Impact of Surface Properties of Core Material on the Stability of Hot Melt-Coated Multiparticulate Systems

Abstract

Hot melt coating (HMC) of an active pharmaceutical ingredient (API) powder with lipid-based excipients is an innovative method for manufacturing patient-convenient dosage forms. However, drug release instability is still its main industrial challenge. The correlation between the unstable pharmaceutical product performance with the solid-state alteration of lipids is currently well-investigated. The remaining problem is the inconsistent release alteration of different APIs coated with the same lipid after storage, such as faster release in some cases and slower release in others. The interaction between API surface and lipid-based coating and its alteration during storage were investigated in this work. The surface properties of five different APIs and the coating composition of tripalmitin and polysorbate 65 were screened via Washburn and pendant drop methods, respectively. Metformin hydrochloride and hydrochlorothiazide particles were each coated with the coating composition. The water sorption alteration of coated particles and the crystal growth of tripalmitin in the coating after storage were measured via tensiometry and X-ray diffraction. The cleavage work necessary to overcome the adhesion of coating composition on the core surface was calculated for each API. The accelerated release of the polar core (metformin) after storage was correlated with a low cleavage work and a distinctive phase separation. In contrast, a decelerated release of the hydrophobic core (hydrochlorothiazide) was favored by the crystal growth of the lipid-based coating. The gained knowledge can be used to design the product stability during the formulation development.

Dry-Coating of Powder Particles is Current Trend in Pharmaceutical Field

“…Interest for using fluid-bed processor in HMC has grown to significant level since 2001 2,3 . Powdered mixture of the meltable and the non-meltable materials fed onto the seeds (powder particle cores) in a fluid-bed processor 24,[34][35][36] . The meltable materials can be added to the starting powder mixture can be in the form of either solid particles or molten liquid 37 .…”

“…Increased meltable material content increases coating thickness decreases dissolution rate of active 38,39 . The temperatures of the inlet-air and the product endpoint have more pronounced effect on parameters of coatings 2,3,36,39 .…”

“…This process eliminates the spraying step thus does not calls for steam jackets, nozzles, and/or heating assembly 3 . Powder particles (termed non-pareils) and powder of PEG (as divided solid particle with size 1.41-3.36 mm) were fluidised together 35,36,44 . The inlet air temperature is increased to melt the PEG thereby transferring them onto the non-pareils 4,44 .…”

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“…H-MC using F-BP: Herein mix of powdered nonmeltable materials & meltable CoMa is applied onto starting seeds (starting particles or powdered particulate cores) in an F-BP for realizing coating 2,[30][31][32] . The meltable CoMa (binder) can apply onto seeds as either molten liquid or solid particles 33 .…”

“…CoPr wherein meltable CoMa sprayed on starting seeds, as a molten liquid, is termed spray-on procedure 16,31 . From an industrial application angle, the procedure of melt-in process is simpler one comparing sprayon process, is favored over spray-on process 30,32 .…”