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.

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Materials
Hermes Arzneimittel GmbH (Pullach, Germany) kindly provided the APIs and the coating material. PharmaZell GmbH (Raubling, Germany) delivered N-acetylcysteine (NAC). Caffeine anhydrous granules were from Siegfried Pharma Chemikalien Minden GmbH (Minden, Germany) and acetylsalicylic acid (ASA) 40–80 mesh from Shandong Xinhua Pharmaceutical Co. LTD (Zibo, China). Hydrochlorothiazide (HCT) and metformin HCl (MET) were acquired from Suzhou Lixin Pharmaceutical Co., Ltd. (Suzhou, China) and Shouguang Fukang Pharmaceutical Co., Ltd. (Shouguang, China), respectively.
Magnesium stearate LIGAMED MF-2-V E470 was obtained from Peter Greven Nederland C.V. (Venlo, Nederland). Tripalmitin (PPP, melting point: 63–68 °C), commercially available as Dynasan®116, was purchased from IOI Oleo GmbH (Witten, Germany). Polysorbate 65 (PS 65, melting point: 33.3 °C, HLB = 10.5), available as TweenTM65, was obtained from Croda International Plc (Snaith, UK). Double distilled, deionized water was used (Ultrapure Water System, Milli-Q Merck Life Science, Darmstadt, Germany). The liquid α-bromonaphthalene (95% purity) was purchased from TCI Deutschland GmbH (Eschborn, Germany), and ethylene glycol (99% purity) and n-hexane (99% purity) were achieved from Carl Roth GmbH + Co. KG (Karlsruhe, Germany). The PTFE foil was obtained from Walfront (Wuhan, China).

About this Article: Schertel, S.; Salar-Behzadi, S.; Zimmer, A. Impact of Surface Properties of Core Material on the Stability of Hot Melt-Coated Multiparticulate Systems. Pharmaceutics 2021, 13, 366. https://doi.org/10.3390/pharmaceutics13030366