Formulation optimization of sustained-release ammonio methacrylate copolymer microspheres. Effects of log p and concentration of polar cosolvents, and role of the drug/copolymer ratio.

The objectives of this work were the formulation optimization of the preparation process parameters and to evaluate spray-dried sustained-release microspheres using ammonio methacrylate copolymer (AMC) as a polymer matrix. The effects of log P and the concentrations of the cosolvents (acetone, methyl ethyl ketone and n-butyl acetate) and different drug/copolymer ratios as independent variables on the physicochemical parameters (the W1/O emulsion viscosity, the microsphere production yield, the average particle size, the encapsulation efficiency) and the cumulative in vitro drug release as dependent variables were studied. The optimization was carried out on the basis of the 33 factorial design study.

Intranasal delivery of human beta-amyloid peptide in rats: effective brain targeting.

(1) Intranasal administration is a non-invasive and effective way for the delivery of drugs to brain that circumvents the blood-brain barrier. The aims of the study were to test a nasal delivery system for human beta-amyloid (A beta) peptides, to measure the delivery of the peptides to brain regions, and to test their biological activity in rats. (2) A beta(1-42), in the form of a mixture of oligomers, protofibrils, and fibrils was dissolved in a nasal formulation containing hydrophobic, hydrophylic, and mucoadhesive components.

Study of gel-forming properties of sucrose esters for thermosensitive drug delivery systems.

Sucrose esters (SEs) are non-toxic, biodegradable, non-ionic surfactants. They have a wide range of hydrophilic-lipophilic balance values (1-16) and are usually applied as surfactants, or as solubility or penetration enhancers. The aims of this work were to study the gelling behaviour of SEs and the effects of this property on drug release.

Sodium hyaluronate as a mucoadhesive component in nasal formulation enhances delivery of molecules to brain tissue.

Intranasal administration of molecules has been investigated as a non-invasive way for delivery of drugs to the brain in the last decade. Circumvention of both the blood-brain barrier and the first-pass elimination by the liver and gastrointestinal tract is considered as the main advantages of this method. Because of the rapid mucociliary clearance in the nasal cavity, bioadhesive formulations are needed for effective targeting.

Evaluation of the binding effect of human serum albumin on the properties of granules.

The main objective of this study was the application of a solution of human serum albumin as a granulating fluid. The properties of the granules formed were evaluated and compared with those when a conventional binder was applied in the same concentration. The powder mixture contained a soluble (mannitol) and an insoluble component (different types of cellulose).

Mucoadhesive behaviour of emulsions containing polymeric emulsifier.

Over the last two decades the attention has been focused on mucoadhesive dosage forms as a possibility to improve the residence time on a specified region of the body. In addition to bioadhesivity, controlled drug release from the dosage form is also desirable. Pemulen TR1 and Pemulen TR2 are cross-linked block copolymers of poly(acrylic acid) and hydrophobic long-chain methacrylates.

[Optimatization of pellet preparation is CF-granulator with factorial design].

Lithium carbonate-containing pellets were made in a laboratory-scale centrifugal granulator in order to investigate the effects of the process parameters (rotor rotation speed, slit airflow rate and spray air rate) on the pellet shape and size distribution. The size distribution and the shape parameters (roundness, roughness, rectangularity and sphericity) of the pellets were measured, and an optimization parameter was then calculated from these shape parameters. The experiment was carried out and evaluated according to a 2(3) full factorial design.

[Formulation of an oral solid dosage form containing human interferon-alpha].

The main objective of this study was to process the human alpha-interferon for the solid dosage form. The first step was the preparation of the intermediate product for the tablet making. Fluid bed apparatus with top spray method was applied for the layering of powdered cellulose with human alpha-interferon solutions.

[Gel-emulsion systems. II. Stability].

Viscosity, elastic character of gel emulsions containing polymeric emulsifiers and change of droplet size distribution under storage were studied. The quantitative change of free (non-bound) water and immobilized one in microgel form, and that of the evaporation rate under storage were examined. The phenomena were divided into two groups: change of i) macrostructure, and ii) microstructure.

[Gel-emulsion systems. I. Physical-chemical characterisation].

Emulsion gels prepared with polyacrylic acid-alkyl acrylate diblock copolymer surfactants were studied. It was supposed that the polymer surfactants surrounding the oil droplets formed a microgel structure and this structure stabilized the emulsions sterically. This assumption was verified by thermoanalytic investigation.

An assessment of the interactions between diclofenac sodium and ammonio methacrylate copolymer using thermal analysis and Raman spectroscopy.

The objective of the work was to assess the possible interactions between the model drug diclofenac sodium (DS) and the water-insoluble ammonio methacrylate copolymer (AMC). Films with different drug/polymer ratios were therefore prepared by the solvent casting method and investigated as a preformulation study towards sustained release microparticles. Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) were used to investigate the dispersed/dissolved state of the DS in the preparation, the thermal stability and the properties of DS-containing AMC films; and Raman spectroscopy was used to confirm the possible interactions between DS and AMC.

[Liberation of active substance from pharmaceutical suspensions I. Effect of surfactants on the active substance dissolving].

Liberation of active agent from suspensions containing sulfadimidine was investigated. There are three physico-chemical steps of the process: (i) dissolving active agent in the vehicle of suspension, (ii) partitioning dissolved molecules between the membrane and the suspension, and (iii) diffusion of active substance through membrane into the acceptor phase. The vehicle of suspensions contained surface active agents in 0.

[Determination of the gelatinization temperature of starches via thermoanalytical and rheological methods].

This work provides a short review concerning the measuring techniques frequently applied to characterize the gelatinization behaviour of starches. The aim of the experiments was to determine the gelatinization temperatures of maize (A-type) and potato (B-type) starches via isothermal microcalorimetry and rheological methods (rotational viscosimetry and dynamic oscillatory testing). A significant difference was observed between the gelatinization temperatures of the aqueous starch suspensions, which can be attributed to the structural differences between A-type and B-type starches.

Formulation of an intermediate product from human serum albumin for the production of a solid dosage form.

The main objective of this study was to evaluate and to increase the processibility of a model protein (human serum albumin (HSA)) for preparation of an intermediate for a solid dosage form. The applicability of the solid forms is easier, and therefore their formulation is a promising method for the application of proteins. The layering of powdered cellulose with HSA solutions of different concentrations in a fluid bed apparatus with the top spray method was applied.

[Investigation of the structure of macromoleculare gels II: analysis of viscosity curves].

Viscosity curves of gels from homo-and copolymers in aqueous medium reviewed in our previous paper were studied. Viscosity vs. rate of shear, and viscosity vs.

[Surfactants in dosage forms and biological systems. Part II].

The 2nd parts of publications are summarized the modern drug delivery systems contained surface active agents and the role of surfactants in the formation and stability of drug delivery systems. This paper reviews the structure and stability of multiple emulsions, and the different associates forming from surfactants. The solubilization is characterized and some mathematic functions between surface tension of surfactants and their solubilization capacity are introduced.

[Preparation and investigation of gemfibrozil + dimethyl-beta-cyclodextrin products and solid dosage forms].

Gemfibrozil is a lipid-regulating active substance. Dimethyl-beta-cyclodextrin products were prepared from this sparingly soluble pharmacon by means of methods such as physical mixing, kneading, spray drying and ultrasonication. Solid dosage forms (hydroxypropylmethyl cellulose /HPMC/ capsules and tablets) were prepared from the selected products on the basis of their dissolution profile and the in vitro membrane diffusion results.

[Investigation of structure of macromoleculare gels, I. Analysis of flow curves].

Six polymers with different structure were investigated. The polymers studied were as follows: methylcellulose, hydroxyethylcellulose, carboxymethylcellulose sodium, polyacrylate sodium-polyacrylamid copolymer (Hostacerin PN 73), poly(vinylpyrrolidone)-poly(vinylacetate) copolymer (Kollidon VA 64) and poly(ethylenoxide)-poly(propylenoxide) blockpolymer. Physical networks from polymers in aqueous media were prepared.

[Surface active agents in drug forms and biological systems].

The application areas of surface active agents in the pharmaceutical technology are surveyed. Three topics are summarized: (i) application of surfactant as traditional additives, (ii) the role of surfactant in modern drug delivery systems, and (iii) biopharmaceutical use of surfactants in different dosage forms. The team dealing with colloid carriers at the Pharmaceutical-Technological Department in Szeged has worked out several relationships in mathematical form.

[Development of signal aquisition and processing software in the preformulation tests of solid dosage forms].

The authors demonstrate the essence and possibility of the computer programming and its role in the pharmaceutical preformulation. The paper surveys its importance in the development of pharmaceutical dosage forms, in the determination of procedure parameters and in the quality assurance.

[Investigation of solubility properties of nifluminic acid containing cyclodextrins and polyvidone].

One of the most important task of the pharmaceutical technology is to reach a possible high gastrointestinal absorbtion of the active ingredient. Therefore, it is necessary to have a good solubility in the gastric/intestinal medium. In this way the applied drug quantity and unwanted side effects can be reduced with solubility increasing.

[Monitoring the temperature distribution during dielectric drying].

Microwave assisted vacuum drying offers never questioned advantageous and it is getting more and more popular lately. In spite of its uniqueness there is a rightful resistance and mistrust because the temperature distribution of the workload is far from being homogeneous as a result of the existing inhomogeneous electromagnetic field. The aim of this study is to survey the heat thus field distribution in the workload to prevent local overheating that endangers the quality of the pharmaceutical product.

The effect of the solvent on the film-forming parameters of hydroxypropyl-cellulose.

In pharmaceutical technology, film-forming agents are often applied in solution during the preparation of solid dosage forms. A wide range of polymers have already been examined, but many of the effects of the applied solvent on the properties of the film are still not fully known. The study of these phenomena might be of great help in the preparation of better films.

[Amorphization in pharmaceutical technology].

The amorphization of crystalline active ingredients may be necessary because of the polymorphism of the active substance, the poor water-solubility of the drug material, difficult processing in the crystalline form and the taking out of a patent for a new (amorphous) form. This article introduces protocols for amorphization, which use methods traditionally applied in pharmaceutical technology. The protocols involve three possible routes: solvent methods, hot-melt technologies and milling procedures.

[Thermostability testing of iron(II) sulphate for formulation of drug product].

The aim of the experimental study was to determine which iron(II) sulphate form, the monohydrate or the heptahydrate, is more suitable for formulation of a retard dosage form with melt technology, and to control the suitable compound from a thermostability aspect according to the ICH (International Conference on Harmonization). Iron(II) sulphate is susceptible to oxidation and a rise in temperature increases the rate of this redox change. The presence of Fe3+ is definitely harmful in the case of enteral administration.