Suitability of κ-carrageenan pellets for the formulation of multiparticulate tablets with modified release.

κ-Carrageenan is a novel pelletisation aid with high formulation robustness and quick disintegration leading to fast drug release unlike the matrix-like release from non-disintegrating microcrystalline cellulose pellets. Compression of pellets into tablets is cost effective. The feasibility of formulating multiparticulate tablets with coated κ-carrageenan pellets was investigated. Pellets containing a highly soluble drug in acid, namely bisacodyl and κ-carrageenan or MCC as pelletisation aid were prepared, enteric coated with a mixture of Kollicoat(®) MAE 30 DP and Eudragit(®) NE 30 D and compressed using silicified microcrystalline cellulose as embedding powder. The effect of coating level, type of pellet core, compression force and punch configurations on drug release were studied. A sufficient coating thickness for κ-carrageenan pellets was necessary to obtain multiparticulate tablets with adequate resistance in the acid stage regardless of the compression pressure used. While κ-carrageenan pellets and their tablets released over 80% of the drug during the neutral stage only about 20-24% was released from MCC pellets and their tablets. The type of punches used (oblong or round) did not significantly influence the drug release from the prepared tablets. Moreover, sufficient prolonged release properties were obtained with κ-carrageenan pellets containing theophylline as a model drug and coated with Kollicoat(®) SR 30 D using Kollicoat(®) IR as pore former. A lower coating level and higher amount of pore former were needed in case of theophylline pellets formulated with MCC as pelletisation aid. The sustained release properties of both coated pellet formulations were maintained after compression at different compression pressures.

[1]  J. Krämer,et al.  Biopharmaceutical aspects of multiparticulates , 1994 .

[2]  R. Bodmeier,et al.  Compression of pellets coated with various aqueous polymer dispersions. , 2004, International journal of pharmaceutics.

[3]  K. Lehmann CHEMISTRY AND APPLICATION PROPERTIES OF POLYMETHACRYLATE COATING SYSTEMS , 1997 .

[4]  R. Bodmeier,et al.  Mechanical Properties of Dry and Wet Cellulosic and Acrylic Films Prepared from Aqueous Colloidal Polymer Dispersions Used in the Coating of Solid Dosage Forms , 1994, Pharmaceutical Research.

[5]  Jean Paul Remon,et al.  Development and in vitro evaluation of an enteric-coated multiparticulate drug delivery system for the administration of piroxicam to dogs. , 2002, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[6]  P. Kleinebudde,et al.  Use of kappa-carrageenan as alternative pelletisation aid to microcrystalline cellulose in extrusion/spheronisation. I. Influence of type and fraction of filler. , 2006, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[7]  Farrukh Zeeshan,et al.  Development and Evaluation of a Novel Modified-Release Pellet-Based Tablet System for the Delivery of Loratadine and Pseudoephedrine Hydrochloride as Model Drugs , 2010, AAPS PharmSciTech.

[8]  P. Nováková,et al.  A Study of the Properties of Compacts from Silicified Microcrystalline Celluloses , 2007, Drug development and industrial pharmacy.

[9]  P. Kleinebudde,et al.  A new multiparticulate delayed release system.: Part I: Dissolution properties and release mechanism , 1997 .

[10]  Deying Cao,et al.  An investigation into the characteristics of chitosan/Kollicoat SR30D free films for colonic drug delivery. , 2009, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[11]  K. Picker-Freyer,et al.  Tableting and tablet properties of alginates: characterisation and potential for Soft Tableting. , 2009, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[12]  N. Pilpel,et al.  Tensile strength and compression of coated pharmaceutical powders: tablets , 1983 .

[13]  P. Kleinebudde,et al.  Effect of drying on extruded pellets based on κ-carrageenan , 2007 .

[14]  Peter Kleinebudde,et al.  Use of kappa-carrageenan as alternative pelletisation aid to microcrystalline cellulose in extrusion/spheronisation. II. Influence of drug and filler type. , 2006, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[15]  P. Schmidt,et al.  Compression of enteric-coated pellets to disintegrating tablets , 1996 .

[16]  Rok Dreu,et al.  Development of a multiple-unit tablet containing enteric-coated pellets , 2011, Pharmaceutical development and technology.

[17]  Roland Bodmeier,et al.  Tableting of coated pellets , 1997 .

[18]  H. Bechgaard,et al.  Controlled-Release Multiple-Units and Single-Unit Doses a Literature Review , 1978 .

[19]  M. Celik Compaction of multiparticulate oral dosage forms , 1994 .

[20]  Peter Kleinebudde,et al.  Compression behaviour of kappa-carrageenan pellets. , 2010, International journal of pharmaceutics.

[21]  J. W. Moore,et al.  Mathematical comparison of dissolution profiles , 1996 .

[22]  P. Kleinebudde,et al.  Properties of pellets manufactured by wet extrusion/spheronization process using κ-carrageenan: Effect of process parameters , 2007, AAPS PharmSciTech.