Investigation of Dissolution Behavior HPMC/Eudragit®/Magnesium Aluminometasilicate Oral Matrices Based on NMR Solid-State Spectroscopy and Dynamic Characteristics of Gel Layer.

Burst drug release is often considered a negative phenomenon resulting in unexpected toxicity or tissue irritation. Optimal release of a highly soluble active pharmaceutical ingredient (API) from hypromellose (HPMC) matrices is technologically impossible; therefore, a combination of polymers is required for burst effect reduction. Promising variant could be seen in combination of HPMC and insoluble Eudragits® as water dispersions. These can be applied only on API/insoluble filler mixture as over-wetting prevention. The main hurdle is a limited water absorption capacity (WAC) of filler. Therefore, the object of this study was to investigate the dissolution behavior of levetiracetam from HPMC/Eudragit®NE matrices using magnesium aluminometasilicate (Neusilin® US2) as filler with excellent WAC. Part of this study was also to assess influence of thermal treatment on quality parameters of matrices. The use of Neusilin® allowed the application of Eudragit® dispersion to API/Neusilin® mixture in one step during high-shear wet granulation. HPMC was added extragranularly. Obtained matrices were investigated for qualitative characteristics, NMR solid-state spectroscopy (ssNMR), gel layer dynamic parameters, SEM, and principal component analysis (PCA). Decrease in burst effect (max. of 33.6%) and dissolution rate, increase in fitting to zero-order kinetics, and paradoxical reduction in gel layer thickness were observed with rising Eudragit® NE concentration. The explanation was done by ssNMR, which clearly showed a significant reduction of the API particle size (150-500 nm) in granules as effect of surfactant present in dispersion in dependence on Eudragit®NE amount. This change in API particle size resulted in a significantly larger interface between these two entities. Based on ANOVA and PCA, thermal treatment was not revealed as a useful procedure for this system.

Biological Effects of Drug-Free Alginate Beads Cross-Linked by Copper Ions Prepared Using External Ionotropic Gelation.

External ionotropic gelation offers a unique possibility to entrap multivalent ions in a polymer structure. The aim of this experimental study was to prepare new drug-free sodium alginate (ALG) particles cross-linked by Cu2+ ions and to investigate their technological parameters (particle size, sphericity, surface topology, swelling capacity, copper content, release of Cu2+ ions, mucoadhesivity) and biological activity (cytotoxicity and efficiency against the most common vaginal pathogens-Herpes simplex, Escherichia coli, Candida albicans) with respect to potential vaginal administration. Beads prepared from NaALG dispersions (3 or 4%) were cross-linked by Cu2+ ions (0.5 or 1.0 M CuCl2) using external ionotropic gelation. Prepared mucoadhesive beads with particle size over 1000 µm exhibited sufficient sphericity (all ˃0.89) and copper content (214.8-249.07 g/kg), which increased with concentration of polymer and hardening solution. Dissolution behaviour was characterized by extended burst effect, followed by 2 h of copper release. The efficiency of all samples against the most common vaginal pathogens was observed at cytotoxic Cu2+ concentrations. Anti-HSV activity was demonstrated at a Cu2+ concentration of 546 mg/L. Antibacterial activity of beads (expressed as minimum inhibition concentration, MIC) was influenced mainly by the rate of Cu2+ release which was controlled by the extent of swelling capacity. Lower MIC values were found for E. coli in comparison with C. albicans. Sample ALG-3_1.0 exhibited the fastest copper release and was proved to be the most effective against both bacteria. This could be a result of its lower polymer concentration in combination with smaller particle size and thus larger surface area.

[The effect of polymeric dispersion type on the release of diclofenac sodium from coated pellets]. / Vliv typu polymerové disperze na uvolnování diklofenaku sodné soli z obalených pelet.

Recently, coated pellets have gained attention of the pharmaceutical industry as they represent a relatively easy way leading to controlled drug release. Pellets of appropriate properties containing approx. 40% of diclofenac sodium were prepared by roto-agglomeration. For the coating, two different aqueous dispersions (Surelease and Eudragit RS 30 D) were selected. Generally, the drug release rate slowed down as the coating load increased from 10 to 22%. However, big differences between diclofenac sodium release from pellets coated with Surelease and Eudragit RS 30 D at equivalent coating loads were observed. Although Eudragit RS 30 D provided membranes successfully controlling drug release over an extended period of 24 hours, the coating process with Surelease led to a film of a very poor quality. Faster release from ethyl cellulose coated pellets could be explained in terms of a higher solubility of diclofenac sodium in alkaline aqueous dispersion of ethyl cellulose and its migration into the coat during the coating process and/or the unsatisfactory curing of the ethyl cellulose film. Therefore possible interactions between the coating and the drug should be always considered as suggested in this study.

[Pellets preparation by the drug layering technique in a rotary processor]. / Príprava pelet vrstvením lécivé látky na inaktivní jádra v rotoprocesoru.

Pelletization by the layering technique can be carried out by applying a liquid (a drug solution or suspension) or a drug powder using either coating drums or a fluidized bed equipment. This technique is used particularly for the formulation of multiparticulate controlled release dosage forms. Application of a drug on inactive beads in a centrifugal fluid-bed equipment (a rotary processor) represents the up-to-date technique of pellets production. Pelletization by the tangential drug-layering process is a multivariate process, and it is important to identify as well as to control the process variables and conditions. The goal of this paper is to give a summary about one of the newest pelletizing technologies - drug layering in a rotary processor, to outline its possibilities, and particularly to describe the influence of formulation and process parameters on the properties of the final product.

[Bioequivalence studies of pharmaceutical preparations]. / Bioekvivalencní studie lécivých prípravku v Ceské republice.

Bioequivalence studies are very important for the development of a pharmaceutical preparation in the pharmaceutical industry. Their rationale is the monitoring of pharmacokinetic and pharmacodynamic parameters after the administration of tested drugs. The target of such study is to evaluate the therapeutic compatibility of tested drugs (pharmaceutical equivalents or pharmaceutical alternatives). The importance of bioequivalence studies is increasing also due to the large growth of the production and consumption of generic products. Generic products represent approximately 50 % of the whole consumption in many European countries and USA. The search output of bioequivalence study is together with the pharmaceutical quality data of medical product one of the main part of the registration file submitted to a national regulatory authorities. The registration of generic products does not demand complicated and expensive clinical study contrary to original product. The comparison of the original and the generic product via bioequivalence study is suggested as sufficient. The aim of this article is to provide to a medical public a summary about the types of bioequivalence studies, their range, rules of their practise and let them gain their own attitude to this question.

[New systems for colonic drug targeting]. / Nové systémy pro targeting léciv do tlustého streva.

Colonic drug delivery systems are useful for the treatment of inflammatory bowel diseases (ulcerative colitis, Crohn's disease), some carcinomas, gastrointestinal infections and diseases that are sensitive to circadian rhythms, such as asthma, angina pectoris and arthritis, where an intention time delay in the absorption of the drug is required. The colon region is a site for the entry of peptides, proteins, nucleotides and vaccines into the systemic circulation due to local absence of digestive enzymes. Colonic drug targeting ensures direct treatment at the disease site and a possible reduction in the administered dose. A drug is not absorbed into the systemic circulation, so the associated systemic adverse effects are reduced. Colonic drug delivery systems are based on exploitation of characteristics that are unique to the gastrointestinal tract (GIT), such as pH gradient along the GIT, long transit time through the GIT, increased intraluminal pressure and a presence of bacterial microflora in these regions.

Some variables influencing rotoagglomeration in the multiprocessor MP-1.

Pellets are of great interest to the pharmaceutical industry for variety reasons, e.g. flexibility in dosage form design and drug efficacy improvement. Rotoagglomeration is the novel method for their production using rotoprocessors or rotogranulators allowing one-piece equipment operation. However this process is sensitive and includes numerous variables that have to be optimalized for successful result-spherical pellets of desired properties. This paper is contributing to study some of them: liquid amount, its spray rate and input powder amount and their influence on lactose-microcrystalline cellulose pellet properties.

[Effect of temperature on drug solubility in complex formation of flubendazole and 2-hydroxypropyl-beta-cyclodextrin]. / Vliv teploty na rozpustnost léciva pri komplexaci flubendazolu s 2-hydroxypropyl-beta-cyklodextrinem.

Flubendazol is a veterinary antiparasitic agent which acts toxically on both adult and larval stages of round worms. It is nearly insoluble in water and it influences not only the selection of the dosage form, but also its biological availability. Its solubility can be increased by adding solutizers and tensides, or by complex-formation with cyclodextrins. In the published experimental paper the method of complex-formation of flubendazol with 2-hydroxypropyl-beta-cyclodextrin was employed and the effect of temperature on the resultant solubility of the active ingredient was examined. The final dosage form was pellets produced with the use of the method of extrusion and spheronisation.