Exploration of Neusilin® US2 as an Acceptable Filler in HPMC Matrix Systems—Comparison of Pharmacopoeial and Dynamic Biorelevant Dissolution Study

Modern pharmaceutical technology still seeks new excipients and investigates the further use in already known ones. An example is magnesium aluminometasilicate Neusilin^® US2 (NEU), a commonly used inert filler with unique properties that are usable in various pharmaceutical fields of interest. We aimed to explore its application in hypromellose matrix systems (HPMC content 10–30%) compared to the traditionally used microcrystalline cellulose (MCC) PH 102.

The properties of powder mixtures and directly compressed tablets containing individual fillers NEU or MCC, or their blend with ratios of 1.5:1, 1:1, and 0.5:1 were investigated. Besides the routine pharmaceutical testing, we have enriched the matrices’ evaluation with a biorelevant dynamic dissolution study and advanced statistical analysis. Under the USP apparatus 2 dissolution test, NEU, individually, did not provide advantages compared to MCC. The primary limitations were the burst effect increase followed by faster drug release at the 10–20% HPMC concentrations. However, the biorelevant dynamic dissolution study did not confirm these findings and showed similarities in dissolution profiles.

It indicates the limitations of pharmacopoeial methods in matrix tablet development. Surprisingly, the NEU/MCC blend matrices at the same HPMC concentration showed technologically advantageous properties. Besides improved flowability, tablet hardness, and a positive impact on the in vitro drug dissolution profile toward zero-order kinetics, the USP 2 dissolution data of the samples N75M50 and N50M50 showed a similarity to those obtained from the dynamic biorelevant apparatus with multi-compartment structure. This finding demonstrates the more predictable in vivo behaviour of the developed matrix systems in human organisms.

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About this article: Bílik, T.; Vysloužil, J.; Naiserová, M.; Muselík, J.; Pavelková, M.; Mašek, J.; Čopová, D.; Čulen, M.; Kubová, K. Exploration of Neusilin^® US2 as an Acceptable Filler in HPMC Matrix Systems—Comparison of Pharmacopoeial and Dynamic Biorelevant Dissolution Study. Pharmaceutics 2022, 14, 127. https://doi.org/10.3390/pharmaceutics14010127

Materials
Caffeine (Zentiva k.s, Prague, Czech Republic) was selected as a slightly soluble model drug. Hypromellose—HPMC K4M (Colorcon Limited, Dartford, UK) was a release-retarding polymeric carrier.
Magnesium aluminometasilicate Neusilin® US2 (Fuji Chemical Industries Co., Ltd., Toyoma, Japan) and microcrystalline cellulose Avicel® PH 102 (MCC) (FMC Biopolymers, Rockland, ME, USA) were added as the compared insoluble fillers. Magnesium stearate (Peter Greven, Bad Münstereifel, Germany) and colloidal SiO2 (Aerosil® 200) (Degussa, Vicenza, IT) were used to facilitate the powder blends flow. The chemicals used for the preparation of dissolution media were as follows: for USP 2 dissolution test—sodium chloride; hydrochloric acid (1 M) for preparation of 1.2 pH artificial gastric juice without pepsin (2 g/80 mL per 1000 g); sodium triphosphate for its pH adjustment to pH 6.8; for dynamic dissolution test—sodium chloride; potassium chloride; and pepsin (all Sigma–Aldrich, St. Louis, MO, USA) for preparation of the pH 1.8 dissolution medium (4 g/0.2 g/2.6 g per 2000 g). For HPLC, a mixture of acetic acid (Dr. Kulich Pharma, Hradec Králové, Czech Republic) and methanol (Honeywell, Bucharest, RO) in an 80:20 ratio was used as a mobile phase.

Also see the first part of our interview with Fuji Chemicals here: