TY - JOUR

T1 - Hot Melt Coating of Amorphous Carvedilol

AU - Bannow, Jacob

AU - Koren, Lina

AU - Salar-Behzadi, Sharareh

AU - Lobmann, Korbinian

AU - Zimmer, Andreas

AU - Rades, Thomas

PY - 2020

Y1 - 2020

N2 - The use of amorphous drug delivery systems is an attractive approach to improve the bioavailability of low molecular weight drug candidates that suffer from poor aqueous solubility. However, the pharmaceutical performance of many neat amorphous drugs is compromised by their tendency for recrystallization during storage and lumping upon dissolution, which may be improved by the application of coatings on amorphous surfaces. In this study, hot melt coating (HMC) as a solvent-free coating method was utilized to coat amorphous carvedilol (CRV) particles with tripalmitin containing 10% (w/w) and 20% (w/w) of polysorbate 65 (PS65) in a fluid bed coater. Lipid coated amorphous particles were assessed in terms of their physical stability during storage and their drug release during dynamic in vitro lipolysis. The release of CRV during in vitro lipolysis was shown to be mainly dependent on the PS65 concentration in the coating layer, with a PS65 concentration of 20% (w/w) resulting in an immediate release profile. The physical stability of the amorphous CRV core, however, was negatively affected by the lipid coating, resulting in the recrystallization of CRV at the interface between the crystalline lipid layer and the amorphous drug core. Our study demonstrated the feasibility of lipid spray coating of amorphous CRV as a strategy to modify the drug release from amorphous systems but at the same time highlights the importance of surface-mediated processes for the physical stability of the amorphous form.

AB - The use of amorphous drug delivery systems is an attractive approach to improve the bioavailability of low molecular weight drug candidates that suffer from poor aqueous solubility. However, the pharmaceutical performance of many neat amorphous drugs is compromised by their tendency for recrystallization during storage and lumping upon dissolution, which may be improved by the application of coatings on amorphous surfaces. In this study, hot melt coating (HMC) as a solvent-free coating method was utilized to coat amorphous carvedilol (CRV) particles with tripalmitin containing 10% (w/w) and 20% (w/w) of polysorbate 65 (PS65) in a fluid bed coater. Lipid coated amorphous particles were assessed in terms of their physical stability during storage and their drug release during dynamic in vitro lipolysis. The release of CRV during in vitro lipolysis was shown to be mainly dependent on the PS65 concentration in the coating layer, with a PS65 concentration of 20% (w/w) resulting in an immediate release profile. The physical stability of the amorphous CRV core, however, was negatively affected by the lipid coating, resulting in the recrystallization of CRV at the interface between the crystalline lipid layer and the amorphous drug core. Our study demonstrated the feasibility of lipid spray coating of amorphous CRV as a strategy to modify the drug release from amorphous systems but at the same time highlights the importance of surface-mediated processes for the physical stability of the amorphous form.

KW - hot melt coating (HMC)

KW - amorphous solids

KW - solid-state

KW - amorphous stability

KW - amorphous drug delivery

KW - dynamic in vitro lipolysis

KW - carvedilol

KW - tripalmitin

KW - SURFACE CRYSTALLIZATION

KW - PHARMACEUTICAL SOLIDS

KW - DRUG FORMULATIONS

KW - DISSOLUTION RATE

KW - DOSAGE FORMS

KW - STABILIZATION

KW - INDOMETHACIN

KW - SOLUBILITY

KW - STRATEGIES

KW - STABILITY

U2 - 10.3390/pharmaceutics12060519

DO - 10.3390/pharmaceutics12060519

M3 - Journal article

C2 - 32517255

VL - 12

JO - Pharmaceutics

JF - Pharmaceutics

SN - 1999-4923

IS - 6

M1 - 519

ER -