I. Erős

Quantitative Determination of Crystallinity of α-Lactose Monohydrate by DSC

In pharmaceutical practice it is important and useful to know the crystallinity of materials and to monitor it during formulation development, production processes and storage. The purpose of this study was to assess the quantitative capability of DSC for determining crystallinity in crystalline/amorphous powder mixtures and to compare the accuracy of the DSC method with that of conventional powder X-ray diffraction. Alpha-lactose monohydrate was chosen as the model material. On the basis of this study it can be concluded, that DSC method can be applied safely for semiquantitative evaluation of the crystallinity of lactose samples consisting of an amorphous content higher than 20%.

Study of thermal behaviour of sugar alcohols

Mannitol and sorbitol are widely used in the pharmaceutical and food industry. There are some technological procedures such as spray-drying, freeze-drying, tablet compression, during which there is a possibility of heat effect. The purpose of this work was to study the thermal properties of sorbitol, mannitol and their mixtures. Furthermore, these materials and their tablet pressing were studied after melting and solidification. The results of the study prove that the use of sorbitol or mannitol alone is disadvantageous in melt technology. The use of mannitol is limited because of its high melting point (165°C) and the polymorph transition after melting. Sorbitol (melting point: 96.8°C) vitrifies from melt, therefore it is hard to handle during further processing. The melting point of the eutectic mixture (1.8% mannitol and 98.2% sorbitol) was 93.6°C. This mixture was unsuited for pressing because of its glassy property. Our results showed that the most favourable composition was the mixture of 30% mannitol and 70% sorbitol (melting point: 131.8°C) for tablet formulation. This mixture can be recommended for the formulation of such lozenge and hard candy tablets, where the active ingredient decomposes at higher temperature (>131.8°C).

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. They are able to stabilize o/w emulsions because their short lipophilic part integrates into the oil droplets whilst their long hydrophilic part forms a micro-gel around the droplet. In this study, correlations between the microstructure of these emulsions and the bioadhesive behaviour were found. Rheological and thermogravimetric methods were used to examine the microstructure of the emulsions. The mucoadhesive measurements were performed by tensile test and the bioadhesive bond between the polymer emulsifier and mucin was visualized by confocal laser scanning microscopy. It was established that (i) these emulsion form a special structure, which depends on the components, (ii) there were no remarkable changes in bioadhesive force and work when the oil content was increased in the emulsions, and (iii) the emulsions in which the polymeric emulsifier formed a special structure showed stronger adhesivity than the ones with simple polymer network.

Study of the microstructure of o/w creams with thermal and rheological methods

Thermogravimetric and rheological investigations of oil/water (o/w) creams prepared with different types of surface-active agents (non-ionic, non-ionic POE-free, ionic) were carried out. Thermogravimetry was aimed at the indirect study of the water bond mechanism in o/w creams and the influence of the composition, type and concentration of the mixed emulsifier on the binding of water incorporated in the structure (interlamellar, bulk) and on the binding proportions. The microstructural changes during application were studied with respect to the stability of the lamellar bilayer.

Intranasal Delivery of Human β-Amyloid Peptide in Rats: Effective Brain Targeting

Abstract(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 β-amyloid (Aβ) peptides, to measure the delivery of the peptides to brain regions, and to test their biological activity in rats. (2) Aβ1-42, in the form of a mixture of oligomers, protofibrils, and fibrils was dissolved in a nasal formulation containing hydrophobic, hydrophylic, and mucoadhesive components. The peptide solution was administered intranasally to rats as a single dose or in repeated doses. (3) Nasally injected Aβ labeled with the blue fluorescent dye amino-methyl coumarinyl acetic acid (AMCA) could be detected by fluorescent microscopy in the olfactory bulb and frontal cortex. The concentration of the peptide was quantified by fluorescent spectroscopy, and a significant amount of AMCA-Aβ peptide could be detected in the olfactory bulb. Unlabeled Aβ also reached the olfactory bulb and frontal cortex of rats as evidenced by intense immunostaining. (4) In behavioral experiments, nasal Aβ treatment did not affect anxiety levels (open-field test) and short-term memory (Y-maze test), but significantly impaired long-term spatial memory in the Morris water maze. The treatments did not result in Aβ immunization. (5) The tested intranasal delivery system could successfully target a bioactive peptide into the central nervous system and provides a basis for developing a non-invasive and cost effective, new model to study amyloid-induced dysfunctions in the brain.

The effect of storage on the behaviour of Eudragit NE free film

Eudragit NE 30 D aqueous dispersion is a commonly used coating material, which contains methacrylate copolymers as film-forming agent and nonoxynol 100 as an endogenous emulsifier. The dissolution of the active ingredient from Eudragit NE-coated samples during storage is known to undergo a change. The crystallization of the emulsifier agent can play an important role in this. This polymer is not soluble in the gastrointestinal tract, but is permeable. Various parameters can influence the permeability of this film, e.g. via the tensile properties of the film. Change in the film thickness can cause the stretching of the film on a solid surface. Alterations in this physical parameter of the film were measured and the effects of different storage conditions were evaluated. The free film was prepared by spraying onto teflon. The crystallization of nonoxynol was followed via the changes in the DSC curve of the free film. A relationship was found between the film thickness and the crystallization of nonoxynol. It was established that the different storage conditions influence these changes. The temperature and the air humidity are important in this phenomenon. Lengthening of the storage time increased the difference in film thickness and crystallisation of emulsifier.

Crystal growth of drug materials by spherical crystallization

One of the crystal growth processes is the production of crystal agglomerates by spherical crystallization. Agglomerates of drug materials were developed by means of non-typical (magnesium aspartate) and typical (acetylsalicylic acid) spherical crystallization techniques. The growth of particle size and the spherical form of the agglomerates resulted in formation of products with good bulk density, flow, compactibility and cohesivity properties. The crystal agglomerates were developed for direct capsule-filling and tablet-making.

Pelletization of needle-shaped phenylbutazone crystals

The flowability of needle- or plate-shaped crystals is very poor and the direct compression of these crystals is difficult. Commercial phenylbutazone consists of needle crystals and it has three polymorphs.The aim of this work was to investigate the solid-state thermal stability of phenylbutazone at condition of the pelletization process (40°C; 60 min). The other aim was the preparation of phenylbutazone pellets with centrifugal granulator.Based non the flowability and the other parameters of, the pellets, they are suitable for capsule filling or tabletting. The centrifugal granulation and the conditions were favourable for the preparation of pellets from phenylbutazone in the form of needle crystals.

Optimization and development of stable w/o/w cosmetic multiple emulsions by means of the Quality by Design approach

The aim of our present work was to develop stable water‐in‐oil‐in‐water (w/o/w) cosmetic multiple emulsions that are proper for cosmetic use and can also be applied on the skin as pharmaceutical vehicles by means of Quality by Design (QbD) concept. This product design concept consists of a risk assessment step and also the ‘predetermination’ of the critical material attributes and process parameters of a stable multiple emulsion system. We have set up the hypothesis that the stability of multiple emulsions can be improved by the development based on such systematic planning – making a map of critical product parameters – so their industrial usage can be increased.

Study of the structure of coherent emulsions.

The object of the study was to analyse relationship between the rheological properties, thermogravimetric behaviour, physical stability, and the wetting contact angle of the lipophilic and aqueous phase of 300 creams of different compositions with a high water content (60-80%, w/w). The starting point was Jungingers theory: water is found in the cream structure in energetic (interlamellar) and steric forms (bulk water). Based on our investigations, an exponential function was found to exist between the contact angle of wetting and the slope of the TG-curves, between the contact angle of wetting and the viscosity of the creams, and between the contact angle of wetting and the evaporation rate of water. A linear relationship was found between the contact angle of wetting and the quantity of water separable by centrifugation.