Compressed Mini Tablets

International Journal of Pharmaceutics 323 (2006) 93–100

Compressed mini-tablets as a biphasic delivery system
Carla M. Lopes a,∗ , Jos´ Manuel Sousa Lobo a , Jo˜ o F. Pinto b , Paulo Costa a e a a b

Departamento de Tecnologia Farmacˆ utica, Faculdade de Farm´ cia, Universidade do Porto, Rua An´bal Cunha 164, 4050-047 Porto, Portugal e a ı Departamento de Tecnologia Farmacˆ utica, Faculdade de Farm´ cia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal e a Received 20 January 2006; received in revised form 9 May 2006; accepted 24 May 2006 Available online 6 June 2006

Abstract Compressed mini-tablets systems are presented as a biphasic delivery system designed for zero-order sustained drug release. The outer layer that fills the void spaces between the mini-tablets was formulated to release the drug in a very short time (fast release), while the mini-tablets provided a prolonged release. Different composition (HPMC or EC) and number (10 or 21) of mini-tablets were used to obtain different drug release rates. The in vitro performance of these systems showed the desired biphasic behaviour: the drug contained in the fast releasing phase (powder enrobing the mini-tablets) dissolved within the first 2 min, whereas the drug contained in the mini-tablets was released at different rates, depending up on formulation. Based on the release kinetic parameters calculated, it can be concluded that mini-tablets containing HPMC were particularly suitable approaching to zero-order (constant) release over 8 h time periods. © 2006 Elsevier B.V. All rights reserved.
Keywords: Biphasic release; Multiple unit dosage form; Compaction of mini-tablets; Tablet characteristics; Tablet dissolution

1. Introduction Oral controlled release drug delivery systems can be classified in two broad groups: single unit dosage forms (SUDFs), such as tablets or capsules, and multiple unit dosage forms (MUDFs), such as granules, pellets or mini-tablets. The concept of

References: Borgquist, P., Nevsten, P., Nilsson, B., Wallenberg, L.R., Axelsson, A., 2004. Simulation of the release from a multiparticulate system validated by single pellet and dose release experiments. J. Contr. Release 97, 453–465. Buri, P., 1984. D´ finition et classification des syst` mes matriciels. S.T.P. Pharm. e e Sci. 3, 193–199. Celik, M., 1994. Compaction of multiparticulate oral dosage forms. In: GhebreSellassier, I. (Ed.), Multiparticulate Oral Drug Delivery. Marcel Dekker, New York, pp. 181–216. Center for Drug Evaluation and Research, 1995. Guidance for industry immediate release solid oral dosage forms scale-up and postapproval changes: chemistry, manufacturing, and controls, in vitro dissolution testing and in vivo bioequivalence documentation, CMC 5. Colombo, P., Conte, U., Caramella, C., Gazzaniga, A., La Manna, A., 1985. Compressed polymeric mini-matrices for drug release control. J. Contr. Release 1, 283–289. Colombo, P., Bettini, R., Santi, P., Peppas, N.A., 2000. Swellable matrices for controlled drug delivery: gel-layer behaviour, mechanisms and optimal performance. PSTT 3, 198–204. Costa, P., Sousa Lobo, J.M., 2001. Modelling and comparison of dissolution profiles. Eur. J. Pharm. Sci. 13, 123–133. Cox, P.J., Khan, K.A., Munday, D.L., Sujja-areevath, J., 1999. Development and evaluation of a multiple unit oral sustained release dosage form for S(+)-ibuprofen: preparation and release kinetics. Int. J. Pharm. 193, 73–84. De Brabander, C., Vervaet, C., Fiermans, L., Remon, J.P., 2000. Matrix minitablets based on starch/microcrystalline wax mixtures. Int. J. Pharm. 199, 195–203. Donbrow, M., Samuelov, Y., 1980. Zero order drug delivery from double-layered porous films: release rate profiles from ethyl cellulose, hydroxypropyl cellulose and polyethylene glycol mixtures. J. Pharm. Pharmacol. 32, 463–470. EMEA, 1999. European Agency for the Evaluation of Medicinal Products, Human Medicines Evaluation Unit, Note for Guidance on Quality of Modified Release Products: A. Oral Dosage Forms; B. Transdermal Dosage Forms; Section I (Quality), CPMP/QWP/604/96. Fell, J.T., Newton, J.M., 1968. The tensile strength of lactose tablets. J. Pharm. Pharmacol. 20, 205–212. Gandhi, R., Kaul, C.L., Panchagnula, R., 1999. Extrusion and spheronization in the development of oral controlled release dosage forms. PSST 2, 160–170. Gross, S.T., Hoffman, A., Donbrow, M., Benita, S., 1986. Fundamentals of the release mechanism interpretation in multiparticulate systems: the prediction of the commonly observed release equations from statistical population models for particle ensembles. Int. J. Pharm. 29, 213–222. Higuchi, T., 1961. Rate of release of medicaments from ointment bases containing drugs in suspension. J. Pharm. Sci. 50, 874–875. Higuchi, T., 1963. Mechanism of sustained-action medication. Theoretical analysis of rate of release of solid drugs dispersed in solid matrices. J. Pharm. Sci. 52, 1145–1149.