scholarly journals SOLID-STATE PROPERTIES AND SOLUBILITY STUDIES OF NOVEL PHARMACEUTICAL COCRYSTAL OF ITRACONAZOLE

2018 ◽  
Vol 10 (5) ◽  
pp. 97
Author(s):  
Stevanus Hiendrawan ◽  
Bambang Veriansyah ◽  
Raymond R. Tjandrawinata
Keyword(s):  
Sebacic Acid ◽  
Aqueous Solubility ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
Solution Ph ◽  
Pharmaceutical Ingredients ◽  
Naphthoic Acid ◽  
Pharmaceutical Cocrystal ◽  
Solvent Evaporation Process ◽  
The Individual

Objective: Pharmaceutical cocrystal is a promising method to improve the solubility of active pharmaceutical ingredients (APIs). Itraconazole (ITZ) is a BCS class II antifungal drug with poor aqueous solubility, therefore an attempt was made to improve the solubility of ITZ using cocrystallization technique. In this work, six novel pharmaceutical cocrystals of ITZ with various coformers, including 4-hydroxybenzoic acid (4HBA), trans-cinnamic acid (TCA), suberic acid (SUB), sebacic acid (SBC), 1-hydroxy-2-naphthoic acid (1H2N), and benzamide (BZD) were prepared.Methods: ITZ cocrystals was prepared by solvent evaporation process. The cocrystals produced were characterized using powder x-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and fourier transform infrared (FTIR) spectroscopy. Solubility analysis was performed to evaluate the cocrystals.Results: PXRD and DSC analysis revealed that the pattern of all ITZ cocrystals was distinguishable from the individual compounds which indicates the formation of new phase. The solubility of ITZ and its cocrystals from highest to lowest after 24 h in 0.1 N HCl solution (pH 1.2) follows the order ITZ-TCA (1.97-fold), ITZ-SBC (1.09-fold), ITZ, ITZ-1H2N (0.58-fold) and ITZ-4HBA (0.46-fold).Conclusion: This study demonstrates that the selection of coformers has pronounced an impact on the physicochemical properties of ITZ. Based on this study, it can be concluded that cocrystallization offers a valuable way to improve the solubility of ITZ.

scholarly journals Study of the Influence of the Almond Shell Variety on the Mechanical Properties of Starch-Based Polymer Biocomposites

Polymers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2049 ◽  
Author(s):  
Ana Ibáñez García ◽  
Asunción Martínez García ◽  
Santiago Ferrándiz Bou
Keyword(s):  
Charpy Impact ◽  
X Ray Diffraction ◽  
Almond Shell ◽  
Scanning Calorimetry ◽  
Commercial Mixture ◽  
Hardness Tests ◽  
Twin Screw ◽  
Ft Ir ◽  
Mechanical Tensile ◽  
The Individual

This article is focused on the development of a series of biodegradable and eco-friendly biocomposites based on starch polymer (Mater-Bi DI01A) filled with 30 wt% almond shell (AS) of different varieties (Desmayo Rojo, Largueta, Marcona, Mollar, and a commercial mixture of varieties) to study the influence of almond variety in the properties of injected biodegradable parts. The different AS varieties are analysed by means of Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), Scanning Electron Microscopy (SEM), and X-ray Diffraction (XRD). The biocomposites are prepared in a twin-screw extruder and characterized in terms of their mechanical (tensile, flexural, Charpy impact, and hardness tests) and thermal properties (differential scanning calorimetry (DSC) and TGA). Despite observing differences in the chemical composition of the individual varieties with respect to the commercial mixture, the results obtained from the mechanical characterisation of the biocomposites do not present significant differences between the diverse varieties used. From these results, it was concluded that the most recommended option is to work with the commercial mixture of almond shell varieties, as it is easier and cheaper to acquire.

scholarly journals Hydrophilic Sugars for Enhancing Dissolution Rate of Cilostazol: Effect of Wet Co-Processing

2020 ◽  
Vol 27 (1) ◽  
pp. 111-120
Author(s):  
Alaa Yosf Bazeed ◽  
Ahmed Nouh ◽  
Ebtessam Ahmed Essa ◽  
Gamal El Maghraby
Keyword(s):  
Aqueous Solubility ◽  
Submicron Particles ◽  
Drug Dissolution ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
X Ray ◽  
Swallowing Difficulties ◽  
Fast Disintegrating Tablets

Background: Cilostazol is an anti-platelets drug with considerable antithrombotic effects in vivo. Therefore, it is widely used by elderly patients. However, it suffers from poor bioavailability due to its low aqueous solubility. The objective of this work was to enhance the dissolution of cilostazol with the aim of formulating fast dissolving tablets for geriatrics and those of swallowing difficulties. Methods: Ethanol-assisted co-grinding of cilostazol with sugar-based excipients was adopted. Sucralose and mannitol were used for this purpose as hydrophilic excipient as well as taste improving agents. The obtained products were investigated regarding differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction, scanning electron microscope (SEM) and in vitro drug dissolution. Fast disintegrating tablets were prepared and evaluated. Results: Thermal behavior of the developed products reflected reduced crystallinity, it also suggested possible existence of new crystalline species with sucralose. Eutexia was also suggested for mannitol mixtures, that was supported by X-ray diffraction data. SEM indicated size reduction with the deposition of the drug as submicron particles over the excipient surface. Co-processing markedly improved cilostazol dissolution compared to unprocessed drug. The optimized formulations were successively formulated into fast disintegrating tablets. Conclusion: This investigation introduced the wet grinding strategy with sugar excipients as a platform for the formulation of easy to use tablets with optimum drug release.

scholarly journals Evaluation of Thermal-Induced Polymorphic Transformation on Desloratadine and Desloratadine-Benzoic Acid Salt

2020 ◽  
Vol 26 (4) ◽  
pp. 399-405
Author(s):  
Ahmad Ainurofiq ◽  
Rachmat Mauludin ◽  
Diky Mudhakir ◽  
Sundani Nurono Soewandhi
Keyword(s):  
Melting Point ◽  
Benzoic Acid ◽  
Polymorphic Transformation ◽  
Heating Process ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
X Ray ◽  
Pharmaceutical Ingredients ◽  
Physicochemical Changes ◽  
Transformation Methods

Background: Active pharmaceutical ingredients face a challenge in manufacturing due to adverse physicomechanical properties. Desloratadine (DES) form I exhibits poor mechanical behavior through the formation of capping during the tableting process. Salt formation from DES and benzoic acid (BA) has been observed to resolve poor mechanical properties. However, the ability to withstand heat from the manufacturing process should be implemented in DES and DES-BA salt. The aim of this study was to determine the differences between thermal treatment results on DES and DES-BA salt and whether it causes them to undergo polymorphic transformation. Methods: Salt was crystallized between DES and BA using the solvent evaporation method. DES and DES-BA salt were heated at 110°C, 159°C (melting point of DES), 181°C (melting point of DES-BA), and 190°C. Following this, characterization was performed using differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and solubility testing. Results: Polymorphic transformation caused by heat occurred in DES, but not in DES-BA salt. The transformation of DES was induced by the effect of heating, which changed polymorph I to a mixture of polymorph I and III at 110°C, to polymorph II at 159°C, and to a mixture of polymorph I, II, and III at 190°C. Under 190oC, DES-BA is still stable and did not undergo a polymorphic transformation. However, at 190oC, decomposition started to occur, which implied decreased solubility, which did not occur in DES. Conclusion: The heating process did not cause DES-BA salt to undergo a polymorphic transformation. However, it caused decomposition at 190oC. DES underwent a polymorphic transformation when exposed to the same condition without decomposition. This provided information to always pay attention to temperature during manufacturing processes that include DES or DES-BA salt to avoid physicochemical changes.

Development of Pediatric Orodispersible Tablets Based on Efavirenz as a New Therapeutic Alternative

2020 ◽  
Vol 18 (5) ◽  
pp. 342-353
Author(s):  
José Lourenço de Freitas Neto ◽  
Ilka do Nascimento Gomes Barbosa ◽  
Camila Gomes de Melo ◽  
Matheus Alves Ângelos ◽  
Larissa Morgana dos Santos Mendes ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Aqueous Solubility ◽  
Dissolution Profile ◽  
Multicomponent Systems ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
Disintegration Time ◽  
Orodispersible Tablets ◽  
Orodispersible Tablet ◽  
Immunodeficiency Syndrome

Background: Efavirenz is the most used medication in the treatment of Acquired Immunodeficiency Syndrome (AIDS). The limited number of pediatric antiretroviral formulations approved by regulatory agencies is the most significant obstacle to adequate and efficient pharmacotherapy for this group of patients. The efavirenz has excellent therapeutic potential, but has low aqueous solubility/bioavailability. Methods: To minimize these limitations, multicomponent systems with β-cyclodextrin and polyvinylpyrrolidone K-30 were obtained. Due to the limited number of pediatric antiretroviral formulations, the development of a pediatric orodispersible tablet is an alternative that is thought easy to administer, since it disintegrates rapidly in the oral cavity. The multicomponent systems were obtained by the method of kneading and characterized by solubility test, X-ray diffraction, differential scanning calorimetry and infrared absorption spectroscopy by Fourier transform. The orodispersible tablets were prepared by direct compression. The quality control of hardness, friability, disintegration, and dissolution was performed. The influence of the components of the formulation on the characteristics of the tablets was evaluated through a 22 factorial design added with three central points, to compare the effect of the dependent variables on the responses. Results: An increase in drug solubility was observed, with a decrease in crystallinity. Besides that, an excellent dissolution profile presented with more than 83% of the drug's content dissolved in less than 15 minutes. Satisfactory disintegration time and friability were observed. Conclusion: It was observed that reduced concentrations of mannitol decreased the hardness and disintegration time of the formulations. The orodispersible tablet composed of efavirenz: β- cyclodextrin: polyvinylpyrrolidone, favors greater absorption and bioavailability. It has several advantages for pediatric patients, as the dosage form disintegrates quickly in the mouth and does not require water for administration, thereby improving patient compliance with the treatment.

scholarly journals Spherical crystals of celecoxib to improve solubility, dissolution rate and micromeritic properties

2007 ◽  
Vol 57 (2) ◽  
pp. 173-184 ◽  
Author(s):  
Venkadari Gupta ◽  
Srinivas Mutalik ◽  
Madhobhai Patel ◽  
Girish Jani
Keyword(s):  
Dissolution Rate ◽  
Spherical Shape ◽  
Aqueous Solubility ◽  
Spectroscopic Studies ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
Acetone Water ◽  
Ir Spectroscopic ◽  
Spherical Crystals

Spherical crystals of celecoxib to improve solubility, dissolution rate and micromeritic propertiesCelecoxib spherical agglomerates were prepared with polyvinylpyrrolidone (PVP) using acetone, water and chloroform as solvent, non-solvent and bridging liquid, respectively. The agglomerates were characterized by differential scanning calorimetry (DSC), X-ray diffraction (XRD), IR spectroscopic studies and scanning electron microscopy (SEM). The IR spectroscopy and DSC results indicated the absence of any interactions between drug and additives. XRD studies showed a decrease in crystallinity in agglomerates. The crystals exhibited significantly improved micromeritic properties compared to pure drug. The loading efficiency (% or mg drug per 100 mg crystals) was in the range of 93.9 ± 2.3 and 97.3 ± 1.3% (n = 3) with all formulations. The aqueous solubility and dissolution rate of the drug from crystals was significantly (p < 0.05) increased (nearly two times). The solubility andin vitrodrug release rates increased with an increase in PVP concentration (from 2.5 to 10%). The SEM studies showed that the crystal posseses a good spherical shape with smooth and regular surface.

scholarly journals Enhancement of solubility and dissolution rate of ebastine fast-disintegrating tablets by solid dispersion method

2020 ◽  
Vol 19 (9) ◽  
pp. 1797-1805
Author(s):  
Nayyer Islam ◽  
Muhammad Irfan ◽  
Nasir Abbas ◽  
Haroon Khalid Syed ◽  
Muhammad Shahid Iqbal ◽  
...  
Keyword(s):  
Dissolution Rate ◽  
Solid Dispersion ◽  
Solid Dispersions ◽  
Aqueous Solubility ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
Disintegration Time ◽  
Kneading Method ◽  
The Impact ◽  
Fast Disintegrating Tablets

Purpose: To investigate the efficiency of different solubilizing agents in improving solubility as well as dissolution rate of ebastine (a BCS class II drug) by incorporating prepared solid dispersion into fast disintegrating tablets.Method: The solubility of ebastine was determined in distilled water, lipids and solubilizing agents. Subsequently, the binary solid dispersions were prepared by kneading method using varying weight ratios of ebastine and solubilizing agents. The solid dispersions were then incorporated into fast disintegrating tablets (SD-FDT). Central composite rotatable design (CCD) was used to determine the impact of super disintegrating agents on disintegration time and friability of tablets. The solubility and dissolution rate of developed SD-FDT were compared with a marketed brand. The solid dispersion particles were characterized by Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), powder x-ray diffraction (P-XRD) and scanning electron microscopy (SEM).Results: The saturated solubility of pure ebastine in water was 0.002 ± 0.041 mg/ml while the aqueous solubility of EBT/poloxamer solid dispersion SET3 (P) was 0.018 ± 2.510 mg/ml; on the other hand, EBT/soluplus solid dispersion SET1(S) has an aqueous solubility of 0.242 ± 1.390 mg/ml. Within 30 min, drug release was 14.00 ± 1.77, 78.00 ± 2.31 and 98.70 ± 2.54 % from pure EBT, SET3 (P) and SET1(S), respectively.Conclusion: The solubility and dissolution rate of ebastine has been successfully enhanced by incorporating its solid dispersion in fast-disintegrating tablets (SD-FDT). Keywords: Ebastine, Solid dispersion, Poloxamer 188, Soluplus, Solubility, Dissolution

scholarly journals The impact of pressure on β-Cyclodextrin·acetaminophen inclusion complexes

2014 ◽  
Vol 70 (a1) ◽  
pp. C264-C264 ◽  
Author(s):  
Sofiane Saouane ◽  
Wolfgang Morgenroth ◽  
Hanns-Peter Liermann ◽  
Carsten Paulmann ◽  
Francesca Fabbiani
Keyword(s):  
High Pressure ◽  
Inclusion Complex ◽  
Aqueous Solubility ◽  
Crystal Form ◽  
Model Systems ◽  
X Ray Diffraction ◽  
X Ray ◽  
Pharmaceutical Ingredients ◽  
The Impact

Cyclodextrins (CDs) have attracted considerable interest as model systems in supramolecular host-guest chemistry. They are described as hollow truncated cones with a hydrophilic outer surface and a nonpolar inner cavity suitable for small molecules' encapsulation.[1] By virtue of their character, CDs are used as excipients to improve the aqueous solubility of active pharmaceutical ingredients (APIs). High-pressure crystallisation techniques have been established as a suitable tool for exploring the phenomenon of polymorphism and solvate formation of pharmaceutical compounds throughout numerous examples reported in the literature.[2] Thus, exploring the inclusion-complex formation and the polymorphic behaviour of CDs with APIs at high pressure would be an interesting extension of the technique. The present work describes the attempt of an in-situ crystallisation of β-CD·acetaminophen inclusion complex and compression studies of the known β-CD·acetaminophen complex[3] in different crystallisation media at pressures up to 1.0 GPa. A new high-pressure crystal form observed at 0.8 GPa as well as unexpected results are presented herein. The crystals have been characterised by means of polarised optical microscopy, Raman spectroscopy and single-crystal X-ray diffraction using both home and synchrotron sources.

scholarly journals Interconvertible Hydrochlorothiazide–Caffeine Multicomponent Pharmaceutical Materials: A Solvent Issue

Crystals ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1088
Author(s):  
Cristóbal Verdugo-Escamilla ◽  
Carolina Alarcón-Payer ◽  
Antonio Frontera ◽  
Francisco Javier Acebedo-Martínez ◽  
Alicia Domínguez-Martín ◽  
...  
Keyword(s):  
Physicochemical Properties ◽  
Intermolecular Forces ◽  
Active Pharmaceutical Ingredients ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
Great Stability ◽  
X Ray ◽  
Pharmaceutical Ingredients ◽  
Interesting Approach ◽  
Pharmaceutical Materials

The design of new multicomponent pharmaceutical materials that involve different active pharmaceutical ingredients (APIs), e.g., drug-drug cocrystals, is a novel and interesting approach to address new therapeutic challenges. In this work, the hydrochlorothiazide-caffeine (HCT–CAF) codrug and its methanol solvate have been synthesized by mechanochemical methods and thoroughly characterized in the solid state by powder and single crystal X-ray diffraction, respectively, as well as differential scanning calorimetry, thermogravimetric analyses and infrared spectroscopy. In addition, solubility and stability studies have also been performed looking for improved physicochemical properties of the codrug. Interestingly, the two reported structures show great similarity, which allows conversion between them. The desolvated HCT–CAF cocrystal shows great stability at 24 h and an enhancement of solubility with respect to the reference HCT API. Furthermore, the contribution of intermolecular forces on the improved physicochemical properties was evaluated by computational methods showing strong and diverse H-bond and π–π stacking interactions.

scholarly journals Melting Diagrams of Adefovir Dipivoxil and Dicarboxylic Acids: An Approach to Assess Cocrystal Compositions

Crystals ◽  
2019 ◽  
Vol 9 (2) ◽  
pp. 70 ◽  
Author(s):  
Hyunseon An ◽  
Insil Choi ◽  
Il Kim
Keyword(s):  
Solid State ◽  
Adefovir Dipivoxil ◽  
Sufficient Conditions ◽  
Dicarboxylic Acids ◽  
Current Approach ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
X Ray ◽  
Pharmaceutical Ingredients ◽  
Solution Crystallization

Pharmaceutical cocrystallization is a useful method to regulate the physical properties of active pharmaceutical ingredients (APIs). Since the cocrystals may form in various API/coformer ratios, identification of the cocrystal composition is the critical first step of any further analysis. However, the composition identification is not always unambiguous if cocrystallization is performed in solid state with unsuccessful solution crystallization. Single melting point and some new X-ray diffraction peaks are necessary but not sufficient conditions. In the present study, the use of melting diagrams coupled with the X-ray diffraction data was tested to identify cocrystal compositions. Adefovir dipivoxil (AD) was used as a model API, and succinic acid (SUC), suberic acid (SUB), and glutaric acid (GLU) were coformers. Compositions of AD/SUC and AD/SUB had been previously identified as 2:1 and 1:1, but that of AD/GLU was not unambiguously identified because of the difficulty of solution crystallization. Melting diagrams were constructed with differential scanning calorimetry, and their interpretation was assisted by powder X-ray diffraction. The cocrystal formation was exhibited as new compositions with congruent melting in the phase diagrams. This method correctly indicated the previously known cocrystal compositions of AD/SUC and AD/SUB, and it successfully identified the AD/GLU cocrystal composition as 1:1. The current approach is a simple and useful method to assess the cocrystal compositions when the crystallization is only possible in solid state.

scholarly journals Enhancement of Aqueous Solubility and Dissolution of Celecoxib through Phosphatidylcholine-Based Dispersion Systems Solidified with Adsorbent Carriers

Pharmaceutics ◽  
2018 ◽  
Vol 11 (1) ◽  
pp. 1 ◽  
Author(s):  
Kanghee Jo ◽  
Jae Min Cho ◽  
Hyunjoo Lee ◽  
Eun Kyung Kim ◽  
Hong Chul Kim ◽  
...  
Keyword(s):  
Aqueous Solubility ◽  
Drug Dissolution ◽  
Dissolution Behavior ◽  
X Ray Diffraction ◽  
Hydrophobic Property ◽  
Scanning Calorimetry ◽  
Solid Dosage ◽  
Poorly Soluble ◽  
Highly Hydrophobic ◽  
Hydrophilic Materials

This study aimed to design phosphatidylcholine (PC)-based solid dispersion (SD) systems for enhancing the apparent aqueous solubility and dissolution of celecoxib (CLC), a selective cyclooxygenase-2 inhibitor with a highly hydrophobic property. Although PC-based dispersion formulations considerably increased solubilities of CLC, the lipidic texture of PC was not appropriate as a solid dosage form for oral administration of CLC. To mask the lipidic texture of PC-based matrices, Neusilin® US2, an adsorbent material with a porous structure and large surface area widely used in the pharmaceutical industry, was employed and thereby fully powderized PC-based dispersion formulations could be fabricated. However, PC matrices containing CLC strongly adsorbed to the pores of Neusilin® US2 was not able to be rapidly released. To address this problem, different hydrophilic materials were examined to promote the release of the CLC-dispersed PC matrices from Neusilin® US2. Among tested hydrophilic materials, croscarmellose sodium was the most suitable to facilitate fast drug dissolution from Neusilin® US2 particles, showing significantly enhanced apparent aqueous solubility and dissolution behavior of CLC. Through differential scanning calorimetry, X-ray diffraction, and Fourier transform infrared spectroscopy (FT-IR) analysis, a considerably reduced crystallinity of CLC dispersed in the PC-based dispersion formulations was demonstrated. The PC-based SD formulations developed in this study would be useful for improving the oral bioavailability of poorly soluble drugs such as CLC.

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