Going green: Development of a sustainable lipid-based enteric coating formulation for low-dose aspirin multiparticulate systems.

There is a rising awareness of pharmaceutical industry of both patient-centric and sustainable product development. Manufacturing of multiparticulate systems (MPS) with functional coating via solvent-free hot melt coating (HMC) can fulfill both requirements. An innovative lipid-based formulation was developed with the composition of palmitic acid and Grindsted® citrem BC-FS (BC-FS) for enteric coating of acetylsalicylic acid (ASA). The ASA crystals were directly hot melt coated to produce user-friendly low-dose ASA MPS for thromboembolism prophylaxis. Prior to HMC, rational boundaries for the process temperature were defined based on the melting and crystallization behavior of coating blend. Stability of coating in terms of resistance to heat stress and solidstate stability were screened via Fourier-transform infrared spectroscopy and x-ray diffraction. Exposure of coating blend to 100 °C for two hours did not cause any chemical degradation. Crystal growth of palmitic acid and polymorphic transformation in BC-FS were observed after storage under accelerated conditions, however did not significantly affect the ASA release from coating. The developed formulation is a unique solvent-free, lipid-based enteric composition and paves the way for sustainable green pharmaceutical manufacturing.

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

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 (90:10) at three different coating amounts (15, 25, and 60%w/w) and once the PPP/PS 65 ratio was varied on 98:2 and 80:20, 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.

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

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.