Preparation and Evaluation of Hot-Melt Extruded Patient-Centric Ketoprofen Mini-Tablets

Abstract

Background Bitter tasting drugs represent a large portion of active pharmaceutical ingredients. Mini-tablets are specifically designed for patients with difficulty in swallowing particular in young children up to 10 years of age, geriatric patients and patients with esophagitis. Objective The present study was aimed to prepare, taste-masked mini-tablets, which are easily swallowed dosage forms, primarily to be used by pediatric and geriatric patients. Methods Ketoprofen (10%–50% w/w) and Eudragit® EPO were blended and extruded with a 5-mm strand die and cut into consistent mini-tablets by using an adapted downstream pelletizer. Results Differential scanning calorimetry and polarized light microscopy-hot stage microscopy studies confirmed that the binary mixtures were miscible under the employed extrusion temperatures. In-vitro release studies showed that drug release was less than 0.5% within the first 2 min in simulated salivary fluid (pH 6.8) and more than 90% in the first 20 min in gastric media (pH 1.0). The results of the electronic tongue analysis were well correlated with the drug release profile of the mini-tablets in the artificial saliva. Scanning electron microscopy revealed no cracks on the surface of the mini-tablets, confirming that the mini-tablets were compact solids. Chemical imaging confirmed the uniform distribution of ketoprofen inside the polymer matrices. Conclusion Eudragit® EPO containing ketoprofen at various drug loads were successfully melt extruded into tasted-masked mini-tablets. The reduced drug release at salivary pH correlated well with Astree e-Tongue studies for taste masking efficiency.

Eudragit®: A Versatile Family of Polymers for Hot Melt Extrusion and 3D Printing Processes in Pharmaceutics

“…Mini-tablets are solid systems with a diameter of 2–5 mm or smaller, having great appeal for children, geriatric patients and patients who have a general difficulty in swallowing. Mini-tablets were obtained by HME with the presence of a pelletizer at the end of the extruder [ 90 , 95 ]. EE was used as a polymeric matrix for the development of HME mini-tablets containing ketoprofen, to mask its bitter taste.…”

“…EE was used as a polymeric matrix for the development of HME mini-tablets containing ketoprofen, to mask its bitter taste. The choice of EE in this formulation was also rationally based on the cationic behavior of this polymer, which facilitated the intermolecular interaction with ketoprofen, an anionic drug [ 90 ]. ERL was also used to develop acetaminophen floating mini-tablets, which were obtained by the injection of pressurized non-toxic and inert CO 2 gas in different zones of the extruder, with the aim of forming pores in the polymeric matrix.…”

Degradable polymeric vehicles for postoperative pain management

“…The least invasive, most popular method affording the greatest patient control method is oral delivery. Oral pills/tablets/capsules can be formulated using various methods, such as compression or injection molding 45,46 , 3-D printing 47,48 , extrusion 49,50 , and coating 51 to name a few. In these systems, an API is typically homogenously mixed into a matrix of controlled release agent(s) to be released via diffusion or degradation of the matrix when introduced to an external environment.…”

Electrosprayed Ultra-Thin Coating of Ethyl Cellulose on Drug Nanoparticles for Improved Sustained Release

“…Among them, polymeric coating is one of the most popular strategies for modifying the drug release kinetics in both the traditional pharmaceutical industry and also the advanced laboratory nanomethods [ 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 ]. Particularly in nanopharmaceutics, the simple and robust nanocoating methods are highly desired [ 14 , 15 , 16 , 17 , 18 ]. In general, there are two kinds of nanofabrication routes, i.e., bottom-up and top-down [ 19 , 20 , 21 ].…”