acta 2_2015

Effect of formulation and process variables on the release... 359Table 1. Formulae for compressed tablets.Formulations (% w/w) A B C D EIbuprofen 5 5 5 5 5Polymer (Entandophragma angolenseor hydroxypropylcellulose)- 2.5 5.0 7.5 10.0Talc 2 2 2 2 2Spray dried lactose 93 90.5 88 85.5 83for the tablets. The tablets were stored over silica gelfor 24 h to allow for elastic recovery and hardeningprior to measuring their weights and dimensions.The packing fractions (relative densities), ρ r , of thetablets were calculated using the equation:ρ r = W / Vρ s (1)where V = volume of tablets, W = weights of tablets,ρ s = particle density of formulation.Direct compressionThe formulae for the compressed tablets aregiven in Table 1, and were prepared initially by premixingthe Entandophragma angolense (or hydroxypropylcellulose)and ibuprofen for 15 min.Subsequently, lactose and talc were incorporatedand the resulting composition was mixed for further15 min. Compression was carried out at predeterminedloads using a Carver hydraulic hand press,equipped with a 10.5 mm flat faced punch and dieset lubricated with a 1% dispersion of magnesiumstearate in acetone prior to compression.Crushing strength and friability testsTen tablets from each formulation were testedfor diametrical crushing test using the Erweka TBH 28hardness tester (Apparatebau GmbH, Germany).Measurements were made in quadruplicate and thecrushing strength results were accepted only if thesamples split clearly into two halves. Tablet friabilitywas determined using the Veego tablets friabilityapparatus (Veego Scientific Devices, Mumbai, India).Determination of tensile strength and brittle fractureindexThe tensile strength of the normal tablets (T)and apparent tensile strength of those containing ahole (T o ) were determined at room temperature bydiametral compression (Erweka TBH 28 hardnesstester). Measurements were made in triplicate onindividual tablets and the results accepted only if thesamples split clearly into two halves. Tensilestrength (MNm -2 ) calculated from equation 2 (18):T (or T o ) = 2F/πdt (2) (2)where F is the load (MN) needed to cause fracture,d is the tablet diameter (m), and t is the tablet thickness(m).The brittle fracture index (BFI) of the tabletswas calculated from T and T o by equation 3:BFI = 0.5 [(T / T o )] ñ 1 (3)where T and To are as defined above (5, 18).Disintegration testTablet disintegration time was determined indistilled water, at 37 ± 0.5 O C with the Apex disintegrationtesting apparatus (Apex Construction Ltd.;Northfleet, Gravesend, Dartford, Kent, UK).Determinations were made in triplicate.Mucoadhesion studiesMucoadhesion studies were carried out todetermine the time of detachment (mucoadhesivestrength) of ibuprofen tablets attached to freshlyexcised intestinal mucosa of pig.The rotating cylinder method, which is a slightlymodified dissolution apparatus described in theUnited States Pharmacopoeia (USP) was used (Fig.1). An intestinal segment of the mucosa was fixedon a stainless steel cylinder with the basolateral sidefacing the cylinder. The tablets were pressed on theapical side and the cylinder was transferred into amedium containing 500 mL of phosphate buffer, pH7.4. The rotation speed was set to 60 rpm. The timetaken for the tablets to detach from the mucosa wasobserved for tablets prepared by both wet granulationand direct compression techniques.Factorial experimental designTo study the effects of nature of binder (denotedby N), concentration of binder (denoted by C)and relative density (denoted by D) and tabletingtechnique (denoted by M) on the disintegration time,tensile strength, brittle fracture index and mucoadhesiontime of the tablets, the experiments were performedbased on the statistical modulation proposedby Woolfall (11). The basis of the experiment was toutilize a two-level factor using the four variables,