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
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.
(C. FUNARO ET AL.)
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.
TH (particles lower than 100 Ám) 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).