Texture Analyzer-Derived SeDeM-ODT Extension for Bisoprolol Fumarate Orodispersible Tablets: Formulation Discrimination Within a Pharmacopoeial Disintegration-Compliant Space

Abstract

Background/Objectives:

Conventional SeDeM-ODT screening relies on physicochemical properties and endpoint disintegration tests, which may have limited discriminatory power among formulations that already meet pharmacopoeial disintegration requirements. This study aimed to extend SeDeM-ODT by incorporating texture analyzer-derived descriptors of low-volume liquid disintegration behavior.

Methods:

Bisoprolol fumarate was used as a low-dose model drug. Selected excipients were characterized using SeDeM and conventional SeDeM-ODT approaches. Texture analyzer distance–time profiles were used to derive swelling efficiency (SE), residue height (RH), and structural transition efficiency (STE), which were converted into SeDeM-compatible parameters. Orodispersible tablets were developed using a two-factor central composite design and evaluated for mechanical properties, pharmacopoeial disintegration, comparative dissolution performance, texture analyzer behavior, and supportive Heckel parameters.

Results:

All formulations met the pharmacopoeial disintegration criteria and showed rapid drug release under the applied dissolution conditions. Conventional endpoint-based responses showed limited discriminatory value within the investigated formulation space. In contrast, SE, RH, and STE differentiated formulation-dependent swelling, residual structural persistence, and transition toward structural collapse under low-volume liquid controlled-force conditions. MCC-rich formulations generally retained greater residual structure, whereas lactose-rich and/or higher-superdisintegrant formulations showed lower residual persistence. Comparative kinetic fitting and Heckel analysis supported these interpretations but did not independently establish a definitive disintegration mechanism.

Conclusions:

Incorporating low-volume liquid texture analyzer-derived parameters into SeDeM-ODT improved the comparative interpretation of excipient and formulation behavior. These findings suggest that pharmacopoeial disintegration compliance may coexist with distinct structural pathways not fully captured by conventional endpoints.

1. Introduction

Orodispersible tablets (ODTs) are solid oral dosage forms designed to disintegrate rapidly in the oral cavity before swallowing, thereby improving ease of administration and patient acceptability, particularly in pediatric, geriatric, dysphagic, and non-compliant patient populations [1,2,3,4]. According to the European Pharmacopeia, orodispersible tablets should disintegrate within 3 min; however, faster, more predictable disintegration is generally desirable to ensure patient comfort and consistent product performance [5]. In addition to rapid disintegration, ODTs must exhibit sufficient mechanical strength to withstand manufacturing, packaging, handling, and administration. Therefore, ODT development requires a careful balance between rapid liquid-mediated breakdown and adequate tablet robustness [3,6].
Direct compression is one of the most attractive manufacturing approaches for ODTs because of its simplicity, cost-effectiveness, limited processing steps, and suitability for scale-up [7,8]. However, the success of direct compression strongly depends on the functional properties of the active pharmaceutical ingredient and excipients [9]. Powder flowability, compactability, compressibility, lubricity, dilution potential, and disintegration behavior all contribute to the manufacturability and performance of the final dosage form [10]. This is particularly important in low-drug-loaded ODT formulations, where the excipient system predominantly governs tablet structure, porosity, mechanical integrity, and disintegration behavior. Consequently, rational excipient selection is essential for developing robust directly compressed ODTs.
The SeDeM Expert System provides a systematic preformulation tool for evaluating the suitability of powders for direct compression [11]. By transforming experimentally determined powder properties into normalized radius values, the SeDeM approach enables visual and numerical assessment of critical powder attributes, including dimensional characteristics, compressibility, flowability, lubricity/stability, and lubricity/dosage [12]. The SeDeM-ODT Expert System further extends this framework by incorporating a disgregability factor, making it more relevant for materials intended for orally disintegrating dosage forms [10,13]. This makes SeDeM and SeDeM-ODT useful tools for identifying functional limitations in APIs and excipients prior to formulation development.
Nevertheless, the conventional disgregability factor in SeDeM-ODT is mainly based on effervescence/dispersion time and pharmacopoeial disintegration testing performed with and without a disk [14,15]. These tests are valuable for confirming whether a material or formulation meets predefined disintegration requirements, but they may provide limited mechanistic information. In particular, endpoint-based or observation-dependent measurements may fail to distinguish materials or formulations that show similar disintegration times but differ in swelling capacity, structural persistence, liquid-mediated weakening, or collapse behavior. This limitation becomes especially relevant when comparing superdisintegrants or when evaluating formulations that already comply with pharmacopoeial disintegration requirements.
Texture analyzer-based disintegration testing offers an opportunity to obtain a more quantitative and mechanistically informative description of tablet disintegration [16]. Under controlled-force and low-volume liquid conditions, the texture analyzer records distance–time profiles that reflect dynamic structural changes during liquid uptake, swelling, structural transition, and residual plateau formation. Previous studies have demonstrated the usefulness of texture analysis for measuring disintegration-related parameters such as swelling distance, onset and end of disintegration, disintegration rate, and residue height [16,17]. However, the integration of texture analyzer-derived descriptors into a SeDeM-compatible framework remains limited. Such integration may improve the discriminatory capacity of SeDeM-ODT by converting profile-derived disintegration behavior into normalized parameters that can be compared with conventional SeDeM indices. In addition, comparative kinetic evaluation of distance–time profiles may support the interpretation of how swelling and structural transition progress over time, without assigning a definitive disintegration or drug-release mechanism.
A quality-by-design-oriented formulation strategy also requires systematic evaluation of how formulation variables affect critical quality attributes [18]. Central composite design (CCD) is widely used to investigate formulation factors, interactions, and nonlinear effects while reducing experimental burden [19,20]. In ODT development, CCD can be used to evaluate how diluent composition and superdisintegrant concentration influence tablet mechanical strength, pharmacopoeial disintegration, dissolution performance, and texture analyzer-derived disintegration behavior. However, when formulations exhibit similar pharmacopoeial disintegration and dissolution outcomes, conventional tests may not be sufficiently discriminatory within the compliant design space. In this context, texture analyzer-derived parameters may provide additional insight into formulation-dependent structural behavior.
Bisoprolol fumarate was selected as a low-dose model drug because its limited drug loading allowed formulation performance to be governed predominantly by the excipient matrix. This study aimed to develop a texture analyzer-derived extension of the SeDeM-ODT framework capable of providing profile-based discrimination among directly compressed ODT formulations that already satisfy the pharmacopoeial disintegration requirement. The novelty of the proposed approach lies in transforming swelling efficiency (SE), residue height (RH), and structural transition efficiency (STE) into SeDeM-compatible parameters, thereby complementing conventional endpoint-based disgregability assessment with quantitative information on swelling development, residual structural persistence, and structural transition under low-volume liquid conditions.

2. Materials and Methods

2.1. Materials

Bisoprolol fumarate was provided by World Medicine (Türkiye). Polyplasdone® XL and Polyplasdone® XL-10 (crospovidone; Ashland, USA), Vivapur® 200 (microcrystalline cellulose; JRS Pharma GmbH & Co. KG, Germany), Avicel® PH 102 (microcrystalline cellulose; IFF Pharma Solutions, USA), and Tablettose® 80 (α-lactose monohydrate; MEGGLE GmbH & Co. KG, Germany) were kindly supplied by Ashland Türkiye. Vivasol® (croscarmellose sodium; JRS Pharma GmbH & Co. KG, Germany) was kindly supplied by Bilim İlaç (Türkiye). Magnesium stearate was obtained from Sigma-Aldrich (St. Louis, MO, USA). All materials were of pharmaceutical grade and were used as received without further modification. Distilled water was used throughout the experiments involving aqueous media.

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Afşin, Ç.; Şahbaz, S.; Özer-Önder, S.; Uğurlu, T. Texture Analyzer-Derived SeDeM-ODT Extension for Bisoprolol Fumarate Orodispersible Tablets: Formulation Discrimination Within a Pharmacopoeial Disintegration-Compliant Space. Pharmaceutics 2026, 18, 940.
https://doi.org/10.3390/pharmaceutics18080940