Development of a Mini-Tablet of Co-Grinded Prednisone–Neusilin Complex for Pediatric Use

Abstract

Abstract. The purpose of this study is to enhance the dissolution rate of prednisone by co-grinding with Neusilin to form a complex that can be incorporated into a mini-tablet formulation for pediatrics. Prednisone-Neusilin complex was co-grinded at various ratios (1:1, 1:3, 1:5, and 1:7). The physicochemical properties of the complex were characterized by various analytical techniques including: differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), scanning electron microscope (SEM), particle size, surface area, solubility, and dissolution rate. The co-grinded prednisone-Neusilin complex (1:7) was blended with other excipients and was formulated into a 2-mm diameter mini-tablet. The minitablets were further evaluated for thickness, weight, content uniformity, and dissolution rate. To improve taste masking and stability, mini-tablets were coated by dip coating with Eudragit® EPO solution. DSC and XRPD results showed that prednisone was transformed from crystalline state into amorphous state after co-grinding with Neusilin. Particle size, surface area, and SEM results confirmed that prednisone was adsorbed to Neusilin's surface. Co-grinded prednisone-Neusilin complex (1:7) had a solubility of 0.24 mg/ mL and 90% dissolved within 20 min as compared to crystalline prednisone which had a solubility of 0.117 mg/mL and 30% dissolved within 20 min. The mini-tablets containing co-grinded prednisoneNeusilin complex (1:7) exhibited acceptable physicochemical and mechanical properties including dissolution rate enhancement. These mini-tablets were successfully dip coated in Eudragit® EPO solution to mask the taste of the drug during swallowing. This work illustrates the potential use of co-grinded prednisone-Neusilin to enhance solubility and dissolution rate as well as incorporation into a mini-tablet formulation for pediatric use.

Feasibility of mini-tablets as a flexible drug delivery tool

“…In the literature, mini-tablet formulations for various types of drug substances (DSs), such as prednisone (Lou et al, 2013;Poller et al, 2017), sodium salicylate (Hagen et al, 2016), risperidone (ElSay et al, 2015), hydrochlorothiazide (Stoltenberg and Breitkreutz, 2011), and quinine, ibuprofen, and plant extract (Tissen et al, 2011) have been documented. Tissen et al (2011) evaluated the manufacturing feasibility of 1 and 2 mm mini-tablets of high concentration (70-90%) powder, dry granules, powder/granule mixtures of ibuprofen, quinine HCl, and spray dried gentian extract.…”

Glibenclamide Mini-tablets with an Enhanced Pharmacokinetic and Pharmacodynamic Performance

“…These results can be explained on the basis of differences in the relative adsorption power of each of the investigated adsorbents. Laponites have the highest adsorption power among the investigated adsorbents due to their extensive specific surface area (surface area per unit mass) reaching 900 m 2 /g [36] followed by Neusilin US2 (300 m 2 /g) [38] and finally, Aerosil 200 and Florite R (135-200 m 2 /g) [39,40]. The superiority of Florite R over Aerosil 200 can be attributed to its extensive internal pore structure [40] as well as its basic nature giving it better affinity towards acidic drugs like GLC [41].…”

Mini-tablets: a contemporary system for oral drug delivery in targeted patient groups

“…The minitablets were based on a prednisone--Neusilin Ò (magnesium aluminosilicate with large surface area; Fuji Chemical Industry) co-ground dispersion (1:7), which provided formation of a stable amorphous drug--carrier complex and thus improved drug solubility and the dissolution rate. Coating mini-tablet cores with pH-sensitive Euragite Ò EPO (Evonik) disabled drug release in simulated saliva (2% within 2.5 min), enabled rapid drug release in simulated gastric fluid and increased drug stability (decreased the moisture uptake and degree of drug recrystallization) [37]. Roberts et al developed 2.5 mg hydrocortisone mini-tablets (3 mm) for accurate pediatric dosing.…”