methylcellulose and betadex

This study focuses on the development of amlodipine bilayer buccal tablets of hydroxypropyl methylcellulose (HPMC) matrix system containing polyacrylate polymer (Carbopol(®))/β-cyclodextrin as the drug layer and ethylcellulose as the non-swellable backing layer, and their biointerfacial phenomena.. Tablets were evaluated for swelling, erosion and mucoadhesion using buccal mucosal tissue ex vivo. In vitro drug release and ex vivo drug transport across mucosal tissue were also performed in phosphate buffer (pH 6.8). The relationship of swelling with buccoadhesion and buccal permeation of various bilayer tablet formulations containing HPMC alone and in combination with Carbopol or drug-β-cyclodextrin complex has been prepared.. Overall buccoadhesion of the tablet with combination of HPMC and Carbopol was increased significantly compared with that of HPMC alone. Presence of cyclodextrin did not change bioadhesion force and swelling behavior significantly. Ex vivo permeation was increased with the increase of HPMC proportion in other formulations as observed in in vitro dissolution.. Drug-cyclodextrin complexes in the tablet improved permeation due to its improved dissolution at the site of biointerface of tablet and buccomucosa. Correlations of ex vivo and in vitro data have been established to predict the buccomucosal permeation from the swelling index or drug release alone.

Topics: Acrylic Resins; Administration, Buccal; Amlodipine; Animals; beta-Cyclodextrins; Biological Transport; Calcium Channel Blockers; Calorimetry, Differential Scanning; Chemistry, Pharmaceutical; Drug Delivery Systems; Lactose; Male; Methylcellulose; Mouth Mucosa; Sheep; Spectroscopy, Fourier Transform Infrared; Tablets

The effect of hydroxypropyl methylcellulose (HPMC) concentration on β-cyclodextrin (β-CD) solubilization of norfloxacin was examined. The solubility and dissolution of norfloxacin/β-CD and norfloxacin/β-CD/HPMC inclusion complexes were studied. The presence of β-CD increased significantly the solubility and dissolution of norfloxacin. The addition of HPMC until 5% (w/w) improved the solubilization of norfloxacin but further addition above 5% (w/w), decreased norfloxacin solubilization. Fourier transformed Infra-red (FTIR) showed that norfloxacin was successfully included into β-CD. Differential scanning calorimetry (DSC) showed that the norfloxacin endothermic peak shifted to a lower temperature with reduced intensity indicating the formation of inclusion complex. The addition of HPMC reduced further the intensity of norfloxacin endothermic peak. Most of the sharp and intense peaks of norfloxacin disappeared with the addition of HPMC. In conclusion, the concentration of hydrophilic polymer used to enhance β-CD solubilization of poorly soluble drugs is very critical.

Topics: beta-Cyclodextrins; Hypromellose Derivatives; Methylcellulose; Norfloxacin; Solubility; Solvents; Volatilization

Supramolecular polymer micelles (SMPMs) were constructed from natural and natural-derived polymers: β-cyclodextrin (β-CD)/maleic anhydride modified β-cyclodextrin (MAh-β-CD) and methylcellulose (MC) in aqueous solution by one-pot self-assembly procedure, in which, β-CD and MAh-β-CD inclusion complexes were used as the hydrophilic shell and the free MC as the core. The shapes of the SMPMs were regular spheres with diameters of 25±5 nm. The critical micelle concentrations, calculated from steady-state fluorescence emission spectra, were around 15.13 and 20.89 mg/L for MC/β-CD and MC/MAh-β-CD SMPMs, respectively. The in vitro drug release behaviors of the micelles were studied using prednisone acetate as a model drug, and the results showed that the MC/MAh-β-CD micelle had a drug-enrichment core and excellent drug released behaviors with a sustaining release time of 700 h.

Topics: beta-Cyclodextrins; Biopolymers; Methylcellulose; Micelles; X-Ray Diffraction

Meloxicam (an oxicam derivative), a relatively new cyclo-oxygenase inhibitor, is a member of enolic acid group of non-steroidal anti-inflammatory drugs. It is generally used in the treatment of rheumatoid arthritis, osteoarthritis and other joint pains. Meloxicam is practically insoluble in water (8µg/ml), which directly influences the C(max), T(max), as well as the bioavailability of the drug. In the present study, an attempt has been made to improve the dissolution of Meloxicam by preparation of its solid dispersion using β-cyclodextrin blended with various water soluble polymer carriers i.e., HPMC (methocel IH), methylcellulose (400cps), PVP K30, HPMC (K(4)M), HPMC (50cps). It is reported that when small amount of water soluble polymer is added to β-cyclodextrin, its nature of solubilization significantly increases due to increase in the apparent complex stability constant. Phase solubility studies were carried out to evaluate the solubilizing power of β-cyclodextrin along with various water soluble polymers. The solid dispersion was prepared and formulated into tablets and suspension, which were evaluated on the basis of various official tests. All the studies suggest that formulations of Meloxicam utilizing solid dispersion technique significantly enhances solubility (90 µg/ml) of the drug and results in superior formulations of the drug by using β-cyclodextrin blended with 0.12% w/w HPMC (Methocel IH). Ternary complexation is a valuable tool for solubility enhancement of drugs.

Topics: beta-Cyclodextrins; Biological Availability; Cyclooxygenase Inhibitors; Excipients; Hydrogen-Ion Concentration; Hypromellose Derivatives; Meloxicam; Methylcellulose; Polyvinyls; Pyrrolidines; Solubility; Solvents; Tablets; Thiazines; Thiazoles

The objective of this study was to investigate the effect of multicomponent complexation (MCC) of vinpocetine (VP), a poorly soluble base-type drug, with beta-cyclodextrin (betaCD), sulfobutylether beta-cyclodextrin (SBEbetaCD), tartaric acid (TA), polyvinylpyrrolidone (PVP) and hydroxypropylmethylcellulose (HPMC), on the design of controlled release hydrophilic HPMC tablets and to evaluate their in vitro release profiles by a pH gradient method. Multicomponent complexation led to enhanced dissolution properties of VP both in simulated gastric and intestinal fluids, and became possible the development of HPMC tablet formulations with more independent pH dissolution profiles. Drug release process was investigated experimentally using USP apparatus 3 and by means of model-independent parameters. Responses studied included similarity of dissolution profiles, time for 60% of the drug to dissolve (T(60%)), percent of VP released after 7 h (PD(7 h)) and the dissolution efficiency parameter at 12 h (DE(12 h)). Influence of multicomponent complexation was proved to increase the release of VP from HPMC tablets and superior PD(7 h) and DE(12 h) values were obtained in formulations containing VP-CD-TA complexes. Results supported the use of HPMC matrices to provide a useful tool in retarding the release of VP and that dissolution characteristics of the drug may be modulated by multicomponent complexation in these delivery systems, suggesting an improvement on VP bioavailability.

Topics: beta-Cyclodextrins; Body Fluids; Drug Compounding; Gastric Mucosa; Humans; Hydrogen-Ion Concentration; Hypromellose Derivatives; Intestinal Mucosa; Kinetics; Methylcellulose; Models, Biological; Solubility; Tablets, Enteric-Coated; Tartrates; Vinca Alkaloids

In an effort to improve the solubility of the insoluble drug scutellarin, a novel complexation of scutellarin with beta-cyclodextrin (beta-CD) was studied. Tetracomponent freeze-dried complex was prepared with scutellarin, beta-CD, Hydroxypropyl Methylcellulose (HPMC), and triethanolamine. To confirm complex formation, complex was characterized by Fourier transform infrared spectroscopy (FT-IR), powder X-ray diffraction, and differential scanning calorimetry (DSC). Phase-solubility analysis suggested the soluble complexes having 1:1 stoichiometry. The beta-CD solubilization of scutellarin could be improved significantly by combining water-soluble polymer and pH adjuster. Comparing the binary, ternary solid systems with tetrary systems, tetracomponent freeze-dried complex showed the best effect of solubilization. A maximal solubility of scutellarin (23.65 mg/ml) was achieved with tetracomponent freeze-dried complex, up to 148-fold increase over scutellarin solubility in water, and the solubility of scutellarin is 15.35 microg/ml (up to 6-fold) in simulated gastric fluid.

Topics: Apigenin; beta-Cyclodextrins; Calorimetry, Differential Scanning; Chemistry, Pharmaceutical; Ethanolamines; Freeze Drying; Gastric Juice; Glucuronates; Hypromellose Derivatives; Methylcellulose; Polyvinyls; Powder Diffraction; Pyrrolidines; Solubility; Spectroscopy, Fourier Transform Infrared; Water; X-Ray Diffraction

The bioavailability of a carbamazepine:beta-cyclodextrin (CBZ:betaCD) complex from hydroxypropylmethylcellulose (HPMC) matrix tablets was evaluated in beagle dogs. A solubility study demonstrated the improvement of CBZ aqueous solubility by adding increasing amounts of betaCD. The 1:1 CBZ:betaCD molar ratio was chosen to produce the complex, which was obtained by spray-drying. Matrix tablets were prepared by direct compressing either a CBZ:betaCD complex or a physical mixture of both substances with HPMC. Both matrix formulations displayed a controlled-release profile when compared to the reference formulation (Tegretol CR 200). CBZ presented a significantly higher bioavailability from matrix tablets containing the CBZ:betaCD complex than that obtained from Tegretol CR 200). Although a high inter-subject variability was observed, the results pointed to the feasibility of using betaCD in order to modulate CBZ release and absorption, as well as to reduce the drug dosage maintaining the same plasma levels.

Topics: Animals; beta-Cyclodextrins; Biological Availability; Carbamazepine; Chemistry, Pharmaceutical; Dogs; Drug Evaluation, Preclinical; Female; Hypromellose Derivatives; Methylcellulose; Tablets

The release kinetics of carbamazepine (CBZ) either complexed or physically mixed with beta-cyclodextrin (betaCD) from hydroxypropylmethylcellulose (HPMC) matrix tablets was investigated using different mathematical equations. The model-dependent approach was compared to the utilization of fit factors. Notwithstanding difference (f1) and similarity (f2) factors allowed the differentiation of the formulations containing CBZ complexed with betaCD from the one containing a simple physical mixture of CBZ and betaCD. The Weibull model was more useful for comparing the release profiles. Weibull parameters were more sensitive to the differences between the two release kinetic data.

Topics: beta-Cyclodextrins; Carbamazepine; Chemistry, Pharmaceutical; Drug Evaluation, Preclinical; Hypromellose Derivatives; Methylcellulose; Models, Theoretical; Tablets, Enteric-Coated

The in vitro release profiles of carbamazepine and beta-cyclodextrin either complexed or simply mixed and subsequently incorporated in hydrophilic matrix tablets containing 15 or 30% hydroxypropyl methylcellulose were evaluated. Solubility studies revealed a linear relationship between the increase in carbamazepine solubility and the increase in beta-cyclodextrin concentration. Drying methods (spray-drying and freeze-drying) were used to obtain carbamazepine/beta-cyclodextrin solid complexes in order to prepare tablets. The results demonstrated that matrix tablets containing carbamazepine/beta-cyclodextrin solid complexes displayed faster carbamazepine and beta-cyclodextrin release compared to that containing simple physical mixture. Gelling and matrix formation was impaired in formulation containing 15% hydroxypropyl methylcellulose and spray-dried complex. The comparison of spray-drying and freeze-drying revealed no significant influence of both drying methods on carbamazepine and beta-cyclodextrin dissolution rate when carbamazepine/beta-cyclodextrin complexes were incorporated in 30% hydroxypropyl methylcellulose matrix tablets. The results point to the possibility of modulating carbamazepine release using a hydroxypropyl methylcellulose matrix associated to the drug complexed with beta-cyclodextrin.

Topics: Anticonvulsants; beta-Cyclodextrins; Calorimetry, Differential Scanning; Carbamazepine; Chemistry, Pharmaceutical; Chromatography, High Pressure Liquid; Cyclodextrins; Excipients; Hypromellose Derivatives; Methylcellulose; Microscopy, Electron, Scanning; Solubility; Spectrophotometry, Infrared; Tablets

The aim of this study was to compare carbamazepine (CBZ) solid dispersions prepared by spray-drying of aqueous dispersions with the corresponding physical mixtures. The influence of the association of beta-cyclodextrin (betaCD) and hydroxypropyl methylcellulose (HPMC) on the CBZ dissolution profile of the preparations was investigated. Results demonstrated that CBZ release from solid dispersions is dependent on the ratio of betaCD and HPMC. The spray-drying process confers better homogeneity to CBZ polymeric dispersions than the physical mixture process. In summary, we demonstrated the feasibility of obtaining a homogeneous polymeric solid dispersion of CBZ from an aqueous media by spray-drying and a clear influence of the betaCD:HPMC ratio on the release profile of CBZ.

Topics: Anticonvulsants; beta-Cyclodextrins; Carbamazepine; Chemistry, Pharmaceutical; Cyclodextrins; Dosage Forms; Drug Compounding; Excipients; Hypromellose Derivatives; Methylcellulose; Solubility; Technology, Pharmaceutical; Time Factors

Solid dispersions containing carbamazepine (CBZ) associated with beta-cyclodextrin (betaCD) and/or hydroxypropyl methylcellulose were prepared by two different methods, spray-drying or physical mixture, and characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), infrared (IR) spectroscopy, and x-ray powder diffraction analysis (XRPD) studies. Scanning electron microscopy pictures showed that spray-drying produced a mixture of hollow, spherical, and partially shrunken microparticles of homogeneous materials, whereas the physical mixtures yielded heterogeneous systems in which all individual components could be identified. Thermal and IR analyses suggest the existence of a strong interaction between CBZ and excipients in spray-dried solid dispersions, but no CBZ polymorphic transition was detected by either IR spectroscopy or XRPD analysis after the spray-drying process.

Topics: Anticonvulsants; beta-Cyclodextrins; Calorimetry, Differential Scanning; Carbamazepine; Chemistry, Pharmaceutical; Cyclodextrins; Dosage Forms; Drug Compounding; Excipients; Hypromellose Derivatives; Methylcellulose; Microscopy, Electron, Scanning; Spectrophotometry, Infrared; Technology, Pharmaceutical; X-Ray Diffraction

A modified release bi-layered tablet of melatonin incorporating a fast release fraction consisting of melatonin-beta-cyclodextrin inclusion complex and a slow release fraction containing melatonin in HPMC K15M and Carbopol 971 P matrices was prepared. The formulation developed showed an initial burst followed by a near zero order release pattern for a period of 8 h. The drug content, physical characteristics and the release profile were unaffected after 3 months of an accelerated stability study at 40 degrees C and 75% relative humidity.

Topics: Acrylic Resins; Antioxidants; beta-Cyclodextrins; Calorimetry, Differential Scanning; Chemistry, Pharmaceutical; Cyclodextrins; Delayed-Action Preparations; Drug Stability; Excipients; Kinetics; Lactose; Melatonin; Methylcellulose; Microscopy, Electron, Scanning; Oxazines; Polyvinyls; Solubility; Spectroscopy, Fourier Transform Infrared; Tablets

This study was undertaken with an objective to increase the dissolution rate and bioavailability of a poorly water soluble drug gliclazide (Gz) by complexation with beta-cyclodextrin (CD) in the presence of hydroxypropylmethylcellulose (HPMC). Phase solubility studies of Gz were performed in aqueous solutions of different concentrations of CD alone and in the presence of some water soluble polymers. Gz-CD complexes were prepared in 1:1 and 1:2 drug:CD molar ratios by autoclaving, neutralization and kneading methods. The complexes were also prepared in the presence of 0.05% w/w HPMC. Physical mixtures of Gz-CD in 1:1 and 1:2 molar ratios were also prepared. Complexes and physical mixtures were characterized and evaluated for in vitro dissolution in distilled water and hypoglycemic activity in rats. CD enhanced the dissolution of Gz to 1.5 to 2.0 fold. Presence of water soluble polymer HPMC in Gz-CD complexes further enhanced the rate and extent of drug dissolution to 2.5 fold. Gz-CD-HPMC complexes were found to be more promising as they produced not only an early onset but also more intense hypoglycemic effect as compared to pure drug powder and commercial tablets.

Topics: Animals; Area Under Curve; beta-Cyclodextrins; Biological Availability; Blood Glucose; Crystallography, X-Ray; Cyclodextrins; Drug Compounding; Excipients; Gliclazide; Hypoglycemic Agents; Lactose; Magnetic Resonance Spectroscopy; Methylcellulose; Oxazines; Rats; Solubility; Spectrophotometry, Infrared; Spectrophotometry, Ultraviolet; Sterilization

Permeation enhancement of ibuprofen from supersaturated solutions formed using the cosolvent technique was investigated using silicone as a model membrane. Hydroxpropyl methyl cellulose and hydroxpropyl-beta-cyclodextrin were used to stabilise the supersaturated states. Physical stability studies showed best results for low drug concentrations in a 40:60 propylene glycol/water cosolvent system. Variations in flux across model silicone membranes from saturated solutions were observed as the PG content was increased. The flux of IBU increased with the degree of saturation for solutions prepared in a 40:60 PG/water cosolvent mixture. HPMC and CD were found to be effective in enhancing the stability of supersaturated solutions of IBU. The mechanisms of action are different for the two additives and are discussed.

Topics: Anti-Inflammatory Agents, Non-Steroidal; beta-Cyclodextrins; Cyclodextrins; Diffusion; Drug Stability; Ibuprofen; Lactose; Methylcellulose; Oxazines; Permeability; Solubility

Since many chiral pharmaceutical excipients, such as cellulose polymers and cyclodextrins, are used as stationary phases for the separation of enantiomers by high performance liquid chromatography (HPLC), it is hypothesized that one enantiomer of a chiral drug will be released faster than the other from a pharmaceutical formulation containing a racemic drug and a chiral excipient. The mechanism of such an event may arise from preferential intermolecular interaction between the chiral excipient and one of the enantiomers. To test this hypothesis, the release of the enantiomers of propranolol hydrochloride into water from formulations containing the chiral excipients, hydroxypropyl methylcellulose (HPMC) or beta-cyclodextrin, was investigated by stereospecific HPLC analysis of the dissolved concentrations of each of the enantiomers from the formulations. The release of the enantiomers of propranolol hydrochloride from the formulations containing HPMC, although variable, was found to be stereoselective. However, the release of propranolol hydrochloride enantiomers from the beta-cyclodextrin complex was found to be non-stereoselective.

Topics: beta-Cyclodextrins; Cyclodextrins; Excipients; Hypromellose Derivatives; Methylcellulose; Propranolol; Solubility; Stereoisomerism

The amounts of beta-cyclodextrin and hydroxyl propyl methyl cellulose (HPMC) affecting the in vitro permeation rate of acetaminophen containing in both aqueous solutions and HPMC hydrogel preparations through the dialyzer tubing and isolated rat rectum were investigated. The partition coefficient of acetaminophen with or without beta-cyclodextrin in water/n-octanol system was also studied. In vivo absorption experiments of these test formulations were carried out by rectal administration in rats. The results indicate that the concentrations of beta-cyclodextrin and HPMC used decreased the amount permeated of acetaminophen from both test formulations. The more the amount of beta-cyclodextrin or HPMC the slower the permeation rate of acetaminophen. The permeation rate of acetaminophen through the dialyzer tubing was higher than that of acetaminophen through the isolated rat rectum. The result also shows beta-cyclodextrin and HPMC markedly reduced the in vivo bioavailability of acetaminophen from both test formulations. The lower partition coefficient and the higher hydrophilic properties of beta-cyclodextrin inclusion complex, and the higher viscosity of HPMC hydrogel matrix might be responsible for decreasing the in vitro permeation rate and depression of in vivo rectal absorption of acetaminophen. The in vitro permeation data was well correlated with in vivo absorption results, suggesting that the in vitro permeation study regardless of the dialyzer tubing method or the isolated rat rectum method might be used to estimate the in vivo rectal absorption of acetaminophen.

Topics: Acetaminophen; Animals; beta-Cyclodextrins; Cyclodextrins; Diffusion; Hypromellose Derivatives; In Vitro Techniques; Intestinal Absorption; Male; Methylcellulose; Permeability; Rats; Rats, Inbred Strains; Rectum

To modify the release rate of piretanide, a potent loop diuretic, a double-layer tablet was designed, and in vitro release was evaluated. For a rapidly releasing portion, hydrophilic beta-cyclodextrin derivatives were employed to form a water-soluble complex with piretanide. For a sustained-release portion, cellulose derivatives were used to provide appropriate hydrophobicity. The release rate of piretanide in the pH range 1.2-6.8 was automatically monitored by a pH-changeable dissolution testing apparatus. The low solubility of piretanide in acidic medium was significantly improved by complexations with dimethyl-beta-cyclodextrin (DM-beta-CyD) and hydroxypropyl-beta-cyclodextrin (HP-beta-CyD). The pH-independent slow release was attained by use of hydroxypropylcellulose (HPC):ethylcellulose (EC) matrices. Then, an optimal formulation of a double-layer tablet was obtained by the combination of each fraction. For example, the tablet consisting of the [DM-beta-CyD/(HPC:EC)] system in the weight ratio [1/3(1:3)] provided a sufficiently slow release of the drug over a period of 8 h in a wide pH region following an initial rapid dissolution.

Topics: beta-Cyclodextrins; Cellulose; Chemistry, Pharmaceutical; Crystallization; Cyclodextrins; Delayed-Action Preparations; Drug Carriers; Hydrogen-Ion Concentration; Hypromellose Derivatives; Methylcellulose; Solubility; Sulfonamides; Tablets; X-Ray Diffraction