Comparative Study of Spray-Drying and Freeze-Drying Techniques for Increasing Fenofibrate’s Solubility and Dissolution Rate

Abstract

Background: Fenofibrate (FF) is a BCS class II compound whose poor solubility poses challenges in drug delivery and bioavailability. Solid self-micro emulsifying drug delivery systems (S-SMEDDS) have emerged as a promising solution to address these issues. These systems are aimed at enhancing the solubility and dissolution rates of poorly soluble drugs, such as FF, by formulating them into solid dosage forms.

Methods: FF solubility was investigated in various oils, surfactants, and co-surfactants to identify the most suitable components for formulating S-SMEDDS. The preparation of S-SMEDDS was carefully evaluated according to parameters including drug content, morphological characteristics, and structural features. Two methods, freeze-drying, and spray-drying, were compared for their efficacy in producing S-SMEDDS. Additionally, in vitro dissolution studies were conducted to assess the dissolution rates of FF-loaded S-SMEDDS tablets compared with conventional tablets.

Results: Among the oils tested, oleic oil achieved the highest FF solubility, whereas Tween 80 and Transcutol HP were identified as the optimal surfactant and co-surfactant, respectively. The preparation method significantly influenced the properties of S-SMEDDS. Freeze-drying outperformed the other methods by enhancing dissolution rates, primarily through increased surface area. Moreover, the solid-state characteristics of S-SMEDDS were dependent on the polymer concentration and processing method. In vitro dissolution studies demonstrated that FF-loaded S-SMEDDS tablets exhibited faster drug release than conventional tablets, owing to the inclusion of the super disintegrating agent CCS and the S-SMEDDS component. Freeze-drying was superior to spray-drying in enhancing dissolution, albeit with potentially higher production costs.

Conclusions: The study highlights the potential of S-SMEDDS to overcome the solubility and bioavailability challenges associated with FF. Freeze-drying emerged as the preferred method for producing S-SMEDDS, because of its superior dissolution enhancement capabilities, despite potentially higher production costs, whereas spray-dried S-SMEDDS offers economic and environmental benefits, but may achieve lower dissolution rates. Overall, our findings underscore the importance of formulation strategy in enhancing the efficacy of poorly soluble drugs such as FF.

Introduction

Advancements in biochemical understanding, combinatorial chemistry, and high-throughput selection have led to the development of NCE with poor water solubility, thus posing challenges in oral drug delivery [1–3]. Using amorphous drug forms increases dissolution rates, thereby overcoming solubility limitations [4–6]. However, amorphous systems are inherently unstable because of their elevated free energy, thus substantially hindering their inclusion in commercially available drug products [7, 8].

Lipid-based drug carriers play a major role in increasing drug molecule solubility, dissolution, and bioavailability within the gastrointestinal tract. SMEDDS formulations use bile salt as well as lipolytic agents to create a solubilized phase, thus aiding in drug release during digestion. After dilution in the aqueous environment, the formulation transitions to small oil-in-water micro-emulsions, thereby enhancing drug delivery [9]. The mechanical churning that naturally occurs in the stomach and intestines during digestion leads to emulsion formation. Beyond enhancing solubilization, the inclusion of fat in these formulations increases drug bioavailability by influencing absorption [10, 11].

Fenofibrate (FF), a BCS class II lipid-lowering medication, poses challenges of low solubility and limited bioavailability [12–15]. Various approaches, including cyclodextrin complexation and solid dispersion, have been explored to address these limitations. SMEDDS and SEDDS formulations have gained attention for enhancing FF’s bioavailability and dissolution [16–21].

Solid self-micro emulsifying drug delivery systems (S-SMEDDS) offer various advantages, such as cost-effective manufacturing; straightforward process control; high stability, consistency; and enhanced patient adherence, solubility and bioavailability. In addition, they can be used for generating nanoparticles, microspheres, and easily flowable powders [22]. Hence, producing solid-state formulations of L-SMEDDS or converting formulations into solid dosage forms are recommended to leverage the combined benefits of SMEDDS. Spray-drying and lyophilization are widely used methods to transform L-SMEDDS into S-SMEDDS. These methods can create dry micro-emulsions containing submicrometer particles, such as microspheres and micro-particles. This technique has recently received substantial interest to effectively solidify liquid SMEDDS. The spray-drying technique is favored for converting liquid SMEDDS in industrial applications. Rapid solvent evaporation increases viscosity, and entraps oil droplets with drug molecules in a carrier matrix [23–25].

Limited research has examined conversion of FF-SMEDDS into solid forms through spray-drying and freeze-drying approaches. The study was aimed at developing solid SMEDDS through these techniques for tablet dosage forms, to increase patient adherence as well as product stability.

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Materials

FF was sourced from Wockhardt Ltd, Aurangabad. Ingredients including Kolliphor RH 40, Cremophore RH 40, PEG 300 and 400, castor oil, oleic acid, Tween 80, and Transcutol HP were obtained from BASF, Mumbai. Maltodextrin was obtained from Nutrichem Products, Mumbai, whereas MCC CCS, talc, and magnesium stearate were obtained from Maple Biotech, Pune.

Aarti P. Nikam, Pawan D. Meshram and Archana V. Vanjari et al. Comparative Study of Spray-Drying and Freeze-Drying Techniques for Increasing Fenofibrate’s Solubility and Dissolution Rate. BIOI. 2024. Vol. 5(1). DOI: 10.15212/bioi-2024-0010