Denisa Circioban | University Of Medicine And Pharmacy Timisoara (original) (raw)

Papers by Denisa Circioban

Research paper thumbnail of Risperidone/Randomly Methylated β-Cyclodextrin Inclusion Complex—Compatibility Study with Pharmaceutical Excipients

Molecules, 2021

Risperidone (RSP) is an atypical antipsychotic drug used in treating schizophrenia, behavioral, a... more Risperidone (RSP) is an atypical antipsychotic drug used in treating schizophrenia, behavioral, and psychological symptoms of dementia and irritability associated with autism. The drug substance is practically insoluble in water and exhibits high lipophilicity. It also presents incompatibilities with pharmaceutical excipients such as magnesium stearate, lactose, and cellulose microcrystalline. RSP encapsulation by randomly methylated β-cyclodextrin (RM-β-CD) was performed in order to enhance drug solubility and stability and improve its biopharmaceutical profile. The inclusion complex formation was evaluated using thermal methods, powder X-ray diffractometry (PXRD), universal-attenuated total reflectance Fourier transform infrared (UATR-FTIR), UV spectroscopy, and saturation solubility studies. The 1:1 stoichiometry ratio and the apparent stability constant of the inclusion complex were determined by means of the phase solubility method. The compatibility between the supramolecular ...

Research paper thumbnail of Solid Polymeric Nanoparticles of Albendazole: Synthesis, Physico-Chemical Characterization and Biological Activity

Molecules, 2020

Albendazole is a benzimidazole derivative with documented antitumor activity and low toxicity to ... more Albendazole is a benzimidazole derivative with documented antitumor activity and low toxicity to healthy cells. The major disadvantage in terms of clinical use is its low aqueous solubility which limits its bioavailability. Albendazole was incorporated into stable and homogeneous polyurethane structures with the aim of obtaining an improved drug delivery system model. Spectral and thermal analysis was used to investigate the encapsulation process and confirmed the presence of albendazole inside the nanoparticles. The in vitro anticancer properties of albendazole encapsulated in polyurethane structures versus the un-encapsulated compound were tested on two breast cancer cell lines, MCF-7 and MDA-MB-231, in terms of cellular viability and apoptosis induction. The study showed that the encapsulation process enhanced the antitumor activity of albendazole on the MCF-7 and MDA-MB-23 breast cancer lines. The cytotoxic activity manifested in a concentration-dependent manner and was accompan...

Research paper thumbnail of Thermal Stability of Desipramine and Imipramine

ADRIANA LEDETI1, GABRIELA VLASE2, IONUT LEDETI1*, TITUS VLASE2, PETRU MATUSZ3, CRISTINA DEHELEAN4... more ADRIANA LEDETI1, GABRIELA VLASE2, IONUT LEDETI1*, TITUS VLASE2, PETRU MATUSZ3, CRISTINA DEHELEAN4, DENISA CIRCIOBAN1, LAVINIA STELEA6, LENUTA MARIA SUTA4 1University of Medicine and Pharmacy Victor Babes, Faculty of Pharmacy, Department Pharmacy I, 2 Eftimie Murgu Sq., 300041, Timisoara, Romania 2West University of Timisoara, Research Centre for Thermal Analysis in Environmental Problems, 16 Pestalozzi Str., 300115 Timisoara, Romania 3University of Medicine and Pharmacy Victor Babes, Faculty of Medicine, Department of Anatomy and Embriology, 2 Eftimie Murgu Sq., 300041, Timisoara, Romania 4University of Medicine and Pharmacy Victor Babes, Faculty of Pharmacy, Department Pharmacy II, 2 Eftimie Murgu Sq., 300041, Timisoara, Romania 5University of Medicine and Pharmacy Victor Babes, Faculty of Medicine, Department of Obstetrics and Gynecology, III Clinic, 2 Eftimie Murgu Sq., 300041, Timisoara, Romania

Research paper thumbnail of Solid-State Thermal Behaviour of Cholic Acid

LENUTA MARIA SUTA1, GABRIELA VLASE2, ADRIANA LEDETI3*, TITUS VLASE2, PETRU MATUSZ4, CRISTINA TRAN... more LENUTA MARIA SUTA1, GABRIELA VLASE2, ADRIANA LEDETI3*, TITUS VLASE2, PETRU MATUSZ4, CRISTINA TRANDAFIRESCU1, DENISA CIRCIOBAN3, SORIN OLARIU5, CODRUT IVAN5, MARIUS-SORIN MURARIU5, LAVINIA STELEA6, IONUT LEDETI3 1University of Medicine and Pharmacy Victor Babes, Faculty of Pharmacy, Department Pharmacy II, 2 Eftimie Murgu Sq., 300041, Timisoara, Romania 2West University of Timisoara, Research Centre for Termal Analysis in Environmental Problems, 16 Pestalozzi Str., 300115 Timisoara, Romania 3University of Medicine and Pharmacy Victor Babes, Faculty of Pharmacy, Department Pharmacy I, 2 Eftimie Murgu Sq., 300041, Timisoara, Romania 4University of Medicine and Pharmacy Victor Babes, Faculty of Medicine, Department of Anatomy and Embriology, 2 Eftimie Murgu Sq., 300041, Timisoara, Romania 5University of Medicine and Pharmacy Victor Babes, Faculty of Medicine, Department of Surgery II, First Surgical Clinic, 2 Eftimie Murgu Sq., 300041, Timisoara, Romania 6University of Medicine and Phar...

Research paper thumbnail of Synthesis and Physico-chemical Characterization of Theophylline-succinic Acid Binary Adduct

DENISA CIRCIOBAN1, CRISTINA DEHELEAN1, LENUTA-MARIA SUTA1, MARIUS MURARIU2, GABRIELA VLASE3, LUCI... more DENISA CIRCIOBAN1, CRISTINA DEHELEAN1, LENUTA-MARIA SUTA1, MARIUS MURARIU2, GABRIELA VLASE3, LUCIAN NITA4, CODRUTA SOICA1*, ADRIANA FULIAS1 1 “Victor Babeo” University of Medicine and Pharmacy, Faculty of Pharmacy, 2 Eftimie Murgu Sq., 300041, Timiooara, Romania 2 “Victor Babeo” University of Medicine and Pharmacy, Faculty of Medicine, Department of Surgery II, First Surgical Clinic, 2 Eftimie Murgu Sq., 300041, Timiooara, Romania 3 West University of Timisoara, Research Centre for Thermal Analysis in Environmental Problems, 16 Pestalozzi Str., 300115, Timiooara, Romania 4 Banat’s University of Agricultural Sciences and Veterinary Medicine, Faculty of Agriculture, 119 Calea Aradului, 300645, Timisoara, Romania

Research paper thumbnail of Solid State Stability and Preformulation Studies for Acetylcholinesterase Inhibitor Drug Tacrine

Timisoara Medical Journal, 2020

In this paper, the acetylcholinesterase inhibitor drug tacrine was investigated by two complement... more In this paper, the acetylcholinesterase inhibitor drug tacrine was investigated by two complementary instrumental techniques, namely infrared spectroscopy and thermal analysis, as pure drug and in solid binary mixtures with nine excipients frequently used in the pharmaceutical industry, namely starch, sodium carboxymethyl cellulose, polyvinylpyrrolidone K30, fumed silica (Aerosil), talc, anhydrous lactose, magnesium stearate, mannitol and calcium lactate pentahydrate. The corroboration of obtained data by the two complementary methods confirmed the incompatibility of this drug with anhydrous lactose, mannitol, magnesium stearate and calcium lactate under both ambient conditions and thermal stress, and thermally induced interactions between tacrine and silica. In the development of new generic solid formulations, four of the investigated excipients (i.e., starch, sodium carboxymethyl cellulose, polyvinylpyrrolidone K30 and talc) can be used, since they are compatible with tacrine und...

Research paper thumbnail of Instrumental analysis and molecular modelling of inclusion complexes containing artesunate

Journal of Thermal Analysis and Calorimetry, 2020

A series of five guest–host inclusion complexes containing the antimalarial and anticancer agent ... more A series of five guest–host inclusion complexes containing the antimalarial and anticancer agent artesunate (ATS) were obtained and characterized in the present study. Different cyclodextrins (CDNs) were used as hosts [α-cyclodextrin (CDN 1 ), β-cyclodextrin (CDN 2 ), γ-cyclodextrin (CDN 3 ), (2-hydroxypropyl)-β-cyclodextrin (CDN 4 ) and (2-hydroxypropyl)-γ-cyclodextrin (CDN 5 )], and the formation of the adducts was simulated using molecular modelling. The results indicating the hypothetical formation of all complexes were confirmed on the prepared samples by FTIR spectroscopy and thermal analysis (TG—thermogravimetric/DTG—derivative thermogravimetric/HF—heat flow). Our results showed that the partially entrapment of ATS inside the cavity of each cyclodextrin is a consequence of H-bonds formation, electrostatic interactions (dipole–dipole) and hydration water substitution. Also, all complexes formed in a 1:1 molecular ratio presented with higher thermal stability than pure ATS, making the analysed adducts possible alternatives in the drug design process of new and improved pharmaceutical formulations containing ATS.

Research paper thumbnail of Thermal stability and kinetic degradation study for dihydroartemisinin

Journal of Thermal Analysis and Calorimetry, 2020

Dihydroartemisinin (DHA), the hydrogenated derivative of the naturally originated sesquiterpene l... more Dihydroartemisinin (DHA), the hydrogenated derivative of the naturally originated sesquiterpene lactone artemisinin, is a well-known antimalarial agent that is currently researched because of its potential as an anticancer medication. Because DHA has been associated with a low oral bioavailability and a short half-life, new formulations meant to overcome these shortcomings are currently under development. As such, the present paper aims to present a comprehensive physico-chemical profile of DHA containing data of great importance for the preformulation stages of the drug design process. As instrumental techniques, attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) spectroscopy and thermal analysis (TG—thermogravimetric/DTG—derivative thermogravimetric/HF—heat flow) were performed, followed by a kinetic study realized using three isoconversional methods (Friedman—Fr, Flynn–Wall–Ozawa—FWO and Kissinger–Akahira–Sunose—KAS), as well as the nonparametric kinetic method (NPK). FTIR spectroscopy confirmed the identity and purity of DHA, and thermal analysis revealed a relatively low thermal stability and a multistep thermooxidation that was proved during the performed kinetic study. The latter unveiled a two-process decomposition determined by both chemical degradations and physical transformations.

Research paper thumbnail of Cytotoxic Activity Evaluation on Breast Cells of Guest-host Complexes Containing Artemisinin

Revista de Chimie, 2019

Artemisinin is a sesquiterpene lactone with vastly proved anti-cancer effects and a low toxicity ... more Artemisinin is a sesquiterpene lactone with vastly proved anti-cancer effects and a low toxicity profile. However, the compound has poor water solubility, bioavailability and a short half-life. As such, the present paper aims to evaluate the cytotoxic effect on breast cells of three guest-host inclusion complexes containing artemisinin as the active compound and different cyclodextrins as hosts. These were tested using two different concentrations (i.e. 12.5 mM and 25 mM) and three cell lines, namely two human breast adenocarcinoma cell lines (MCF7 and MDA-MB-231) and one human non-tumorigenic breast epithelial cell line (MCF10A) employing the colorimetric microculture tetrazolium assay. After a 72h stimulation period, the most promising results were obtained for the complex containing artemisinin and Heptakis(2,3,6-tri-O-methyl)-b-cyclodextrin, the cell viability decrease being significant for the estrogen positive MCF7 cell line (80.0 � 2.3 %), making the complex a potential candi...

Research paper thumbnail of Stability and Compatibility Studies of Levothyroxine Sodium in Solid Binary Systems—Instrumental Screening

Pharmaceutics, 2020

The influence of excipients on the stability of sodium levothyroxine pentahydrate (LTSS) under am... more The influence of excipients on the stability of sodium levothyroxine pentahydrate (LTSS) under ambient conditions and thermal stress was evaluated. Since LTSS is a synthetic hormone with a narrow therapeutic index, the interactions of LTSS with excipients can lead to a drastic diminution of therapeutic activity. Ten commonly used pharmaceutical excipients with different roles in solid formulations were chosen as components for binary mixtures containing LTSS, namely, starch, anhydrous lactose, D-mannitol, D-sorbitol, gelatin, calcium lactate pentahydrate, magnesium stearate, methyl 2-hydroxyethyl cellulose (Tylose), colloidal SiO2 (Aerosil) and talc. As investigational tools, universal attenuated total reflectance- Fourier transform infrared spectroscopy UATR-FTIR spectroscopy and thermal analysis were chosen and used as follows: UATR-FTIR spectra were drawn up for samples kept under ambient conditions, while thermoanalytical tools (TG/DTG/HF data) were chosen to evaluate the induci...

Research paper thumbnail of Study of kinetic characteristics of 6-ethyl chenodeoxycholic acid and deoxycholic acid decomposition in non-isothermal conditions

Journal of Thermal Analysis and Calorimetry, 2018

6-ethyl chenodeoxycholic acid (6ECDA) and deoxycholic acid (DCA) are two similar-structured chola... more 6-ethyl chenodeoxycholic acid (6ECDA) and deoxycholic acid (DCA) are two similar-structured cholanoic acids, the first being used in the treatment of primary biliary cholangitis, while the second is one of the natural secondary bile acids, currently being tested as a treatment component in the destruction of gallstones. This study was realised as no literature reference was found over thermal behaviour and the evaluation of the decomposition kinetics of the compounds from this class. Both acids were characterised by UATR-FTIR spectroscopy, thermal analysis and the kinetics of decomposition in dynamic oxidative atmosphere, by employing three isoconversional methods, namely Friedman, Kissinger-Akahira-Sunose and Flynn-Wall-Ozawa, respectively, the modified NPK method. Isoconversional methods suggested that no modification of the decomposition mechanism occurs with the modification of thermal treatment of the samples. Later, the modified NPK method was employed in order to estimate the kinetic triplet that describes the decomposition process of both compounds. All kinetic methods indicate a very good thermal stability of the bile acids, with apparent activation energies between 190.6 and 208.7 kJ mol-1 for the decomposition of 6ECDA and 205.5 and 221.7 kJ mol-1 for the decomposition of CDA, respectively. The modified NPK method suggested that both bile acids are degraded by the contribution of two distinctive chemical processes without any physical process associated. Keywords Biliary acids Á Kinetic study Á Thermal behaviour Á NPK method Á Gallstones List of symbols b Heating rate t Time a Conversion degree T Temperature A Pre-exponential factor f(a) and g (a) Conversion functions E a Apparent activation energy R Universal gas constant k(T) The temperature dependence function

Research paper thumbnail of Thermal degradation, kinetic analysis and evaluation of biological activity on human melanoma for artemisinin

Journal of Thermal Analysis and Calorimetry, 2018

Research paper thumbnail of Study of solid-state degradation of prochlorperazine and promethazine

Journal of Thermal Analysis and Calorimetry, 2018

Prochlorperazine (PCP) and promethazine (PMT) are dopamine (D2) receptor antagonists with a pheno... more Prochlorperazine (PCP) and promethazine (PMT) are dopamine (D2) receptor antagonists with a phenothiazinic structure that used nowadays mainly for their antiemetic properties, including for the pre-and postoperative setting. In this paper, the thermal behavior of PCP and PMT was studied, including a complete kinetic analysis for the evaluation of the degradation process in heterogenous media. Samples were analyzed using Fourier transform infrared spectroscopy, thermogravimetric analysis (TG/DTG/HF) and a preliminary kinetic analysis using the ASTM E698 kinetic method, the obtained data being later completed with an in-depth kinetic analysis according to ICTAC 2000 protocol, using the isoconversional methods of Friedman, Ozawa-Flynn-Wall, Kissinger-Akahira-Sunose, respectively, the modified nonparametric kinetics method, the latter allowing the determination of the kinetic triplet without using any approximation, but as well the separation of parallel reaction that occurs at decomposition. The results confirmed that PCP dimaleate has a better stability in comparison with PMT hydrochloride, in terms of apparent energy of activation, probably due to solid-state structure of solid and the contribution of intermolecular bondings.

Research paper thumbnail of Kinetics of heterogeneous-induced degradation for artesunate and artemether

Journal of Thermal Analysis and Calorimetry, 2018

This paper presents the results obtained after the investigation of two artemisinin derived sesqu... more This paper presents the results obtained after the investigation of two artemisinin derived sesquiterpenes, namely artesunate and artemether, currently studied for their antitumor properties. The chosen methods of analysis included UATR-FTIR spectroscopy, characterization of the thermal behavior (TG/DTG/HF) in oxidative dynamic atmosphere, and a complete kinetic analysis. The latter was realized using two integral methods (Kissinger-Akahira-Sunose and Flynn-Wall-Ozawa), a differential one (Friedman), and was later completed with the modified NPK method. The study showed that both compounds show similar thermal stability in terms of apparent activation energies and the degradation processes occur in two parallel steps for each compound, this being solely due to chemical transformations. Keywords Sesquiterpene Á Isoconversional kinetic study Á Artesunate Á Artemether Á NPK method Abbreviations T Time T Temperature A Conversion degree f(a) The differential conversion function R The universal gas constant g(a) The integral conversion function b The heating rate k(T) The temperature dependence function A The pre-exponential factor E a The apparent activation energy given by the Arrhenius equation

Research paper thumbnail of Thermal behavior of entacapone, a catechol-O-methyltransferase inhibitor used in Parkinson’s disease

Journal of Thermal Analysis and Calorimetry, 2018

Entacapone, a selective and reversible inhibitor of catechol-O-methyltransferase, is used in the ... more Entacapone, a selective and reversible inhibitor of catechol-O-methyltransferase, is used in the treatment of Parkinson's disease in combination with levodopa/carbidopa to treat the symptoms of end-of-dose ''wearing-off'' effect. Considering that new formulations are researched constantly, proper knowledge of the active pharmaceutical ingredients is crucial in the preformulation stages. Kinetic analysis was performed using three methods: one integral-Flynn-Wall-Ozawa method, one differential-Friedman method, and modified nonparametric kinetics method (NPK). The thermoanalytical curves were registered at five different heating rates: b = 5, 7, 10, 12, and 15°C min-1. Analysis was conducted in the dynamic air atmosphere to highlight potential thermooxidative processes. This paper deals with the investigation of solid-state stability and compatibility of binary mixture of entacapone with various pharmaceutical excipients by two instrumental techniques, such as universal attenuated total reflection Fourier transform infrared and thermal analysis (TG/DTG/HF). The excipients used in the mixture were: mannitol, silicon dioxide, talc, sorbitol, magnesium stearate, and povidone.

Research paper thumbnail of Guest–host interactions and complex formation for artemisinin with cyclodextrins: instrumental analysis and evaluation of biological activity

Journal of Thermal Analysis and Calorimetry, 2018

Artemisinin is one of the most important naturally occurring compound found in Artemisia annua, b... more Artemisinin is one of the most important naturally occurring compound found in Artemisia annua, being highly active against Plasmodium falciparum, the malaria causing parasite, and currently studied in the oncological field. The aim of this study was to obtain and characterize the host-guest inclusion complexes formed between artemisinin and three functionalized cyclodextrins, namely Randomly methylated-b-cyclodextrin (CD1), Heptakis(2,6-di-O-methyl)-b-cyclodextrin (CD2) and Heptakis(2,3,6-triO methyl)-b-cyclodextrin (CD3). As instrumental tools, thermal analysis (TG/DTG/HF) and UATR-FTIR spectroscopy were used. Later on, the inclusion complexes were tested as to evaluate their antioxidant (AOA) and in vitro activity on both healthy keratinocytes and a human melanoma cell line, A375. Both instrumental techniques suggested the formation of inclusion complexes and the increase of thermal stability of artemisinin in complexes versus pure compound. Regarding the antioxidant activity evaluation of all samples, it was shown that this is significantly inferior in comparison to ascorbic acid, while the in vitro biological activity showed that inclusion complexes (CPX2 and CPX3) exerted an inhibitory effect on human melanoma cells growth, similar to the effect induced by artemisinin.

Research paper thumbnail of Comparative instrumental investigations of some bile acids

Journal of Thermal Analysis and Calorimetry, 2018

In this paper, we present the spectroscopic description (by the means of UATR-FTIR spectroscopy) ... more In this paper, we present the spectroscopic description (by the means of UATR-FTIR spectroscopy) for four naturally occurring bile acids, namely lithocholic acid (LC), taurocholic acid sodium salt hydrate (TC), taurodeoxycholic acid sodium salt hydrate (TDC) and chenodeoxycholic acid (CDC), as well as their thermal behaviour in dynamic oxidative atmosphere, by TG/DTG/HF means. It was shown that all samples have a good thermal stability, favourized by the presence of cholan-24-oic structural moiety in all samples, as well as the solid-state structure (intermolecular H-bondings for the carboxylic acids CDC and LC and saline structures for TDC and TC, respectively). These data are simple, but of great interest in identifying the presence of these compounds by fast, reproducible and precise instrumental techniques in complex mixtures, such as biliary stones.

Research paper thumbnail of Compatibility study between antiparkinsonian drug Levodopa and excipients by FTIR spectroscopy, X-ray diffraction and thermal analysis

Journal of Thermal Analysis and Calorimetry, 2017

Levodopa (L-Dopa or LD) is nowadays considered one of the essential medicines in the World Health... more Levodopa (L-Dopa or LD) is nowadays considered one of the essential medicines in the World Health Organization list, being a main treatment component for Parkinson's disease. This paper deals with the investigation of solid-state stability and compatibility of binary mixtures of Levodopa with various pharmaceutical excipients, by employment of several instrumental techniques, such as attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy, powder X-ray diffraction (PXRD) data and thermal analysis (TG/DTG/HF). Along L-Dopa, eleven pharmaceutical excipients were investigated, namely calcium lactate (CaL), mannitol (Man), magnesium stearate (MgSt), anhydrous lactose (LAnh), talc (T), magnesium citrate (MgC), sorbitol (Sb), silica (SiO 2), polyvinylpyrrolidone K30 (PVP), sodium carboxymethylcellulose (NaCMC) and starch (St). FTIR analysis suggested possible interactions with calcium lactate, mannitol, magnesium stearate, anhydrous lactose, talc and SiO 2 , which were confirmed by PXRD patterns, except for talc. When the samples were subjected to thermal stress, solely magnesium citrate did not present interactions in binary mixture, while all other excipients were incompatible with L-Dopa. Keywords L-Dopa Á Levodopa Á Compatibility study Á Excipient Á FTIR Á PXRD Á Thermal analysis Ionut Ledeti and Sorin Bolintineanu have contributed equally to this work.

Research paper thumbnail of Evaluation of thermal stability and kinetic of degradation for levodopa in non-isothermal conditions

Journal of Thermal Analysis and Calorimetry, 2017

In this paper, we present the results obtained during the investigation of thermal stability of a... more In this paper, we present the results obtained during the investigation of thermal stability of antiparkinsonian drug Levodopa in oxidative atmosphere and under non-isothermal conditions. As investigational tools, thermoanalytical methods were used along with ATR-FTIR spectroscopy and later completed with kinetic study for the main degradative process that occurs in the 260-330°C temperature range, at four heating rates. Four kinetic methods were used as follows: ASTM E698 which leads to an activation energy of 209.72 kJ mol-1 , while isoconversional methods suggested the values 177.6 ± 13.1 kJ mol-1 (Friedman) and 188.8 ± 4.5 kJ mol-1 (Kissinger-Akahira-Sunose), with a clear indication of multistep degradation. The last method used was NPK, which revealed that the degradation occurs in three steps, with different physical and chemical contributions with mean activation energy equal to 191.3 ± 9.5 kJ mol-1. Keywords L-Dopa Á Thermal stability Á Non-isothermal kinetic study Á Isoconversional methods Á ASTM E698 Á NPK method Abbreviations A Pre-exponential factor (s-1) E Activation energy (kJ mol-1) R Universal gas constant (8.314 J mol-1 K-1) t Time (s) T Temperature (°C or K) f(a) Differential form of kinetic mechanism function g(a) Integral form of kinetic mechanism function a Conversion degree b Heating rate (°C min-1) k(T) Rate constant Adriana Ledeti, Tudor Olariu, and Angelica Caunii contributed equally to this work.

Research paper thumbnail of Evaluation of solid-state thermal stability of donepezil in binary mixtures with excipients using instrumental techniques

Journal of Thermal Analysis and Calorimetry, 2017

Donepezil (Don) is one of the main compounds used in the therapy of Alzheimer's disease. In this ... more Donepezil (Don) is one of the main compounds used in the therapy of Alzheimer's disease. In this study, donepezil hydrochloride was investigated for solid-state compatibility with several pharmaceutical excipients like calcium lactate (CaL), mannitol (Man), magnesium stearate (MgSt), anhydrous lactose (LAnh), talc (T), magnesium citrate (MgC), sorbitol (Sb), silica (SiO 2), polyvinylpyrrolidone K30 (PVP), sodium carboxymethylcellulose (NaCMC) and starch (St) under ambient conditions, by ATR-FTIR spectroscopy and PXRD data, and later by thermoanalytical techniques (TG/DTG/HF), in order to evaluate the thermal-induced interactions. The instrumental investigations carried at ambiental temperature revealed no interaction between Don and selected excipients, while thermal treatment induced interactions between components in eight binary mixtures, except the ones containing magnesium citrate, talc and polyvinylpyrrolidone.

Research paper thumbnail of Risperidone/Randomly Methylated β-Cyclodextrin Inclusion Complex—Compatibility Study with Pharmaceutical Excipients

Molecules, 2021

Risperidone (RSP) is an atypical antipsychotic drug used in treating schizophrenia, behavioral, a... more Risperidone (RSP) is an atypical antipsychotic drug used in treating schizophrenia, behavioral, and psychological symptoms of dementia and irritability associated with autism. The drug substance is practically insoluble in water and exhibits high lipophilicity. It also presents incompatibilities with pharmaceutical excipients such as magnesium stearate, lactose, and cellulose microcrystalline. RSP encapsulation by randomly methylated β-cyclodextrin (RM-β-CD) was performed in order to enhance drug solubility and stability and improve its biopharmaceutical profile. The inclusion complex formation was evaluated using thermal methods, powder X-ray diffractometry (PXRD), universal-attenuated total reflectance Fourier transform infrared (UATR-FTIR), UV spectroscopy, and saturation solubility studies. The 1:1 stoichiometry ratio and the apparent stability constant of the inclusion complex were determined by means of the phase solubility method. The compatibility between the supramolecular ...

Research paper thumbnail of Solid Polymeric Nanoparticles of Albendazole: Synthesis, Physico-Chemical Characterization and Biological Activity

Molecules, 2020

Albendazole is a benzimidazole derivative with documented antitumor activity and low toxicity to ... more Albendazole is a benzimidazole derivative with documented antitumor activity and low toxicity to healthy cells. The major disadvantage in terms of clinical use is its low aqueous solubility which limits its bioavailability. Albendazole was incorporated into stable and homogeneous polyurethane structures with the aim of obtaining an improved drug delivery system model. Spectral and thermal analysis was used to investigate the encapsulation process and confirmed the presence of albendazole inside the nanoparticles. The in vitro anticancer properties of albendazole encapsulated in polyurethane structures versus the un-encapsulated compound were tested on two breast cancer cell lines, MCF-7 and MDA-MB-231, in terms of cellular viability and apoptosis induction. The study showed that the encapsulation process enhanced the antitumor activity of albendazole on the MCF-7 and MDA-MB-23 breast cancer lines. The cytotoxic activity manifested in a concentration-dependent manner and was accompan...

Research paper thumbnail of Thermal Stability of Desipramine and Imipramine

ADRIANA LEDETI1, GABRIELA VLASE2, IONUT LEDETI1*, TITUS VLASE2, PETRU MATUSZ3, CRISTINA DEHELEAN4... more ADRIANA LEDETI1, GABRIELA VLASE2, IONUT LEDETI1*, TITUS VLASE2, PETRU MATUSZ3, CRISTINA DEHELEAN4, DENISA CIRCIOBAN1, LAVINIA STELEA6, LENUTA MARIA SUTA4 1University of Medicine and Pharmacy Victor Babes, Faculty of Pharmacy, Department Pharmacy I, 2 Eftimie Murgu Sq., 300041, Timisoara, Romania 2West University of Timisoara, Research Centre for Thermal Analysis in Environmental Problems, 16 Pestalozzi Str., 300115 Timisoara, Romania 3University of Medicine and Pharmacy Victor Babes, Faculty of Medicine, Department of Anatomy and Embriology, 2 Eftimie Murgu Sq., 300041, Timisoara, Romania 4University of Medicine and Pharmacy Victor Babes, Faculty of Pharmacy, Department Pharmacy II, 2 Eftimie Murgu Sq., 300041, Timisoara, Romania 5University of Medicine and Pharmacy Victor Babes, Faculty of Medicine, Department of Obstetrics and Gynecology, III Clinic, 2 Eftimie Murgu Sq., 300041, Timisoara, Romania

Research paper thumbnail of Solid-State Thermal Behaviour of Cholic Acid

LENUTA MARIA SUTA1, GABRIELA VLASE2, ADRIANA LEDETI3*, TITUS VLASE2, PETRU MATUSZ4, CRISTINA TRAN... more LENUTA MARIA SUTA1, GABRIELA VLASE2, ADRIANA LEDETI3*, TITUS VLASE2, PETRU MATUSZ4, CRISTINA TRANDAFIRESCU1, DENISA CIRCIOBAN3, SORIN OLARIU5, CODRUT IVAN5, MARIUS-SORIN MURARIU5, LAVINIA STELEA6, IONUT LEDETI3 1University of Medicine and Pharmacy Victor Babes, Faculty of Pharmacy, Department Pharmacy II, 2 Eftimie Murgu Sq., 300041, Timisoara, Romania 2West University of Timisoara, Research Centre for Termal Analysis in Environmental Problems, 16 Pestalozzi Str., 300115 Timisoara, Romania 3University of Medicine and Pharmacy Victor Babes, Faculty of Pharmacy, Department Pharmacy I, 2 Eftimie Murgu Sq., 300041, Timisoara, Romania 4University of Medicine and Pharmacy Victor Babes, Faculty of Medicine, Department of Anatomy and Embriology, 2 Eftimie Murgu Sq., 300041, Timisoara, Romania 5University of Medicine and Pharmacy Victor Babes, Faculty of Medicine, Department of Surgery II, First Surgical Clinic, 2 Eftimie Murgu Sq., 300041, Timisoara, Romania 6University of Medicine and Phar...

Research paper thumbnail of Synthesis and Physico-chemical Characterization of Theophylline-succinic Acid Binary Adduct

DENISA CIRCIOBAN1, CRISTINA DEHELEAN1, LENUTA-MARIA SUTA1, MARIUS MURARIU2, GABRIELA VLASE3, LUCI... more DENISA CIRCIOBAN1, CRISTINA DEHELEAN1, LENUTA-MARIA SUTA1, MARIUS MURARIU2, GABRIELA VLASE3, LUCIAN NITA4, CODRUTA SOICA1*, ADRIANA FULIAS1 1 “Victor Babeo” University of Medicine and Pharmacy, Faculty of Pharmacy, 2 Eftimie Murgu Sq., 300041, Timiooara, Romania 2 “Victor Babeo” University of Medicine and Pharmacy, Faculty of Medicine, Department of Surgery II, First Surgical Clinic, 2 Eftimie Murgu Sq., 300041, Timiooara, Romania 3 West University of Timisoara, Research Centre for Thermal Analysis in Environmental Problems, 16 Pestalozzi Str., 300115, Timiooara, Romania 4 Banat’s University of Agricultural Sciences and Veterinary Medicine, Faculty of Agriculture, 119 Calea Aradului, 300645, Timisoara, Romania

Research paper thumbnail of Solid State Stability and Preformulation Studies for Acetylcholinesterase Inhibitor Drug Tacrine

Timisoara Medical Journal, 2020

In this paper, the acetylcholinesterase inhibitor drug tacrine was investigated by two complement... more In this paper, the acetylcholinesterase inhibitor drug tacrine was investigated by two complementary instrumental techniques, namely infrared spectroscopy and thermal analysis, as pure drug and in solid binary mixtures with nine excipients frequently used in the pharmaceutical industry, namely starch, sodium carboxymethyl cellulose, polyvinylpyrrolidone K30, fumed silica (Aerosil), talc, anhydrous lactose, magnesium stearate, mannitol and calcium lactate pentahydrate. The corroboration of obtained data by the two complementary methods confirmed the incompatibility of this drug with anhydrous lactose, mannitol, magnesium stearate and calcium lactate under both ambient conditions and thermal stress, and thermally induced interactions between tacrine and silica. In the development of new generic solid formulations, four of the investigated excipients (i.e., starch, sodium carboxymethyl cellulose, polyvinylpyrrolidone K30 and talc) can be used, since they are compatible with tacrine und...

Research paper thumbnail of Instrumental analysis and molecular modelling of inclusion complexes containing artesunate

Journal of Thermal Analysis and Calorimetry, 2020

A series of five guest–host inclusion complexes containing the antimalarial and anticancer agent ... more A series of five guest–host inclusion complexes containing the antimalarial and anticancer agent artesunate (ATS) were obtained and characterized in the present study. Different cyclodextrins (CDNs) were used as hosts [α-cyclodextrin (CDN 1 ), β-cyclodextrin (CDN 2 ), γ-cyclodextrin (CDN 3 ), (2-hydroxypropyl)-β-cyclodextrin (CDN 4 ) and (2-hydroxypropyl)-γ-cyclodextrin (CDN 5 )], and the formation of the adducts was simulated using molecular modelling. The results indicating the hypothetical formation of all complexes were confirmed on the prepared samples by FTIR spectroscopy and thermal analysis (TG—thermogravimetric/DTG—derivative thermogravimetric/HF—heat flow). Our results showed that the partially entrapment of ATS inside the cavity of each cyclodextrin is a consequence of H-bonds formation, electrostatic interactions (dipole–dipole) and hydration water substitution. Also, all complexes formed in a 1:1 molecular ratio presented with higher thermal stability than pure ATS, making the analysed adducts possible alternatives in the drug design process of new and improved pharmaceutical formulations containing ATS.

Research paper thumbnail of Thermal stability and kinetic degradation study for dihydroartemisinin

Journal of Thermal Analysis and Calorimetry, 2020

Dihydroartemisinin (DHA), the hydrogenated derivative of the naturally originated sesquiterpene l... more Dihydroartemisinin (DHA), the hydrogenated derivative of the naturally originated sesquiterpene lactone artemisinin, is a well-known antimalarial agent that is currently researched because of its potential as an anticancer medication. Because DHA has been associated with a low oral bioavailability and a short half-life, new formulations meant to overcome these shortcomings are currently under development. As such, the present paper aims to present a comprehensive physico-chemical profile of DHA containing data of great importance for the preformulation stages of the drug design process. As instrumental techniques, attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) spectroscopy and thermal analysis (TG—thermogravimetric/DTG—derivative thermogravimetric/HF—heat flow) were performed, followed by a kinetic study realized using three isoconversional methods (Friedman—Fr, Flynn–Wall–Ozawa—FWO and Kissinger–Akahira–Sunose—KAS), as well as the nonparametric kinetic method (NPK). FTIR spectroscopy confirmed the identity and purity of DHA, and thermal analysis revealed a relatively low thermal stability and a multistep thermooxidation that was proved during the performed kinetic study. The latter unveiled a two-process decomposition determined by both chemical degradations and physical transformations.

Research paper thumbnail of Cytotoxic Activity Evaluation on Breast Cells of Guest-host Complexes Containing Artemisinin

Revista de Chimie, 2019

Artemisinin is a sesquiterpene lactone with vastly proved anti-cancer effects and a low toxicity ... more Artemisinin is a sesquiterpene lactone with vastly proved anti-cancer effects and a low toxicity profile. However, the compound has poor water solubility, bioavailability and a short half-life. As such, the present paper aims to evaluate the cytotoxic effect on breast cells of three guest-host inclusion complexes containing artemisinin as the active compound and different cyclodextrins as hosts. These were tested using two different concentrations (i.e. 12.5 mM and 25 mM) and three cell lines, namely two human breast adenocarcinoma cell lines (MCF7 and MDA-MB-231) and one human non-tumorigenic breast epithelial cell line (MCF10A) employing the colorimetric microculture tetrazolium assay. After a 72h stimulation period, the most promising results were obtained for the complex containing artemisinin and Heptakis(2,3,6-tri-O-methyl)-b-cyclodextrin, the cell viability decrease being significant for the estrogen positive MCF7 cell line (80.0 � 2.3 %), making the complex a potential candi...

Research paper thumbnail of Stability and Compatibility Studies of Levothyroxine Sodium in Solid Binary Systems—Instrumental Screening

Pharmaceutics, 2020

The influence of excipients on the stability of sodium levothyroxine pentahydrate (LTSS) under am... more The influence of excipients on the stability of sodium levothyroxine pentahydrate (LTSS) under ambient conditions and thermal stress was evaluated. Since LTSS is a synthetic hormone with a narrow therapeutic index, the interactions of LTSS with excipients can lead to a drastic diminution of therapeutic activity. Ten commonly used pharmaceutical excipients with different roles in solid formulations were chosen as components for binary mixtures containing LTSS, namely, starch, anhydrous lactose, D-mannitol, D-sorbitol, gelatin, calcium lactate pentahydrate, magnesium stearate, methyl 2-hydroxyethyl cellulose (Tylose), colloidal SiO2 (Aerosil) and talc. As investigational tools, universal attenuated total reflectance- Fourier transform infrared spectroscopy UATR-FTIR spectroscopy and thermal analysis were chosen and used as follows: UATR-FTIR spectra were drawn up for samples kept under ambient conditions, while thermoanalytical tools (TG/DTG/HF data) were chosen to evaluate the induci...

Research paper thumbnail of Study of kinetic characteristics of 6-ethyl chenodeoxycholic acid and deoxycholic acid decomposition in non-isothermal conditions

Journal of Thermal Analysis and Calorimetry, 2018

6-ethyl chenodeoxycholic acid (6ECDA) and deoxycholic acid (DCA) are two similar-structured chola... more 6-ethyl chenodeoxycholic acid (6ECDA) and deoxycholic acid (DCA) are two similar-structured cholanoic acids, the first being used in the treatment of primary biliary cholangitis, while the second is one of the natural secondary bile acids, currently being tested as a treatment component in the destruction of gallstones. This study was realised as no literature reference was found over thermal behaviour and the evaluation of the decomposition kinetics of the compounds from this class. Both acids were characterised by UATR-FTIR spectroscopy, thermal analysis and the kinetics of decomposition in dynamic oxidative atmosphere, by employing three isoconversional methods, namely Friedman, Kissinger-Akahira-Sunose and Flynn-Wall-Ozawa, respectively, the modified NPK method. Isoconversional methods suggested that no modification of the decomposition mechanism occurs with the modification of thermal treatment of the samples. Later, the modified NPK method was employed in order to estimate the kinetic triplet that describes the decomposition process of both compounds. All kinetic methods indicate a very good thermal stability of the bile acids, with apparent activation energies between 190.6 and 208.7 kJ mol-1 for the decomposition of 6ECDA and 205.5 and 221.7 kJ mol-1 for the decomposition of CDA, respectively. The modified NPK method suggested that both bile acids are degraded by the contribution of two distinctive chemical processes without any physical process associated. Keywords Biliary acids Á Kinetic study Á Thermal behaviour Á NPK method Á Gallstones List of symbols b Heating rate t Time a Conversion degree T Temperature A Pre-exponential factor f(a) and g (a) Conversion functions E a Apparent activation energy R Universal gas constant k(T) The temperature dependence function

Research paper thumbnail of Thermal degradation, kinetic analysis and evaluation of biological activity on human melanoma for artemisinin

Journal of Thermal Analysis and Calorimetry, 2018

Research paper thumbnail of Study of solid-state degradation of prochlorperazine and promethazine

Journal of Thermal Analysis and Calorimetry, 2018

Prochlorperazine (PCP) and promethazine (PMT) are dopamine (D2) receptor antagonists with a pheno... more Prochlorperazine (PCP) and promethazine (PMT) are dopamine (D2) receptor antagonists with a phenothiazinic structure that used nowadays mainly for their antiemetic properties, including for the pre-and postoperative setting. In this paper, the thermal behavior of PCP and PMT was studied, including a complete kinetic analysis for the evaluation of the degradation process in heterogenous media. Samples were analyzed using Fourier transform infrared spectroscopy, thermogravimetric analysis (TG/DTG/HF) and a preliminary kinetic analysis using the ASTM E698 kinetic method, the obtained data being later completed with an in-depth kinetic analysis according to ICTAC 2000 protocol, using the isoconversional methods of Friedman, Ozawa-Flynn-Wall, Kissinger-Akahira-Sunose, respectively, the modified nonparametric kinetics method, the latter allowing the determination of the kinetic triplet without using any approximation, but as well the separation of parallel reaction that occurs at decomposition. The results confirmed that PCP dimaleate has a better stability in comparison with PMT hydrochloride, in terms of apparent energy of activation, probably due to solid-state structure of solid and the contribution of intermolecular bondings.

Research paper thumbnail of Kinetics of heterogeneous-induced degradation for artesunate and artemether

Journal of Thermal Analysis and Calorimetry, 2018

This paper presents the results obtained after the investigation of two artemisinin derived sesqu... more This paper presents the results obtained after the investigation of two artemisinin derived sesquiterpenes, namely artesunate and artemether, currently studied for their antitumor properties. The chosen methods of analysis included UATR-FTIR spectroscopy, characterization of the thermal behavior (TG/DTG/HF) in oxidative dynamic atmosphere, and a complete kinetic analysis. The latter was realized using two integral methods (Kissinger-Akahira-Sunose and Flynn-Wall-Ozawa), a differential one (Friedman), and was later completed with the modified NPK method. The study showed that both compounds show similar thermal stability in terms of apparent activation energies and the degradation processes occur in two parallel steps for each compound, this being solely due to chemical transformations. Keywords Sesquiterpene Á Isoconversional kinetic study Á Artesunate Á Artemether Á NPK method Abbreviations T Time T Temperature A Conversion degree f(a) The differential conversion function R The universal gas constant g(a) The integral conversion function b The heating rate k(T) The temperature dependence function A The pre-exponential factor E a The apparent activation energy given by the Arrhenius equation

Research paper thumbnail of Thermal behavior of entacapone, a catechol-O-methyltransferase inhibitor used in Parkinson’s disease

Journal of Thermal Analysis and Calorimetry, 2018

Entacapone, a selective and reversible inhibitor of catechol-O-methyltransferase, is used in the ... more Entacapone, a selective and reversible inhibitor of catechol-O-methyltransferase, is used in the treatment of Parkinson's disease in combination with levodopa/carbidopa to treat the symptoms of end-of-dose ''wearing-off'' effect. Considering that new formulations are researched constantly, proper knowledge of the active pharmaceutical ingredients is crucial in the preformulation stages. Kinetic analysis was performed using three methods: one integral-Flynn-Wall-Ozawa method, one differential-Friedman method, and modified nonparametric kinetics method (NPK). The thermoanalytical curves were registered at five different heating rates: b = 5, 7, 10, 12, and 15°C min-1. Analysis was conducted in the dynamic air atmosphere to highlight potential thermooxidative processes. This paper deals with the investigation of solid-state stability and compatibility of binary mixture of entacapone with various pharmaceutical excipients by two instrumental techniques, such as universal attenuated total reflection Fourier transform infrared and thermal analysis (TG/DTG/HF). The excipients used in the mixture were: mannitol, silicon dioxide, talc, sorbitol, magnesium stearate, and povidone.

Research paper thumbnail of Guest–host interactions and complex formation for artemisinin with cyclodextrins: instrumental analysis and evaluation of biological activity

Journal of Thermal Analysis and Calorimetry, 2018

Artemisinin is one of the most important naturally occurring compound found in Artemisia annua, b... more Artemisinin is one of the most important naturally occurring compound found in Artemisia annua, being highly active against Plasmodium falciparum, the malaria causing parasite, and currently studied in the oncological field. The aim of this study was to obtain and characterize the host-guest inclusion complexes formed between artemisinin and three functionalized cyclodextrins, namely Randomly methylated-b-cyclodextrin (CD1), Heptakis(2,6-di-O-methyl)-b-cyclodextrin (CD2) and Heptakis(2,3,6-triO methyl)-b-cyclodextrin (CD3). As instrumental tools, thermal analysis (TG/DTG/HF) and UATR-FTIR spectroscopy were used. Later on, the inclusion complexes were tested as to evaluate their antioxidant (AOA) and in vitro activity on both healthy keratinocytes and a human melanoma cell line, A375. Both instrumental techniques suggested the formation of inclusion complexes and the increase of thermal stability of artemisinin in complexes versus pure compound. Regarding the antioxidant activity evaluation of all samples, it was shown that this is significantly inferior in comparison to ascorbic acid, while the in vitro biological activity showed that inclusion complexes (CPX2 and CPX3) exerted an inhibitory effect on human melanoma cells growth, similar to the effect induced by artemisinin.

Research paper thumbnail of Comparative instrumental investigations of some bile acids

Journal of Thermal Analysis and Calorimetry, 2018

In this paper, we present the spectroscopic description (by the means of UATR-FTIR spectroscopy) ... more In this paper, we present the spectroscopic description (by the means of UATR-FTIR spectroscopy) for four naturally occurring bile acids, namely lithocholic acid (LC), taurocholic acid sodium salt hydrate (TC), taurodeoxycholic acid sodium salt hydrate (TDC) and chenodeoxycholic acid (CDC), as well as their thermal behaviour in dynamic oxidative atmosphere, by TG/DTG/HF means. It was shown that all samples have a good thermal stability, favourized by the presence of cholan-24-oic structural moiety in all samples, as well as the solid-state structure (intermolecular H-bondings for the carboxylic acids CDC and LC and saline structures for TDC and TC, respectively). These data are simple, but of great interest in identifying the presence of these compounds by fast, reproducible and precise instrumental techniques in complex mixtures, such as biliary stones.

Research paper thumbnail of Compatibility study between antiparkinsonian drug Levodopa and excipients by FTIR spectroscopy, X-ray diffraction and thermal analysis

Journal of Thermal Analysis and Calorimetry, 2017

Levodopa (L-Dopa or LD) is nowadays considered one of the essential medicines in the World Health... more Levodopa (L-Dopa or LD) is nowadays considered one of the essential medicines in the World Health Organization list, being a main treatment component for Parkinson's disease. This paper deals with the investigation of solid-state stability and compatibility of binary mixtures of Levodopa with various pharmaceutical excipients, by employment of several instrumental techniques, such as attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy, powder X-ray diffraction (PXRD) data and thermal analysis (TG/DTG/HF). Along L-Dopa, eleven pharmaceutical excipients were investigated, namely calcium lactate (CaL), mannitol (Man), magnesium stearate (MgSt), anhydrous lactose (LAnh), talc (T), magnesium citrate (MgC), sorbitol (Sb), silica (SiO 2), polyvinylpyrrolidone K30 (PVP), sodium carboxymethylcellulose (NaCMC) and starch (St). FTIR analysis suggested possible interactions with calcium lactate, mannitol, magnesium stearate, anhydrous lactose, talc and SiO 2 , which were confirmed by PXRD patterns, except for talc. When the samples were subjected to thermal stress, solely magnesium citrate did not present interactions in binary mixture, while all other excipients were incompatible with L-Dopa. Keywords L-Dopa Á Levodopa Á Compatibility study Á Excipient Á FTIR Á PXRD Á Thermal analysis Ionut Ledeti and Sorin Bolintineanu have contributed equally to this work.

Research paper thumbnail of Evaluation of thermal stability and kinetic of degradation for levodopa in non-isothermal conditions

Journal of Thermal Analysis and Calorimetry, 2017

In this paper, we present the results obtained during the investigation of thermal stability of a... more In this paper, we present the results obtained during the investigation of thermal stability of antiparkinsonian drug Levodopa in oxidative atmosphere and under non-isothermal conditions. As investigational tools, thermoanalytical methods were used along with ATR-FTIR spectroscopy and later completed with kinetic study for the main degradative process that occurs in the 260-330°C temperature range, at four heating rates. Four kinetic methods were used as follows: ASTM E698 which leads to an activation energy of 209.72 kJ mol-1 , while isoconversional methods suggested the values 177.6 ± 13.1 kJ mol-1 (Friedman) and 188.8 ± 4.5 kJ mol-1 (Kissinger-Akahira-Sunose), with a clear indication of multistep degradation. The last method used was NPK, which revealed that the degradation occurs in three steps, with different physical and chemical contributions with mean activation energy equal to 191.3 ± 9.5 kJ mol-1. Keywords L-Dopa Á Thermal stability Á Non-isothermal kinetic study Á Isoconversional methods Á ASTM E698 Á NPK method Abbreviations A Pre-exponential factor (s-1) E Activation energy (kJ mol-1) R Universal gas constant (8.314 J mol-1 K-1) t Time (s) T Temperature (°C or K) f(a) Differential form of kinetic mechanism function g(a) Integral form of kinetic mechanism function a Conversion degree b Heating rate (°C min-1) k(T) Rate constant Adriana Ledeti, Tudor Olariu, and Angelica Caunii contributed equally to this work.

Research paper thumbnail of Evaluation of solid-state thermal stability of donepezil in binary mixtures with excipients using instrumental techniques

Journal of Thermal Analysis and Calorimetry, 2017

Donepezil (Don) is one of the main compounds used in the therapy of Alzheimer's disease. In this ... more Donepezil (Don) is one of the main compounds used in the therapy of Alzheimer's disease. In this study, donepezil hydrochloride was investigated for solid-state compatibility with several pharmaceutical excipients like calcium lactate (CaL), mannitol (Man), magnesium stearate (MgSt), anhydrous lactose (LAnh), talc (T), magnesium citrate (MgC), sorbitol (Sb), silica (SiO 2), polyvinylpyrrolidone K30 (PVP), sodium carboxymethylcellulose (NaCMC) and starch (St) under ambient conditions, by ATR-FTIR spectroscopy and PXRD data, and later by thermoanalytical techniques (TG/DTG/HF), in order to evaluate the thermal-induced interactions. The instrumental investigations carried at ambiental temperature revealed no interaction between Don and selected excipients, while thermal treatment induced interactions between components in eight binary mixtures, except the ones containing magnesium citrate, talc and polyvinylpyrrolidone.