Impact of polysorbate 65 on tripalmitin crystal growth and release stability of hot melt coated multiparticulate systems.

ABSTRACT

Hydrochlorothiazide (HCT) multiparticulate systems (MPS) were hot melt coated with the binary mixture of tripalmitin (PPP) and polysorbate 65 (PS 65) to gain an immediate release profile. Once, HCT MPS were produced with a constant ratio of PPP/PS 65 (9010) at three different coating amounts (15, 25, and 60%w/w) and once the PPP/PS 65 ratio was varied on 982 and 8020, by keeping the coating amount at 60%w/w. PS 65 induced the polymorphic transformation of PPP from the α-form to its most stable ß-form right after the hot melt coating (HMC). A release alteration of HCT, either accelerated or decelerated, occurred after the storage under accelerated conditions. The effect of the API core on the lipid lamellar configuration, the thermal behavior of lipid coating, and the effect of PS 65 concentration on the crystal growth of PPP were investigated via X-ray diffraction and DSC. While a low amount of PS 65 was sufficient to promote crystal growth of PPP and resulted in a decelerated release of HCT from the coating, a higher PS 65 concentration favored phase separation of PPP and PS 65 and led to an accelerated release. The increase in PS 65 reinforced the molecular interaction with the lipophilic HCT, reflected in less crystal growth and decelerated release. The knowledge presented in this study supports understanding the instability of binary emulsifier-lipid coating systems, paving the way for developing robust HMC formulations.