Fabrication of 3D-Printed Hydrocortisone Triple Pulsatile Tablet Using Fused Deposition Modelling Technology.

Hydrocortisone (HC) is the optimal drug for adolescents diagnosed with congenital adrenal hyperplasia (CAH). Because traditional dosage regimens HC are inconvenient, our study used fused deposition modeling (FDM) three-dimensional (3D) printing technology to solve the problems caused by traditional preparations. First, we designed a core-shell structure tablet with an inner instant release component and an outer delayed release shell. The instant release component was Kollicoat IR: glycerol (GLY): HC = 76.5:13.5:10. Then, we used Affinisol® HPMC 15LV to realize delayed release. Furthermore, we investigated the relationship between the thickness of the delayed release shell and the delayed release time, and an equation was derived through binomial regression analysis. Based on that equation, a novel triple pulsatile tablet with an innovative structure was devised. The tablet was divided into three components, and the drug was released multiple times at different times. The dose and release rate of the tablets can be adjusted by modifying the infill rate of the printing model. The results indicated that the triple pulsatile tablet exhibited desirable release behavior in vitro. Moreover, the physicochemical properties of the drug, excipients, filaments, and tablets were characterized. All these results indicate that the FDM 3D printing method is a convenient technique for producing preparations with intricate structures.

Unidirectional drug release from 3D printed personalized buccal patches using FDM technology.

Oromucosal delivery of active ingredients of drugs provides a superior administration route for the treatment of oral diseases, due to avoidance of the first pass effect. In the present work, in view of the characteristics of large differences between oral ulcer symptoms and different lesion sizes, dexamethasone acetate unidirectional drug release buccal patches has been prepared based on Fused Deposition Modelling (FDM). Unidirectional drug release was achieved by covering the top and side with ethyl cellulose. Polyvinyl alcohol as a drug carrier, xylitol as a plasticizer. First, the protection effect of different thicknesses of the protective layer is investigated to determine the thickness of the protective layer. Co-extrusion printing method was adapted, utilizing blank filament to regulate preparations with different areas' drug loading. The results show that co-extrusion had no significant impact on the overall patches' drug release and adhesion properties. The physicochemical properties of the patches were also characterized. Evaluation of irritation is showed that these patches do not cause irritation to the oral mucosa of rats. Pharmacodynamic evaluation results showed that the preparation could promote the reduction of ulcer area. The results showed that FDM printing is a convenient and practical approach in manufacturing buccal patches.

Role of polymers in the physical and chemical stability of amorphous solid dispersion: A case study of carbamazepine.

Incorporating the amorphous drug in polymeric components has been demonstrated as a feasible approach to enhance the bioavailability of poorly water-soluble drugs. The objective of this study was to investigate the role of polymers in the stability of amorphous solid dispersion (ASD) by evaluating the drug-polymer interaction, microenvironmental pH, and stability of ASD. Carbamazepine (CBZ), a Biopharmaceutics Classification System Class II compound, was utilized as a model drug. Polyvinylpyrrolidone (PVP), poly(1-vinylpyrrolidone-co-vinyl acetate) (PVPVA), polyacrylic acid (PAA), and hydroxypropyl methylcellulose (HPMCAS) were selected as model polymers. CBZ ASDs were characterized by X-ray diffractometry (XRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Fourier transform infrared (FTIR) spectroscopy, and dissolution studies. Molecular modeling was conducted to understand the strength of interaction between CBZ and each polymer. FTIR spectroscopy and molecular modeling results show that the interaction between CBZ and PAA is the strongest among all the ASDs, as PAA is an acidic polymer with the potential to form strong hydrogen bonding with CBZ. Besides, hydrophobic interaction is detected between CBZ and HPMCAS. CBZ-PAA and CBZ-HPMCAS ASDs reveal better physical stability than CBZ-PVP and CBZ-PVPVA ASDs under 40 °C/75% RH for 8 weeks. However, CBZ-PAA ASD shows chemical degradation after stability testing due to its acidic microenvironmental pH. This paper shows that strong intermolecular interactions between CBZ and polymers contribute to the physical stability of the ASDs. Additionally, acidic polymers yield an acidic microenvironment pH of the ASDs that causes chemical degradation during storage. Hence, a balance between the ability of a given polymer to promote physical stability and chemical stability may need to be considered.