Characterization of Celecoxib β-Cyclodextrin Inclusion Complexes Using Solvent Evaporation Method

An alternative cyclodextrin based formulation for oral anticancer drug exemestane: In vitro and cell culture studies

The study was designed to investigate the effect of cyclodextrins (CDs) on the solubility, dissolution rate, and bioavailability of cilostazol by forming inclusion complexes. Natural CDs like beta-CD, gamma-CD, and the hydrophilic beta-CD derivatives, DM-beta-CD and HP-beta-CD, were used to prepare inclusion complexes with cilostazol. Phase solubility study was carried out and the stability constants were calculated assuming a 1:1 stoichiometry. Solid cilostazol complexes were prepared by coprecipitation and kneading methods and compared with physical mixtures of cilostazol and cyclodextrins. Prepared inclusion complexes were characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry (DSC), and X-ray diffraction (XRD) studies. In vitro dissolution study was performed using phosphate buffer pH 6.4, distilled water, and HCl buffer pH 1.2 as dissolution medium. The optimized inclusion complex was studied for its bioavailability in rabbit and the results were compared with those of pure cilostazol and Pletoz-50. Phase solubility study showed dramatic improvement in the solubility of drug by formation of complexes, which was further increased by pH adjustment. The dissolution rate of cilostazol was markedly augmented by the complexation with DM-beta-CD. DSC and XRD curves showed sharp endothermic peaks indicating the reduction in the microcrystallinity of cilostazol. Selected inclusion complex was also stable at ambient temperature up to 6 months. The in vivo study revealed that DM-beta-CD increased the bioavailability of cilostazol with low variability in the absorption. Among all cilostazol-cyclodextrins complexes, cilostazol-DM-beta-CD inclusion complex (1:3) prepared by coprecipitation method showed 1.53-fold and 4.11-fold increase in absorption along with 2.1-fold and 2.97-fold increase in dissolution rate in comparison with Pletoz-50 and pure cilostazol, respectively.

Influence of surfactants (present in the dissolution media) on the release behaviour of tolbutamide from its inclusion complex with β-cyclodextrin

The formation of hydrochlorothiazide inclusion complexes has been carried out to improve the physicochemical properties and increase the dissolution rate of hydrochlorothiazide. Inclusion complexes were made by co-grinding using ß cyclodextrin at a ratio of 1:1 mol, with variations in milling time, namely 30 minutes (F1), 1 hour (F2), and 2 hours (F3). The inclusion complexes formed were characterized by X-ray diffraction analysis, differential scanning calorimetry (DSC), Fourier transforms infrared (FT-IR), scanning electron microscopy, and dissolution tests. X-ray diffraction results showed a decrease in hydrochlorothiazide intensity, the DSC thermogram showed a decrease in endothermic peaks and enthalpy values, and FT-IR spectrum analysis showed that there was a chemical interaction between hydrochlorothiazide and ß-cyclodextrin. All characterization checks carried out met the requirements and confirmed an increase in the dissolution rate. The dissolution yield of hydrochlorothiazide was 41.711%, the physical mixture was 57.135%, the F1 inclusion complex was 59.52%, the F2 inclusion complex was 79.17%, and the F3 inclusion complex was 103.62%. This proves that the formation of inclusion complexes with the addition of ß-cyclodextrin can significantly increase the dissolution

Aceclofenac (AC) is a potent non-steroidal anti-inflammatory drug (NSAID) known for its anti-inflammatory, analgesic, and antipyretic properties. Its effectiveness is comparable to other NSAIDs, with a similar onset of action. As a Biopharmaceutical Classification System (BCS) Class II compound, the oral bioavailability of AC is limited by its dissolution rate in the gastrointestinal tract. Enhancing the dissolution rate of AC is crucial for improving its bioavailability and therapeutic efficacy. This study aimed to prepare and characterize solid dispersions of AC using a mixed excipient system of β-cyclodextrin and polyvinylpyrrolidone K30 (PVP K30) as carriers, and to examine their effect on the drug's dissolution rate. Solid dispersions were created via physical mixture and solvent evaporation methods using different ratios of AC to the excipient system. The formulations were evaluated for parameters such as practical yield, drug content, bulk and tapped density, Hausner’s ratio, Carr’s index, angle of repose, and in vitro drug release. The results showed a significant increase in drug release for the solid dispersions compared to the pure drug, with the solvent evaporation method proving more effective than the physical mixture method. Solid dispersion techniques offer numerous benefits by altering drug release characteristics, leading to faster drug release within the body. The study demonstrated that the solubility of poorly soluble drugs like AC can be significantly improved through solid dispersion methods. The use of water-soluble carriers such as PVP K30 and β-cyclodextrin effectively modified the drug release profiles. Solid dispersions of AC with PVP K30 were prepared in drug-to-carrier ratios of 1:1 to 1:5 using the solvent evaporation method, while inclusion complexes with β-cyclodextrin were prepared by the kneading method in similar ratios. The formulations were screened for yield, texture, color, physical characteristics, and suitability.

Inclusion complexes using β-cyclodextrin were manufactured by solvent evaporation method. Then, sustained release (SR) hydroxypropylmethylcellulose (HPMC) matrix tablets containing inclusion complex were prepared via direct compression. Isradipine was chosen as a model drug due to its low solubility, photo-instability and short elimination half-life. The physicochemical properties of the inclusion complexes were examined using differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR). The solubility test and dissolution behaviours were also investigated. Based on the solubility experiments, a 1:2 molar ratio (isradipine:β-Cyclodextrin) was best and chosen to prepare inclusion complexes. In addition, the crystal structure of isradipine was converted to an amorphous structure, as confirmed by Fourier transform infrared spectroscopy (FT-IR) and DSC. The photostability of isradipine in the inclusion complex was more stable than pure isradipine after 4 days radiation. By using hypromellose as the hydrophilic sustained release material, the dissolution rate was retarded during 24 h. A combined method of inclusion complex and SR technology showed increased and sustained release profile above that of Dynacirc® SR Cap. 5 mg.

Cyclodextrins possess the ability to increase the apparent solubility and dissolution rate of poorly water soluble drugs. The objectives of the study were to investigate the effect of β-cyclodextrin, hydroxypropyl-β-cyclodextrin and sulfobutyl ether7 β-cyclodextrin on solubility and dissolution rate of docetaxel. Four different methods (physical mixture, kneading, freeze drying and solvent evaporation) were employed for inclusion complexation, at varying drug to cyclodextrin ratios 1:1, 1:2 and 1:4. The inclusion complexes of docetaxel with β-cyclodextrin, hydroxypropyl-β-cyclodextrin and sulfobutyl ether7 β-cyclodextrin at molar ratios 1:1 were characterized by fourier transform infrared spectroscopy (FTIR), X-ray diffractometry (XRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and proton nuclear magnetic resonance (1H NMR). The dissolution profiles of inclusion complexes were compared with pure drug. The results revealed formation of inclusion complexes between drug and β-cyclodextrin, hydroxypropyl-β-cyclodextrin and sulfobutyl ether7 β-cyclodextrin as confirmed by FTIR. 1H NMR revealed inclusion of drug within cyclodextrin cavity with appearance of proton shifts. Drug crystallinity was reduced with physical mixing and kneading method while amorphous form was attained by freeze drying and solvent evaporation method as revealed by XRD. The DSC and TGA confirmed the formation of inclusion complexes with the absence of melting peak of drug. The effect on solubility and dissolution rate of docetaxel was greater with sulfobutyl ether7 β-cyclodextrin than hydroxypropyl-β-cyclodextrin and β-cyclodextrin when prepared with similar methods. Drug to cyclodextrin ratio 1:1 was the optimum ratio to increase the solubility and dissolution of docetaxel irrespective of the method. It is concluded that sulfobutyl ether7 β-cyclodextrin had greater effect on solubility and dissolution rate of docetaxel than β-cyclodextrin and hydroxypropyl-β-cyclodextrin at molar ratios 1:1.

The physicochemical properties and dissolution profile of zaleplon (ZPN) β-cyclodextrin (βCD) inclusion complex were investigated. The phase solubility profile of ZPN with β-cyclodextrin was classified as AL-type. Stability constant with 1:1 molar ratio was calculated from the phase solubility diagram and the aqueous solubility of ZPN was found to be enhanced by 714% (p < 0.001) for β-cyclodextrin. Binary systems of ZPN with βCD were prepared by kneading method. The solid-state properties of complex were characterized by differential scanning calorimetry, Fourier transformation-infrared spectroscopy and powder X-ray diffractometry. It could be concluded that ZPN could form inclusion complex with β-cyclodextrin. The dissolution profile of inclusion complex was determined and compared with those of ZPN alone and its physical mixture. The dissolution rate of ZPN was significantly increased by complexation with βCD, as compared with pure drug and physical mixture.

Piperine, a secondary metabolite compound, has a low solubility in water. In this study, through the formation of multicomponent crystals, glutamic acid is employed as a coformer to enhance the physicochemical characteristics and improve the dissolution rate of piperine. Solvent drop grinding was used to create multicomponent crystals using molar ratios of piperine and glutamic acid of 1:1 (F1), 1:2 (F2), and 2:1 (F3). Characterization of the solids’ properties was performed using X-ray diffraction (XRD) analysis, differential scanning calorimetry (DSC), Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM), and dissolution profiles in accordance with the United States Pharmacopoeia (USP), facilitating a comparison with the physical mixture and pure piperine. XRD results showed a decrease in intensity, and DSC showed a decrease in the endothermic peak transition temperature and significant decreases in enthalpy value. The FT-IR spectra showed a change in wave numbers, and no new functional groups were formed. SEM revealed changes in particle morphology forming new crystal habits. When contrasted with the physical mixture and pure piperine, the dissolution profiles of multicomponent crystals F1, F2, and F3 demonstrate increased dissolution rates, F2 exhibiting a 1.57-fold increase, followed by 1.44-fold for F1 and 1.49-fold for F3. Multicomponent crystals F1, F2, and F3 show a better dissolution profile than the physical mixture and pure piperine, with dissolved substance percentages of 63.60±6.56, 68.59±2.53, 65.25±12.10, 44.91±10.95, and 43.58±8.92, respectively, after 60 minutes at 37±0.5 °C. The multicomponent crystals produced using solvent drop grinding exhibited enhanced physicochemical features and an increased dissolution rate.&nbsp;

Inclusion complexes of β-sitosterol and β-cyclodextrin were prepared by mixing an equimolar ratio of the components in distilled water followed by freeze-drying. The solid state complexes were characterized by differential scanning calorimetry, Fourier-transform infrared spectroscopy, and scanning electron microscopy. Physical mixtures of the two components showed two distinct melting endothermic peaks at 139 and 169 °C. The two melting peaks were attributable to the individual component (i.e., β-sitosterol and β-cyclodextrin). The inclusion complex, however, shows a single sharp melting endothermic peak at 186 °C indicating the formation of a crystalline complex. Scanning electron micrographs show the formation of well-defined needle-like crystals for the inclusion complexes. The crystalline inclusion complexes were readily soluble in water. The inclusion complexes were characterized in the solution state by nuclear magnetic resonance (NMR) spectroscopy. The continuous variation method, using NMR data, suggests the formation of a 1:1 β-sitosterol to β-cyclodextrin inclusion complex. Cross peaks observed in the rotating-frame overhauser effect spectroscopy NMR spectra suggests that both ends of the β-sitosterol i.e., the aliphatic tail and the cyclic head were encapsulated within the β-cyclodextrin cavity. Computational modeling on the inclusion complexes carried out using density functional theory support the conclusions obtained from NMR spectroscopy. The results of the study show that the β-sitosterol and β-cyclodextrin form water soluble inclusion complex.

Objective: The aims of the study to enhance solubility and dissolution of famotidine using natural polymer. Solubility study of a drug is one of the contributing factors of its oral bioavailability. The formulation of poorly soluble drugs for oral delivery presents a challenge to the formulation technologists.&#x0D; Methods: The present study has shown that it is possible to raise the solubility for poorly soluble drugs like famotidine, by preparing solid dispersion using natural water-soluble polymer (xyloglucan and hyaluronic acid) as solubilizer through solvent evaporation method. Physical mixture and solid dispersion of famotidine with xyloglucan (XG) or hyaluronic acid in a ratio of 1:1, 1:2, 1:3 were prepared. Solubility study, drug content, dissolution profile and compatibility study were performed for famotidine in solid dispersions XS1, XS2, XS3, HS4, HS5, HS6 as well as in physical mixtures at a ratio 1:1 for both polymer (XG and hyaluronic acid).&#x0D; Results: It was observed that solid dispersions of each drugs showed an increase in dissolution rate in comparison with its pure drug in the ratio of 1:1 (Drug: carrier). It can be concluded that with the care and proper use of xyloglucan, the solubility of drugs poorly soluble can be improved.&#x0D; The prepared solid dispersion showed improvement of drug solubility in all prepared formulas. The best result was obtained with formula XS1 (famotidine: xyloglucan at ratio 1:1) that showed 26 fold increase in solubility compared to the solubility of pure drug.&#x0D; Conclusion: The natural solid dispersion, increased wettability and reduced crystallinity of the drug which leads to improving solubility and dissolution.

A polyelectrolyte complex (PEC) of sodium alginate with polyethyleneimine, loaded with (5 wt.%) inclusion complex (IC) of sulfobutylether β-cyclodextrin with dexame­thasone, was formed from aqueous solutions. Dexamethasone (DM) is a medical and ve­terinary synthetic glucocorticosteroid with anti-inflammatory and immunosuppressive effects, used in the treatment of various di­seases. The structure of the obtained compositions was analyzed by X-ray diffraction method, confirming the interaction PEC and IC through both Coulombic forces between the ionic groups of PEC and hydrogen bonding involving the proton-donor and proton-acceptor polar groups of PEC and IC. These findings were supported by pyrolytic mass spectrometry data and differential scanning calorimetry. The decrease in PEC swelling degree further supports the above conclusions. Testing the obtained PEC films for drug release using UV spectrophotometry revealed that the release kinetics were nonlinear and partially dependent on the release medium, indicating their potential as materials for creating polymer matrices with prolonged therapeutic effects.

Preparation and characterization of solid dispersions of celecoxib obtained by spray-drying ethanolic suspensions containing PVP-K30 or isomalt

Complexation of celecoxib with β-cyclodextrin and hydroxypropyl-β-cyclodextrin in the presence and absence of polyvinylpyrrolidone and the effect of polyvinylpyrrolidone on the solubilizing efficiency of cyclodextrins and on the dissolution rate of celecoxib from the cyclodextrin complexes were investigated. The phase solubility studies indicated the formation of celecoxib-β-cyclodextrin and celecoxib-hydroxypropyl-β-cyclodextrin inclusion complexes at a 1:1 M ratio in solution, both in the presence and absence of polyvinylpyrrolidone. The complexes formed were quite stable. The solubility and dissolution rate of celecoxib were markedly enhanced by complexation with β-cyclodextrin and hydroxypropyl-β-cyclodextrin. Celecoxib-hydroxypropyl-β-cyclodextrin (1:2) inclusion complex gave a 36.57-fold increase in the dissolution rate of celecoxib. Addition of polyvinylpyrrolidone resulted in higher complexation efficiency and markedly enhanced solubilizing efficiency of β-cyclodextrin and hydroxypropyl-β-cyclodextrin. Solid inclusion complexes of cyclodextrins with polyvinylpyrrolidone gave several times higher rates of dissolution than those of celecoxib and its complexes with cyclodextrins alone.

The purpose of this research was to evaluate the inclusion complex composed of osthole and hydroxypropyl-β-cyclodextrin (HP-β-CD) by using two preparative techniques, neutralization and high-pressure homogenization (HPH) method. The solid complexes were characterized by differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), particle size determination, and dissolution test. The DSC diagrams indicated that the solid complex from the HPH method led to more complete complexation than that of physical mixture and neutralization method. The formation of inclusion complex between drug and cyclodextrin (CD) was verified by FTIR analysis. The smallest mean particle size of solid complex was acquired from the HPH method. The results proved that the rate of drug release for the inclusion complex obtained from the HPH method was much faster than those of neutralization, physical mixture, HP-β-CD and osthole alone.