betadex and triacetyl-beta-cyclodextrin

Topics: beta-Cyclodextrins; Drug Carriers; Drug Compounding; Drug Delivery Systems; Molecular Structure; Nanoparticles; Polyesters; Polyethylene Glycols; Pterins; Spectrum Analysis; Structure-Activity Relationship

The main objective of this study was to investigate thermosensitive Pluronic F-127 (PF-127) hydrogel for the modified release of a potent alcohol and opioid antagonist, naltrexone (NTX) hydrochloride, in a subcutaneous injectable dosage form.. The NTX hydrogels were prepared by the cold method, and the in vitro release profiles of various formulations were evaluated at 37°C using the Franz diffusion cell system. We examined the different PF-127 concentrations, pH of solution, and inorganic salts on drug release from these gels.. The data showed an increase in PF-127 content from 20% to 35%, resulting in a decrease in the rate of NTX release. Among the formulations prepared in different pH solutions, pH 7.4 produced the slowest drug release rate. The addition of inorganic salts had no significant effect on drug release. However, these factors appeared to have limited effects on drug release rate. Therefore, to achieve a sustained-release formulation, a NTX and triacetyl β-cyclodextrin (TAβCD) complex was evaluated. The binary systems of NTX/TAβCD in different molar ratios were prepared by the kneading method, and complex formation was demonstrated by differential scanning calorimetry.. The results of the current in vitro study indicate that PF-127 gel formulations containing drug complexes with hydrophobic cyclodextrin could be useful for the preparation of a controlled delivery system of water-soluble drugs such as NTX, for a period of more than 140 hours.

Topics: beta-Cyclodextrins; Calorimetry, Differential Scanning; Delayed-Action Preparations; Excipients; Hydrogels; Hydrogen-Ion Concentration; Injections, Subcutaneous; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Poloxamer; Temperature

The low bioavailability and short half-life of metformin hydrochloride (MH) make the development of sustained-release forms desirable. However, drug absorption is limited to the upper gastrointestinal (GI) tract, thus requiring suitable delivery systems providing complete release during stomach-to-jejunum transit. This study was undertaken to develop a MH sustained-release formulation in compliance with these requirements. The strategy proposed is based on direct-compressed matrix tablets consisting of a combination of MH with the hydrophobic triacetyl-beta-cyclodextrin (TAbetaCD), dispersed in a polymeric material. Different polymers were tested as excipients, i.e. hydroxypropylmethylcellulose, xanthan gum, chitosan, ethylcellulose, Eudragit L100-55, and Precirol. Compatibility among the formulation components was assessed by DSC analysis. All the tablets were examined for drug release pattern in simulated gastric and jejunal fluids used in sequence to mimic the GI transit. Release studies demonstrated that blends of a hydrophobic swelling polymer (hydroxypropylmethylcellulose or chitosan) with a pH-dependent one (Eudragit L100-55) were more useful than single polymers in controlling drug release. Moreover, the main role played by the MH-TAbetaCD system preparation method (i.e. grinding or spray-drying) in determining the behaviour of the final formulation was evidenced. In fact, for a given matrix-tablet composition, different sustained-release effects were obtained by varying the relative amounts of MH-TAbetaCD as ground or spray-dried product. In particular, the 1:1 (w/w) blend of such systems, dispersed in a Eudragit-chitosan polymeric matrix, fully achieved the prefixed goal, giving about 30% released drug after 2h at gastric pH, and overcoming 90% released drug within the subsequent 3h in jejunal fluid.

Topics: beta-Cyclodextrins; Delayed-Action Preparations; Hypoglycemic Agents; Metformin; Tablets

Interaction products of metformin hydrochloride (MF.HCl), an oral anti-hyperglycaemic agent highly soluble in water, with triacetyl-beta-cyclodextrin (TAbetaCyD), a hydrophobic CyD derivative practically insoluble in water, were prepared to evaluate their suitability for the development of a sustained-release dosage form of the drug. Equimolar MF.HCl-TAbetaCyD solid compounds were obtained by different techniques, i.e., physical mixing, kneading, co-grinding, sealed-heating, and spray-drying, in order to investigate and compare their effectiveness and influence on the physical-chemical properties of the final products. Differential scanning calorimetry, X-ray powder diffractometry, Fourier transform infrared spectroscopy and scanning electron microscopy were used for the solid-state characterization of the different MF.HCl-TAbetaCyD systems, whereas their in vitro dissolution properties were determined according to the dispersed amount method. According to the results of solid-state studies, the ability of the different preparation methods to promote effective interactions between drug and CyD varied in the order: spray-drying>co-grinding>kneading>sealed-heating approximately physical mixing. The same effectiveness rank order was observed also in dissolution studies. In fact the time to dissolve 100% drug varied increased from 1 min, for pure drug, to 3, 7, 40, 120 up to 420 min for physically mixed, sealed-heated, kneaded, co-ground and spray-dried products, respectively. Thus the drug-TA(CyD products obtained by spray drying and co-grinding were selected as the best candidates for the future development of a suitable prolonged-release oral dosage form of MF.HCl.

Topics: beta-Cyclodextrins; Calorimetry, Differential Scanning; Delayed-Action Preparations; Drug Carriers; Hypoglycemic Agents; Metformin; Microscopy, Electron, Scanning; Solubility; X-Ray Diffraction

The feasibility of using complexes with cyclodextrins (CDs) in nicardipine (NC) controlled delivery has been examined, with a view to extending the pharmaceutical applications spectrum of these carriers. For a fast release fraction, a hydrophilic beta-cyclodextrin derivative (hydroxypropyl-beta-cyclodextrin) was employed to form a water-soluble complex. For the sustained-releasing portion, triacetyl-beta-cyclodextrin (TAbetaCD) was used to provide complexes with appropriate hydrophobicity. An optimal formulation was designed by the combination of each fraction in different mixing ratios. The release behaviour of the complexes, as well as of their mixtures, was examined in simulated gastric (pH 1.2) and intestinal (pH 6.8) fluids. The formulations released the drug rapidly at the initial stage, followed by a slow release. The drug release rate was markedly retarded in the increasing order of the amount of NC/TAbetaCD complex. When NC was administered to rabbits, its absorption was very rapid with a short elimination half-life, while a prolonged maintenance of the plasma levels was obtained for the two selected formulations. The drug bioavailability was considerably improved especially after the administration of the mixture of hydrophilic and hydrophobic complexes, when compared with the NC/TAbetaCD complex. The results suggested that the critical combination of hydrophilic and hydrophobic CDs complexes, in appropriate ratios, could be a promising drug delivery system with a prolonged therapeutic effect coupled with a more balanced bioavailability.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Animals; beta-Cyclodextrins; Biological Availability; Calcium Channel Blockers; Chemical Phenomena; Chemistry, Physical; Chromatography, High Pressure Liquid; Cyclodextrins; Delayed-Action Preparations; Nicardipine; Rabbits; Solubility; Spectrophotometry, Ultraviolet

Proton nuclear magnetic resonance spectroscopy (1H NMR), which has become an important tool for in vitro study of cyclodextrin (CD) complexes, was used to study and structurally characterize the inclusion compounds formed in solution between nicardipine hydrochloride (NC) and beta-cyclodextrin (betaCD), hydroxypropyl-beta-cyclodextrin (HPbetaCD) and triacetyl-beta-cyclodextrin (TAbetaCD). The large variation of chemical shifts from protons located around the interior of the hydrophobic cavity (i.e. H-3, H-5 and H-6) coupled with minimal variation of shifts from protons located on the outer sphere of the betaCD (i.e. H-1, H-2 and H-4) provided clear evidence of inclusion complexation. In the presence of the different CDs, the aromatic protons of NC were the most affected, suggesting a strong involvement of the phenyl groups in the inclusion mechanism. The application of continuous variation method indicated the presence of complexes with a 1:1 host/guest stoichiometry for all the studied CDs. Two-dimensional rotating frame nuclear Overhauser effect spectroscopy (ROESY) experiments were carried out to further support the proposed inclusion mode. Inspection of the ROESY spectra allowed the establishment of spatial proximities between several aromatic hydrogens of the guest and the CD protons, indicating that the inclusion occurs by accommodation of the two aromatic groups of NC. All the experimental data were further rationalized to elaborate possible three-dimensional geometric models of inclusion complexes. From the aforementioned observations, we concluded there is no preference for inclusion of a particular aromatic ring. Instead, two types of 1:1 complexes with different inclusion structures may exist simultaneously in solution, being alternatively included through the wider side of the cavity, i.e. the so-called multimodal inclusion occurs in the interaction of NC with the different CDs.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; beta-Cyclodextrins; Chemistry, Pharmaceutical; Cyclodextrins; Hydrogen Bonding; Magnetic Resonance Spectroscopy; Models, Molecular; Molecular Structure; Nicardipine; Protons; Solutions

The inclusion ability of triacetyl-beta-cyclodextrin (TAbetaCD), a hydrophobic cyclodextrin (CD) derivative was examined, using nicardipine hydrochloride (NC) as model drug. The binary compounds were prepared in a 1 : 1 molar ratio by the kneading and the spray-drying techniques. In order to confirm the complexation between NC and TAbetaCD in the solid state, differential scanning calorimetry, X-ray diffractometry, Fourier transformation-infrared spectroscopy and scanning electron microscopy were carried out and the results were compared with the corresponding physical mixture in the same molar ratio. The kneaded product presented only slight modifications on the drug physicochemical and morphological properties, which could mean that no complex formation occurred during this process. In contrast, spray-drying was found to produce inclusion complexes with amorphous nature. In vitro dissolution studies were carried out in simulated gastric (pH 1.2) and intestinal (pH 6.8) fluids, according to the United States Pharmacopoeia (USP) basket method. The NC in vitro release from the kneaded and spray-dried products was markedly retarded in both dissolution media. However, this retarding effect was significantly more evident for the spray-dried compound. It was concluded that the formation of real inclusion complexes could only be achieved by the spray-drying method.

Topics: beta-Cyclodextrins; Calorimetry, Differential Scanning; Cyclodextrins; Delayed-Action Preparations; Drug Compounding; Hydrogen-Ion Concentration; Hydrophobic and Hydrophilic Interactions; Microscopy, Electron, Scanning; Nicardipine; Solubility; Spectroscopy, Fourier Transform Infrared; Surface Properties; X-Ray Diffraction