSN	1097-9867 ; 1083-7450
ISSN (online)	1097-9867
ISSN	1083-7450
DOI	10.1080/10837450.2023.2274394
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Article: Microemulsions as novel drug carriers: the formation, stability, applications and toxicity.

Karasulu, H Yesim

Expert opinion on drug delivery

2008 Volume 5, Issue 1, Page(s) 119–135

Abstract: A microemulsion, made from water, oil, surfactants and cosurfactant is a thermodynamically stable system. The presence of the cosurfactant is often required in order to lower the interfacial tension of this interface, because a low interfacial tension is ...

Abstract	A microemulsion, made from water, oil, surfactants and cosurfactant is a thermodynamically stable system. The presence of the cosurfactant is often required in order to lower the interfacial tension of this interface, because a low interfacial tension is essential for the formation of microemulsions. The transparency of microemulsions arises from their small droplet diameter. The droplet diameter in stable microemulsions is usually within the range of 10 - 140 nm. Microemulsions are graphically represented as stability areas in triangular phase diagrams where each triangular corner designates a certain component. Microemulsions are actually quaternary (pseudoternary) systems. In pharmaceutical fields, the interest in microemulsions is increasing and, thus, they are applied to various administration routes.
MeSH term(s)	Animals ; Drug Carriers/chemistry ; Drug Carriers/toxicity ; Drug Compounding ; Drug Stability ; Emulsions/chemistry ; Emulsions/toxicity ; Humans ; Microchemistry ; Pharmaceutical Preparations/administration & dosage ; Thermodynamics
Chemical Substances	Drug Carriers ; Emulsions ; Pharmaceutical Preparations
Language	English
Publishing date	2008-01
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2167286-6
ISSN	1744-7593 ; 1742-5247
ISSN (online)	1744-7593
ISSN	1742-5247
DOI	10.1517/17425247.5.1.119
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Zs.A 6012: Show issues

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Article ; Online: Formulation and In Vitro Evaluation of Self Microemulsifying Drug Delivery System Containing Atorvastatin Calcium.

Diril, Mine / Türkyılmaz, Gülbeyaz Yıldız / Karasulu, H Yeşim

Current drug delivery

2019 Volume 16, Issue 8, Page(s) 768–779

Abstract: Objective: The aim of this study was to develop a new dosage form as an alternative to the classical tablet forms of atorvastatin calcium (AtrCa). The formulation strategy was to prepare an optimum self micro emulsifying drug delivery system (SMEDDS) to ...

Abstract	Objective: The aim of this study was to develop a new dosage form as an alternative to the classical tablet forms of atorvastatin calcium (AtrCa). The formulation strategy was to prepare an optimum self micro emulsifying drug delivery system (SMEDDS) to overcome the problem of low solubility of the active substance. Methods: In this study, pseudo ternary phase diagrams were plotted determined by the solubility studies. According to the solubility studies; oleic acid was used as the oil phase, Tween 20 and Span 80 were used as the surfactants and ethanol was used as the co-surfactant. SMEDDS formulations were characterized according to pH, electrical conductivity, density, refractive index, viscosity, emulsification time, dispersibility, robustness of dilution stability, droplet size, polidispersity index, zeta potential, transmittance %, cloud point, content quantification %, chemical and physical stability. The lipolysis study was conducted under fed and fasted conditions. In vitro release studies and kinetic evaluation were carried out. Permeability studies were also examined with Caco-2 cell culture. Results: The droplet size of the optimized formulation did not change significantly in different medias over the test time period. Improved SMEDDS formulation will progress steadily without precipitating along the gastrointestinal tract. Lipolysis studies showed that the oil solution had been exposed to high amount of lipolysis compared to the SMEDDS formulation. The release rate of AtrCa from AtrCa- SMEDDS formulation (93.8%, at 15 minutes) was found as increased when the results were compared with commercial tablet formulation and pure drug. The permeability value of AtrCa from AtrCa- SMEDDS formulation was found higher than pure AtrCa and commercial tablet formulation, approximately 9.94 and 1.64 times, respectively. Conclusion: Thus, lipid-based SMEDDS formulation is a potential formulation candidate for lymphatic route in terms of the increased solubility of AtrCa.
MeSH term(s)	Atorvastatin/chemistry ; Caco-2 Cells ; Drug Compounding ; Drug Delivery Systems ; Emulsions/chemistry ; Ethanol/chemistry ; Hexoses/chemistry ; Humans ; Lipids/chemistry ; Oleic Acid/chemistry ; Particle Size ; Polysorbates/chemistry ; Solubility ; Surface Properties ; Surface-Active Agents/chemistry ; Tumor Cells, Cultured
Chemical Substances	Emulsions ; Hexoses ; Lipids ; Polysorbates ; Surface-Active Agents ; sorbitan monooleate (06XEA2VD56) ; Oleic Acid (2UMI9U37CP) ; Ethanol (3K9958V90M) ; Atorvastatin (A0JWA85V8F)
Language	English
Publishing date	2019-08-20
Publishing country	United Arab Emirates
Document type	Journal Article
ZDB-ID	2185284-4
ISSN	1875-5704 ; 1567-2018
ISSN (online)	1875-5704
ISSN	1567-2018
DOI	10.2174/1567201816666190820143957
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Zs.A 6415: Show issues

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Article ; Online: Synthesis, molecular modeling, in vivo study and anticancer activity against prostate cancer of (+) (S)-naproxen derivatives.

Birgül, Kaan / Yıldırım, Yeliz / Karasulu, H Yeşim / Karasulu, Ercüment / Uba, Abdullah Ibrahim / Yelekçi, Kemal / Bekçi, Hatice / Cumaoğlu, Ahmet / Kabasakal, Levent / Yılmaz, Özgür / Küçükgüzel, Ş Güniz

European journal of medicinal chemistry

2020 Volume 208, Page(s) 112841

Abstract: In this study, (S)-naproxen thiosemicarbazides (3a-d), 1,2,4-triazoles (4a-c), triazole-thioether hybride compounds (5a-p) were synthesized and their structures (3a, 3d, 4a and 5a-p) were confirmed by FT-IR, ...

Abstract	In this study, (S)-naproxen thiosemicarbazides (3a-d), 1,2,4-triazoles (4a-c), triazole-thioether hybride compounds (5a-p) were synthesized and their structures (3a, 3d, 4a and 5a-p) were confirmed by FT-IR,
MeSH term(s)	Animals ; Antineoplastic Agents/chemical synthesis ; Antineoplastic Agents/metabolism ; Antineoplastic Agents/therapeutic use ; Apoptosis/drug effects ; Cell Line, Tumor ; Drug Screening Assays, Antitumor ; Enzyme Inhibitors/chemical synthesis ; Enzyme Inhibitors/metabolism ; Enzyme Inhibitors/therapeutic use ; Humans ; Male ; Methionyl Aminopeptidases/antagonists & inhibitors ; Methionyl Aminopeptidases/metabolism ; Mice, Nude ; Molecular Docking Simulation ; Molecular Dynamics Simulation ; Molecular Structure ; Naproxen/analogs & derivatives ; Naproxen/metabolism ; Naproxen/therapeutic use ; Prostatic Neoplasms/drug therapy ; Protein Binding ; Stereoisomerism ; Structure-Activity Relationship
Chemical Substances	Antineoplastic Agents ; Enzyme Inhibitors ; Naproxen (57Y76R9ATQ) ; METAP2 protein, human (EC 3.4.11.18) ; Metap2 protein, mouse (EC 3.4.11.18) ; Methionyl Aminopeptidases (EC 3.4.11.18)
Language	English
Publishing date	2020-09-16
Publishing country	France
Document type	Journal Article
ZDB-ID	188597-2
ISSN	1768-3254 ; 0009-4374 ; 0223-5234
ISSN (online)	1768-3254
ISSN	0009-4374 ; 0223-5234
DOI	10.1016/j.ejmech.2020.112841
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Zs.B 784: Show issues

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Article ; Online: Preparation and evaluation of novel microemulsion-based hydrogels for dermal delivery of benzocaine.

Üstündağ Okur, Neslihan / Çağlar, Emre Şefik / Arpa, Muhammet Davut / Karasulu, H Yeşim

Pharmaceutical development and technology

2017 Volume 22, Issue 4, Page(s) 500–510

Abstract: The purpose of the current research was to prepare and evaluate the potential use of microemulsion-based hydrogel (MBH) formulations for dermal delivery of benzocaine (BZN). The pseudoternary-phase diagrams were constructed for various microemulsions ... ...

Abstract	The purpose of the current research was to prepare and evaluate the potential use of microemulsion-based hydrogel (MBH) formulations for dermal delivery of benzocaine (BZN). The pseudoternary-phase diagrams were constructed for various microemulsions composed of isopropyl myristate (IPM) as oil phase, Span 20, Tween 20, Tween 80, cremophor EL and cremophor RH40 as surfactants, ethanol as cosurfactant and distilled water as aqueous phase. Finally, concentration of BZN in microemulsions was 2% (w/w). The physicochemical properties, such as conductivity, viscosity, pH, droplet size, polydispersity index and zeta potential of microemulsions, were measured. Carbopol 940 was used to convert BZN-loaded microemulsions into gel form without affecting their structure. Furthermore, excised rat abdominal skin was used to compare permeation and penetration properties of BZN loaded M3 and M3BHs with BZN solution. According to ex vivo study results, BZN-loaded M3BH1 showed highest flux values and high release rate values, and furthermore, this gel formulation had low surfactant content. Finally, in order to learn the localization of formulations within the dermal penetration, formulations and BZN solution were labeled with red oil O and subjected to fluorescence observation. In conclusion, BZN-loaded MBHs could be offered as a promising strategy for dermal drug delivery.
MeSH term(s)	Acrylic Resins/chemistry ; Administration, Cutaneous ; Anesthetics, Local/administration & dosage ; Anesthetics, Local/pharmacokinetics ; Animals ; Benzocaine/administration & dosage ; Benzocaine/pharmacokinetics ; Drug Carriers/chemistry ; Emulsions/chemistry ; Hydrogels/chemistry ; Male ; Myristates/chemistry ; Polyethylene Glycols/chemistry ; Polysorbates/chemistry ; Rats, Wistar ; Skin Absorption
Chemical Substances	Acrylic Resins ; Anesthetics, Local ; Drug Carriers ; Emulsions ; Hydrogels ; Myristates ; Polysorbates ; isopropyl myristate (0RE8K4LNJS) ; Polyethylene Glycols (30IQX730WE) ; cremophor (39279-69-1) ; carbopol 940 (4Q93RCW27E) ; Benzocaine (U3RSY48JW5)
Language	English
Publishing date	2017-06
Publishing country	England
Document type	Journal Article
ZDB-ID	1331774-x
ISSN	1097-9867 ; 1083-7450
ISSN (online)	1097-9867
ISSN	1083-7450
DOI	10.3109/10837450.2015.1131716
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Article ; Online: Spirulina platensis (Cyanophyta) İle Hazırlanan Tablet ve Kapsüllerin in vitro Kalite Kontrol Çalışmaları.

H. Yeşim Karasulu / Meltem Conk Dalay / Evren Şanal / Tamer Güneri

Su Ürünleri Dergisi, Vol 18, Iss

2015 Volume 1

Keywords	- ; Aquaculture. Fisheries. Angling ; SH1-691 ; Ecology ; QH540-549.5
Language	English
Publishing date	2015-12-01T00:00:00Z
Publisher	Ege University
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Permeation studies and histological examination of sheep nasal mucosa following administration of different nasal formulations with or without absorption enhancers.

Karasulu, Ercüment / Yavasoğlu, Altug / Evrensanal, Z / Uyanikgil, Yigit / Karasulu, H Yesim

Drug delivery

2008 Volume 15, Issue 4, Page(s) 219–225

Abstract: This study was designed to investigate the possible histological effects of different intranasal (IN) formulations of indomethacin (IND) on nasal mucosa in sheep. For this purpose, oil-in-water (O/W) emulsion (E) and solution (S) formulations including 3 ...

Abstract	This study was designed to investigate the possible histological effects of different intranasal (IN) formulations of indomethacin (IND) on nasal mucosa in sheep. For this purpose, oil-in-water (O/W) emulsion (E) and solution (S) formulations including 3 mg/mL of IND were prepared. Penetration enhancers such as polyvinylpyrolidone (PVP), citric acid (CA) and sodium taurocholate (NaT) were added to emulsion (1%) at the final step into the formulations. First, the effect of penetration enhancers on permeation of IND was evaluated by in vitro permeation studies in which sheep nasal mucosa was used. According to the permeation studies PVP showed the highest enhancing effect on the permeation rate of IND from sheep nasal mucosa. Furthermore, the IND permeation from E containing PVP (1.624 +/- 0.045 mg) was significantly higher than that obtained from E (0.234 +/- 0.012 mg) (p < 0.05). For the histological studies, white Karaman sheep of approximately 20 +/- 5 kg, aged 4 to 8 months were used. They were randomly divided into eight groups, each including three sheep. Five experimental groups received different formulations of IND emulsion without/ with penetration enhancers (E-PVP, E-CA, E-NaT, E) and IND solution (S), respectively. Parallel controls were composed of either untreated groups and were given blank emulsion or isotonic sodium chloride solution (0.31 mg/kg). 2 mL of each experimental formulation was applied to both nostrils of sheep, and 1/3 central and lower regions of the nose were dissected and prepared for light microscopy. Specimens stained with hematoxylin and eosin and Gomori's trichrome were examined by light microscopy. No signs of inflammation or erosion were noticed in the nasal mucosa of the control groups. Widened epithelial intercellular spaces were noticed in E-CA, E-NaT, and E-PVP groups as well with the E-PVP group showing the largest intraepithelial separations. E-CA and E-NaT groups showed significant decrease in the amount of goblet cells, while hypoplasia was considerably moderate in the E-PVP group. Finally, intranasal administration of IND emulsion with PVP may be considered as an alternative to intravenous and per oral administrations of IND to overcome their adverse effects.
MeSH term(s)	Administration, Intranasal ; Animals ; Anti-Inflammatory Agents, Non-Steroidal/administration & dosage ; Anti-Inflammatory Agents, Non-Steroidal/adverse effects ; Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics ; Citric Acid/chemistry ; Emulsions/chemistry ; Emulsions/pharmacokinetics ; Excipients/chemistry ; Extracellular Space/metabolism ; Goblet Cells/metabolism ; Indomethacin/administration & dosage ; Indomethacin/adverse effects ; Indomethacin/pharmacokinetics ; Microscopy ; Nasal Mucosa/metabolism ; Oils/chemistry ; Permeability ; Pharmaceutical Solutions ; Povidone/chemistry ; Random Allocation ; Sheep ; Taurocholic Acid/chemistry ; Water/chemistry
Chemical Substances	Anti-Inflammatory Agents, Non-Steroidal ; Emulsions ; Excipients ; Oils ; Pharmaceutical Solutions ; Water (059QF0KO0R) ; Citric Acid (2968PHW8QP) ; Taurocholic Acid (5E090O0G3Z) ; Povidone (FZ989GH94E) ; Indomethacin (XXE1CET956)
Language	English
Publishing date	2008-04-21
Publishing country	England
Document type	Journal Article
ZDB-ID	1213261-5
ISSN	1521-0464 ; 1071-7544
ISSN (online)	1521-0464
ISSN	1071-7544
DOI	10.1080/10717540802006377
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Article ; Online: Effect of microemulsion formulation on biodistribution of

İlem-Özdemir, Derya / Üstündağ-Okur, Neslihan / Ay Şenyiğit, Zeynep / Oruç, Nevin / Aşıkoğlu, Makbule / Özütemiz, Ömer / Karasulu, H Yeşim

Drug delivery

2016 Volume 23, Issue 8, Page(s) 3055–3062

Abstract: Background: Aprotinin is a monomeric globular polypeptide, which derived from bovine lung tissue and theoretically attractive molecule in ameliorating the effects of acute pancreatitis. Acute pancreatitis is an inflammatory condition of the pancreas ... ...

Abstract	Background: Aprotinin is a monomeric globular polypeptide, which derived from bovine lung tissue and theoretically attractive molecule in ameliorating the effects of acute pancreatitis. Acute pancreatitis is an inflammatory condition of the pancreas that is painful and at times deadly. Over the following two decades Aprotinin therapeutic potential on pancreatitis is proven experimentally, its clinical therapeutic success is limited due to low targeting to pancreas. Objective: The aim of this study was to evaluate the biodistribution of Technetium-99m ( Method: Aprotinin was radiolabeled with Results: Aprotinin was radiolabeled by Conclusion: This might be concluding that microemulsions may be suggested as promising formulations for selectively targeting Aprotinin to pancreas inflammation.
MeSH term(s)	Animals ; Aprotinin/metabolism ; Chemistry, Pharmaceutical/methods ; Disease Models, Animal ; Emulsions/metabolism ; Male ; Pancreatitis/metabolism ; Particle Size ; Radionuclide Imaging/methods ; Radiopharmaceuticals/metabolism ; Rats ; Rats, Wistar ; Technetium/metabolism ; Tissue Distribution
Chemical Substances	Emulsions ; Radiopharmaceuticals ; Technetium (7440-26-8) ; Aprotinin (9087-70-1)
Language	English
Publishing date	2016-10
Publishing country	England
Document type	Journal Article
ZDB-ID	1213261-5
ISSN	1521-0464 ; 1071-7544
ISSN (online)	1521-0464
ISSN	1071-7544
DOI	10.3109/10717544.2016.1145306
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Article: Different geometric shaped hydrogel theophylline tablets: statistical approach for estimating drug release.

Karasulu, H Yeşim / Ertan, Gökhan

Farmaco (Societa chimica italiana : 1989)

2002 Volume 57, Issue 11, Page(s) 939–945

Abstract: The objective of this study was to develop a mathematical equation for the calculation of drug release from different shaped matrix tablets. By this way, release rate related to the geometric shape could be predicted with the help of the developed ... ...

Abstract	The objective of this study was to develop a mathematical equation for the calculation of drug release from different shaped matrix tablets. By this way, release rate related to the geometric shape could be predicted with the help of the developed mathematical equation. So, drug release could be estimated before the dissolution. Hydroxypropylmethylcellulose (HPMC) E50 as polymer and theophylline as active substance were used in the matrix tablets prepared for this purpose. Matrix tablets in three different geometrical shapes, namely in triangular, cylindrical and half-spherical forms were prepared by using two different drug-polymer ratio (1:0.5, 1:1) and diluent's in three different percentages (0, 20, 40%). Using rotating paddle and basket methods reported in USP XXIII carried out the release rate studies of these tablets. The Higuchi square-root time model best described the dissolution data. Differential scanning calorimetry (DSC) analysis was performed to identify any solid-state inactivation of the drug. The practical benefit of this work is to improve mathematical equation that can be used to predict accurately the required composition and in order to achieve the desired release profiles of different geometric shaped tablets. By using this equation new pharmaceutical products can be easily improved.
MeSH term(s)	Analysis of Variance ; Calorimetry, Differential Scanning ; Data Interpretation, Statistical ; Hydrogels ; Kinetics ; Reproducibility of Results ; Solubility ; Tablets ; Theophylline/analysis
Chemical Substances	Hydrogels ; Tablets ; Theophylline (C137DTR5RG)
Language	English
Publishing date	2002-12-13
Publishing country	France
Document type	Journal Article
ZDB-ID	130072-6
ISSN	1879-0569 ; 0014-827X
ISSN (online)	1879-0569
ISSN	0014-827X
DOI	10.1016/s0014-827x(02)01297-1
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