Solid State Analysis and In-Vitro Dissolution Behavior of MeloxicamHydroxy Propyl Beta Cyclodextrin-Ethanolamines Ternary Complexes

The present study was aimed to improve the aqueous solubility and dissolution rate of an NSAID meloxicam by hydroxy propyl β-cyclodextrin ternary complexes employing ethanolamines. Initially, meloxicam (MLX) binary complexes with Hydroxy propyl β-Cyclodextrin (HPβCD) were formulated by kneading and solvent evaporation techniques which was followed by ternary complex preparation of selected MLX-HPβCD binary complex employing different ethanolamines by solvent evaporation method. The solvent evaporationwas used in preparing ternary complexes of MLX, because it was proved to be the best method comparatively in yielding promising binary complexes of meloxicam in the initial stage of this study. MLX formed 1:1 M stoichiometric binary and ternary inclusion complexes as demonstrated by the AL-type of phase solubility curve. An increment in the stability constant value (Kc) of MLX- HPβCD complex in the presence of ethanolamines conceded higher complexation efficiency. Solid state analysis (FTIR, TGA, and SEM studies) of ternary compounds evidenced the perfect inclusion complex formation. Ternary complexes showed significant improvement in drug dissolution compared topure MLX and MLX-HPβCD binary complex. The ternary complex containing 1:1:1 molar ratio of MLX-HPβCD-DEA exhibited 86.91% drug dissolution in 1 hour, which was significantly high in relation to ternary complexes containing mono and tri ethanolamines, and it was found to follow imperatively matrix order release mechanism. On aging studied complexes showed no significant change in physical appearance, drug content and drug dissolution attributes, which clearly shows high in-vitro stability of the complexes.

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Improved Solubility and Dissolution Rate of Ketoprofen by Beta Cyclodextrin Ternary Complexes Incorporating Hydrophilic Polymers

International Journal of Drug Delivery Technology ◽

10.25258/ijddt.v7i1.8916 ◽

2017 ◽

Vol 7 (1) ◽

Author(s):

Mohammed Jafar ◽

Sadath Ali ◽

Hassan Ghonaim

Keyword(s):

Dissolution Rate ◽

Ternary Complex ◽

Solvent Evaporation ◽

Ternary Complexes ◽

Hydrophilic Polymers ◽

Drug Dissolution ◽

Release Mechanism ◽

Phase Solubility ◽

Binary Complex ◽

Binary Complexes

The aim of the presentstudy wasto improve the aqueous solubility and dissolution rate of a BCS Class-IIdrug,ketoprofen by β-cyclodextrin ternary complexes incorporating hydrophilic polymers polyethylene glycol 6000 (PEG6000) and polyvinyl pyrrolidone (PVP). Initially,ketoprofen (KPF)binary complexes with β-Cyclodextrin (βCD)wereformulated by physical mixing,co-grinding, and solvent evaporation methods which was followed by ternary complex formulation of selected KPF-βCD binary complex incorporatingPEG6000 and PVP.The solvent evaporation method was used in the formulation of ternary complexesof ketoprofen, sincein the beginning of this study, it was proved to be the best methodcomparatively in yielding promising binary complexes of ketoprofen.Ketoprofen formed 1:1 M stoichiometric binary and ternary inclusion complexes as demonstrated by the AL-type of phase solubility graph. An increase in the stability constant value (Kc) of KPF- βCD complex in the presence of PEG6000 and PVP conceded higher complexation competency. FTIR and SEM studies evidenced the perfect ternary inclusion complex formation. Ternary complexes showed improved drug dissolution compared with Ketoprofenalone and KPF-βCD binary complex. The ternary complex containg 1:1:2 molar ratio of KPF:βCD:PEG6000exhibited 94.24% drug dissolution in 2 hours, which was significantly high in relation to ternary complexes containg PVPand it was found to follow first order release mechanism. Complex studied for stabilityshowed no significant change in physical appearance, drug content and drug dissolution characteristic indicating high stability.

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DEVELOPMENT OF BINARY AND TERNARY COMPLEX OF CEFUROXIME AXETIL WITH CYCLODEXTRIN FOR IMPROVING PHARMACEUTICAL CHARACTERISTICS

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2020v12i6.38927 ◽

2020 ◽

pp. 107-117

Author(s):

SAKSHI KAUSHIK ◽

RAVINDER VERMA ◽

DEEPIKA PUROHIT ◽

PARIJAT PANDEY ◽

MANISH KUMAR ◽

...

Keyword(s):

Drug Release ◽

Ternary Complex ◽

Cefuroxime Axetil ◽

Ternary Complexes ◽

In Vitro Dissolution ◽

Taste Masking ◽

Binary Complex ◽

Binary And Ternary Complexes ◽

Binary Complexes

Objective: The current research objective is systematic development and characterization of binary and ternary inclusion complexes of cefuroxime axetil with β-cyclodextrin to improve its pharmaceutical characteristics by using the kneading method. Methods: Phase solubility study was carried out using Higuchi and Connors method. Based on its result, binary complexes of cefuroxime axetil with different ratio of β-cyclodextrin were developed and characterized using differential scanning calorimeter (DSC), fourier transform infrared spectroscopy (FT-IR) and X-ray powder diffractometry (XRD). Then, binary complexes were analyzed for in vitro dissolution testing. The ternary complexes were developed using different ratio of PVP K-30 as a ternary component and evaluated for in vitro dissolution testing and in vitro taste masking. Results: Binary complex of cefuroxime axetil with β-cyclodextrin (1:1) showed better drug release than pure drug. During the development of the ternary complex, β-cyclodextrin (1:1) and 1% w/v PVP K-30 as a ternary agent resulted in an optimized ternary complex. The DSC, FT-IR and XRD studies clearly revealed the formation of binary and ternary complexes. The ternary complex showed better drug release of>85% within 30 min. in comparison to binary complex. The in vitro taste-masking study revealed the taste masking efficiency of the ternary complex of cefuroxime with β-cyclodextrin. Conclusion: The developed binary and ternary complex of cefuroxime axetil based on β-cyclodextrin with PVP K-30 showed improved in vitro dissolution rate and taste masking in comparison to pure drug. The drug release was better in ternary complexes. The present research work successfully shows the utility of binary and ternary complexes for improving pharmaceutical characteristics of cefuroxime axetil.

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Different BCS Class II Drug-Gelucire Solid Dispersions Prepared by Spray Congealing: Evaluation of Solid State Properties and In Vitro Performances

Pharmaceutics ◽

10.3390/pharmaceutics12060548 ◽

2020 ◽

Vol 12 (6) ◽

pp. 548 ◽

Cited By ~ 1

Author(s):

Serena Bertoni ◽

Beatrice Albertini ◽

Nadia Passerini

Keyword(s):

Solid State ◽

Drug Carrier ◽

Solid Dispersions ◽

Class Ii ◽

Water Soluble ◽

Drug Dissolution ◽

Crystalline Solid ◽

Dissolution Behavior ◽

Bcs Class Ii

Delivery of poorly water soluble active pharmaceutical ingredients (APIs) by semi-crystalline solid dispersions prepared by spray congealing in form of microparticles (MPs) is an emerging method to increase their oral bioavailability. In this study, solid dispersions based on hydrophilic Gelucires® (Gelucire® 50/13 and Gelucire® 48/16 in different ratio) of three BCS class II model compounds (carbamazepine, CBZ, tolbutamide, TBM, and cinnarizine, CIN) having different physicochemical properties (logP, pKa, Tm) were produced by spray congealing process. The obtained MPs were investigated in terms of morphology, particles size, drug content, solid state properties, drug-carrier interactions, solubility, and dissolution performances. The solid-state characterization showed that the properties of the incorporated drug had a profound influence on the structure of the obtained solid dispersion: CBZ recrystallized in a different polymorphic form, TBM crystallinity was significantly reduced as a result of specific interactions with the carrier, while smaller crystals were observed in case of CIN. The in vitro tests suggested that the drug solubility was mainly influenced by carrier composition, while the drug dissolution behavior was affected by the API solid state in the MPs after the spray congealing process. Among the tested APIs, TBM-Gelucire dispersions showed the highest enhancement in drug dissolution as a result of the reduced drug crystallinity.

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NADP-Dependent Aldehyde Dehydrogenase from Archaeon Pyrobaculum sp.1860: Structural and Functional Features

Archaea ◽

10.1155/2016/9127857 ◽

2016 ◽

Vol 2016 ◽

pp. 1-14

Author(s):

Ekaterina Yu. Bezsudnova ◽

Tatiana E. Petrova ◽

Natalia V. Artemova ◽

Konstantin M. Boyko ◽

Ivan G. Shabalin ◽

...

Keyword(s):

Aldehyde Dehydrogenase ◽

Active Sites ◽

Ternary Complex ◽

Binary Complex ◽

Relay Systems ◽

Binary Complexes ◽

Proton Relay ◽

Functional Features

We present the functional and structural characterization of the first archaeal thermostable NADP-dependent aldehyde dehydrogenase AlDHPyr1147. In vitro, AlDHPyr1147 catalyzes the irreversible oxidation of short aliphatic aldehydes at 60–85°С, and the affinity of AlDHPyr1147 to the NADP+ at 60°С is comparable to that for mesophilic analogues at 25°С. We determined the structures of the apo form of AlDHPyr1147 (3.04 Å resolution), three binary complexes with the coenzyme (1.90, 2.06, and 2.19 Å), and the ternary complex with the coenzyme and isobutyraldehyde as a substrate (2.66 Å). The nicotinamide moiety of the coenzyme is disordered in two binary complexes, while it is ordered in the ternary complex, as well as in the binary complex obtained after additional soaking with the substrate. AlDHPyr1147 structures demonstrate the strengthening of the dimeric contact (as compared with the analogues) and the concerted conformational flexibility of catalytic Cys287 and Glu253, as well as Leu254 and the nicotinamide moiety of the coenzyme. A comparison of the active sites of AlDHPyr1147 and dehydrogenases characterized earlier suggests that proton relay systems, which were previously proposed for dehydrogenases of this family, are blocked in AlDHPyr1147, and the proton release in the latter can occur through the substrate channel.

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Binding characteristics of pro-insulin-like growth factor-II from cancer patients: binary and ternary complex formation with IGF binding proteins-1 to -6

Journal of Endocrinology ◽

10.1677/joe.0.1650253 ◽

2000 ◽

Vol 165 (2) ◽

pp. 253-260 ◽

Cited By ~ 34

Author(s):

JJ Bond ◽

S Meka ◽

RC Baxter

Keyword(s):

Complex Formation ◽

Ternary Complex ◽

Binding Proteins ◽

Ternary Complexes ◽

Binary Complex ◽

Igf Binding Proteins ◽

Ternary Complex Formation ◽

Binary Complexes ◽

Igf Binding ◽

Igfbp 3

Many tumours secrete IGF-II in incompletely processed precursor forms. The ability of these pro-IGF-II forms to complex with the six IGF binding proteins (IGFBPs) is poorly understood. In this study, pro-IGF-II has been extracted from the serum and tumour tissue of two patients with non-islet cell tumour hypoglycaemia. These samples were used to study binary complex formation with IGFBPs-1 to -6 using competitive IGF-II binding assays and ternary complex formation with IGFBP-3 and IGFBP-5. In each case, IGFBPs-1 to -6 showed little difference in their ability to form binary complexes with recombinant IGF-II or tumour-derived pro-IGF-II forms, when the preparations were standardised according to IGF-II immunoreactivity. As previously described, ternary complex formation by acid-labile subunit (ALS) with IGFBP-3 and pro-IGF-II was greatly decreased compared with complex formation with mature IGF-II. In contrast, ALS bound similarly to IGFBP-5 in the presence of pro-IGF-II and mature IGF-II. These studies suggest that pro-IGF-II preferentially forms binary complexes with IGFBPs, and ternary complexes with IGFBP-5, rather than ternary complexes with IGFBP-3 as seen predominantly in normal serum. This may increase the tissue availability of serum pro-IGF-II, allowing its insulin-like potential to be realised.

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Sensitization of Eriochromeazurol-B in Presence of Cetyldimethylethylammonium Bromide for the Microdetermination of Some Lanthanides

E-Journal of Chemistry ◽

10.1155/2012/587240 ◽

2012 ◽

Vol 9 (4) ◽

pp. 2394-2406 ◽

Cited By ~ 1

Author(s):

Anil B. Zade ◽

Pawan P. Kalbende ◽

Mayuri S. Umekar ◽

Gajanan W. Belsare

Keyword(s):

Metal Ion ◽

Ternary Complex ◽

Bathochromic Shift ◽

Stoichiometric Composition ◽

Formation Constants ◽

Ternary Complexes ◽

Binary Complex ◽

Modified Method ◽

Binary Complexes ◽

Lanthanide Metal

Cetyldimethylethylammonium bromide, a cationic surfactant has been used to decolorize eriochromeazurol B, an anionic triphenylmethane type of dye. Addition of specific lanthanide metal ion to this decolorized solution resulted into intense colored stable ternary complex with large bathochromic shift from 540 nm (binary complex) to 650 nm (ternary complex) with increase in absorbance values at shifted wavelength. CDMEAB thus decreases the color intensity of ECAB and increases the absorbance value of ternary complexes. This two fold advantage resulted into enhancement in molar absorptivities and sensitivities at shifted wavelength of ternary complexes with stoichiometric composition 1:(1:3)2, [Ln : (R:S)] for all lanthanides understudy namely yttrium, neodymium, europium, terbium and ytterbium. The ternary complexes at pH 6.0 exhibited absorption maxima at 650 nm with molar absorptivities 69000 L.mol-1.cm-2for Y(III), 66000 L.mol-1.cm-2for Nd(III), 69000 L.mol-1.cm-2for Eu(III), 64000 L.mol-1.cm-2for Tb(III), 70000 L.mol-1.cm-2for Yb(III). Beer's law were obeyed in concentration range 0.11-0.94, 0.19-1.53, 0.2-1.41, 0.21-1.69 and 0.23-1.11 ppm for Y(III), Nd(III), Eu(III), Tb(III) and Yb(III) respectively. Conditional formation constants and various analytical parameters have been evaluated and compared the results of newly formed ternary complexes with binary complexes. Finally newly suggested modified method have been recommended for the microdetermination of lanthanides understudy.

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Equilibrium Studies of Binary and Ternary Complexes of Palladium(II) Involving Amino Acids

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19931103 ◽

1993 ◽

Vol 58 (5) ◽

pp. 1103-1108 ◽

Cited By ~ 4

Author(s):

Mohamed M. Shoukry ◽

Eman M. Shoukry

Keyword(s):

Amino Acids ◽

Relative Stability ◽

Ternary Complex ◽

Formation Constants ◽

Ternary Complexes ◽

Conductivity Measurements ◽

Equilibrium Studies ◽

Binary And Ternary Complexes ◽

Binary Complexes

The formation constants of the binary and ternary complexes of palladium(II) with diethylenetriamine and amino acids as ligands have been determined potentiometrically at 25 °C in 0.1 M NaNO3 solution. The relative stability of each ternary complex was compared with that of the corresponding binary complexes in terms of ∆logK values. The mode of chelation was ascertained by conductivity measurements.

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In Silico Prediction of Plasma Concentrations of Fluconazole Capsules with Different Dissolution Profiles and Bioequivalence Study Using Population Simulation

Pharmaceutics ◽

10.3390/pharmaceutics11050215 ◽

2019 ◽

Vol 11 (5) ◽

pp. 215 ◽

Cited By ~ 2

Author(s):

Marcelo Dutra Duque ◽

Daniela Amaral Silva ◽

Michele Georges Issa ◽

Valentina Porta ◽

Raimar Löbenberg ◽

...

Keyword(s):

Reference Product ◽

Plasma Concentrations ◽

Drug Dissolution ◽

In Vitro Dissolution ◽

Dissolution Behavior ◽

Dissolution Profile ◽

Time Data ◽

Simulation Results ◽

Population Simulation

A biowaiver is accepted by the Brazilian Health Surveillance Agency (ANVISA) for immediate-release solid oral products containing Biopharmaceutics Classification System (BCS) class I drugs showing rapid drug dissolution. This study aimed to simulate plasma concentrations of fluconazole capsules with different dissolution profiles and run population simulation to evaluate their bioequivalence. The dissolution profiles of two batches of the reference product Zoltec® 150 mg capsules, A1 and A2, and two batches of other products (B1 and B2; C1 and C2), as well as plasma concentration–time data of the reference product from the literature, were used for the simulations. Although products C1 and C2 had drug dissolutions < 85% in 30 min at 0.1 M HCl, simulation results demonstrated that these products would show the same in vivo performance as products A1, A2, B1, and B2. Population simulation results of the ln-transformed 90% confidence interval for the ratio of Cmax and AUC0–t values for all products were within the 80–125% interval, showing to be bioequivalent. Thus, even though the in vitro dissolution behavior of products C1 and C2 was not equivalent to a rapid dissolution profile, the computer simulations proved to be an important tool to show the possibility of bioequivalence for these products.

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COMPLEX OF ELUXADOLINE WITH SODIUM CAPRYLATE FOR IMPROVED SOLUBILITY AND DISSOLUTION RATE

INDIAN DRUGS ◽

10.53879/id.57.11.11857 ◽

2021 ◽

Vol 57 (11) ◽

pp. 22-26

Author(s):

Manisha Dhere ◽

◽

Arti Majumdar ◽

Neelesh Malviya

Keyword(s):

Dissolution Rate ◽

Solvent Evaporation ◽

Drug Dissolution ◽

Dissolution Enhancement ◽

Solvent Evaporation Method ◽

Scanning Calorimetry ◽

Evaporation Method ◽

Solubility Study ◽

Sodium Caprylate

In the present research, newly developed complex with sodium caprylate was investigated for solubility and dissolution enhancement of eluxadoline. Complexes were prepared in different ratios by solvent evaporation method and characterised solubility study, Infrared spectroscopy (IR), Diffrential scanning calorimetry (DSC), X-Ray Diffraction (XRD), drug content analysis and in vitro Drug release. The solubility and dissolution rate revealed most suitable ratio of eluxadoline and sodium caprylate (1:4). The IR, DSC and X-RD data also confirmed the results. It was concluded that complex prepared with (1:4 drug:sodium caprylate ratio) using solvent evaporation method showed significant improvement in solubility and drug dissolution.

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