Thermal analysis of systems containing theophylline and three types of Compritol

The use of fluid-bed or spray-drying processing in the development and production of solid dosage forms is increasing. These processes are traditionally used for granulation and the drying and coating of powders, granules, tablets, beads. Generally speaking, the coating material is dissolved in a solvent (water or organic) prior to spraying. During and after coating the solvent must be evaporated. The use of solvents nowadays is under constraint due to the problems of trace levels, while recovering a solvent often proves expensive. Moreover also long evaporation time of the solvent (especially water) could be a problem. In order to avoid such problems and to reduce costs, it is appealing to use meltable materials, such as waxes or derivatives or other different low-melting lipid materials – as coating agents. The aim of the present study was to analyse the ability of different types of Compritol, namely Compritol 888 ATO (glyceryl di-behenate), Compritol E ATO (mixture of mono-, di- e tri-glycerides of behenic acid: mp 67-80°C) and Compritol HD5 ATO (mixture of glyceril di-behenate and PEG -mp. 60-67°C) to sustain the release of theophylline, used as tracer model drugs incorporated into a solid dispersion prepared by the melting method using the three lipid materials. Formulations with drug:Compritol 10, 20 and 30 % w/w were evaluated: physical mixtures were heat treated at 80°C for 10 min to prepare the solid dispersions. The material thus obtained was maintained at -20° for 2 days and then milled and sieved. Samples of each formulation were analyzed by DSC and HSM, revealing the different solvent ability of the molten phase of each Compritol. In fact at HSM, after the melting of the carrier, undissolved theophylline particles are clearly evident at all the compositions examined that demonstrated to dissolve into the molten carrier at increasing temperature. This event was not documented by DSC thermograms that therefore did not offer important information. HSM technique revealed also suitable to examine the effects of aging. After 6 months comparison of similar situations (composition, temperature, and nature of the carrier) revealed the presence of a larger amount of crystallized material. Increased particle amount was due to crystallization of previously dissolved drug, during the preparation of the solid dispersion that, in the presence of the solid carrier was only delayed. This fact was also confirmed by dissolution profiles: a control of the release was obtained only at the lowest concentration, while at higher concentrations no difference could be observed with respect to pure theophylline: this was hypothesized as due to better coating of the drug particles by the lipid carrier, suggesting at the same time that the concentration range, useful to obtain a control of the release of theophylline, is quite restricted. Better results, in terms of control of the release, were obtained if the molten phase was spray-congealed using an ultrasound assisted device. In this case the process allowed obtaining spherically shaped microparticles: SEM and HSM observation indicated that single theophylline particles were coated by the lipid material that could slow down dissolution of the drug with respect to pure drug. On the contrary in the final dispersion, after solidification, the milling could have acted along fracture lines that made free the drug particle surface, hindering any control to the release by the lipid material.