Comparative evaluation of the effect of cyclodextrins and pH on aqueous solubility of apigenin.

The aqueous solubility of a flavonoid, apigenin, was studied in the presence of first generation cyclodextrins (α-CyD, ß-CyD, γ-CyD), ionic and nonionic synthetic derivatives of ß-CyD, namely SBE-ß-CyD, HP-ß-CyD and RM-ß-CyD at various physiological pH. The order of solubility enhancement was as follows: RM-ß-CyD>SBE-ß-CyD>γ-CyD>HP-ß-CyD>ß-CyD>α-CyD. The phase solubility diagrams of HP-ß-CyD and SBE-ß-CyD indicated Higuchi AL subtype behavior, suggesting 1:1 stoichiometry of the complex. In contrast, AP subtype, so higher order complex formation can be assumed in the case of RM-ß-CyD and γ-CyD. The formation of inclusion complexes has been confirmed by absorption and fluorescence spectroscopic measurements. Increased antioxidant activity was observed due to the inclusion complexes. These results prove that synthetic derivatives of ß-CyD will be potentially useful excipients in the development of drug delivery systems for healthcare products containing flavonoids.

Drug release profiles and microstructural characterization of cast and freeze dried vitamin B12 buccal films by positron annihilation lifetime spectroscopy.

Solvent cast and freeze dried films, containing the water-soluble vitamin B12 as model drug were prepared from two polymers, sodium alginate (SA), and Carbopol 71G (CP). The proportion of the CP was changed in the films. The microstructural characterization of various samples was carried out by positron annihilation lifetime spectroscopy (PALS). The drug release kinetics of untreated and stored samples was evaluated by the conventionally applied semi-empirical power law. Correlation was found between the changes of the characteristic parameters of the drug release and the ortho-positronium (o-Ps) lifetime values of polymer samples. The results indicated that the increase of CP concentration, the freeze-drying process and the storage at 75% R.H. decreased the rate of drug release. The PALS method enabled the distinction between the micro- and macrostructural factors influencing the drug release profile of polymer films.

Supramolecular elucidation of the quality attributes of microcrystalline cellulose and isomalt composite pellet cores.

The major objective of this study was to disclose the relationships between the physical quality attributes and supramolecular structure of novel composite pellet cores containing microcrystalline cellulose (MCC) and isomalt in different ratios. The novel composite pellet cores were manufactured by an extrusion/spheronisation process. The micro or supramolecular structure of pellets was tracked by positron annihilation lifetime spectroscopy (PALS) based on the o-Ps lifetime values. The results indicate a correlation between the examined macro and microstructural properties of the inert cores. The higher free volume holes indicated by the higher o-Ps lifetime values resulted in a more mobile micro- and supramolecular structure of MCC cores thus increasing the plastic deformation and the tensile strength of the cores. A physical interaction was found between the microcrystalline cellulose and isomalt which supports the osmotic effect of the water soluble sugar alcohol in the composite pellet cores regarding drug release.

[Formulation of multiparticular drug delivery systems by compressing pellets into tablets]. / Multipartikuláris gyógyszerhordozó rendszer formulálása tablettába préselt pelletek alkalmazásával.

The use of multiparticulate drug delivery systems can contribute to more efficient and safe therapy while stability and incompatibility problems can be avoided as well. The aim of the present work was to review the possible ways of production of pellets containing multiparticulate units and studying the most important factors influencing the product quality attributes after tablet compression. The relationship between the formulation variables (compression pressures, different amounts of tableting excipients) and the dissolution profile of the gastroresistant coated beads were investigated.

[Formulation strategies of intraoral dosage forms]. / Intraorális gyógyszerformák fejlesztési lehetoségei.

The active pharmaceutical ingredient can be administered by several different routes. Although the oral route (per os) has been one of the most convenient and widely accepted delivery system for most drugs, it has number of disadvantages like the very low pH of the stomach, the high enzymatic activity, and extensive first-pass metabolism. Difficulty in swallowing (dysphagia) is common among all age groups, especially in "problematic" subpopulations like children and the elderly. Several novel intraoral dosage forms (IODs) have recently become available to modulate the physicochemical and pharmacokinetic characteristics of drugs, while improving patient compliance. The present article summarizes and categorizes their formulation possibilities.

Dissolution profile of novel composite pellet cores based on different ratios of microcrystalline cellulose and isomalt.

There is a growing interest towards the application of inert cores as starting materials for pharmaceutical pellet manufacturing. They serve as alternatives to develop and adapt a relatively simple manufacturing technology compared with an extrusion/spheronisation process. The major objective of this study was to investigate the effect of the compositions of core materials on the drug release profile. Pure microcrystalline cellulose (MCC), isomalt and different types of novel composite MCC-isomalt cores were layered with model drug (sodium diclofenac) and were coated with acrylic polymer. The effect of the osmolality in the gastrointestinal tract was simulated using glucose as osmotically active agent during in vitro dissolution tests. The results demonstrated the dependence of drug dissolution profile on the ratio of MCC and isomalt in the core and the influence of osmotic properties of the dissolution medium. Isomalt used in the composite core was able to decrease the vulnerability of the dissolution kinetics to the changes in the osmotic environment.

[Formulation aspects and ex-vivo examination of buccal drug delivery systems]. / Bukkális hatóanyag-leadó rendszerek formulálásának és ex vivo vizsgálatának lehetoségei.

Application of buccal dosage forms has several advantages. Buccal route can be used for systemic delivery because the mucosa has a rich blood supply and it is relatively permeable. This route of drug delivery is of special advantages, including the bypass of first pass effect and the avoidance of presystemic elimination within the GIT. Buccal delivery systems enable the systemic delivery of peptides and proteins. In our previous study the physiological background of this application and the excipients of the possible formulations were reviewed. In the present work the formulation and ex vivo examination aspects of buccal drug delivery systems are summarized.

Evaluation of drug release from coated pellets based on isomalt, sugar, and microcrystalline cellulose inert cores.

The objective of the present study was to investigate the effect of the pellet core materials isomalt, sugar, and microcrystalline cellulose on the in vitro drug release kinetics of coated sustained-release pellets as well as to evaluate the influence of different ratios of polymethacrylate copolymers exhibiting different permeability characteristics on the drug release rate. For characterization of the drug release process of pellets, the effect of osmolality was studied using glucose as an osmotically active agent in the dissolution medium. The pellet cores were layered with diclofenac sodium as model drug and coated with different ratios of Eudragit RS30D and Eudragit RL30D (ERS and ERL; 0:1 and 0.5:0.5 and 1:0 ratio) in a fluid bed apparatus. Physical characteristics such as mechanical strength, shape, and size proved that the inert cores were adequate for further processing. The in vitro dissolution tests were performed using a USP Apparatus I (basket method). The results demonstrated that, besides the ratio of the coating polymers (ERS/ERL), the release mechanism was also influenced by the type of starter core used. Sugar- and isomalt-type pellet cores demonstrated similar drug release profiles.

[Application of computer image analysis for characterization of pellets]. / Számítógépes képanalízis alkalmazása gyógyszeres pelletek jellemzésére.

The morphological characteristics of pellets are critical parameters, because of their physico-chemical features depend on the size, shape and surface geometric of the particles. To ensure the spherical shape and required particle of pharmaceutical pellets size is a prerequisite. The detailed technology is basic requirement for the successful and cost efficient production of particles of acceptable quality. Since the determination of the particle size is influenced by the particle shape, therefore microscopic examination is always suggested, which together with image analysis is suitable for the assesment of the most typical parameters. The method of the microscopic image analysis is useful not only for particle size measurement, but also for particle shape and texture evaluation, with a high sensitivity. Using the microscopic method particle shape may be defined either qualitatively and quantitatively. Reviewing the related articles and results on the investigation of sugar pellets demonstrate that roundness characterization is strongly influenced by the applied statistical shape parameters.

[Importance and pharmaceutical technological considerations of neutral pellets]. / Neutrális pelletmagok jelentosége és gyógyszertechnológiai vonatkozásai I.

There is a growing interest toward the application of neutral pellets as starting excipients for pharmaceutical pellet manufacturing. They serve as alternatives to develope and adapt a relatively simple manufacturing technology compared to pellet agglomeration. Their application has benefits considering the low dose of drugs and the requirement for content uniformity. Further use may be advantageous for preparation of orodispersible tablets or modified release preparations.