Development and Evaluation of Amorphous Oral Thin Films Using Solvent-Free Processes: Comparison between 3D Printing and Hot-Melt Extrusion Technologies

Abstract

Conventional oral dosage forms may not always be optimal especially for those patients suffering from dysphasia or difficulty swallowing. Development of suitable oral thin films (OTFs), therefore, can be an excellent alternative to conventional dosage forms for these patient groups. Hence, the main objective of the current investigation is to develop oral thin film (OTF) formulations using novel solvent-free approaches, including additive manufacturing (AM), hot-melt extrusion, and melt casting. AM, popularly recognized as 3D printing, has been widely utilized for on-demand and personalized formulation development in the pharmaceutical industry. Additionally, in general active pharmaceutical ingredients (APIs) are dissolved or dispersed in polymeric matrices to form amorphous solid dispersions (ASDs). In this study, acetaminophen (APAP) was selected as the model drug, and Klucel™ hydroxypropyl cellulose (HPC) E5 and Soluplus® were used as carrier matrices to form the OTFs. Amorphous OTFs were successfully manufactured by hot-melt extrusion and 3D printing technologies followed by comprehensive studies on the physico-chemical properties of the drug and developed OTFs. Advanced physico-chemical characterizations revealed the presence of amorphous drug in both HME and 3D printed films whereas some crystalline traces were visible in solvent and melt cast films. Moreover, advanced surface analysis conducted by Raman mapping confirmed a more homogenous distribution of amorphous drugs in 3D printed films compared to those prepared by other methods. A series of mathematical models were also used to describe drug release mechanisms from the developed OTFs. Moreover, the in vitro dissolution studies of the 3D printed films demonstrated an improved drug release performance compared to the melt cast or extruded films. This study suggested that HME combined with 3D printing can potentially improve the physical properties of formulations and produce OTFs with preferred qualities such as faster dissolution rate of drugs.

Quality by design-based development and optimization of fourth-generation ternary solid dispersion of standardized Piper Longum extract for melanoma therapy

“…Apart from this, no potential degradation was observed up to 300.78°C, demonstrating the thermal stability of Soluplus ® up to this temperature. Similar TGA data of Soluplus ® was reported previously [82,81]. Further, a continuous weight loss of 21.961% between 300.78°C to 355.183°C, 67.97% between 355.183°C to 464°C, and 7.508% between 464°C to 800°C were due to its degradation.…”

Rapid Prototyping Technologies: 3D Printing Applied in Medicine

“…We found that 3D printing technology has the following applications in pharmacy: To print pills according to the individual condition of the patient [ 118 ]; To make the dosage more suitable for each patient’s own physical condition [ 119 , 120 , 121 , 122 ]; To print tablets with specific shapes and structures to control the release rate [ 123 , 124 ]; To precisely control the distribution within cells [ 125 ]; To develop biomaterials to build organs [ 126 , 127 , 128 , 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 , 141 , 142 , 143 , 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 ]; To develop biomaterials to build organs-on-a-chip for drug testing [ 152 ]; To make transdermal microneedle patches to reduce pain in patients [ 153 ]. …”

Orodispersible Films: Current Innovations and Emerging Trends

“…The advanced physicochemical analyses, including Raman mapping, revealed the existence of drugs in an amorphous state in both the HME and 3D-printed films. Nevertheless, a relatively consistent distribution of amorphous drugs was observed in the 3D-printed films in comparison to the films fabricated using other techniques [ 116 ]. The findings indicate that combining the HME and 3DP methods holds significant promise for improving the physical attributes of formulations and producing ODFs with favorable features, such as rapid drug dissolution rates.…”