scholarly journals Preparation and in vitro Evaluation of Inclusion Complexes of Nelfinavir with Chemically Modified ?-cyclodextrins

2013 ◽  
Vol 11 (2) ◽  
pp. 107-116 ◽  
Author(s):  
Shivanand Hiremath ◽  
Ganesh Godge
Keyword(s):  
Inclusion Complex ◽  
Inclusion Complexes ◽  
Solubility Diagram ◽  
Aqueous Solubility ◽  
Water Soluble ◽  
Phase Solubility ◽  
Ir Study ◽  
Order Complexes ◽  
Phase Solubility Diagram

Nelfinavir is a poorly water-soluble antiretroviral drug with relatively low bioavailability. In the present study, the practically insoluble drug, nelfinavir (NFV) and its inclusion complexes with hydroxypropyl-?-cyclodextrin (HP-?-CD) were investigated to improve the aqueous solubility and the dissolution rate of the drug, thus enhancing its bioavailability. The phase solubility diagram with HP-?-CD was classified as AL-type at all temperatures investigated, indicating the formation of higher order complexes. The apparent complexation constants (K1:1) calculated from phase solubility diagram were 145.49, 188.45 and 255.54 M-1 at 25, 37 and 45 ± 0.5°C, respectively. Aqueous solubility and dissolution studies indicated that the dissolution rates were remarkably increased; this could be mainly attributed to the improved solubility and dissolution associated with inclusion complex between drug and HP- ? -CD. Absence of endothermic and characteristic diffraction peaks corresponding to NFV was observed for the inclusion complex in DSC and PXRD. FT-IR study indicated that the presence of intermolecular hydrogen bonds between NFV and HP-?-CD in inclusion complex, resulting in the formation of amorphous form. DOI: http://dx.doi.org/10.3329/dujps.v11i2.14558 Dhaka Univ. J. Pharm. Sci. 11(2): 107-116, 2012 (December)

BEHAVIOURAL STUDY OF CYCLODEXTRIN INCLUSION COMPLEX ON ENHANCEMENT OF SOLUBILITY OF ACECLOFENAC

INDIAN DRUGS ◽  
2015 ◽  
Vol 52 (11) ◽  
pp. 19-23
Author(s):  
J Shaikh ◽  
◽  
S. V. Deshmane ◽  
R. N Purohit ◽  
K. R. Biyani
Keyword(s):  
Inclusion Complex ◽  
Solid Dispersion ◽  
Water Soluble ◽  
In Vitro Dissolution ◽  
Phase Solubility ◽  
Solubility Study ◽  
Cyclodextrin Inclusion ◽  
Poorly Water Soluble ◽  
Cyclodextrin Inclusion Complex

The main objective of the present study was to enhance the solubility and dissolution rate of poorly water soluble aceclofenac using its solid dispersion with β-cyclodextrin. FTIR and DSC study was carried out to find out any incompatibility. The phase solubility of drug was carried out in 1, 2, 5, and 10% of β-cyclodextrin in distilled water. Kneading method and solvent evaporation method was use to prepared solid dispersion of aceclofenac and β-cyclodextrin. Different evaluation tests like solubility study in different solvents, PXRD and in vitro dissolution study of aceclofenac- β-cyclodextrin inclusion complex were carried out. The overall finding indicated that β-cyclodextrin is a desirable water soluble carrier, that helps in increasing solubility of drug. Due to its structural feature, β-cyclodextrin forms a good inclusion complex that decreases contact angle of drug with water molecules by increasing wetting properties. Hence, it can be concluded that, β-cyclodextrin is better water soluble carrier molecule in terms of its compatibility and increasing solubility behavior of poorly water soluble drug aceclofenac.

scholarly journals Cyclodextrin inclusion complexes of the antioxidant α-lipoic acid

2014 ◽  
Vol 70 (a1) ◽  
pp. C992-C992 ◽  
Author(s):  
Mino Caira ◽  
Susan Bourne ◽  
Buntubonke Mzondo
Keyword(s):  
Inclusion Complex ◽  
Inclusion Complexes ◽  
Lipoic Acid ◽  
Aqueous Solubility ◽  
Phase Solubility ◽  
Monoclinic System ◽  
Space Group ◽  
Racemic Form ◽  
Native Host

Owing to its potent antioxidant activity,α-lipoic acid (1,2-dithiolane-3-pentanoic acid) is widely used as a supplement and is recommended for treating a number of conditions including chronic liver disease and diabetes. The poor aqueous solubility of the acid (~0.003 M at 250C) has prompted studies of its interaction with cyclodextrins (CDs) as a possible route to improving its solubility. However, relatively few studies have focused on the isolation of solid CD inclusion complexes of the antioxidant, and in most cases the racemic form of the acid was employed. In the comprehensive study reported here, the bioactive (R)-(+)-enantiomeric form of the molecule was used exclusively, resulting in the isolation and structural characterization of its inclusion complexes with each of the native host CDs (α-, β- and γ-CD) as well as permethylated α-CD (TRIMEA), permethylated β-CD (TRIMEB) and 2,6-dimethylated-β-CD (DIMEB). The α-CD complex crystallizes in the trigonal system, space group R32, with three independent CD molecules in the asymmetric unit and is not isostructural with any known CD complex while the β-CD complex crystallizes in the monoclinic system (C2). With the host γ-CD, an orthorhombic (pseudo-tetragonal) inclusion complex was identified, an unusual result as γ-CD complexes generally crystallize in the tetragonal space group P4212. The complexes with TRIMEA and TRIMEB crystallize in the orthorhombic system (P212121), the modes of inclusion of the (R)-(+)-α-lipoic acid molecule in the respective hosts being reversed: the guest molecule is fully encapsulated by the former host with the dithiolane ring located at the secondary rim, while in the latter host, the dithiolane ring rests on the concave surface of the host cavity at the primary side. A significant level of guest disorder was detected in the inclusion complex with DIMEB (P21). Thermal and phase-solubility analyses complemented the X-ray structural studies.

scholarly journals Preparation and characterization of artemether inclusion complexes with hydroxypropyl-β-cyclodextrin

2017 ◽  
Vol 16 (10) ◽  
pp. 2359-2364
Author(s):  
Zwanden Sule Yahaya ◽  
Kenneth C. Ofokansi ◽  
Suzane T. Allagh ◽  
Pat G. Bhatia
Keyword(s):  
Complex Formation ◽  
Inclusion Complex ◽  
Dissolution Rate ◽  
Inclusion Complexes ◽  
In Vitro Dissolution ◽  
Phase Solubility ◽  
Inclusion Complex Formation ◽  
Scanning Calorimetry ◽  
Ft Ir

Purpose: To investigate experimentally the inclusion of artemether into the cavity of  hydroxypropyl-β-cyclodextrin and examine its effect on the solubility and dissolution rate of the drug.Methods: Inclusion complexes of artemether with hydroxypropyl-β-cyclodextrin of molar ratios 1:1, 1:2 and 1:3 were prepared using the kneading method. Phase solubility analysis and in vitro dissolution studies were utilized in evaluating the influence of inclusion complex formation on the solubility and dissolution rate of the drug. The complexes were characterized using differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR). The inclusion complex containing equimolar concentrations of artemether and hydroxypropyl-β-cyclodextrin was then formulated into tablets via direct compression and  evaluated for various pharmaceutical characteristics including hardness, friability, absolute drug content and comparative in vitro dissolution profiles with some  commercially available brands of artemether.Results: The phase solubility diagram for the formed complexes in water at 37 oC indicated a linear curve soluble complex system (referred to as the AL system), and a stability constant (KC) value of 143 M-1. Evidence consistent with inclusion complex formation was obtained using FT-IR and DSC. The formulated inclusion complex tablets exhibited a higher rate of dissolution than the pure drug and commercial brands, showing 3.9-, 1.8- and 1.6-fold increases, respectively, over a period of 15 min.Conclusion: Inclusion complexation of artemether with hydroxypropyl-β-cyclodextrin is a promising approach to enhance the solubility and dissolution rate of the drug.Keywords: Artemether, 2-Hydroxypropyl-β-cyclodextrin, Dissolution, Solubility enhancement, Inclusion complex

PCL-based nanofibers containing ibuprofen/cyclodextrins nanocontainers: A potential candidate for drug delivery application

2018 ◽  
Vol 48 (9) ◽  
pp. 1420-1438 ◽  
Author(s):  
Saeideh Masoumi ◽  
Sahar Amiri ◽  
Seyed Hajir Bahrami
Keyword(s):  
Drug Delivery ◽  
Inclusion Complex ◽  
Aqueous Solubility ◽  
Microscopy Study ◽  
Electron Microscopy Study ◽  
In Vitro Dissolution ◽  
Phase Solubility ◽  
Potential Candidate ◽  
Scanning Calorimetry

Poor solubility and low dissolution rate of ibuprofen (IBU) in the aqueous gastro-intestinal fluids restrict its application, absorption, distribution, target organ delivery, and bioavailability. For improvement of aqueous solubility of IBU, supramolecular nanocontainers of IBU/cyclodextrin were prepared via formation of inclusion complex between ibuprofen and cyclodextrins (α-cyclodextrin and β-cyclodextrin) at various conditions (at room temperature at 25℃ and under sonic energy). The formation of inclusion complex between IBU and cyclodextrins can be confirmed by hydrogen nuclear magnetic resonance, differential scanning calorimetry, fourier transform Infrared spectroscopy (FTIR), X-ray diffraction, and scanning electron microscopy study. FTIR of pure IBU and cyclodextrins is similar to the obtained complex, which indicated intactness of drug in the complex. The encapsulation of IBU in cyclodextrins cavity improved its solubility, phase solubility, and in vitro dissolution and also controlled its release which ensures the long-term delivery. Electro-spun nanofibers of poly-ɛ-caprolactone containing IBU/cyclodextrins is a promising method for controlled drug delivery electro-spun which is bead-free without any aggregation on the surface.

Oral Bioavailability Enhancement of Amisulpride: Complexation and its Pharmacokinetics and Pharmacodynamics Evaluations

2020 ◽  
Vol 13 (2) ◽  
pp. 132-144
Author(s):  
Prajapati Jagruti B. ◽  
Sawant Krutika K. ◽  
Bhramanand Dubey
Keyword(s):  
Complex Formation ◽  
Inclusion Complex ◽  
Oral Bioavailability ◽  
Water Solubility ◽  
Solubility Diagram ◽  
Phase Solubility ◽  
Linear Type ◽  
Market Product ◽  
Pure Drug ◽  
Phase Solubility Diagram

Background: Many CNS drugs have low bioavailability due to their poor water solubility of extensive first-pass metabolism and hence have less effectiveness. Objective: The present study aims to enhance the solubility and oral bioavailability of poorly watersoluble antipsychotic drug Amisulpride (AMS) through complexation with 2-hydroxypropyl β- cyclodextrin (HPβCD). It has slow and erratic absorption after oral administration. Methods: This report describes the study of the phase solubility diagram, preparation of the inclusion complex and tablet of prepared inclusion complex, characterization of the physico-chemical properties of the inclusion complex and tablet. Results: In-vitro study (100 % drug release in 15 minutes), and in-vivo study of an AL-type (linear type) phase solubility diagram indicated a complex of AMS-HP-β-CD with the constant complex formation of 13245 M−1 at 37°C. The complex formation was confirmed by DSC, IR, and X-ray diffraction. The extent of absorption of the complex was determined in rats and was compared with that of pure drug and the market product. The peak plasma concentration of pure drug was 30.05 ± 1.3 ng/ml (Cmax) at 60 ± 3 min, whereas with the market product the value was 54.85 ± 1.2 ng/ml at 40 ± 1 min and with AMS-HPβCD inclusion complex the value was 79.01 ± 1.5 ng/ml. The AUCtot of the pure drug was 2980.34±3.6, the market product was 7238.73±2.9 and of the inclusion complex was 11871.1±2.8. Conclusion: Pharmacodynamic studies in mice showed improved effectiveness of drug compared to pure drug. The oral bioavailability of AMS was improved from 48% to 78%.

Influence of β-Cyclodextrin and Hydroxypropyl-β-Cyclodextrin on Enhancement of Solubility and Dissolution of Isradipine

2017 ◽  
Vol 10 (3) ◽  
pp. 3752-3757
Author(s):  
Narendar D ◽  
Ettireddy S
Keyword(s):  
Inclusion Complex ◽  
Dissolution Rate ◽  
Solid Dispersions ◽  
Physical Stability ◽  
Molecular Complexes ◽  
In Vitro Dissolution ◽  
Molar Ratio ◽  
Phase Solubility ◽  
Cyclodextrin Complexation

The content of this investigation was to study the influence of β-cyclodextrin and hydroxy propyl-β-cyclodextrin complexation on enhancement of solubility and dissolution rate of isradipine. Based on preliminary phase solubility studies, solid complexes prepared by freeze drying method in 1:1 molar ratio were selected and characterized by DSC for confirmation of complex formation. Prepared solid dispersions were evaluated for drug content, solubility and in vitro dissolution. The physical stability of optimized formulation was studied at refrigerated and room temperature for 2 months. Solid state characterization of optimized complex performed by DSC and XRD studies.  Dissolution rate of isradipine was increased compared with pure drug and more with HP-β-CD inclusion complex than β-CD. DSC and XRD analyzes that drug was in amorphous form, when the drug was incorporated as isradipine β-CD and HP-β-CD inclusion complex. Stability studies resulted in low or no variations in the percentage of complexation efficiency suggesting good stability of molecular complexes. The results conclusively demonstrated that the enhancement of solubility and dissolution rate of isradipine by drug-cyclodextrin complexation was achieved.   

Fenofibrate Solid Dispersion for Improving Oral Bioavailability: Preparation, and Characterization and in vivo Evaluation

2020 ◽  
Vol 13 (5) ◽  
pp. 5102-5109
Author(s):  
Venu Madhav K ◽  
Somnath De ◽  
Chandra Shekar Bonagiri ◽  
Sridhar Babu Gummadi
Keyword(s):  
Oral Bioavailability ◽  
Oral Delivery ◽  
Solid Dispersions ◽  
In Vitro Release ◽  
Aqueous Solubility ◽  
Water Soluble ◽  
Scanning Calorimetry ◽  
In Vivo Evaluation

Fenofibrate (FN) is used in the treatment of hypercholesterolemia. It shows poor dissolution and poor oral bioavailability after oral administration due to high liphophilicity and low aqueous solubility. Hence, solid dispersions (SDs) of FN (FN-SDs) were develop that might enhance the dissolution and subsequently oral bioavailability. FN-SDs were prepared by solvent casting method using different carriers (PEG 4000, PEG 6000, β cyclodextrin and HP β cyclodextrin) in different proportions (0.25%, 0.5%, 0.75% and 1% w/v). FN-SDs were evaluated solubility, assay and in vitro release studies for the optimization of SD formulation. Differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM) analysis was performed for crystalline and morphology analysis, respectively. Further, optimized FN-SD formulation evaluated for pharmacokinetic performance in Wistar rats, in vivo in comparison with FN suspension.  From the results, FN-SD3 and FN-SD6 have showed 102.9 ±1.3% and 105.5±3.1% drug release, respectively in 2 h. DSC and PXRD studies revealed that conversion of crystalline to amorphous nature of FN from FT-SD formulation. SEM studies revealed the change in the orientation of FN when incorporated in SDs. The oral bioavailability FN-SD3 and FN-SD6 formulations exhibited 2.5-folds and 3.1-folds improvement when compared to FN suspension as control. Overall, SD of FN could be considered as an alternative dosage form for the enhancement of oral delivery of poorly water-soluble FN.

Solubility Enhancement of the Poorly Water-Soluble Antiulcer Drug Famotidine by Inclusion Complexation

2013 ◽  
Vol 6 (1) ◽  
pp. 1983-1989 ◽  
Author(s):  
Shabnam Ain ◽  
V Gupta ◽  
Babita K ◽  
Q Ain ◽  
J Dahiya
Keyword(s):  
Inclusion Complex ◽  
Dissolution Rate ◽  
Phosphate Buffer ◽  
Physical Mixture ◽  
Water Soluble ◽  
Molar Ratio ◽  
Phase Solubility ◽  
Distilled Water ◽  
Physicochemical Interaction ◽  
Mixture Phase

Aqueous solubility is a critical factor for optimum drug delivery. In the present study, we investigated the potential of drug-cyclodextrin complexation as an approach for improving the solubility and bioavailability of famotidine, an H2-receptor antagonist and acid reducing drug which has poor solubility and bioavailability. Solubility improvement of drug by β-cyclodextrin was done by simple complexation approach using physical, kneading and co-precipitation methods and compared with physical mixture. Phase solubility profile indicated that the solubility of famotidine was significantly increased in presence of β-cyclodextrin and shows a linear graph with β-cyclodextrin indicating formation of inclusion complexes in a 1:1 molar ratio. β-Cyclodextrin-famotidine mixture have maximum stability constant 1477.6 M-1. The inclusion complex ratio 1:1 of kneading mixture was selected based on drug release profile and compared with physical mixture. Further characterization was done by  using Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM) to identify the physicochemical interaction between drug and carrier and its effect on dissolution. Dissolution rate studies for selected inclusion complex was performed in 0.1 N HCl (pH 1.2), phosphate buffer (pH 7.5) and distilled water (pH 6.8) and compared these to pure drug profile which was found to be 2.34 fold increase in distilled water, 1.83 fold in HCl and 2.01 fold in phosphate buffer (pH 7.5). These results suggest that the kneaded complex of famotidine with β-cyclodextrin as hydrophilic complexation agent can substantially enhance the solubility and dissolution rate. Such complex has promising potential to improve the bioavailability of famotidine.  

scholarly journals Solubility enhancement of carvedilol using drug–drug cocrystallization with hydrochlorothiazide

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Shivarani Eesam ◽  
Jaswanth S. Bhandaru ◽  
Chandana Naliganti ◽  
Ravi Kumar Bobbala ◽  
Raghuram Rao Akkinepally
Keyword(s):  
Aqueous Solubility ◽  
Sem Analysis ◽  
Water Soluble ◽  
High Permeability ◽  
Poorly Water Soluble Drugs ◽  
Drug Discovery And Development ◽  
Water Soluble Drugs ◽  
Poorly Water Soluble ◽  
Dissolution In Vitro

Abstract Background Increasing hydrophilicity of poorly water-soluble drugs is a major challenge in drug discovery and development. Cocrystallization is one of the techniques to enhance the hydrophilicity of such drugs. Carvedilol (CAR), a nonselective beta/alpha1 blocker, used in the treatment of mild to moderate congestive heart failure and hypertension, is classified under BCS class II with poor aqueous solubility and high permeability. Present work is an attempt to improve the solubility of CAR by preparing cocrystals using hydrochlorothiazide (HCT), a diuretic drug, as coformer. CAR-HCT (2:0.5) cocrystals were prepared by slurry conversion method and were characterized by DSC, PXRD, FTIR, Raman, and SEM analysis. The solubility, stability, and dissolution (in vitro) studies were conducted for the cocrystals. Results The formation of CAR-HCT cocrystals was confirmed based on melting point, DSC thermograms, PXRD data, FTIR and Raman spectra, and finally by SEM micrographs. The solubility of the prepared cocrystals was significantly enhanced (7.3 times), and the dissolution (in vitro) was improved by 2.7 times as compared to pure drug CAR. Further, these cocrystals were also found to be stable for 3 months (90 days). Conclusion It may be inferred that the drug–drug (CAR-HCT) cocrystallization enhances the solubility and dissolution rate of carvedilol significantly. Further, by combining HCT as coformer could well be beneficial pharmacologically too.

scholarly journals Improving the Solubilization and Bioavailability of Arbidol Hydrochloride by the Preparation of Binary and Ternary β-Cyclodextrin Complexes with Poloxamer 188

2021 ◽  
Vol 14 (5) ◽  
pp. 411
Author(s):  
Md. Khalid Anwer ◽  
Muzaffar Iqbal ◽  
Mohammad Muqtader Ahmed ◽  
Mohammed F. Aldawsari ◽  
Mohd Nazam Ansari ◽  
...  
Keyword(s):  
Antiviral Agent ◽  
Aqueous Solubility ◽  
Phase Solubility ◽  
Pharmacokinetic Studies ◽  
Solubility Curve ◽  
Cyclodextrin Complexes ◽  
Poloxamer 188 ◽  
The Stability

In the current study, the effect of poloxamer 188 on the complexation efficiency and dissolution of arbidol hydrochloride (ADL), a broad-spectrum antiviral agent, with β-cyclodextrin (β-CD) was investigated. Phase solubility studies confirmed a stoichiometry of a 1:1 ratio for both ADL:β-CD and ADL/β-CD with a 1% poloxamer 188 system with an AL type of phase solubility curve. The stability constants (K1:1) calculated from the AL type diagram were 550 M-1 and 2134 M-1 for AD:β-CD and ADL/β-CD with 1% poloxamer 188, respectively. The binary ADL/β-CD and ternary ADL/β-CD with 1% poloxamer 188 complexes were prepared by kneading and a solvent evaporation method and were characterized by aqueous solubility, FTIR, PXRD, DSC and SEM in vitro studies. The solubility (13.1 fold) and release of ADL were markedly improved in kneaded ternary ADL/β-CD with 1% poloxamer 188 (KDB). The binding affinity of ADL and β-CD was confirmed by 1H NMR and 2D ROSEY studies. The ternary complex (KDB) was further subjected for in vivo pharmacokinetic studies in rats and a significant improvement in the bioavailability (2.17 fold) was observed in comparison with pure ADL. Therefore, it can be concluded that the solubilization and bioavailability of ADL can be remarkably increased by ADL/β-CD complexation in the presence of a third component, poloxamer 188.

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