G. Csóka

New formulation of in situ gelling Metolose-based liquid suppository

Context: An in situ gelling liquid suppository is liquid at room temperature but forms a gel at body temperature. In our work, Metolose® SM-4000 (methylcellulose) is studied that basically shows thermal gelation at 68°C (2%, w/w). Objective: The objective was to study the potency of different factors (concentration, pH, additives) to change the value of thermal gelation temperature (T t) for Metolose® to form an in situ gelling liquid suppository. Materials and methods: We studied the effect of Metolose® concentration, pH, and salts (sodium chloride, potassium chloride, sodium hydrogen carbonate, and sodium monohydrogen phosphate) on T t by viscosimetry. To choose the appropriate compound, in vitro drug release was examined. Rectal safety test was performed on rats in vivo after 12-hour application. Results: Increasing the Metolose® concentrations (0.5–4%, w/w), T t can be decreased, but it also altered the consistency of gel. pH does not affect the T t. The water-soluble salts allowed reducing the gelation temperature to 37°C. Sodium monohydrogen phosphate in 4.5% concentration was found to be the most appropriate. The impact of examined factors on in vitro drug release of piroxicam from the in situ-formed gel was characterized according to Fickian diffusion. Metolose® and the chosen salt did not cause any morphological damage on the rectal tissues. Discussion: According to our study, Metolose® has the physical and chemical potential to be used as base for liquid suppositories.

Formulation of thermoresponsive and bioadhesive gel for treatment of oesophageal pain and inflammation

The aim of this study was the formulation and examination of a novel thermoresponsive and bioadhesive, in situ gelling drug delivery system, which can be used in the treatment of oesophageal pain and inflammation. A bioadhesive cellulose derivative (Metolose) 60SH) was used as a thermoresponsive material, because Metolose has thermal gelation properties at certain temperature. The thermal gelation temperature (T(2)) of Metolose 60SH 2 w/w% solution is above body temperature (65-66 degrees C), but by using different methods (Metolose 60SH concentration, auxiliary materials), it can be shifted near to body temperature. The pH alteration between pH=2-10 and the application of different alcohols did not influence the gelation temperature, but using water-soluble salts and changing the concentration of Metolose 60SH solution between 2 and 3 w/w% the thermal gelation point could be decreased. Different NSAIDs were used as model drugs and which had not influence on thermal gelation temperature, but difference in in vitro liberation and penetration can be observed. In vitro adhesion test pointed out that the condition of investigated membrane can change the adhesion. Morphological test of oesophageal tissue showed that investigated materials had no irritative or tissue-damaging effect on the oesophageal mucosa even after 12h.

Coating Polymer-plasticizer Interaction in Relation to the Enthalpy Relaxation of Polymer

In the course of the formulation of coated dosage forms, the selection of the suitable composition of the coating system is of great importance in respect of the final dosage form. Since the applied coating systems are multicomponent, the possible interactions between the components determine the physico-chemical stability of the formulated dosage form, the drug release process, as well as the formulation parameters. In the present study, the influence of the applied plasticizer, dibutyl sebacate on the enthalpy relaxation of casted Eudragit L 30D films was determined as a function of the plasticizer concentration. The enthalpy relaxation was recorded by DSC during the applied isothermal recovery process of Eudragit films. The obtained results indicate that enthalpy relaxation can be measured by DSC at 20 mass/mass% dibutyl sebacate concentration, which refers to the increased molecular mobility consequently to the effect of the interaction between the polymer and plasticizer.

Preparation of pH-sensitive beads for NSAID using three-component gel systems

The aim of this study is to prepare novel pH-sensitive beads to obtain a gastric mucosa protective formulation and to ensure drug delivery into the intestine. Diclofenac sodium was used as a model drug. Bead formation was achieved by ionotropic gelation method using three-component gel system containing sodium alginate (Na-Alg), hydroxyethylcellulose (HEC) and hydroxypropylmethylcellulose (HPMC). Factors influencing the characteristics of beads (exposure time, cross-linking agent concentration, polymer ratio) were investigated by swelling and erosion tests based on gravimetric method. Drug release was tested in distilled water and/or artificial digestive fluids and evaluated with Korsmeyer-Peppas equation and Baker-Lonsdale model. The encapsulation behaviour was qualitatively indicated by differential scanning calorimetry (DSC) method. In vivo experiments were conducted to test ulcerogenicity and intestinal absorption in rats. HPMC increased the encapsulation efficiency (EE) and HEC improved the drug release in the intestinal fluids. The equilibrium water uptake (EWU) was correlated with exposure time, calcium chloride concentration and HEC amounts. Bead erosion increased proportionately to exposure time, while it reduced when calcium chloride concentrations were increased. Higher amounts of HEC increased, while higher pH values reduced the encapsulation efficacy. The in vivo experiments demonstrated that the studied encapsulation technology markedly reduced the ulcerogenic effect of diclofenac.

The preparation and examination of polymorphous vincristine sulphate

The examination of the polymorphism of tumour inhibitory vincristine sulphate with a bis-indole skeleton is described. The changes in molality with temperature were followed thermo-osmometrically. It could be shown by X-ray diffraction that a sample separated by cooling the solution had an amorphous structure and the proportion of the X-ray-amorphous part of the substance along with the crystalline phase increased when the temperature of the solution was lowered from 50°C to 40°C to 30°C. At lower temperatures, a mixture of molecular associations of different masses coexists in dynamic equilibrium. Polymorphic modifications of various compositions, characterized by different ratios of the crystalline and amorphous phases in the solid substance, can be obtained during the course of crystallization.