W Sutananta

An evaluation of the mechanisms of drug release from glyceride bases

A series of dispersions containing theophylline in Gelucires 43/01, 54/02, 50/02, 50/13 and 55/18 was prepared and the physical structures studied using differential scanning calorimetry. The dissolution, erosion and swelling profiles of the drug dispersions were assessed.

The effects of ageing on the thermal behaviour and mechanical properties of pharmaceutical glycerides

Abstract The thermal behaviour of stored Gelucires 43/01, 50/02, 54/02, 50/13 and 55/18 has been studied, particularly with a view to examining the relationship between preparation conditions and physical stability. The endotherms of Gelucire 43/01 samples were found to approach an equilibrium shape on storage, with samples which had been fast cooled from the melt adopting this shape over the shortest period of time. Tempering of these materials at elevated temperatures resulted in alterations in the distribution of endotherms and represents a possible method of accelerating the transition to the equilibrium form. Ageing of Gelucires which contain mixes of glycerides and polyethylene glycol (PEG) esters resulted in changes in the endotherm shape but no evidence for an equilibrium profile was obtained. Studies on Gelucire 55/18, which contains only PEG esters, showed that the main endothermic peak exhibited little evidence for ageing effects, although a lower temperature shoulder was observed on storage. Tensile strength (/gs) measurements indicated that the strength of the Gelucires also changed on storage. It was noted that materials containing either glycerides or PEG esters tended to show an increase in /gs on storage, while Gelucires containing a mixture of the two components showed a decrease in strength.

An investigation into the effect of preparation conditions on the structure and mechanical properties of pharmaceutical glyceride bases

Abstract The structures of a range of pharmaceutical glycerides (Gelucires 43/01, 50/02, 54/02, 50/13 and 55/18) have been studied using polarized light microscopy fitted with a hot-stage facility and differential scanning calorimetry (DSC). In particular, the effects of preparation conditions on the structure and melting behaviour of the samples have been examined using protocols involving solvent crystallisation and solidification from the melt using different cooling rates. Despite the chemical complexity of these systems, the Gelucires crystalled into distinct regions which could be differentiated using polarized light microscopy. Hot-stage microscopy studies showed that the solvent and slow melt crystallisation processes generally resulted in a greater proportion of material in the higher melting point forms. DSC produced a series of broad peaks which yielded melting data which was in reasonable agreement with those obtained using the microscopy studies. A greater dependence on preparation conditions was found for Gelucires with a higher glyceride content. The tensile strengths of tablets moulded from the various Gelucires were examined and were shown to be dependent on the preparation conditions used.

AN INVESTIGATION INTO THE EFFECTS OF PREPARATION CONDITIONS AND STORAGE ON THE RATE OF DRUG-RELEASE FROM PHARMACEUTICAL GLYCERIDE BASES

The effects of preparation conditions on the release of theophylline from Gelucires 50/13 and 55/18 have been investigated. Samples were prepared by melting physical mixes under controlled conditions, followed by either slow or fast (ambient) cooling to the solid state.

THE USE OF LOW-FREQUENCY DIELECTRIC-SPECTROSCOPY AS A NOVEL MEANS OF INVESTIGATING THE STRUCTURE OF PHARMACEUTICAL GLYCERIDE BASES

Abstract The dielectric responses of five glyceride bases have been assessed using low frequency dielectric spectroscopy. It was observed that each base showed different electrical behaviour. In addition, samples were either slow or fast cooled from the melt in order to change the physical structure of each material; in all cases where differences were observed, the slow cooled samples showed a greater response than fast cooled materials. The results are discussed in terms of both the movement of charges within the system and the relationship between these charge movements and the physical structure of the material. It is proposed that the differences in dielectric response between the various samples may be influenced by a number of factors, particularly chemical composition, while the differences between the responses of fast and slow cooled materials may be a reflection of segregation of the components of the bases into distinct regions. These studies indicate that dielectric analysis may be used as a novel means of characterising solid materials of pharmaceutical interest.

The use of dielectric analysis as a means of characterising the effects of moisture uptake by pharmaceutical glyceride bases

The effects of storing Gelucires 43/01, 50/02, 50/13 and 55/18 under dry conditions (5% RH) and conditions of elevated humidity (80% RH) have been investigated using differential scanning calorimetry (DSC), viscosity measurements, low frequency dielectric spectroscopy and dissolution studies. DSC investigations indicated that Gelucires containing a high proportion of polyethylene glycol (PEG) stearates showed more marked changes when stored at elevated humidities than did those containing a higher proportion of glycerides. Similarly, Gelucire 55/18, which contains only PEG stearates, showed evidence of degradation on storage at high humidities. Dielectric studies indicated that samples containing a higher proportion of PEG stearates demonstrated an increase in response after storage at elevated humidities compared to freshly prepared samples, while those stored under dry conditions generally showed a decrease. Dissolution studies indicated that while the rate of theophylline release from Gelucire 50/02 samples decreased on storage at elevated humidities, the dissolution rate from Gelucire 50/13 samples increased. This may be a reflection of the different mechanisms of drug release from the two bases.