Formulation of Orally Disintegrating Films as an Amorphous Solid Solution of a Poorly Water-Soluble Drug

Abstract

The objective of the present study was to develop an orally disintegrating film (ODF) for a poorly water-soluble drug, phenytoin (PHT), using the cosolvent solubilization technique to achieve the amorphization of the drug, followed by the preparation of ODFs. Eleven formulations were prepared with different polymers, such as polyvinyl alcohol (PVA) and high methoxyl pectin (HMP) by the solvent casting method. The prepared films were subjected to characterization for weight variations, thickness, surface pH, disintegration time and mechanical strength properties. Then, differential scanning calorimetry, X-ray diffraction analysis and the drug release patterns of the selected films were evaluated. Among the prepared formulations, the formulation composed of 1% w/w of PVA, 0.04% w/w of sodium starch glycolate with polyethylene glycol 400, glycerin and water as cosolvents (PVA-S4) showed promising results. The physical appearance and mechanical strength properties were found to be good. The PVA-S4 film was clear and colorless with a smooth surface. The surface pH was found to be around 7.47 and the in vitro disintegration time was around 1.44 min. The drug content of the PVA-S4 film was 100.27%. X-ray diffractometry and thermal analysis confirmed the transition of phenytoin in the PVA-S4 film into a partially amorphous state during film preparation using the cosolvent solubilization approach. The resulting PVA-S4 film showed a higher dissolution rate in comparison to the film without a cosolvent. Overall, this study indicated the influence of cosolvents on enhancing the solubility of a poorly water-soluble drug and its film dissolution.

“Success Depends on Your Backbone”—About the Use of Polymers as Essential Materials Forming Orodispersible Films

“…From the obtained formulations, these consisting of 1% (w/w) PVA, 0.04% (w/w) sodium starch glycolate and PEG 400, glycerin and water as cosolvents led to development of promising products. The physical appearance (transparent and colorless ODF with a smooth surface), mechanical strength, drug content and disintegration time were found to be optimal [73].…”

Thermogelling Hydroxypropyl Methylcellulose Nanoemulsions as Templates to Formulate Poorly Water-Soluble Drugs into Oral Thin Films Containing Drug Nanoparticles

“…In the past decade, oral films have emerged as a novel solid dosage form that shows great potential over other solid dosage forms for the delivery of poorly water-soluble drugs. ,, Their large surface area-to-volume ratios enable the rapid dissolution and absorption of drugs in the gastrointestinal tract, leading to significantly increased bioavailability . In addition, they are easy to swallow and thus show exceptional acceptability for geriatric, pediatric, and dysphagic patients. , In a typical film-forming process, a nanosuspension is first prepared and then mixed with a film-forming polymer solution to form a film precursor for casting and drying. − Wet stirred media milling is one of the most extensively used techniques to formulate nanoparticle suspensions because it is a robust and well-established process that can be applied to many hydrophobic drugs. , However, it generally involves long milling durations (3–12 h), , and the erosion of milling media may cause severe contamination of drugs. , In addition, irreversible nanoparticle aggregation during long-time processing and drying is still a common problem that can reduce the dissolution rate of drug nanoparticles and negatively affect the drug uniformity in oral films. , The aggregation problem becomes even more prominent when more drug nanoparticles are incorporated in oral films, rendering the oral film technology limited to low drug loading capacity. , Other film-forming technologies involve the incorporation of amorphous solid dispersions − and solid lipid nanoparticles, − both of which provide improved bioavailability of poorly water-soluble drugs. However, amorphous solid dispersions are susceptible to recrystallization that undermines the drug efficacy, , and the recrystallization becomes more significant with increasing drug loadings .…”

Embedding of Poorly Water-Soluble Drugs in Orodispersible Films—Comparison of Five Formulation Strategies

“…In another study, ethanol and PEG (polyethylene glycol) were used as co-solvents to improve the solubility of the poorly water-soluble API phenytoin. Promising ODFs in terms of film properties such as disintegration time and mechanical properties could be prepared by using PVA (polyvinyl alcohol) as a film-forming polymer, but X-ray diffraction patterns of the films still indicated a crystalline nature of the API [ 17 ].…”