Quality by design approach for fabrication of extended-release buccal films for xerostomia employing hot-melt extrusion technology.

The study endeavors the fabrication of extended-release adipic acid (APA) buccal films employing a quality by design (QbD) approach. The films intended for the treatment of xerostomia were developed utilizing hot-melt extrusion technology. The patient-centered quality target product profile was created, and the critical quality attributes were identified accordingly. Three early-stage formulation development trials, complemented by risk assessment aligned the formulation and process parameters with the product quality standards. Employing a D-optimal mixture design, the formulations were systematically optimized by evaluating three formulation variables: amount of the release-controlling polymer Eudragit® (E RSPO), bioadhesive agent Carbopol® (CBP 971P), and pore forming agent polyethylene glycol (PEG 1500) as independent variables, and % APA release in 1, 4 and 8 h as responses. Using design of experiment software (Design-Expert®), a total of 16 experimental runs were computed and extruded using a Thermofisher ScientificTM twin screw extruder. All films exhibited acceptable content uniformity and extended-release profiles with the potential for releasing APA for at least 8 h. Films containing 30% E RSPO, 10% CBP 971P, and 20% PEG 1500 released 88.6% APA in 8 h. Increasing the CBP concentration enhanced adhesiveness and swelling capacities while decreasing E RSPO concentration yielded films with higher mechanical strength. The release kinetics fitted well into Higuchi and Krosmeyer-Peppas models indicating a Fickian diffusion release mechanism.

Advanced 3D Electrospinning "Xspin" System: Fabrication of Bifiber Floating Oral Pharmaceutical Scaffolds for Controlled Drug Delivery.

Electrospinning has become a widely used and efficient method for manufacturing nanofibers from diverse polymers. This study introduces an advanced electrospinning technique, Xspin - a multi-functional 3D printing platform coupled with electrospinning system, integrating a customised 3D printhead, MaGIC - Multi-channeled and Guided Inner Controlling printheads. The Xspin system represents a cutting-edge fusion of electrospinning and 3D printing technologies within the realm of pharmaceutical sciences and biomaterials. This innovative platform excels in the production of novel fiber with various materials and allows for the creation of highly customized fiber structures, a capability hitherto unattainable through conventional electrospinning methodologies. By integrating the benefits of electrospinning with the precision of 3D printing, the Xspin system offers enhanced control over the scaffold morphology and drug release kinetics. Herein, we fabricated a model floating pharmaceutical dosage for the dual delivery of curcumin and ritonavir and thoroughly characterized the product. Fourier transform infrared (FTIR) spectroscopy demonstrated that curcumin chemically reacted with the polymer during the Xspin process. Thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) confirmed the solid-state properties of the active pharmaceutical ingredient after Xspin processing. Scanning electron microscopy (SEM) revealed the surface morphology of the Xspin-produced fibers, confirming the presence of the bifiber structure. To optimize the quality and diameter control of the electrospun fibers, a design of experiment (DoE) approach based on quality by design (QbD) principles was utilized. The bifibers expanded to approximately 10-11 times their original size after freeze-drying and effectively entrapped 87% curcumin and 84% ritonavir. In vitro release studies demonstrated that the Xspin system released 35% more ritonavir than traditional pharmaceutical pills in 2 h, with curcumin showing complete release in pH 1.2 in 5 min, simulating stomach media. Furthermore, the absorption rate of curcumin was controlled by the characteristics of the linked polymer, which enables both drugs to be absorbed at the desired time. Additionally, multivariate statistical analyses (ANOVA, pareto chart, etc.) were conducted to gain better insights and understanding of the results such as discern statistical differences among the studied groups. Overall, the Xspin system shows significant potential for manufacturing nanofiber pharmaceutical dosages with precise drug release capabilities, offering new opportunities for controlled drug delivery applications.

A new dual function orodissolvable/dispersible meclizine HCL tablet to challenge patient inconvenience: in vitro evaluation and in vivo assessment in human volunteers.

Meclizine hydrochloride (MCZ), a first-generation antihistamine of the piperazine class, is antiemetic and intended for the management of nausea and vomiting with few adverse effects. The introduction of orodispersible tablet (ODT) would solve the problems encountered in the administration of this drug to pediatric, geriatric, and psychiatric patients. It would be even more advantageous if the MCZ tablet could provoke rapid and prolonged efficacy. Achieving concomitant rapid and prolonged drug therapeutic effects in orodissolvable/dispersible dosage forms would be challenging. In this respect, the authors prepared tablets with coats and cores for immediate and prolonged drug absorption. To achieve this goal, nanoparticles of MCZ from chitosan (CS) and shellac (SH) were prepared by ionic crosslinking and then directly compressed with excipients to form the core in a coated tablet. The immediate release coat with MCZ with the same excipients as in the core was amenable by direct compression. MCZ in the coat dissolved in the presence of a superdisintegrant, leading to rapid absorption from the buccal cavity. Meanwhile, enteric-coated nanoparticles were swallowed and dissolved in the GIT. Intuitively, the absorption process was prolonged. The in vitro release characteristics of all the tablets were studied in comparison with a commercial tablet (CT). Additionally, evaluation of the in vivo pharmacokinetic profile of both the prepared and commercial tablets was performed in humans. The dual function tablet disintegrated in 58 s at pH 5.5. In vivo, noncompartmental pharmacokinetic analysis showed concomitant rapid absorption, possibly from the coat, followed by prolonged absorption from the core. Successfully, these good results confirm that combined rapid and prolonged MCZ therapy with the prepared dual function orodissolvable/dispersible tablet could be a promising oral drug delivery system to enhance convenience for patients. Hopefully, dual function tablets will confer a benefit through the accommodation of more than a single medication in the case of multiple therapies.