Study of the Recrystallization in Coated Pellets

Coated multiparticulate systems are increasingly popular on the market. Their manufacture in a fluid bed often requires polymer binders. Polymers have been widely studied as inhibitors of crystallization [1]. Migration of drugs into the coating layer has also been described [2] but the influence of the coating polymers on the crystallization of the drug is yet to be studied in more depth. In our experiments we studied the thermal behaviour of diltiazem hydrochloridelayered pellets before and after coating. The multiparticulate pellet samples were prepared in a Strea-1 (Niro Aeromatic, Bubendorf, Switzerland) fluid bed Wurster chamber. Acryl-EZE dispersion (a fully formulated USP copolymer type C coating system) was prepared and applied following the guidelines provided by the manufacturer as a 20% aquous dispersion. The thermoanalytical examinations were carried out with a Mettler-Toledo 821 instrument with a dynamic method in the interval of 0–400°C, at a heating rate of 10°C/minute. We found that the coated samples exhibited an exothermic peak between 90110°C that wasn’t characteristic of any of the used materials. Further examinations suggested that the exothermic peak is the result of recrystallization; this theory was tested with XRD. Results showed that the uncoated drug-containing pellets contained only a relatively small amount of the crystalline drug. Coated samples behaved similarly. XRD examinations after heating the samples to 120°C (above the range of the exothermic peak) showed a definite increase in the crystallinity of the drug. Thermal examinations showed a correlation between the thickness of the coating and the extent of recrystallization. One explanation of the above is that the water-soluable drug dissolves into the aqueous coating dispersion on the surface of the pellets during the coating and crystallizes only in a small extent as the film is dryed; most of the drug forms a molecular dispersion in the film. Crystallization is completed only on heating, as can also be proven by microscopic evidence. This work was supported by “Stiftung Aktion Österreich-Ungarn“.