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.  

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.   

scholarly journals Studying the Complex Formation of Sulfonatocalix[4]naphthalene and Meloxicam towards Enhancing Its Solubility and Dissolution Performance

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 994
Author(s):  
Tayel Al Hujran ◽  
Mousa Magharbeh ◽  
Samer Al-Gharabli ◽  
Rula Haddadin ◽  
Manal Al Soub ◽  
...  
Keyword(s):  
Inclusion Complex ◽  
Dissolution Rate ◽  
Physical Mixture ◽  
Drug Dissolution ◽  
In Vitro Dissolution ◽  
Molar Ratio ◽  
Solubility Study ◽  
Solubility Behavior ◽  
Ft Ir

The interaction between meloxicam and sulfonatocalix [4] naphthalene was investigated to improve the meloxicam solubility and its dissolution performance. Solubility behavior was investigated in distilled water (DW) and at different pH conditions. Besides, solid systems were prepared in a 1:1 molar ratio using coevaporate, kneading, and simple physical mixture techniques. Further, they were characterized by PXRD, FT-IR, DCS, and TGA. In vitro dissolution rate for coevaporate, kneaded, and physical mixture powders were also investigated. Solubility study revealed that meloxicam solubility significantly increased about 23.99 folds at phosphate buffer of pH 7.4 in the presence of sulfonatocalix [4] naphthalene. The solubility phase diagram was classified as AL type, indicating the formation of 1:1 stoichiometric inclusion complex. PXRD, FT-IR, DCS, and TGA pointed out the formation of an inclusion complex between meloxicam and sulfonatocalix [4] naphthalene solid powders prepared using coevaporate technique. In addition, in vitro meloxicam dissolution studies revealed an improvement of the drug dissolution rate. Furthermore, a significantly higher drug release (p ≤ 0.05) and a complete dissolution was achieved during the first 10 min compared with the other solid powders and commercial meloxicam product. The coevaporate product has the highest increasing dissolution fold and RDR10 in the investigated media, with average values ranging from 5.4–65.28 folds and 7.3–90.7, respectively. In conclusion, sulfonatocalix [4] naphthalene is a promising host carrier for enhancing the solubility and dissolution performance of meloxicam with an anticipated enhanced bioavailability and fast action for acute and chronic pain disorders.

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 Solid Dispersion and Inclusion Complex for Solubility Enhancement of Rifabutine: A Comparative Study

2020 ◽  
Vol 11 (SPL4) ◽  
pp. 1772-1778
Author(s):  
Jyoti Maithani ◽  
Ranjit Singh ◽  
Sanjay Singh ◽  
Kapil Kalra
Keyword(s):  
Inclusion Complex ◽  
Solid Dispersion ◽  
Amorphous Structure ◽  
Solvent Evaporation ◽  
Physical Mixture ◽  
Complex Method ◽  
Physicochemical Interaction ◽  
Dissolution Profile ◽  
Formulation Development ◽  
Peg 4000

Improvement in the solubility of a hydrophobic drug has a significant role in formulation development. The target of this study was the use of solid dispersion and inclusion complex method to enhance and to compare the watery solubility and dissolution qualities of Rifabutin. Various strategies in various proportions have been used in the preparation of the consideration complex with ß-cyclodextrin (ß-CD) and Hydroxypropyl-ß-cyclodextrin (HPß-CD) and found that the better-improved solubility has been seen in kneading technique (AK1) in comparison to the physical mixture method and solvent evaporation method. Various techniques were applied in the preparation of the solid dispersion of Mannitol and polyethene glycol (PEG) 4000. They observed that solvent evaporation (CS4) had shown the better improvement of solubility when compared with the physical mixture method and kneading method. As the two methodologies were analysed, it was observed that the inclusion complex technique was far better as it caused a noteworthy enhancement in dissolution profile (99.23±0.25). The drug content was calculated (99.15±0.14) and % inclusion yield was calculated (99.5 %), which was found to be maximum with the kneading technique (AK1). The characterization FTIR and SEM of the complexes shows that the drug had an amorphous structure. The amorphous structure of a drug has higher dissolution potential than the crystalline structure of the drug. The IR Spectroscopy and Scanning electron microscopy (SEM) were done to check their impact on dissolution behaviour and any if there was any physicochemical interaction between the carrier and the drug.

scholarly journals Enhancing dissolution profile of diazepam using hydrophilic polymers by solid dispersion technique

2012 ◽  
Vol 1 (12) ◽  
pp. 423-430 ◽  
Author(s):  
Md. Sariful Islam Howlader ◽  
Jayanta Kishor Chakrabarty ◽  
Khandokar Sadique Faisal ◽  
Uttom Kumar ◽  
Md. Raihan Sarkar ◽  
...  
Keyword(s):  
Dissolution Rate ◽  
Solid Dispersion ◽  
Solid Dispersions ◽  
Water Soluble ◽  
Distilled Water ◽  
Dissolution Profile ◽  
Peg 6000 ◽  
Solvent Method ◽  
Pure Drug ◽  
Dispersion Technique

The aim of the present study was to improve the solubility and dissolution rate of a poorly water-soluble drug by a solid dispersion technique, in order to investigate the effect of these polymers on release mechanism from solid dispersions. Diazepam was used as a model drug to evaluate its release characteristics from different matrices. Solid dispersions were prepared by using polyethylene glycol 6000 (PEG-6000), HPMC, HPC and Poloxamer in different drug-to-carrier ratios (1:2, 1:4, 1:6, 1:8, 1:10). The solid dispersions were prepared by solvent method. The pure drug and solid dispersions were characterized by in vitro dissolution study. Distilled water was used as dissolution media, 1000 ml of distilled water was used as dissolution medium in each dissolution basket at a temperature of 37°C and a paddle speed of 100 rpm. The very slow dissolution rate was observed for pure Diazepam and the dispersion of the drug in the polymers considerably enhanced the dissolution rate. This can be attributed to improved wettability and dispersibility, as well as decrease of the crystalline and increase of the amorphous fraction of the drug. SEM (Scanning Electron microscope) studies shows that the solid dispersion having a uniform dispersion. Solid dispersions prepared with PEG-6000, Poloxamer showed the highest improvement in wettability and dissolution rate of Diazepam. Solid dispersion containing polymer prepared with solvent method showed significant improvement in the release profile as compared to pure drug, Diazepam.DOI: http://dx.doi.org/10.3329/icpj.v1i12.12453 International Current Pharmaceutical Journal 2012, 1(12): 423-430

scholarly journals Preparation and Evaluation of Inclusion Complex of the Lipid Lowering Drug Lovastatin with ?-Cyclodextrin

1970 ◽  
Vol 6 (1) ◽  
pp. 25-36 ◽  
Author(s):  
RP Patel ◽  
MM Patel
Keyword(s):  
Dissolution Rate ◽  
Inclusion Complexation ◽  
Physical Mixture ◽  
Lipid Lowering ◽  
In Vitro Dissolution ◽  
Phase Solubility ◽  
Stoichiometric Ratio ◽  
Significant Difference ◽  
Insoluble Drugs

Several attempts have been made to improve the solubility of water insoluble drugs. Over the years, inclusion complexation of drugs with ?-cyclodextrin has emerged as a viable attempt to improve the dissolution of water insoluble drugs. The aim of the present work was to improve the dissolution rate of lovastatin, a water insoluble drug, by inclusion complexation with ?-cyclodextrin. The stoichiometric ratio determined by phase solubility analysis for inclusion complexation of lovastatin with ?-cyclodextrin was 1:1. The solubility of lovastatin increased with increasing amount of ?-cyclodextrin in water. Gibbs free energy (?Gtr°) values were all negative, indicating the spontaneous nature of lovastatin solubilization. Complexes of lovastatin were prepared with ?-cyclodextrin by various methods such as kneading, coevaporation and physical mixing. The complexes were characterized by Fourier-transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), and X-ray diffraction (XRD) patterns. These studies indicated the inclusion of lovastatin in the cavity of ?-cyclodextrin. The complexation resulted in a marked improvement in the solubility of lovastatin. The complex prepared by kneading method showed fastest and highest in vitro dissolution rate compared to the tablets of pure of lovastatin. Physical mixture of ?-cyclodextrin/lovastatin also showed significant improvement in the dissolution rate compared to pure lovastatin. Mean dissolution time (MDT) of lovastatin decreased significantly after preparation of complexes and physical mixture of lovastatin with ?-cyclodextrin. Similarity factor (f2) indicated significant difference between the release profiles of lovastatin from complexes and from pure lovastatin. Key words: Lovastatin, ?-cyclodextrin, inclusion complexation, in vitro dissolution studies. Dhaka Univ. J. Pharm. Sci. 6(1): 25-36, 2007 (June) The full text is of this article is available at the Dhaka Univ. J. Pharm. Sci. website

scholarly journals CHARACTERIZATION AND INTRINSIC DISSOLUTION RATE STUDY OF MICROWAVE ASSISTED CYCLODEXTRIN INCLUSION COMPLEXES OF GEMFIBROZIL

2016 ◽  
Vol 8 (10) ◽  
pp. 160
Author(s):  
S. Ain ◽  
R. Singh ◽  
Q. Ain
Keyword(s):  
Inclusion Complex ◽  
Dissolution Rate ◽  
Inclusion Complexes ◽  
Microwave Drying ◽  
Phase Solubility ◽  
Intrinsic Dissolution ◽  
Intrinsic Dissolution Rate ◽  
Solubility Study ◽  
Microwave Assisted ◽  
Rate Study

<p><strong>Objective: </strong>The aim of the present study was to carry out characterization and intrinsic dissolution rate study of microwave assisted inclusion complex of poorly water soluble, lipid lowering agent gemfibrozil [5-(2,5-dimethylphenoxy)-2,2-dimethylpentanoic acid]<strong> </strong>with naturally occurring β-cyclodextrins (CDs) or cycloheptaamylase.</p><p><strong>Methods: </strong>In this work, the phase solubility study was performed to find the ratio of drug and cyclodextrin complexes. Inclusion complexes were prepared by kneading and the prepared complex was subjected to microwave drying and conventional drying techniques. The prepared complexes were evaluated by intrinsic dissolution rate studies and equilibrium solubility study. Further characterization was done by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and X-ray powder diffractometry (DSC).</p><p><strong>Results: </strong>The phase solubility studies showed a linear A<sub>L</sub>-type diagram indicating the formation of inclusion complexes in 1:1 molar ratio β-CD-gemfibrozil complex with maximum stability constant of 148.88 M<sup>-1</sup>was selected for preparation of inclusion complex. The microwave dried product was identified as the inclusion complex with maximum IDR when compared to the conventional dried product.</p><p><strong>Conclusion: </strong>This study was concluded that the microwave drying is the most suitable of the previously occurring drying techniques. Since it showed the highest solubility and IDR value.</p>

scholarly journals Spectroscopic Investigation for Photo stability of Hydrochlorothiazide Complexes with β-Cyclodextrin and HPMC.

2017 ◽  
Vol 10 (7) ◽  
pp. 314
Author(s):  
Pallavi Shrirang Dhekale
Keyword(s):  
Water Soluble ◽  
Molar Ratio ◽  
Phase Solubility ◽  
Test Results ◽  
Photo Degradation ◽  
Water Soluble Drug ◽  
Kneading Method ◽  
Auxiliary Substance ◽  
Photo Stability ◽  
Poorly Water Soluble Drug

Hydrochlorothiazide (HCT) is a poorly water-soluble drug. The aim of this study was to determine whether inclusion complexes between β-cyclodextrin and HCT are formed and also studied effect of auxiliary substance (HPMC) on HCT, photo-stability of HCT and to characterize these. Equimolar HCT/ βCD solid systems in the presence or absence of 0.2% (w/v) of HPMC were prepared by kneading method. The systems were characterized by phase solubility, Dissolution study, FTIR, DSC and the photo-stability test followed by u.v. spectroscopy.  The results suggest that true binary and ternary inclusion complex. The test results have proved that the complexed HCT with hydroxypropyl β- cyclodextrin enhance the photo degradation rate and resolute the optimal molar ratio HCT to hydroxypropyl β- cyclodextrin as 1:1.

Design, Fabrication and Characterization of Esomeprazole Nanocrystals for Enhancing the Dissolution Rate and Stability

2020 ◽  
Vol 14 ◽  
Author(s):  
Vijay Agarwal ◽  
Meenakshi Bajpai
Keyword(s):  
Particle Size ◽  
Dissolution Rate ◽  
Crystalline State ◽  
Physical Mixture ◽  
Water Soluble ◽  
Dissolution Behavior ◽  
Physical Treatment ◽  
Pxrd Pattern ◽  
Freeze Dried ◽  
Bulk Drug

Background: Poor solubility and low dissolution rate limit the work at poorly water-soluble drugs like Esomeprazole. To overcome this problem, different technologies had to be used but could not resolve the problem, significantly. The main aim of this study was to prepare the nanocrystals using evaporative precipitation ultrasonication method in order to improve the dissolution rate and stability of Esomeprazole (ESM). Methods: For getting the nanocrystals, different nanoformulations were prepared using the pluronic F-68 in different concentration, and then screened formulation was lyophilized in presence of two distinct cryoprotectants; mannitol and sucrose. The obtained nanocrystals were characterized for their re-dispersibility, crystalline state, dissolution behavior, particle size, polydispersibility index and morphology. Dissolution study of ESM nanocrystals was performed in buffer solution of pH-7.4, and compare to that of bulk ESM sample and ESM/pluronic F-68 physical mixture. Results: Cryoprotectant containing nanocrystals exhibit the re-dispersion in water after the manual shaking. 5% mannitol containing nanocrystals showed the least polydispersity index (0.42 ± 0.11) and narrowest particle size (186 ± 12.9 nm). The powder x-ray diffraction (PXRD) pattern and differential scanning calorimeter (DSC) thermograms revealed that crystalline state of drug was not changed after the different physical treatment. Freeze-dried nanocrystals showed a faster dissolution rate and almost 99.45% of drug was released within 60 min. However, the bulk drug and a physical mixture of bulk drug/pluronic F-68 showed only 22.65% and 21.3% of drug release, respectively, after 60 min. Conclusion: The different findings revealed that nanocrystals could be a potential alternate for solving the dissolution rate and stability issue of ESM like poorly soluble drugs.

scholarly journals EVALUATION OF ORALLY DISINTEGRATING TABLET OF IBUPROFEN-β-CYCLODEXTRIN INCLUSION COMPLEX

2020 ◽  
pp. 60-64
Author(s):  
NUR AINI DEWI PURNAMASARI ◽  
PRATAMA ANGGI SAPUTRA
Keyword(s):  
Inclusion Complex ◽  
Dissolution Rate ◽  
Spray Drying ◽  
Water Solubility ◽  
The Other ◽  
Molar Ratio ◽  
Taste Masking ◽  
Scanning Calorimetry ◽  
Orally Disintegrating Tablet ◽  
Dissolution Efficiency

Objective: This study aims to determine the effect of the inclusion complex formation of ibuprofen (IB) with β-cyclodextrin (β-CD) in improving water solubility and taste masking as well as to study the effect of the combined use of super disintegrants in IB-β-CD ODT (Orally disintegrating tablet). Methods: IB-β-CD inclusion complex was prepared by spray drying technique with a 1:1 molar ratio. ODTs were prepared by the direct compression method using various ratios of Ac-Di-Sol® and Kollidon® CL as super disintegrant. The inclusion complex was characterized using spectroscopy FT-IR (Fourier-transform infrared) and DSC (Differential Scanning Calorimetry). The physical properties and dissolution rate of ODTs were evaluated. Dissolved drug concentration at 60 min (Q60) and Dissolution Efficiency (DE60) was calculated using the dissolution test result. Results: The unpleasant taste of IB had been successfully masked by IB-β-CD. Formula 1 was observed having 14.5 sec of disintegration, fastest compared to the other formulas. Moreover DE60 value of formula I was higher than the other formulas (113.45). Conclusion: IB-β-CD Inclusion complex prepared by spray drying method (1: 1) increased the water solubility and masked the unpleasant taste compared to IB moreover combination of Ac-Di-Sol® and Kollidon® CL increased ODT dissolution rate.

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