A comparative study of the dissolution characteristics of capsule and tablet dosage forms of melt granulations of paracetamol--diluent effects.
The dissolution characteristics of melt granulations of paracetamol in capsule and tablet dosage form were compared to determine whether the dissolution characteristics of the granules can be actualized by formulating them as rapidly disintegrating tablets. The term melt granulation refers here to the wax-matrix granules that were formed by triturating the drug powder (paracetamol) with a melted carnauba wax. The matrix granules were admixed with diluents (lactose, alpha-cellulose or microcrystalline cellulose) also in granular form to prevent size separation during encapsulation or tableting. The granules were filled into hard gelatin capsules (mean content weight, 500 +/- 6.2 mg) or tableted (mean weight 500 +/- 5.1 mg, and tensile strength 1.36 +/- 0.2 to 1.7 +/- 0.3 MN/m2). The capsules and tablets were subjected to disintegration and in vitro dissolution tests. The dissolution data were analyzed on the basis of zero, first order rate kinetics and Higuchi square root of time relationship. The results showed that the dissolution profiles were generally consistent with a first order rate kinetics (r = 0.95). The first order dissolution rate constants of capsules and tablets of the matrix granules only (without diluents) were 0.31 +/- 0.02 min(-1) and 0.20 +/- 0.03 min(-1), respectively, indicating faster dissolution from the capsules. Therefore, the dissolution characteristics of the matrix particles were not intact after tableting. Addition of diluents to the capsule formulations had no effect on dissolution rates, whereas in the tablets, dissolution rates increased. For instance, inclusion of a diluent up to 50% w/w in the tablets increased the dissolution rate constants to 0.34 +/- 0.04 min(-1) (lactose), 0.42 +/- 0.02 min(-1) (alpha-cellulose), and 0.46 +/- 0.03 min(-1) (microcrystalline cellulose). Thus, alpha-cellulose and microcrystalline cellulose produced greater enhancer effect on the tablet dissolution rates compared to lactose. Both the capsules and the tablets disintegrated rapidly within 2 to 3 minutes. The dissolution enhancer effect of the diluents in the tablets only, relates to the aqueous swelling of the disintegrated particles.
Department of Pharmaceutics, University of Benin, Benin City, Nigeria. mike2003u@yahoo.com
Michael U
MU
Uhumwangho
Roland S
RS
Okor
D000082:Acetaminophen / Q000737:chemistry*; D018712:Analgesics, Non-Narcotic / Q000737:chemistry*; D002214:Capsules; D002482:Cellulose / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D005079:Excipients / Q000737:chemistry*; D005780:Gelatin; D006244:Hardness; D007700:Kinetics; D007785:Lactose / Q000737:chemistry; D012995:Solubility; D013607:Tablets; D013718:Tensile Strength; D014885:Waxes / Q000737:chemistry*
D018712:Analgesics, Non-Narcotic; D002214:Capsules; D003692:Delayed-Action Preparations; D005079:Excipients; D013607:Tablets; D014885:Waxes; D000082:Acetaminophen; D005780:Gelatin; D002482:Cellulose; D007785:Lactose; C109691:microcrystalline cellulose; C026344:carnauba wax