EFFECT OF FORMULATION TECHNIQUES ON DRUG RELEASE FROM PARACETAMOL TABLETS

ABSTRACT

Drug manufacturers employ various formulation techniques in the manufacture of the same dosage form and this may influence the rate of drug release from such dosage forms. The objective of this study was to investigate the effect of formulation techniques on drug release, using paracetamol as a drug model. Three formulation techniques were employed in this study to formulate paracetamol granules i.e. (aqueous dispersion, solid dispersion and wet granulation). 15% w/v aqueous dispersion of Eudragit polymer RS PO® obtained by coacervation technique, was used to wet mass 20g of paracetamol. In another approach, 15% w/v and 20% w/v of Eudragit polymer RS PO® with the addition of 20g of paracetamol each, were dissolved in ethanol overnight and allowed to evaporate at room temperature to form solid dispersion of paracetamol granules. Conventional granules were formed also with 15% w/v maize starch mucilage as binder by wet granulation. The resulting granules were subjected to flow properties and tableting characteristics. The parameters evaluated were; angle of repose, bulk density, tapped density, carr’s index and hausner ratio. The granules were mixed with maize starch (5% w/w) and magnesium stearate (1% w/w) before being compressed into 500.40±0.60mg tablets. The tablets were evaluated for hardness, friability, disintegration times and dissolution rates. Replicate determinations were carried out and mean values were reported with their standard deviations. The results from the flow properties of the granules are as follows: angle of repose ranged from (35.68±0.48 - 36.72±0.50º), carr’s index (10.50±0.50 - 14.26±0.05%), hausner ratio (1.11±0.02 – 1.14±0.01). The hardness values ranged from (8.40±0.40 – 10.80±0.45 kp) and friability values ranged from (0.23±0.03 – 0.92±0.02%). The disintegration times of the paracetamol tablets formulated by coacervation technique or solid dispersion failed the BP specification of 15 minutes, whereas the conventional tablets passed. The disintegration times are as follows: conventional tablets (4.72±0.86 minutes), aqueous dispersion (48.84±0.14 minutes) and solid dispersion (15% w/v-80.86±0.60, 20% w/v-100.38±0.32 minutes) respectively. Hence the tablets formed by coacervation and solid dispersion technique may be regarded as matrix tablets. The results of the dissolution tests showed that the conventional tablets released 99.97% of their drug content at 1 hour, while the maximum drug release from the matrix tablets was ≥ 96.10% of their drug content at 6 hours.