INTRODUCTION
Tablets represent the most common dosage form available in the market, but they present both pharmaceutical and clinical issues (1). Tablet compression is compromised when using a hygroscopic drug with low density (2,3). Moreover, drugs with low solubility, which are 60% of marketed compounds, would have a low dissolution into the gastrointestinal tract, causing a reduced bioavailability (4). Even if an oral tablet denotes easy administration for most of the patients, it represents a cause of discomfort for patients with swallowing aversion, pediatric and geriatric population, or with altered absorption diseases that do not benefit from conventional oral route (5–7). Some of the factors associated with low compliance are side effects experienced by the patient and the complexity of treatment, such as multiple dosing times every day (8). Therefore, tablets are not always preferred route of administration.
Oral cavity film administration has recently emerged as a promising alternative to solid dosage forms (9). Drug delivery via the oral cavity can take place by placing film under the tongue or placing the film on inner cheek allowing rapid absorption of the drug and is, therefore, suitable for fast-release formulations (10). An important factor influencing oral cavity drug delivery is lack of keratinization in cheek mucosa and sublingual regions resulting in high permeability and systemic delivery (11,12). Therefore, patches applied to buccal mucosa have a potential advantage to by-pass first-pass metabolism leading to an increase in the bioavailability (7,13,14). Furthermore, in comparison to oral tablets, films are ultrathin, flexible, and tend to be less obtrusive and therefore more acceptable (15).
Solvent casting is a prominent method used to prepare solid dispersion as an oral film where the cast solution is dried and cut into the desired size (16). This method is widely used to improve the dissolution of poorly water-soluble drugs and, therefore, to enhance their bioavailability in the body (17). Pharmaceutical film improvement in dissolution rate is often due to the use of hydrophilic polymers which cause an increase in solubilization effect of carrier (18). Furthermore, solid dispersions lead to a drug particle size reduction, improving drug wettability (19). In solid dispersion formulation, a key element is the morphological structure of compounds that could be either amorphous or crystalline affecting release profile of API from formulation (20). Modica de Mohac et al., in 2020, described as the different morphological structure could influence release profile and, therefore, important in polymer selection while improvement in release profile is sought (21). Mainly, crystalline and amorphous drugs present different enthalpy, entropy, and free energy that affect stability and dissolution rate of final dosage form (22). Amorphous materials show weaker attractive intermolecular forces that are more easily broken compared to crystalline counterparts, resulting in more soluble material and having a faster dissolution rate (20). However, several studies have shown that the formulation of solid microcrystalline dispersions could both improve dissolution rate and dosage form stability (16,23).
The overall aim of this study was to formulate a solid microcrystalline dispersion as a pharmaceutical film to investigate the effect of the combination of polyvinyl alcohol (PVA) and poly-N-hydroxyethyl-aspartamide (PHEA) concentration to increase drug dissolution profile by maintaining its crystalline state. PVA was selected as based polymer due to its water solubility and excellent film-forming properties (24). Furthermore, it is odorless and non-toxic. PVA was combined with novel polymer PHEA (25–27) that has many attractive properties, such as water solubility and absence of toxicity (28). Additionally, it is biodegradable and was used previously in drug delivery systems (29). PHEA is also very hydrophilic and has a high degree of mucoadhesion when formulated at 2.5% w/v in combination with PVA at 5% w/v (30). Present work aimed to prove that increasing concentration of PVA in conjunction with new polymer PHEA would allow obtaining a fast-release profile. Ibuprofen sodium was used as model drugs due to its low solubility of 0.0219 mg/mL (31). The oral film was produced via solvent casting and film physicochemical properties were characterized using attenuated total reflection Fourier transform infrared spectroscopy (ATR­FTIR), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). In vitro dissolution studies mimicking oral cavity were also conducted.