The daily variations in the environment brought on by the rotation of the globe (for example, the amount of sunshine) are what determine all forms of life on Earth [1,2]. Hence it should come as no surprise that many aspects of mammalian physiology and behavior change periodically with the time of day (referred to as “circadian rhythms”; “circadian” means “about a day”). Without any entraining inputs, circadian rhythms are strictly speaking free-running or endogenous rhythms [3]. The occurrence of circadian rhythm illness events has a well-documented temporal relationship with circadian variation in a few physiologic variables [4,5]. Moreover, some triggers have been demonstrated to raise the chance of the onset of a disease event [6]. As the need for more dynamic treatment and preventative techniques has been recognized, there has been an increase in interest in chronotherapeutics recently. To stop cardiovascular events, scientists are researching pharmacological technology and dose schemes.

Researchers working on drug delivery in academic and industrial labs face difficulties because most new chemical entities and many current medications have low water solubilities [7,8]. Despite the potential for these medications to have great pharmacological action, their low water solubility causes poor absorption and, as a result, subtherapeutic drug concentrations in the target tissues. The drug's hydrophobicity (defined as its reduced capacity to form hydrogen bonds with water) and a high crystal lattice energy are two factors that contribute to its insolubility (which prevents drug molecules from dissolving to form a solution) [9,10]. To improve the biopharmaceutical performance and absorption of poorly soluble medicines, numerous strategies have been investigated. Drug solubility has been shown to benefit from modifications at the molecular and particle levels [11]. Lastly, over the past two decades, the development of nanoparticle-based drug delivery systems has attracted significant attention, with polymer- or lipid-based nanoparticles among the most pertinent methods for the administration of hydrophobic chemicals [12,13]. Unfortunately, these strategies have several negative effects, many of which are connected to the physicochemical properties of the medication molecule itself. For instance, it must have the required molecular size and three-dimensional conformation to fit in dispersions techniques or be soluble in the lipid phase to be loaded into lipid-based nanocarriers [14]. Moreover, poor drug loading (5–30% w/w), a lack of long-term stability, and in some circumstances, the requirement for the inclusion of organic solvents is frequently linked to the production of nanocarriers. Few attempts have been to increase the flurbiprofen solubility by Bhaskar Daravath et al., In their present study, solvent evaporation method was used to prepare flurbiprofen solid dispersions and confirmed more solubility in higher pH values for solid dispersion formulations than compared to the fast-dissolving tablets [15]. Chronotherapeutic approach has been tried for flurbiprofen by few researchers. Matta Nalini Krishna Reddy et all. Developed Pulsatile tablets of flurbiprofen for chronotherapeutic drug delivery [16]. In another study the effect of double-compression coating on flurbiprofen core mini-tablets was studied to achieve the pulsatile colonic delivery to deliver the drug at a specific time as per the patho-physiological need of the disease that results in improved therapeutic efficacy [17].

In this situation, one of the most promising methods for improving the biopharmaceutical performance of hydrophobic medications is the formulation of drug nanocrystals (NC). Originally developed to boost the absorption of medications taken orally, NCs have several advantages over other nanoparticle-based drug delivery systems that are specific to this platform [18]. NC is free of carrier components, in contrast to lipid-based and polymeric nanocarriers, which raises their drug-loading capability to 100%. Moreover, they are easily scalable, have neutral pH, and long-term stability, and may be produced without the use of solvents. NCs are an intriguing formulation strategy for the distribution of hydrophobic actives across a variety of administration routes because of these factors [19].

The initial purpose of compression coating was to create incompatible medication formulations. Due to the advantages over solvent coatings, such as the lack of solvent consumption, quick manufacturing times, and the ability to add more weight to the core tablet, compression coating is growing in popularity, and formulation scientists are expressing interest in producing the modified release products [20]. Using a standard or specifically built tablet compression machine, the compression coating process compresses coating ingredients around a prefabricated core tablet without the requirement of a special solvent for coating. The term “press coating” or “solvent-free coating technique” or “dry coating technique” are also used to describe it [21]. Compositionally, a compression-coated tablet is made up of an interior core and an exterior coating. A single turret is used to produce the tiny, porous core tablet. You require a second turret with a larger die cavity to create the compression coating for the core tablet. Compression-coated tablets are created by first filling the die cavity with half of the coating material, placing the core tablet carefully in the centre, then filling the die cavity with the remaining half of the coating material to surround the core tablet and squeeze the powder that is contained within the core tablet. Finding a reproducible centre placement for the core tablet inside a compression-coated tablet is the biggest disadvantage of this technology [22].

Due to its effectiveness in treating rheumatoid arthritis, flurbiprofen (FP) has been selected as a model medication [23]. Rheumatoid arthritis often exhibits diurnal variations, with the highest disease activity in the early morning. This phenomenon is associated with the body's circadian rhythms and cytokine production, leading to increased inflammation and pain during these hours. Flurbiprofen is a non-steroidal anti-inflammatory drug (NSAID) that effectively reduces inflammation. By delivering it specifically to the colon, we take advantage of the natural circadian fluctuations in gastrointestinal blood flow, which can maximize drug availability during the early morning hours when symptoms are most pronounced. Flurbiprofen, like many NSAIDs, can lead to systemic side effects such as gastrointestinal irritation and cardiovascular risks. By utilizing colon-specific drug delivery, we aim to reduce the systemic exposure to the drug. This targeted delivery minimizes the risk of side effects, especially when compared to conventional oral NSAID administration that could lead to higher systemic drug levels.

In this study, NC compressed minitablets were developed and subsequently, compression coating was performed. Compression coating was optimized by using Quality by Design principles. Optimized formulation was further studied for its efficacy. The purpose of this study was to develop a compression-coated tablet that can deliver a virtually complete release of the drug in 4–6 h while limiting the drug's premature release to 10% or less for at least 6 h.