Minitablets Coated in a Solid-Wall Pan for Theophylline Sustained-Release Capsules

The authors describe an alternative approach to compressing and coating minitablets for use in a sustained-release, solid oral-dosage form. This article is part of a special Drug Delivery issue.
Nov 01, 2010
Volume 2010 Supplement, Issue 6

This article is part of a special issue on Drug Delivery

The production of minitablets for the sustained release of a drug is a new and promising area in pharmaceutical research. Minitablets (also known as microtablets) have a diameter equal to or smaller than 2–3 mm and can be filled into hard gelatine capsules (1).

Minitablets are multiple-unit dosage forms, therefore, they present all the advantages of these systems over the single-unit dosage forms. These advantages include a low risk of dose dumping, less inter- and intra-subject variability, and a high degree of dispersion in the digestive tract, thus minimizing the risks of high local drug concentrations and reproducible bioavailability.

Minitablets are good substitutes for other multiparticulate dosage forms (e.g., granules and pellets) because they can be manufactured by direct compression. As a consequence, the use of solvents is avoided and high production yields are obtained compared to extrusion and spheronization processes. Furthermore, due to the manufacturing process, defined size and strengths can easily be produced, with small variability within and between batches (1, 2).

Sustained-release minitablets can be produced either by matrix or by coating them in a fluid bed or coating pan (3–6). Unfortunately, little published information is available on both minitablet-coating technologies and the coating of minitablets in a pan (5, 6). However, from an industrial point of view, the coating of minitablets in a pan should be extremely convenient because it provides higher production capabilities, lower waste of coating materials, and faster equipment cleaning time with respect to the fluid bed.

The aim of this research was to investigate the possibility of manufacturing a sustained-release, multiple-dosage form by coating minitablets, produced by direct compression, in a solid wall pan. Theophylline (TH) was used as the model drug, and an innovative ready-to-use pigment dispersion was tested to evaluate the possibility of reducing production time when compared with a traditional coating formulation. Finally, coated minitablets were filled into hard gelatine capsules.

Experimental methods

Materials. TH (particles lower than 100 µm) was purchased from BASF (Ludwigshafen, Germany). Avicel PH 102 was supplied by FMC Biopolymer (Brussels). Spray-dried lactose, magnesium stearate, talc, titanium dioxide, trietilcitrate and yellow quinoline (all European Pharmacopoeia-grade) were purchased from Polichimica (Bologna, Italy) and used as received. Eudragit RL, Eudragit RS (Evonik, Darmstadt, Germany, polymer conforms to Ammonio Methacrylate Copolymer, Type A USP/NF 31) and WAS (a product containing talc, titanium dioxide, yellow quinoline and trietilcitrate) were supplied by Rofarma Italia (Milano, Italy). Hard gelatine capsules size 0 were purchased from Capsugel (Colmar, France).

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