Klára Pintye-Hódi

The compressibility and compactibility of different types of lactose

Objective: The purpose of this study was to investigate and quantify flow properties, compressibility, and compactibility of various pharmaceutical lactose powders found on the market today (DCL-11, DCL-21, M‐200, Flowlac-100, and Tablettose 70, 80, and 100). Methods: Flow properties were estimated by measuring flow time, angle of repose, and the Hausner ratio. Particle rearrangement was studied using Kawakitas linear model. Compressibility was studied using two ‘out-of-die’ methods: (i) the Heckel model and (ii) a modified Walker model. Compactibility was quantified using two methods: (i) the tensile strength profile (Cp) and (ii) the compactibility factor (Pr). Statistical approach was used to analyze the results. Results: Flow properties of all materials were passable or better, except for M-200, which has very poor flowability. Compressibility results demonstrated that the most compressible lactose is spray-dried grade of lactose (Flowlac-100) and the least compressible is milled lactose (M-200). Compactibility studies showed that β‐lactose (DCL-21) forms tablets with superior tensile strength in comparison with α-lactose. Conclusion: Results of the compressibility study showed that the discriminative power of modified Walker model is greater in comparison with Heckel model. Compactibility methods yield similar and comparable results.

Evaluation of surface and microstructure of differently plasticized chitosan films

Surface and structural investigations of natural biopolymer (chitosan) films containing various conventionally applied hydrophilic plasticizers (glycerol and poly(ethylene glycol) 400) were performed and the results were compared, with the aim of acquiring new information concerning the formation of these plasticized films. The surface tests revealed that the water uptake, the water-binding properties (moisture content) and the polarity were higher for the film containing glycerol as plasticizer. Positronium lifetime measurements and NMR studies performed to evaluate the effects of the plasticizer on the polymer structure demonstrated relevant differences in the effects of the plasticizers. The influence of glycerol on the structure of the film formed was more intensive than that of PEG 400. It can be concluded that the surface properties of the films, which are very important for their storage and application, cannot be established exactly by means of structural tests. Both surface and structural tests must be performed before the formulation of this type of plasticized mucoadhesive films.

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.

Study of the recrystallization in coated pellets - Effect of coating on API crystallinity

Coated diltiazem hydrochloride-containing pellets were prepared using the solution layering technique. Unusual thermal behavior was detected with differential scanning calorimetry (DSC) and its source was determined using thermogravimetry (TG), X-ray powder diffraction (XRPD) and hot-stage microscopy. The coated pellets contained diltiazem hydrochloride both in crystalline and amorphous form. Crystallization occurs on heat treatment causing an exothermic peak on the DSC curves that only appears in pellets containing both diltiazem hydrochloride and the coating. Results indicate that the amorphous fraction is situated in the coating layer. The migration of drugs into the coating layer can cause changes in its degree of crystallinity. Polymeric coating materials should therefore be investigated as possible crystallization inhibitors.

Surface Treatment of Indomethacin Agglomerates with Eudragit

Indomethacin is a widely used anti‐inflammatory drug with serious side‐effects. This drug was used as a model drug for the coating of agglomerates with a permeable film (Eudragit NE). The agglomeration of the crystals increased the flowability of the bulk crystals. The coating further improved the flowability, and also the uniformity of the mass of the filled capsules. The coating film also influenced the wetting of the samples. The coating decreased the surface free energy and therefore reduced the adhesion forces between both the dry and the wet particles. The modification of the flow properties and the even capsule filling can be explained by this phenomenon. Since coating film does not dissolve in the artificial gastric juice, the dissolution test was performed only in the artificial intestinal juice. The dissolution of indomethacin from the coated sample was changed significantly. Accordingly, coating of the crystals can be performed in order to protect the mucosa of the gastrointestinal tract or to promote the preparation of solid dosage form.

Role of surface free energy and spreading coefficient in the formulation of active agent-layered pellets

Formulation of layered pellets can be a useful method for the preparation of multiparticulate systems. The aims of this work were to study the properties of hydrophilic active agent (pirenzepine dihydrochloride) layers formed on different pellet cores, the efficacy of layering and the connection between the core and the layers. The carrier pellets were prepared from mixtures of a hydrophilic (microcrystalline cellulose) and a hydrophobic (magnesium stearate) component in different ratios. These cores were coated in a fluid bed apparatus with an aqueous solution of active agent, with or without the addition of hydroxypropyl methyl cellulose (HPMC) as an adhesive component. The wettability of the pharmaceutical powders was assessed by means of Enslin number and contact angle measurements, and the surface energy was determined. Spreading coefficients of the components were also calculated and correlated with pellet properties such as the content of active agent, the friability and the morphological appearance of the layered product. An increased friability of the layer formed and the lower effectiveness of the process were experienced with a reduction in the wetting of the core. The efficiency of layering on a less polar core could be increased by the addition of HPMC, but the sensitivity of these pirenzepine layers to mechanical stress was higher. The type of the abrasion of these particles was dissimilar to that for samples prepared without HPMC. Peeling of the layers containing HPMC was observed for hydrophobic cores, but this phenomenon was not detected for the hydrophilic ones. These results can be explained by the spreading coefficients, which revealed an insufficient adhesion of layers for the samples that exhibited peeling.

Study of in vitro and in vivo dissolution of theophylline from film-coated pellets

Tests were performed on the influence of polymer coating films on the rates and the extents of in vitro and in vivo liberation of theophylline from pellets. Uncoated and coated pellets were used in the experiments. The coating material was Eudragit L; The film thickness was varied. The in vivo liberation of theophylline was studied in rabbits. The serum level of the released drug measured with a TDX Analyser. No appreciable difference was observed between the uncoated and the coated pellets as concern the maximum release data, but a significant shift was found in t(max) for Eudragit L coated pellets.

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.

Evaluation of powder mixtures and hydrophilic gastroretentive drug delivery systems containing zinc acetate and sodium bicarbonate

The aim of this study was to develop and study floating controlled drug delivery systems consisting of a model drug (zinc acetate dihydrate), different forms of a matrix-forming polymer (Metolose 90 SH) and sodium bicarbonate as an effervescent component. The proportions of Metolose and bicarbonate were varied, and the effects of the different ratios on the properties of the resulting powders and tablets were determined. The water uptakes of different powder mixtures were initially evaluated. These tests indicated the interaction of the active and effervescent agent, this phenomenon leading to an unpredicted increase in the amount of liquid taken up. This interaction was evaluated as concerns the degradation of the hydrophilic matrix system. The disintegration of tablets with different compositions revealed that this interaction increases the time required for the disintegration of these systems. The study demonstrated that the interaction of the components induced significant changes in the parameters of this new sensitive delivery system. In the last steps, the buoyancy and dissolution properties of tablets that appeared appropriate for the formulation of a controlled drug delivery system were investigated.

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.