Study of Co-processed Excipient for Direct Compression Using the SeDeM-ODT Expert System

Abstract

Background

This study aimed to identify suitable excipients for the development of vitamin C orally disintegrating tablets (ODTs) using the SeDeM-ODT expert system as a systematic preformulation tool for direct compression.

Methods

Vitamin C and seven excipients, including both co-processed materials (Prosolv® ODT G2, Parteck® ODT, Ludiflash® , and Ludipress® LCE) and single-component excipients (Emdex®, Ceolus™ UF-702, and Ceolus™ UF-711), were evaluated based on SeDeM-ODT parameters related to powder flowability, compressibility, lubricity/stability, lubricity/dosage, and disintegrability. The suitability of each material for direct compression was assessed using the Index of Good Compressibility and Bucodispersibility (IGCB).

Results

Vitamin C alone exhibited poor compressibility, flowability, and disintegrability, resulting in an IGCB value below the acceptable limit and confirming its unsuitability for direct compression ODT formulation. Among the investigated excipients, Ludiflash^®, Parteck^® ODT, and Ceolus™ UF-702 achieved IGCB values above the acceptance threshold and were therefore selected for tablet formulation studies. Tablets prepared with these excipients (100 mg vitamin C, 200 mg excipient, and 1% magnesium stearate) were produced by direct compression and evaluated for mechanical strength, friability, disintegration time, and dissolution performance. All formulations exhibited acceptable tablet characteristics, including uniform weight, adequate mechanical strength, and rapid disintegration within pharmacopeial limits for ODTs. Dissolution testing confirmed rapid drug release, with more than 75% of vitamin C released within 45 min, and early-stage release occurring within the first minutes after disintegration.

Conclusion

Overall, the results demonstrate that the SeDeM-ODT expert system provides a reliable framework for excipient selection in ODT development, and confirm that Ludiflash^®, Parteck^® ODT, and Ceolus™ UF-702 are suitable excipients for the preparation of vitamin C orally disintegrating tablets by direct compression.

Introduction

Orally disintegrating tablets (ODTs) are solid oral dosage forms designed to disintegrate or disperse rapidly in the oral cavity (typically within seconds), forming a dispersion that is swallowed, which can facilitate subsequent drug dissolution and improve patient acceptability and adherence. To achieve fast disintegration, the formulated tablet must ensure high porosity, low density, and low tablet breaking force [1]. Over the past decade, there has been a substantial increase in the demand for the development of ODTs, significantly impacting patient compliance [2]. Particularly beneficial for those with difficulty swallowing, ODTs address the common issue of dysphagia across age groups, notably in the pediatric and geriatric population [3, 4]. Despite the advantages of orally disintegrating tablets for pediatric and geriatric populations, the palatability of the dosage form remains a major formulation challenge. Referred to by various names such as orodispersible tablets, quick disintegrating tablets, mouth dissolving tablets, fast disintegrating tablets, fast dissolving tablets, rapid dissolving tablets, porous tablets, and rapid melts [5, 6]. The United States Pharmacopoeia (USP) officially recognizes them as orally disintegrating tablets, with the FDA defining ODT as ‘‘A solid dosage form containing medicinal substance or active ingredient which disintegrates rapidly, usually within a matter of seconds when placed upon the tongue’’ [7]. The European Pharmacopoeia terms them “Orodispersible tablets” if they disperse readily in the mouth within 3 min before swallowing [8].

Multiple methods are available for manufacturing ODTs, including molding, lyophilization, freeze-drying, and direct compression. There are other methods available, such as cotton candy and spray drying [9, 10]. While lyophilization and spray drying were previously common methods with low disintegration time, conversely, low mechanical strength [11, 12]. Special packing was required for ODTs prepared by these techniques, and they were highly fragile. Additionally, these methods necessitated specialized equipment and were unsuitable for large doses of water-insoluble drugs [13]. Direct compression is now widely used. However, optimization of powder blend characteristics remains a challenge in direct compression. For the direct compression method to meet official requirements, the powder blend must possess optimum powder flow properties, mechanical strength, and disintegration behavior [14].

Co-processed excipients are attracting attention as they enhance functionality by combining the properties of individual excipients into a single particle. Produced through physical processing without chemical modification, they usually require less extensive toxicological evaluation [15]. By combining the favorable properties of individual excipients, co-processed excipients tend to be effective physical mixtures in pharmaceutical properties [16, 17]. Previous research has reported that combining excipients by co-processing can enhance content uniformity and reduce segregation problems in dosage units [16]. A co-processed excipient is used to support tablet manufacturing through the direct compression method. Despite their well-recognized technological advantages, the use of co-processed excipients in pharmaceutical formulations may present regulatory and registration challenges [15].

In the past, the development of pharmaceutical formulations relied mainly on experiments and research experience, which were slow and expensive processes. However, the SeDeM expert system, developed by Carreras et al. [18], has the potential to streamline this process by implementing the concept of pharmaceutical quality by design (QbD). QbD is a systematic approach that employs quality risk management and sound scientific principles to create new pharmaceutical products [19]. This is a new galenic method that is used in tablet pre-formulation and formulation studies, particularly for the DC method. Evaluating the powder characteristics of active pharmaceutical ingredients (APIs) and excipients by using the SeDeM diagram to determine their suitability for DC manufacturing or the need for additional excipients. Lately, the SeDeM-ODT expert system, an advancement, includes a Disgregability factor, enhancing the assessment of excipient properties [20].

This study aimed to predict suitable developed co-processed excipients using the SeDeM-ODT expert system to obtain orally disintegrating tablets for Vitamin C by the direct compression method. Although the SeDeM-ODT expert system and the investigated excipients are not novel individually, the originality of this work lies in their integrated and comparative application to a mechanically challenging API. By systematically evaluating excipients from different functional classes within a single SeDeM-ODT framework and validating the screening outcomes with tablet-level performance data, this study provides a decision-oriented approach to excipient selection for direct compression ODT development.

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Materials

Vitamin C (ascorbic acid) was received as a gift from HL Vitamin (Luwei Pharmaceutical Group Co., Ltd., China). The co-processed excipients for DC tablets were generously obtained as gifts from suppliers, including Prosolv® ODT G2 and Emdex® (JRS Pharma, USA), Ceolus™ UF-702 and Ceolus™ UF-711 (Asahi Kasei Chemicals Co., Japan), Parteck® ODT (Merck, Germany), Ludiflash® and Ludipress® LCE (BASF, Germany). Magnesium stearate was also received as a gift from Faci (Faci Asia Pacific Pte Ltd, Singapore). All other chemicals were analytical grade.

Al-Mohaya, M., Yeşilkaya, E., Ulu, H. et al. Study of Co-processed Excipient for Direct Compression Using the SeDeM-ODT Expert System. J Pharm Innov 21, 420 (2026). https://doi.org/10.1007/s12247-026-10623-w

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