ACETYLATION AND CHARACTERIZATION OF ENSET STARCH AND EVALUATION OF ITS DIRECT COMPRESSION AND DRUG RELEASE SUSTAINING PROPERTIES Efrem Nigussu, Anteneh Belete and Tsige Gebre-Mariam*

Enset (Ensete ventricosum, Musaceae), a plant widely cultivated in south and southwest of Ethiopia, has been shown to be a rich source of starch. In an effort to produce directly compressible matrixforming excipient, native enset starch was acetylated. Starch acetates (SA) with degrees of substitution (DS) of 0.672 and 2.142 were evaluated. Fourier transform infrared (FTIR) spectra of the modified starches verified the acetylation of the starch molecules. Further investigations revealed that acetylation increased swelling power and solubility, improved flow property and compactability of the starch. The tensile strength of SA matrix tablets increased with an increase in DS. Plain tablets of SA with DS 0.672 disintegrated within 3 min while those of SA with DS 2.142 did not disintegrate over a period of 2 h. Dissolution studies of theophylline loaded SA tablets conducted in 0.1 N HCl for the first 1.5 h and in phosphate buffer pH 6.8 for the remaining study time revealed the change in drug release rate from rapid to sustained release (>12 h) as the DS increased from 0.672 to 2.142. The dissolution data obtained best fitted Higuchi model with R > 0.99. The drug release diffusional exponent (n), obtained from Korsemeyer-Peppas model, varied between 0.4899 0.6369 for different theophylline/SA ratios and the goodness of the fit was > 0.99 in each case which indicated the deviation from Fickian diffusion. Accordingly, high degree of acetylation renders enset starch highly compressible and suitable for sustained release formulations that makes it amenable for use as an alternative pharmaceutical excipient. INTRODUCTION: Native starches are less favored in direct compression of tablet dosage form and are inappropriate for controlling drug release. Hence, they are chemically modified to improve their direct compression and drug release sustaining properties 1-7 .

[1]  T. Gebre-Mariam,et al.  Cross-linking Enset Starch Microspheres, Physicochemical Characterization and Study on Their Drug Loading and Release Properties , 2010 .

[2]  A. Biswas,et al.  Acetylation of starch with vinyl acetate in imidazolium ionic liquids and characterization of acetate distribution , 2010 .

[3]  F. Onofre,et al.  Hydroxypropylated starches of varying amylose contents as sustained release matrices in tablets. , 2010, International journal of pharmaceutics.

[4]  M. Mateescu,et al.  Carboxymethyl high amylose starch as excipient for controlled drug release: mechanistic study and the influence of degree of substitution. , 2009, International journal of pharmaceutics.

[5]  Cheon-Seok Park,et al.  Ultra high pressure (UHP)-assisted acetylation of corn starch , 2009 .

[6]  B. Bhandari,et al.  Preparation of crosslinked starch microspheres and their drug loading and releasing properties , 2008 .

[7]  Vivek S. Dave,et al.  Compression and Compaction , 2008 .

[8]  L. Cartilier,et al.  High-amylose sodium carboxymethyl starch matrices for oral, sustained drug-release: formulation aspects and in vitro drug-release evaluation. , 2008, International journal of pharmaceutics.

[9]  K. Picker-Freyer,et al.  Analysis of the Material and Tablet Formation Properties of four Dioscorea Starches , 2007 .

[10]  Si-yuan Guo,et al.  Acetylated starch-based biodegradable materials with potential biomedical applications as drug delivery systems , 2007 .

[11]  M. Khan,et al.  Controlled Release Multiparticulate Beads Coated with Starch Acetate: Material Characterization, and Identification of Critical Formulation and Process Variables , 2007, Pharmaceutical development and technology.

[12]  H W Frijlink,et al.  The effect of powder blend and tablet structure on drug release mechanisms of hydrophobic starch acetate matrix tablets. , 2005, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[13]  L. Kaur,et al.  Effect of acetylation on some properties of corn and potato starches , 2004 .

[14]  M. Hanna,et al.  Synthesis and Characterization of Starch Acetates with High Substitution , 2004 .

[15]  A. Urtti,et al.  Determination of the degree of substitution of acetylated starch by hydrolysis, 1H NMR and TGA/IR , 2004 .

[16]  M. Al-Higari,et al.  Acylation of starch with vinyl acetate in water , 2004 .

[17]  A. Urtti,et al.  Evaluation of novel starch acetate-diltiazem controlled release tablets in healthy human volunteers. , 2004, Journal of controlled release : official journal of the Controlled Release Society.

[18]  P. Paronen,et al.  Starch acetate as a tablet matrix for sustained drug release. , 2004, Journal of controlled release : official journal of the Controlled Release Society.

[19]  E. Pérez,et al.  Effect of Acetylation on Some Properties of Rice Starch , 2002 .

[20]  P. Paronen,et al.  Acetylation Enhances the Tabletting Properties of Starch , 2002, Drug development and industrial pharmacy.

[21]  P. Paronen,et al.  Starch Acetates—Multifunctional Direct Compression Excipients , 2000, Pharmaceutical Research.

[22]  S. Neau,et al.  Sustained release theophylline tablets by direct compression: Part 1: formulation and in vitro testing , 1998 .

[23]  W C Grabb,et al.  The experimental method. , 1972, Plastic and reconstructive surgery.

[24]  J. Newton,et al.  Determination of tablet strength by the diametral-compression test. , 1970, Journal of pharmaceutical sciences.

[25]  P. Paronen,et al.  Effects of physical properties for starch acetate powders on tableting , 2008, AAPS PharmSciTech.

[26]  Jaspreet Singh,et al.  Factors influencing the physico-chemical, morphological, thermal and rheological properties of some chemically modified starches for food applications--A review , 2007 .

[27]  R. Sutinen,et al.  Starch acetate--a novel film-forming polymer for pharmaceutical coatings. , 2002, Journal of pharmaceutical sciences.

[28]  O. Paredes-López,et al.  Acetylation and characterization of banana (Musa paradisiaca) starch. , 2000, Acta cientifica venezolana.

[29]  R. Shogren.  Preparation, thermal properties, and extrusion of high-amylose starch acetates , 1996 .

[30]  P. Schmidt,et al.  Isolation and Physico‐chemical Properties of Enset Starch , 1996 .

[31]  P. Schmidt,et al.  An evaluation of the disintegration efficiency of a sodium starch glycolate prepared from enset starch in compressed tablets , 1996 .