Dissolution Rate Of Celecoxib Research Articles

Synthesis of Celecoxib-Eutectic Mixture Particles via Supercritical CO2 Process and Celecoxib Immediate Release Tablet Formulation by Quality by Design Approach.

Significant improvements in the wettability and dissolution rate of celecoxib (CEL), a poorly soluble selective cyclooxygenase-2 (COX-2) inhibitor, have been shown by Huyn et al., 2019 by combining the binary pharmaceutical compositions including CEL and one of the two co-formers, adipic acid (ADI) and saccharin (SAC), into eutectic mixtures (EM). Purpose: In this study, we developed a therapeutic eutectic system for CEL which is a promising approach for oral delivery to enhance bioavailability. CEL EM were synthesized by novel techniques including supercritical CO2 techniques and new tablet formulations were purposed. Methods: CEL EM were synthesized by evaporation crystallization method, spray drying, supercritical fluid (SCF) techniques. The CEL EM particles were then characterized by differential scanning calorimetry, powder X-ray diffraction, Fourier-transform infrared spectroscopy, scanning electron microscope, and particle size analysis. Dissolution studies were carried out. With a quality by design approach, a statistical method through design of experiment and data analysis by JMP® (SAS institute) was applied to CEL EM immediate release tablet formulation development. Results: CEL EM produced by spray drying technique, supercritical fluid (SCF) techniques were identified and characterized. The enhancement of dissolution was observed for SCF processed samples. The design space for CEL-ADI EM IR tablet and control limits for individual parameters were determined.

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

Celecoxib is a non-steroidal anti-inflammatory drug (NSAID) used for the treatment of pain and inflammation. Celecoxib is included in class II in the Biopharmaceutis ClassificationAsystem drug (BCS) which has low solubility and high permeability. This study aims to increase the solubility and dissolution rate of celecoxib by characterizing the inclusion complex of celecoxib β-cyclodextrin. Inclusion complexes were prepared by the solvent evaporation method using a water-soluble polymer, β-cyclodextrin. The inclusion complexes were prepared in a 1: 1 ratio between celecoxib and β-cyclodextrins. As a comparison, a physical mixture with the same composition was made. Powder mixtures of physics and inclusion complexes characterized by physicochemical properties include: FT-IR spectroscopy analysis, DSC analysis, assay and dissolution test. The dissolution test was determined by the paddle method. The results of characterization of the inclusion complex using FT-IR spectrophotometry showed a shift in the wave number as well as the physical interaction between celecoxib and β-cyclodextrin. The results of the DSC (Differential Scanning Calorimetry) decreased the enthalpy and melting point between celecoxib, the physical mixture and the inclusion complex. The dissolution test showed an increase in dissolution rate at 60 minutes, namely Celecoxib 55.03%, physical mixture 61.58% and inclusion complex 67.53%.

Transformation of nanoparticles into compacts: A study on PLGA and celecoxib nanoparticles

Oral delivery of nanoparticles possesses many advantages for delivery of active pharmaceutical ingredients (APIs) to the gastrointestinal tract. However, the poor physical stability of nanoparticles in liquid state is often a challenge. Removing water from the nanosuspensions and transforming the nanoparticles into solid particulate matter in the form of, e.g., tablets could be a potential approach to increase the stability of nanoparticles. The aim of this study was to transform nanoparticles into compacts and to investigate the redispersion of nanoparticles from compacts as well as the dissolution behavior of these compacts. DL-lactide-co-glycolide copolymer (PLGA) nanoparticles and celecoxib (CLX) nanoparticles were used as two model nanoparticle systems and fabricated into nano-embedded microparticles (NEMs) and subsequently compressed into compacts. The compacts were evaluated with respect to the redispersibility of the nanoparticles, as well as the dissolution characteristics of CLX. The results showed that the NEMs could be readily compressed into compacts with sufficient mechanical strength. The size of the redispersed PLGA nanoparticles from the compacts using 2-hydroxypropyl-β-cyclodextrin (HPβCD) as stabilizer was comparable to the original nanoparticles. In contrast, the redispersibility of CLX nanoparticles from the compacts was not as effective as for the PLGA nanoparticles evidenced by a significant increase in the size and polydispersity index (PDI) of the redispersed nanoparticles. Nonetheless, an obvious enhancement in dissolution rate of CLX was observed from the compacts with CLX nanoparticles. It is concluded that transforming polymeric nanoparticles into compacts via NEMs provides stabilization and allows redispersion into original nanoparticles. Despite the reduced redispersibility, compacts loaded with nanoparticles exhibited improved dissolution rate compared with the crystalline drug. Loading of nanoparticles into compacts is a promising approach to overcome the poor stability of nanoparticle within oral drug delivery of nanoparticles.

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

Celecoxib (CLX) is an anti-inflammatory drug that is used for acute pain treatment, but it has very low oral bioavailability owing to its poor water solubility. In this study, CLX solid dispersions are prepared by spray-drying using hydrophilic carriers with the aim of improving its apparent solubility and dissolution rate. Blends with different ratios of CLX, isomalt (ISO) and PVP were prepared in ethanol, and solid dispersions were obtained using a spray dryer. The saturation solubility and dissolution kinetics in 0.25% SLS and 0.04 M Na3PO4 containing media were determined. Also, SEM, DSC, XRPD, and stability studies were used to characterize the systems. Physicochemical analysis demonstrated the presence of amorphous CLX in the spray dried samples. The saturation solubility and dissolution rate of CLX from these formulations were higher than those for pure celecoxib and its physical mixtures. Amorphous CLX showed a lower dissolution rate compared to its crystalline form in 0.25% SLS medium, while this tendency was reversed under alkaline conditions. The CLX:PVP:ISO 3:5:2 spray dried sample showed the highest dissolution rate in both media. Exposure of samples to high moisture (75% humidity) recrystallized some of the amorphous CLX. Thus, the results showed that the dissolution rate of CLX was enhanced in 0.25% SLS, whereas a reduction in dissolution rate was observed in 0.04 M Na3PO4.

Anomalous dissolution behavior of celecoxib in PVP/Isomalt solid dispersions prepared using spray drier

Celecoxib is a COX II inhibitor NSAID which is used for joint pains, rheumatoid arthritis and osteoarthritis, however due to its poor water solubility it shows very low oral bioavailability. Using solid dispersion formulations is one of the most promising strategies to increase solubility of poorly water soluble drugs. The purpose of this study is dissolution enhancement of celecoxib by preparation of solid dispersions via spray drying technique using PVP and Isomalt as hydrophilic carriers.Different ratios of celecoxib, Isomalt and PVP K30 (7:3:0, 5:5:0, 3:7:0, 1:9:0 and 3:5:2, 3:2:5) were prepared from 2% hydroalcoholic solutions (70:30 ethanol:water) using spray drier. Particle size analyzing, saturation solubility, SEM, DSC, FT-IR, XRPD and dissolution studies in 0.25% SDS and 0.04M Na3HPO4 mediums were performed. Stability of samples was also studied after a week and a month storage at 75% humidity condition.The results showed that the saturation solubility of celecoxib in solid dispersion samples is 20–30 folds higher than raw celecoxib. Similar results have been shown for dissolution studies. Solid state analyses showed glass solution state of celecoxib in PVP/Isomalt matrixes. FTIR studies exhibited the formation of hydrogen bonding between celecoxib and PVP in these samples. Spray dried celecoxib (amorphous celecoxib) without usage of carrier showed lower dissolution rate compare to its crystalline state (in 0.25% SDS dissolution medium) whilst these results is vise versa in Na3PO4 dissolution medium. Interestingly almost all samples exhibited higher dissolution rate (in 0.25% SDS) after storage in 75% humidity. XRPD analysis demonstrated the crystallization of amorphous celecoxib after 1month storage.In general using PVP K30 and Isomalt as hydrophilic carriers could increase solubility and dissolution rate of celecoxib in solid dispersion formulations.

Experimental Design to Predict Process Variables in the Microcrystals of Celecoxib for Dissolution Rate Enhancement Using Response Surface Methodology.

The purpose of the present investigation was to increase the solubility and dissolution rate of celecoxib (CLX) by preparing microcrystals of drug by solvent change precipitation. This procedure was optimized in order to obtain stable and homogeneous particles with a small particle size, high yield and fast dissolution rate. CLX agglomerates were prepared with brij35 (stabilizer agent) using acetone as solvent, water as non-solvent, respectively. The agglomerates were characterized by DSC, XRD, FTIR studies. A full-factorial design was employed to study the effect of independent variables, the amounts of stirring rate (X1), volume of organic solvent (X2), volume of aqueous solvent (X3), time of stirring (X4), concentration of Brij (X5), concentration of Tween 80 (X6), concentration of HPMC (X7) on dependent variables, particle size (PS), drug content (DC), drug released after 15 min (Q15), crystal yield (CY), Gibbs free energy change (ΔG°tr), antalpy change (ΔH) and saturated solubility (Ss). The DSC and FTIR results indicated the absence of any interactions between drug and stabilizers. These studies showed a decrease in crystalinity in agglomerates. The crystals exhibited significantly improved micromeritic properties compared to pure drug. The drug content and crystal yield were in the range of 32.84-48.22% and 64.55-83.33% with all formulations, respectively. The solubility and drug release rates increased with an increase in concentration of stabilizer. The results show that microcrystals of the drug in stabilizer considerably enhanced the dissolution rate.

Solubility enhancement of celecoxib using solidified Tween 80 for the formulation of tablet dosage forms

Celecoxib is a non-steroidal, anti-inflammatory drug used in the treatment of pain and inflammation associated with rheumatoid arthritis, and several other inflammatory disorders. It is a class II compound according to the Biopharmaceutics Classification System owing to its low water solubility and high membrane permeability. The objective of this study was to improve the solubility and dissolution rate of celecoxib using solid surfactant technology that might be useful in developing solid dosage forms. Solid surfactant was developed by mixing and grinding together a liquid surfactant (Tween 80) with various inorganic carriers like Fujicalin® (Dibasic Calcium Phosphate Anhydrous), Pineflow® (Porous-structured Maltodextrin), Neusilin® (Magnesium Alumino metasilicate) and Aerosil® (Colloidal Silicon dioxide) in a mortar and pestle in different ratios of liquid surfactant and the carrier to obtain solid surfactants. The celecoxib tablets prepared with solid surfactants were then evaluated for their solubility and dissolution properties. Among the fillers used, Fujicalin showed the highest solubilization capacity for celecoxib. The dissolution behaviors of various tablets prepared with solidified surfactants were compared to those of conventional celecoxib tablets in a simulated gastric fluid. Celecoxib tablets prepared using solidified surfactants showed improved dissolution behaviors when compared to the conventional counterparts. Fujicalin solidified Tween 80 was further analyzed by powder X-ray diffraction analysis, differential scanning calorimetry thermographs and reverse phase high performance liquid chromatography.

Systematic in vitro and in vivo study on porous silicon to improve the oral bioavailability of celecoxib

Mesoporous materials are promising candidates for improving dissolution rate of poorly water-soluble drugs in vitro and their bioavailability in vivo. In the present study, sixteen batches of celecoxib-loaded PSi particles with pore sizes ranging from 17 to 58 nm and celecoxib content from 5 to 36 w-% were prepared and a detailed physicochemical characterization of the drug was performed by several methods. Interaction between co-culture of Caco-2/HT29-MTX cells and unloaded PSi particles was tested in toxicity assays, and increased toxicity for particles with large pore size was observed. Dissolution rate of celecoxib was improved in vitro by lowering the drug loading degree which hindered the recrystallization of celecoxib on the external surface of the particles. The fastest permeation of loaded celecoxib through the co-culture monolayer as well as the highest bioavailability in rats was observed with the particles with small pore size and low loading degree. New insights were obtained on how various parameters of the mesoporous delivery system affect the state of the drug inside the pores and its release in vitro and in vivo.

The mechanism for increasing the oral bioavailability of poorly water-soluble drugs using uniform mesoporous carbon spheres as a carrier

Uniform mesoporous carbon spheres (UMCS) were used as a carrier to improve the bioavailability of the model drug, celecoxib (CEL). Furthermore, we investigated the mechanism responsible for the improved bioavailability of CEL. The association, adhesion and uptake of UMCS by intestinal epithelial cells were studied by transmission electron microscopy (TEM), fluorescence-activated cell sorting (FACS) and laser confocal scanning microscopy (LCSM). UMCS was found to promote cellular uptake of CEL. Drug transport in Caco-2 cell monolayers proved that UMCS can significantly reduce the rate of drug efflux and improve CEL permeability. The dissolution rate of CEL from drug-loaded samples was markedly improved compared with pure crystalline CEL; moreover, oral bioavailability of CEL loaded into UMCS was also markedly improved compared with that of commercially available capsules. UMCS indicates the advantages and potential of this method to achieve improved oral absorption by increasing the dissolution rate, cellular uptake and permeability of the drug.

Mesoporous carbon with spherical pores as a carrier for celecoxib with needle-like crystallinity: Improve dissolution rate and bioavailability

The purposes of this investigation are to design mesoporous carbon (MC) with spherical pore channels and incorporate CEL to it for changing its needlelike crystal form and improving its dissolution and bioavailability. A series of solid-state characterization methods, such as SEM, TEM, DSC and XRD, were employed to systematically investigate the existing status of celecoxib (CEL) within the pore channels of MC. The pore size, pore volume and surface area of samples were characterized by nitrogen physical absorption. Gastric mucosa irritation test was carried out to evaluate the safety of mesoporous carbon as a drug carrier. Dissolution tests and in vivo pharmacokinetic studies were conducted to confirm the improvement in drug dissolution kinetics and oral bioavailability. Uptake experiments were conducted to investigate the mechanism of the improved oral bioavailability. The results of solid state characterization showed that MC was prepared successfully and CEL was incorporated into the mesoporous channels of the MC. The crystallinity of CEL in MC was affected by different loading methods, which involve evaporation method and melting method. The dissolution rate of CEL from MC was found to be significantly higher than that of pure CEL, which attributed to reduced crystallinity of CEL. The gastric mucosa irritation test indicated that the MC caused no harm to the stomach and produced a protective effect on the gastric mucosa. Uptake experiments indicated that MC enhanced the amount of CEL absorbed by Caco-2 cells. Moreover, oral bioavailability of CEL loaded within the MC was approximately 1.59-fold greater than that of commercial CEL. In conclusion, MC was a safe carrier to load water insoluble drug by controlling the crystallinity or crystal form with improvement in drug dissolution kinetics and oral bioavailability.

Exploitation of 3D face-centered cubic mesoporous silica as a carrier for a poorly water soluble drug: Influence of pore size on release rate

The purposes of the present work were to explore the potential application of 3D face-centered cubic mesoporous silica (FMS) with pore size of 16.0nm as a delivery system for poorly soluble drugs and investigate the effect of pore size on the dissolution rate. FMS with different pore sizes (16.0, 6.9 and 3.7nm) was successfully synthesized by using Pluronic block co-polymer F127 as a template and adjusting the reaction temperatures. Celecoxib (CEL), which is a BCS class II drug, was used as a model drug and loaded into FMS with different pore sizes by the solvent deposition method at a drug–silica ratio of 1:4. Characterization using scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transformation infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), nitrogen adsorption, X-ray diffraction (XRD), and differential scanning calorimetry (DSC) was used to systematically investigate the drug loading process.The results obtained showed that CEL was in a non-crystalline state after incorporation of CEL into the pores of FMS-15 with pore size of 16.0nm. In vitro dissolution was carried out to demonstrate the effects of FMS with different pore sizes on the release of CEL. The results obtained indicated that the dissolution rate of CEL from FMS-15 was significantly enhanced compared with pure CEL. This could be explained by supposing that CEL encountered less diffusion resistance and its crystallinity decreased due to the large pore size of 16.0nm and the nanopore channels of FMS-15. Moreover, drug loading and pore size both play an important role in enhancing the dissolution properties for the poorly water-soluble drugs. As the pore size between 3.7 and 16.0nm increased, the dissolution rate of CEL from FMS gradually increased.

Ternary Solid Dispersions of Celecoxib: from Physical Characterization to Dissolution Enhancement

The poor solubility and wettability of a non steroidal anti inflammatory drug, celecoxib leads to poor dissolution and hence, low bioavailability after oral administration. The objective of the present study was to formulate solid dispersions of celecoxib, with water soluble polymers poly vinyl pyrrolidine (PVP K30), poly ethylene glycol (PEG 6000), hydroxypropyl methylcellulose 5cps (HPMC) and a super disintegrant namely pregelatinised starch (PGS) by common solvent and solvent evaporation methods. Solid Dispersions prepared were evaluated for dissolution rate and dissolution efficiency in comparison to the corresponding pure drug. Solid dispersions of celecoxib showed a marked enhancement in dissolution rate and dissolution efficiency. The increasing order of dissolution rate of solid dispersions of celecoxib with various polymers was HPMC > PVP > PEG. Solid dispersions at 2:2:6 ratio of C: HPMC: PGS, a 53.57 fold increase in the dissolution rate of celecoxib was observed. Solid dispersions were characterized by infrared spectroscopy (IR), differential scanning calorimetry (DSC) and X-ray diffractogram (XRD). Solid dispersions in combined carriers gave much higher rates of dissolution than super disintegrant PGS alone. Super disintegrant PGS alone or in combination with hydrophilic polymers could be used to enhance the dissolution rate of poorly soluble drug celecoxib. Finally, in-vitro dissolution studies showed that celecoxib release was greatly improved by formation of solid dispersion.

IMPROVEMENT THE RELEASE AND AVAIALBILITY OF CELECOXIB CO-ADSORBATE FROM FLOATING CAPSULES

Celecoxib is a selective COX-2 inhibitor non-steroidal anti-inflammatory drug (NSAID) used in the treatment of osteoarthritis, rheumatoid arthritis, and to reduce numbers of colon and rectum polyps in patients with familial adenomatous polyposis. Celecoxib is practically inslouble in GIT pH. Consequently, it suffers from low and variable bioavailability following oral administration of solutions (64-88%) and capsules (20-40%) In the present study, gastroretentive controlled release single-unit floating capsules of Celecoxib were designed and evaluated. Various grades of low and high viscosity polymers of HPMC 4000 and 15.000 cps and NaCMC were used for formulation of Celecoxib capsules. For the purpose of enhancing the poor dissolution rate of Celecoxib, co-adsorption with Tween 80 onto surface of Florite® was investigated in this study. Thus, controlled release limited by drug solubility was percluded and delivery of active material was controlled by the formulation. In the present study conventional capsules containing Celecoxib using HPMC and NaCMC were developed and evaluated. Floating capsules containing Celecoxib, co-adsorption with Tween 80 onto surface of Florite and Aerosil 200 in different ratios were also formulated and investigated for the release of the drug from these capsules. The results obtained of this study showed that Celecoxib capsules containing HPMC 15000cps as a swelling matrix has a good floating behaviour and retarding effect on the drug release. Also, different concentrations of sodium bicarbonate confirmed and maintained the floating properties of the prepared formulations without affecting the drug release. From DSC and X-ray diffraction studies it was found that crystalline Celecoxib was converted into the amorphous form in the presence of Florite® at (1:5 w/w drug: carrier ratio) in the adsorbate and co-adsorbate with Tween 80. The loaded and ground mixtures of Celecoxib with either Florite® or Aerosil 200 increased the dissolution rate of the drug. Furthermore, co-adsorbate of the drug with Florite® and Tween 80 at these ratios of (1:5:3 and 1:5:5) gave the highest percentage released of Celecoxib (reached about 100% at 30 and 45 min., respectively).

Inclusion of celecoxib into fibrous ordered mesoporous carbon for enhanced oral bioavailability and reduced gastric irritancy

Fibrous ordered mesoporous carbon (FOMC) was developed as a new drug delivery system for loading an insoluble drug, designed to be orally administered, and then to enhance the drug loading capacity, improve the dissolution rate, enhance the oral bioavailability and reduce the gastric damage. Celecoxib (CEL) was chosen as a model drug. The nanostructures and effect of different pore sizes (4.4–7.0nm) on drug loading and release properties were studied. The results showed that FOMC has a high drug loading capacity (0.599g/g, drug weight/carrier weight) and the dissolution rate of CEL from FOMC was much faster than pure crystalline CEL using buffer (pH 6.8) as a dissolution medium. Moreover, the oral bioavailability of CEL loaded into FOMC was significantly improved compared with that of CEL capsules and the gastric damage caused by CEL which was loaded in FOMC was also reduced, demonstrating the protective effect of FOMC.

Employment of Combined Carriers for Dissolution Enhancement of Celecoxib

Solid Dispersions of celecoxib (C) with water soluble polymers polyvinylpyrrolidine (PVP), polyethylene glycol (PEG), hydroxylpropylmethylcellulose (HPMC) and a superdisintegrant namely microcrystalline cellulose (MCC) were prepared by common solvent and solvent evaporation methods employing methanol as solvent. Solid Dispersions prepared were evaluated for dissolution rate and dissolution efficiency in comparison to the corresponding pure drug. Solid dispersions of celecoxib showed a marked enhancement in dissolution rate and dissolution efficiency. Solid dispersions of C:HPMC:MCC at 2:2:10 ratio showed 7.71 fold increase in the dissolution rate of celecoxib. Solid dispersions in combined carriers gave much higher rates of dissolution than MCC alone. MCC alone or in combination with hydrophilic polymers could be used to enhance the dissolution rate of poorly soluble drug celecoxib.

The use of spray-drying to enhance celecoxib solubility

The present research investigates the enhancement of the dissolution rate of celecoxib by using spray-drying to prepare a solid dispersion with various polymers, namely Kollicoat IR® (Kollicoat), polyvinyl alcohol (PVA) 22000, or polyethylene glycol 6000 (PEG). The investigated drug-to-polymer mass ratios were 1:1, 1:2, and 1:4 by weight. Hydroalcoholic or methylene chloride solvent systems were used. The obtained yields ranged from 65% to 78%, whereas the entrapment efficiencies were between 68% and 82%. The results revealed an increase in the dissolution rate of the prepared particles up to 200% within 20 min. The prepared particles were investigated using differential scanning calorimetry, scanning electron microscopy, X-ray diffraction, and Fourier transform infrared spectroscopy. The increased dissolution rate was attributed to hydrogen bond formation between celecoxib and each polymer together with the reduced size of the formed particles offering a greater overall surface area. It was concluded that spray-drying may be considered a successful one-step technique to improve the dissolution rate of celecoxib when using Kollicoat, PVA, or PEG as the carrier polymer.

Preparation and evaluation of celecoxib-loaded microcapsules with self-microemulsifying core

The purpose of this study was to prepare alginate microcapsules with a self-microemulsifying system (SMES) containing celecoxib in the core. An Inotech IE-50 R encapsulator equipped with a concentric nozzle was used to prepare the microcapsules. The encapsulated SMES was shown to increase celecoxib solubility over that of the pure drug more than 400-fold. Microcapsules prepared with a high SMES:celecoxib ratio exhibited distinct core vesicles containing liquid SMES. By modifying the SMES and including an additional chitosan coating, drug loading in the range from 12–40% could be achieved with the degree of encapsulation ranging from 60–82%. Alginate microcapsules loaded with SMES and celecoxib showed increased dissolution rate of celecoxib over that of alginate microcapsules loaded with celecoxib or of the celecoxib alone. Compared to the previous report, drug loading capacity was significantly improved, enabling the formulation of dosage forms which are of suitable size for peroral application.

Formulation, Characterization, and Optimization of Fast-Dissolve Tablets Containing Celecoxib Solid Dispersion

Celecoxib is a poorly water-soluble drug, and bioavailability from its crystalline form is very low. The purpose of the present investigation was to increase the solubility and dissolution rate of celecoxib by preparing a solid dispersion with polyvinyl pyrrolidone K30 (PVP-K30) using a solvent-evaporation method. The dissolution profiles of developed formulations in distilled water containing 1% SLS were studied. Drug–polymer interactions were investigated using differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR). For the preparation of celecoxib fast-dissolve tablets, a 1:2 solid dispersion with PVP-K30 was used with croscarmellose sodium as a superdisintegrant and Pearlitol 200SD (pearlitol) as a pore-forming agent. A 3 2 full-factorial design was employed to study the effect of independent variables, the amounts of croscarmellose sodium (X1) and pearlitol (X2), on dependent variables, disintegration time, percentage friability, wettability, and percentage of drug released after 20 min (Q20). The results show that a dispersion of the drug in polymer considerably enhanced the dissolution rate. The drug-to-carrier ratio is the controlling factor for dissolution improvement. FTIR spectra show no chemical incompatibility between the drug and PVP-K30. FTIR and DSC data indicate that celecoxib was in the amorphous form, which explains the faster dissolution rate of the drug from its solid dispersions. Concerning the optimization study, multiple regression analysis reveals that an optimum concentration of croscarmellose sodium and a higher percentage of pearlitol are required for obtaining rapidly disintegrating tablets.

Physicochemical characterization and in vitro dissolution behaviour of celecoxib-β-cyclodextrin inclusion complexes

In this study, attempts were made to investigate the effects of beta-cyclodextrin (beta-CD) on the aqueous solubility and dissolution rate of celecoxib. Inclusion complexes were prepared by the kneading method and characterized by SEM, NMR, IR, DSC, and X-ray powder diffraction. Dissolution rate of the complexes was significantly greater than that of the corresponding physical mixtures and pure drug, indicating that the formation of inclusion complex increased the solubility of the poorly soluble drug celecoxib.

Influence of hydrophilic polymers on celecoxib complexation with hydroxypropyl beta-cyclodextrin.

Complexation of celecoxib with hydroxypropyl beta-cyclodextrin (HPbetaCD) in the presence and absence of 3 hydrophilic polymers-polyvinyl pyrrolidone (PVP), hydroxypropyl methylcellulose (HPMC), and polyethylene glycol (PEG)-was investigated with an objective of evaluating the effect of hydrophilic polymers on the complexation and solubilizing efficiencies of HPbetaCD and on the dissolution rate of celecoxib from the HPbetaCD complexes. The phase solubility studies indicated the formation of celecoxib-HPbetaCD inclusion complexes at a 1:1M ratio in solution in both the presence and the absence of hydrophilic polymers. The complexes formed were quite stable. Addition of hydrophilic polymers markedly enhanced the complexation and solubilizing efficiencies of HPbetaCD. Solid inclusion complexes of celecoxib-HPbetaCD were prepared in 1:1 and 1:2 ratios by the kneading method, with and without the addition of hydrophilic polymers. The solubility and dissolution rate of celecoxib were significantly improved by complexation with HPbetaCD. The celecoxib-HPbetaCD (1:2) inclusion complex yielded a 36.57-fold increase in the dissolution rate of celecoxib. The addition of hydrophilic polymers also markedly enhanced the dissolution rate of celecoxib from HPbetaCD complexes: a 72.60-, 61.25-, and 39.15-fold increase was observed with PVP, HPMC, and PEG, respectively. Differential scanning calorimetry and X-ray diffractometry indicated stronger drug amorphization and entrapment in HPbetaCD because of the combined action of HPbetaCD and the hydrophilic polymers.