The Formulation and Evaluation of Customized Prednisolone Gel Tablets Prepared by an Automated Extrusion-Based Material Deposition Method

Abstract

Background/Objectives: An automated extrusion-based material deposition is a contemporary and rapid method for pharmaceutical dose-dispensing and preparing (printing) individualized solid dosage forms. The aim of this study was to investigate and gain knowledge of the feasibility of automated extrusion-based material deposition technology in preparing customized prednisolone (PRD)-loaded gel tablets for veterinary applications (primarily for dogs and cats). Methods: The PRD loads of the extrusion-based deposited gel tablets were 0.5% and 1.0%, and the target weights of tablets were 0.250 g, 0.500 g, and 1.000 g. The effects of the material deposition processes on the physical solid state, in vitro dissolution, and the physicochemical stability of PRD gel tablets were investigated. Results: The small-sized gel tablets presented a uniform round shape with an exceptionally smooth outer surface texture. The actual average weight of the tablets (n = 10) was very close to the target weight, showing the precision of the process. We found that PRD was in a pseudopolymorphic sesquihydrate form (instead of an initial PRD crystalline form II) in the gel tablets. In all the immediate-release gel tablets studied, more than 70% of the drug load was released within 30 min. The soft texture and dimensions of gel tablets affected the dissolution behaviour in vitro, suggesting the need for further development and standardization of a dissolution test method for such gel tablets. A short-term storage stability study revealed that the content of PRD did not decrease within 3 months. Conclusions: Automated extrusion-based material deposition is a feasible method for the rapid preparation of gel tablets intended for veterinary applications. In addition, the present technology and gel tablets could be used in pediatric and personalized medicine where precise dosing is crucial.

Keywords: automated extrusion-based material deposition; dissolution in vitro; gel tablet; prednisolone; solid-state change; storage stability; veterinary medicine.

Figure 1

Photograph of the gel tablets with different target weights prepared by an automated extrusion-based material deposition method. From left to right: tablet 0.250 g, tablet 0.500 g, and 1.000 g mass.

Figure 2

(A,B): Scanning electron microscopy (SEM) images of prednisolone (PRD) #1 powder crystals. (C–F): The surface of gel tablets. The reference gel tablet without API (C,D). The gel tablet (1.000 g) containing 10 mg (1%) of PRD (E,F). (G–J): The cross-section of gel tablets. The reference gel tablet without API (G,H). The gel tablet (1.0 g) containing 10 mg (1%) of PRD (I,J). Partial re-crystallization of PRD on the surface of gel tablet (E,F) and to a minor extent inside a gel tablet (I,J) is indicated with white arrows. Magnification in the left column 1500× (scale bar 20 µm) and in the right column 5000× (scale bar 10 µm).

Figure 3

Raman spectra of prednisolone (PRD) #1 powder and gel tablets. Vertical lines and asterisks are used to indicate the most important peaks of PRD #1 powder. The Raman spectra of gel tablets are presented for both blister packaging (B) and tube (T) samples. * indicates characteristic peaks of PRD.

Figure 4

(A) Fourier-transform infrared (FTIR) spectra of prednisolone (PRD) #1 and PRD #2 powders. (B) FTIR spectra of gel tablets and PRD) #1 powder investigated in the present study. The FTIR spectra of gel tablets are presented for the tablets packed in a blister pack (B) and in a tube (T).

Figure 5

X-ray diffraction (XRD) patterns for (A) prednisolone (PRD) #1 powder and gel tablets, and for (B) the physical mixtures of Curavet™ components with (green line) and without (black line) PRD. The target weight for the gel tablets were 0.250 g, 0.500 g, and 1.000 g, and the tablets were stored in blister packs. Key: MCC = microcrystalline cellulose, PRD I = PRD polymorphic form I, PRD II = PRD polymorphic form II, and * = the major peaks of a PRD sesquihydrate form. The corresponding theoretical X-ray diffractograms are retrieved from the Cambridge Structural Database [35].

Figure 6

In vitro dissolution profiles of prednisolone (PRD) gel tablets (n = 4–10). The dissolution tests were conducted one week after the gel-printing process and after the storage of three months in a refrigerator (+3–8 °C). Key: (A) PRD gel tablets 0.5%/0.500 g originally packed in blisters (Batch II); (B) PRD gel tablets 1%/0.500 g packed in blisters (Batch II); (C) PRD gel tablets 1%/0.250 g packed in blisters (Batch III); (D) PRD gel tablets 1%/1.000 g packed in blisters (Batch III). The standard deviation (SD) of all dissolution results was less than 16.3%, and in most cases, in the range of 0.5–3.5%.

Figure 7

In vitro dissolution profiles of prednisolone (PRD) gel tablets with a drug load of 1% (n = 4–10). The weight of the tablets were 0.250 g (Batch III), 0.500 g (Batch II), and 1.000 g (Batch III). The dissolution tests were conducted one week after the printing process. The gel tablets were packed in a blister pack. The standard deviation (SD) of dissolution results was less than 5% for the gel tablets 0.25 g and 1.0 g, and less than 16.3% for the gel tablets 0.5 g.