Influence of talc and hydrogenated castor oil on the dissolution behavior of metformin-loaded pellets with acrylic-based sustained release coating

Multi-unit pellet system (MUPS) is of great interest as it is amenable to customization. MUPS comprises multi-particulates, usually as pellets or spheroids, which can be coated with diffusion barrier coatings. One commonly used diffusion barrier coating is the methacrylic acid copolymer, which can be used as a taste masking, enteric or sustained release polymer. While the versatility of methacrylic acid copolymers makes them pliable for pellet coating, there are impediments associated with their use. Additives commonly required with this polymer, including plasticizer and anti-adherent, have been shown to weaken the film strength. The objective of this study was to investigate the impact of osmotic pressure within the core on the sustained release coat integrity and functionality. Hydrogenated castor oil (HCO) was chosen as the additive to be studied.

Metformin-loaded pellets, prepared via extrusion-spheronization, were coated with ethyl acrylate and methyl methacrylate copolymer (Eudragit RS 30 D) with talc, talc-HCO, or HCO to different coat thicknesses. Drug release was investigated using the USP dissolution apparatus 2 and an ultraviolet imager. The swelling of the pellets when wetted was monitored by video imaging through a microscope. When coated to 7.5 % coat weight gain, coats with HCO slowed down drug release more than the other pellets. The pellets also swelled the most, which suggests that they were more resistant to the osmotic pressure exerted by metformin. For drugs which exert high osmotic pressure, HCO can serve as an efficient alternative to talc in the preparation of methacrylic acid copolymer coatings.

Materials

Metformin (metformin HCl; Granules India, Hyderabad, India) was the model drug. Lactose monohydrate (Granulac 200, Meggle, Wasserburg, Germany) was the filler, and microcrystalline cellulose (MCC; Avicel PH 101, FMC BioPolymer, Cork, Ireland) was the spheronizing aid. Methacrylic acid copolymer (ERS; Eudragit RS 30 D, Evonik, Essen, Germany) was employed as the coating polymer with triethyl citrate (TEC; Merck Schuchardt OHG, Hohenbrunn, Germany) as the plasticizer. Talc

Tze Ning Hiew, Leong Wai Siew, Suchipha Wannaphatchaiyong, Ramy N. Elsergany, Wiwat Pichayakorn, Prapaporn Boonme, Paul Wan Sia Heng, Celine Valeria Liew, Influence of talc and hydrogenated castor oil on the dissolution behavior of metformin-loaded pellets with acrylic-based sustained release coating, International Journal of Pharmaceutics, 2023, 122984, ISSN 0378-5173, https://doi.org/10.1016/j.ijpharm.2023.122984.

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