Glycerol monostearate-based solid oleogels for dosage form individualization by molding designed using Design of Experiments

Abstract

Solidification of lipid-based formulations and dosage form individualization are two trends seen in oral drug delivery. This study proposes an approach for obtaining individualized solid lipid-based formulations, namely, glycerol monostearate-based solid oleogels individualized by molding. Oleogels consist of oil immobilized by a gelling agent. We investigated if it is possible to obtain glycerol monostearate-based oleogels that possess textural properties enabling them to be handled as solid dosage forms.

Highlights

• Oleogelation as an alternative solidification approach for lipid-based formulations
• Molding for dosage form individualization requiring no special equipment
• Design of Experiments to efficiently establish the design space of solid oleogels
• Disintegrants enhanced solid oleogel disintegration and ibuprofen release

Using DoE, the design space for preparing solid oleogels was established. Here, hardness and stiffness, derived from texture analysis, were used as responses in addition to moldability. The DoE study showed that glycerol monostearate-based solid oleogels can be obtained within a certain design space dependent on the gelling agent concentration, sorbitan monooleate concentration and gel setting temperature. Here, addition of sorbitan monooleate influenced the textural properties in a non-linear manner. The moldability evaluation yielded limits for hardness and stiffness where molding was possible. To assess the predictability of the DoE models, oleogels with new compositions within the design space were prepared and tested. As a proof-of-concept, ibuprofen-loaded oleogels were prepared and characterized in terms of textural properties, correctness of dosing, and drug release.

The textural properties of ibuprofen-loaded oleogels were similar to those without ibuprofen when avoiding low gel setting temperatures. Correct dosing is possible as indicated by tests for uniformity of mass and content uniformity. Before testing ibuprofen release, disintegration was evaluated, indicating very slow disintegration. Disintegration was significantly improved by croscarmellose sodium and sodium starch glycolate. Similarly, during dissolution testing 70 and 25 % ibuprofen was released from glycerol monostearate-based solid oleogels with and without disintegrant, respectively. This study has established a first platform for moldable solid oleogels.

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Chemicals

The gelling agent used in this study was glycerol monostearate (GMS) with a purity of >95 % from Thermo Scientific (Thermo Fisher Scientific, Waltham, MA, USA). Four different oils were used in this study: rapeseed oil, sunflower oil, peanut oil, and tricaprylin. Rapeseed oil and sunflower oil, long-chain triglycerides, were obtained from a local supermarket. Peanut oil, a long-chain triglyceride with mainly oleic acid (35–76 %) and linoleic acid (8–43 %) as fatty acids, was obtained from Thermo Scientific via avantor™. Tricaprylin (Captex 8000), a medium-chain triglyceride, was kindly gifted by ABITEC Corporation (Columbus, OH, USA). Furthermore, croscarmellose sodium (VIVASOL® GF), crospovidone (polyvinylpolypyrrolidone, VIVAPHARM® PVPP XL), and sodium starch glycolate Type A (EXPLOTAB®) gifted from JRS Pharma GmbH & Co.KG (Rosenberg, Germany) and sorbitan monooleate (Span® 80) from Fluka™ obtained from avantor™ were used as oleogel additives. During the preparation of GMS oleogels, methanol and acetone of technical grade were used. As a model drug, ibuprofen was used, which was of pharmaceutical grade, and obtained from Caelo (Caesar & Loretz GmbH, Hilden, Germany).

Asta Kabels, Helena Sundgaard Trabjerg, Felix Paulus, Ingunn Tho, Ann-Christin Jacobsen, Glycerol monostearate-based solid oleogels for dosage form individualization by molding designed using Design of Experiments, Journal of Controlled Release, 2025, 114140, ISSN 0168-3659, https://doi.org/10.1016/j.jconrel.2025.114140.

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