Preparation and evaluation of an ispaghula based directly compressible matrixing agent for controlled release

The objective of the present investigation was to prepare and evaluate an ispaghula husk based directly compressible (DC) adjuvant that can be used as matrixing agent using an agglomeration technique. Addition of hydroxypropyl methylcellulose was found necessary to improve cohesion. Lactose (X1), calcium hydrogen phosphate dihydrate (X2) and Avicel PH101 (X3), used along with ispaghula in preparation of agglomerates, were selected as three independent variables in a simplex lattice design affecting compressional and dissolution characteristics of the drug from the DC adjuvant. The agglomerates were evaluated for their flow properties. Tablets were prepared using 70% agglomerates and 30% acetaminophen, a poorly compressible drug, and were subjected to in vitro drug release study. Amounts of the drug released at the end of 60 min (Y60), 300 min (Y300) and 480 min (Y480) were selected as dependent variables in a simplex lattice design. Batch IH05 that contained lactose and calcium hydrogen phosphate dihydrate in a 1:2 ratio could control the release for 12 hours and thus form the basis for twice a-day-dosing. Cilj rada bila je priprava i vrednovanje pomoćne tvari za izravnu kompresiju dobivene iz ljuski ispagule, primjenjive u izradi pripravaka metodom aglomeracije. Dodatak hidroksipropil metilceluloze bio je neophodan za povećanje kohezije. U pripravi aglomerata s ispagulom upotrebljeni su laktoza (X1), kalcijev hidrogenfosfat dihidrat (X2) i Avicel PH101 (X3). U eksperimentalnom dizajnu (simplex lattice design) te tri tvari izabrane su kao nezavisne varijable. Proučavan je njihov utjecaj na kompresibilnost i oslobađanje ljekovite tvari iz pripravka dobivenih izravnom kompresijom te svojstva tečnosti aglomerata. Tako dobiveni aglomerati upotrebljeni su za pripravu tableta teško kompresibilne tvari acetaminofena (omjer aglomerata i ljekovite tvari 7:3). Količine oslobođene tvari in vitro pri kraju 60 min (Y60), 300 min (Y300) i 480 min (Y480) bile su zavisne varijable. Iz pripravka IH05 koji sadrži laktozu i kalcijev hidrogenfosfat dihidrat u omjeru 1:2 kontrolirano se oslobađa ljekovita tvar tijekom 12 sati, što je dobar temelj za doziranje dva puta dnevno.