Polymorphic characterization and compatibility study of clozapine: implications on its stability and some biopharmaceutics properties

Dias, Simone Buarque Tavares; Nascimento, Ticiano Gomes do; Santos, Ana Flávia Oliveira; Viana, Iana Mayane Mendes Nicácio; Almeida, Rusiene M. de; Júnior, Irinaldo Diniz Basílio; Macêdo, Rui Oliveira; Araújo-Júnior, João Xavier de

doi:10.1007/s10973-014-4142-3

Cited by 12 publications

(4 citation statements)

References 28 publications

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“…51 Clozapine performs a mass loss of 5.5% in the temperature range 80-150 °C, while complete decomposition of the drug occurs at temperatures above 260 °C. 52 Based on the above, the high removal rates observed for these drugs, especially in the temperature range 200-220 °C for runs 2, 6, 9, 11 and 15 (79.1%, 88.7%, 77.8%, 79.5% and 77.6% respectively), are reasonable. Nevertheless, in some cases compounds are resistant to the applied temperatures, resulting in their residual detection in the produced hydrochar.…”

Section: Fate Of Organic Pollutants During Htcmentioning

confidence: 57%

“…Moreover, fluoxetine compound begins to decompose at a temperature of >160 °C, with the release of 4‐trifluoromethylphenol, methylamine and hydrochloric acid in the first step, 50 while citalopram is disintegrated at temperatures >190 °C 51 . Clozapine performs a mass loss of 5.5% in the temperature range 80–150 °C, while complete decomposition of the drug occurs at temperatures above 260 °C 52 . Based on the above, the high removal rates observed for these drugs, especially in the temperature range 200–220 °C for runs 2, 6, 9, 11 and 15 (79.1%, 88.7%, 77.8%, 79.5% and 77.6% respectively), are reasonable.…”

Section: Resultsmentioning

confidence: 99%

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Removal of organic pollutants (pharmaceuticals and pesticides) from sewage sludge by hydrothermal carbonization using response surface methodology (RSM)

Miserli

Nastopoulou

Konstantinou

2022

J of Chemical Tech & Biotech

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BACKGROUND Conventional wastewater treatment plants (WWTPs) cannot degrade completely emerging pollutants such as pharmaceuticals and pesticides. The release of such contaminants through WWTP effluents or sludge disposal is of high environmental concern. Hydrothermal treatment has been adopted as alternative treatment technology for sludge to recover energy and valuable products. This study demonstrates the removal of inherent concentration levels of organic pollutants from the previous classes under variable reaction conditions, i.e. temperature, reaction time and sludge‐to‐water (%wt) ratio. RESULTS Response surface methodology (RSM) was applied to model removal efficiency for the sum of detected pharmaceutical compounds and to evaluate the significant operational parameters. The results showed that higher values of temperature and time enhanced the percent degradation efficiency while sludge‐to‐water (%wt) ratio was not a significant factor affecting the removal process. The maximum removal efficiency of pharmaceutical residues reached 89.8% under the following conditions: 220 °C, 360 min reaction time, 7.50%wt sludge‐to‐water ratio. Additionally, hydrothermal treatment removed completely trace levels of detected pesticides, regardless of the applied conditions. RSM was also applied separately to those pharmaceuticals (i.e., amisulpride and amitriptyline) detected most frequently and at higher concentrations in sludge samples. Both compounds have been degraded at >90% using reaction temperatures from 205 to 220 °C and reaction time between 297 and 360 min with 7.5% sludge/H2O ratio. CONCLUSION Hydrothermal treatment is a suitable and promising technology for sewage sludge treatment for the efficient destruction of organic pollutants and the production of renewable hydrochars. © 2022 Society of Chemical Industry (SCI).

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Section: Fate Of Organic Pollutants During Htcmentioning

confidence: 57%

Section: Resultsmentioning

confidence: 99%

Removal of organic pollutants (pharmaceuticals and pesticides) from sewage sludge by hydrothermal carbonization using response surface methodology (RSM)

Miserli

Nastopoulou

Konstantinou

2022

J of Chemical Tech & Biotech

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“…It is a lipophilic drug having massive first pass metabolism following its oral administration which results in poor bioavailability ranged from 27 to 50%. 11 Recently many nasal CLZ nano preparations have been developed; nanosized binary mixed micelles intranasal gel was developed using poloxamer/polysorbate which improved both drug permeation rate through nasal sheep mucosa and system stability. 12 Patel et al formulated CLZ nanosuspension for nose to brain delivery which demonstrated higher CLZ concentration and faster absorption in the brain compared with CLZ suspension.…”

Section: Introductionmentioning

confidence: 99%

Self-Assembling Lecithin-Based Mixed Polymeric Micelles for Nose to Brain Delivery of Clozapine: In-vivo Assessment of Drug Efficacy via Radiobiological Evaluation

Elsharkawy¹,

Amin²,

Shamsel-Din³

et al. 2023

IJN

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The research objective is to design intranasal brain targeted CLZ loaded lecithin based polymeric micelles (CLZ-LbPM) aiming to improve central systemic CLZ bioavailability. Methods: In our study, intranasal CLZ loaded lecithin based polymeric micelles (CLZ-LbPM) were formulated using soya phosphatidyl choline (SPC) and sodium deoxycholate (SDC) with different CLZ:SPC:SDC ratios via thin film hydration technique aiming to enhance drug solubility, bioavailability and nose to brain targeting efficiency. Optimization of the prepared CLZ-LbPM using Design-Expert® software was achieved showing that M6 which composed of (CLZ:SPC: SDC) in respective ratios of 1:3:10 was selected as the optimized formula. The optimized formula was subjected to further evaluation tests as, Differential Scanning Calorimetry (DSC), TEM, in vitro release profile, ex vivo intranasal permeation and in vivo biodistribution. Results:The optimized formula with the highest desirability exhibiting (0.845), small particle size (12.23±4.76 nm), Zeta potential of (−38 mV), percent entrapment efficiency of > 90% and percent drug loading of 6.47%. Ex vivo permeation test showed flux value of 27 μg/cm².h and the enhancement ratio was about 3 when compared to the drug suspension, without any histological alteration. The radioiodinated clozapine ([ 131 I] iodo-CLZ) and radioiodinated optimized formula ([ 131 I] iodo-CLZ-LbPM) were formulated in an excellent radioiodination yield more than 95%. In vivo biodistribution studies of [ 131 I] iodo-CLZ-LbPM showed higher brain uptake (7.8%± 0.1%ID/g) for intranasal administration with rapid onset of action (at 0.25 h) than the intravenous formula. Its pharmacokinetic behavior showed relative bioavailability, direct transport percentage from nose to brain and drug targeting efficiency of 170.59%, 83.42% and 117% respectively. Conclusion:The intranasal self-assembling lecithin based mixed polymeric micelles could be an encouraging way for CLZ brain targeting.

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“…Clozapine (CLO) is a potent antipsychotic widely used to suppress both positive and negative symptoms of schizophrenia and some neuroleptic responses [1]. CLO is classified as a class II drug according to biopharmaceutics classification systems (BCS), due to its high permeability and low solubility [2]. The bioavailability of CLO is 27 to 50% [3].…”

Section: Introductionmentioning

confidence: 99%

Solubility Enhancement of Clozapine Through Co-Crystal Formation with Isonicotinamide

et al. 2019

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Clozapine (CLO) is an effective atypical antipsychotic to control the symptoms of psychosis and schizophrenia. Clozapine has low solubility and high permeability, so it is classified as a class II in the biopharmaceutical classification system. The aim of this study was to improve the solubility and dissolution rate of clozapine by clozapine-isonicotinamide (CLO-INA) co-crystal formation. CLO-INA co-crystal was prepared by solvent-drop grinding (SDG) method using water as a solvent. Characterization of SDG result was conducted by powder X-ray diffraction (PXRD) and Fourier transform infrared (FTIR). Solubility test was performed in water at room temperature. The dissolution test was performed in 900 mL of pH 6.8 phosphate buffer solution, 50 rotation per minute of paddle rotation, and at 37±0.5 °C. The PXRD pattern of SDG result of CLO-INA has many different peaks from its parent components, and this may indicate the co-crystal formation. The solubility of the co-crystal clozapine was fifteen folds higher than pure clozapine. The dissolution rate of CLO-INA co-crystal increased in the first 10 minutes compared to pure clozapine. Percentage of clozapine dissolved after 10 minutes from CLO-INA co-crystal and pure CLO were 10.2 and 2.4%, respectively. CLO and INA can form co-crystal by SDG method that can improve the solubility and dissolution rate of clozapine.Keywords: Clozapine, Isonicotinamide, Co-crystal, Solubility, Dissolution

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Polymorphic characterization and compatibility study of clozapine: implications on its stability and some biopharmaceutics properties

Cited by 12 publications

References 28 publications

Removal of organic pollutants (pharmaceuticals and pesticides) from sewage sludge by hydrothermal carbonization using response surface methodology (RSM)

Removal of organic pollutants (pharmaceuticals and pesticides) from sewage sludge by hydrothermal carbonization using response surface methodology (RSM)

Self-Assembling Lecithin-Based Mixed Polymeric Micelles for Nose to Brain Delivery of Clozapine: In-vivo Assessment of Drug Efficacy via Radiobiological Evaluation

Solubility Enhancement of Clozapine Through Co-Crystal Formation with Isonicotinamide

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